Latest documents http://publikationen.ub.uni-frankfurt.de/index/index/ Tue, 05 Mar 2013 14:09:09 +0200 Tue, 05 Mar 2013 14:09:09 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29498 Recent clinical data support the clinical use of oral lavender oil in patients suffering from subsyndromal anxiety. We identified the molecular mechanism of action that will alter the perception of lavender oil as a nonspecific ingredient of aromatherapy to a potent anxiolytic inhibiting voltage dependent calcium channels (VOCCs) as highly selective drug target. In contrast to previous publications where exorbitant high concentrations were used, the effects of lavender oil in behavioral, biochemical, and electrophysiological experiments were investigated in physiological concentrations in the nanomolar range, which correlate to a single dosage of 80 mg/d in humans that was used in clinical trials. We show for the first time that lavender oil bears some similarities with the established anxiolytic pregabalin. Lavender oil inhibits VOCCs in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines in the same range such as pregabalin. Interestingly, Silexan does not primarily bind to P/Q type calcium channels such as pregabalin and does not interact with the binding site of pregabalin, the α2δ subunit of VOCCs. Lavender oil reduces non-selectively the calcium influx through several different types of VOCCs such as the N-type, P/Q-type and T-type VOCCs. In the hippocampus, one brain region important for anxiety disorders, we show that inhibition by lavender oil is mainly mediated via N-type and P/Q-type VOCCs. Taken together, we provide a pharmacological and molecular rationale for the clinical use of the oral application of lavender oil in patients suffering from anxiety. Anita M. Schuwald; Michael Nöldner; Thomas Wilmes; Norbert Klugbauer; Kristina Leuner; Walter E. Müller article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29498 Fri, 03 May 2013 14:09:09 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29268 During the second part of the TROCCINOX campaign that took place in Brazil in early 2005, chemical species were measured on-board of the high altitude research aircraft Geophysica (ozone, water vapor, NO, NOy, CH4 and CO) in the altitude range up to 20 km (or up to 450 K potential temperature), i.e. spanning the TTL region roughly extending between 350 and 420 K. Analysis of transport across TTL is performed using a new version of the Chemical Lagrangian Model of the Stratosphere (CLaMS). In this new version, the stratospheric model has been extended to the earth surface. Above the tropopause, the isentropic and cross-isentropic advection in CLaMS is driven by ECMWF winds and heating/cooling rates derived from a radiation calculation. Below the tropopause the model smoothly transforms from the isentropic to hybrid-pressure coordinate and, in this way, takes into account the effect of large-scale convective transport as implemented in the ECMWF vertical wind. As with other CLaMS simulations, the irreversible transport, i.e. mixing, is controlled by the local horizontal strain and vertical shear rates. Stratospheric and tropospheric signatures in the TTL can be seen both in the observation and in the model. The composition of air above ≈350 K is mainly controlled by mixing on a time scale of weeks or even months. Based on CLaMS transport studies where mixing can be completely switched off, we deduce that vertical mixing, mainly driven by the vertical shear in the outflow regions of the large-scale convection and in the vicinity of the subtropical jets, is necessary to understand the upward transport of the tropospheric air from the main convective outflow around 350 K up to the tropical tropopause around 380 K. This mechanism is most effective if the outflow of the mesoscale convective systems interacts with the subtropical jets. Paul Konopka; Gebhard Günther; Rolf Müller; Fábio Henrique Silva dos Santos; Cornelius Schiller; Fabrizio Ravegnani; Alexey Ulanovsky; Hans Schlager; C.-Michael Volk; Silvia Viciani; Laura L. Pan; Daniel-S. McKenna; Martin Riese article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29268 Fri, 22 Mar 2013 13:18:02 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29259 The Match method for quantification of polar chemical ozone loss is investigated mainly with respect to the impact of mixing across the vortex edge onto this estimate. We show for the winter 2002/03 that significant mixing across the vortex edge occurred and was accurately modeled by the Chemical Lagrangian Model of the Stratosphere. Observations of inert tracers and ozone in-situ from HAGAR on the Geophysica aircraft and sondes and also remote from MIPAS on ENVISAT were reproduced well. The model even reproduced a small vortex remnant that was isolated until June 2003 and was observed in-situ by a balloon-borne whole air sampler. We use this CLaMS simulation to quantify the impact of cross vortex edge mixing on the results of the Match method. It is shown that a time integration of the determined vortex average ozone loss rates as performed in Match results in larger ozone loss than the polar vortex average ozone loss in CLaMS. Also, the determination of the Match ozone loss rates can be influenced by mixing. This is especially important below 430 K, where ozone outside the vortex is lower than inside and the vortex boundary is not a strong transport barrier. This effect and further sampling effects cause an offset between vortex average ozone loss rates derived from Match and deduced from CLaMS with an even sampling for the entire vortex. Both, the time-integration of ozone loss and the determination of ozone loss rates for Match are evaluated using the winter 2002/03 CLaMS simulation. These impacts can explain the differences between CLaMS and Match column ozone loss. While the investigated effects somewhat reduce the apparent discrepancy in January ozone loss rates, a discrepancy between simulations and Match remains. However, its contribution to the accumulated ozone loss over the winter is not large. Jens-Uwe Grooß; Rolf Müller; Paul Konopka; Hildegard-Maria Steinhorst; Andreas Engel; Tanja Möbius; C.-Michael Volk article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29259 Thu, 21 Mar 2013 08:38:48 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29258 Strong perturbations of the Arctic stratosphere during the winter 2002/2003 by planetary waves led to enhanced stretching and folding of the vortex. On two occasions the vortex in the lower stratosphere split into two secondary vortices that re-merged after some days. As a result of these strong disturbances the role of transport in and out of the vortex was stronger than usual. An advection and mixing simulation with the Chemical Lagrangian Model of the Stratosphere (CLaMS) utilising a suite of inert tracers tagging the original position of the air masses has been carried out. The results show a variety of synoptic and small scale features in the vicinity of the vortex boundary, especially long filaments peeling off the vortex edge and being slowly mixed into the mid latitude environment. The vortex folding events, followed by re-merging of different parts of the vortex led to strong filamentation of the vortex interior. During January, February, and March 2003 flights of the Russian high-altitude aircraft Geophysica were performed in order to probe the vortex, filaments and in one case the merging zone between the secondary vortices. Comparisons between CLaMS results and observations obtained from the Geophysica flights show in general good agreement. Gebhard Günther; Rolf Müller; Marc von Hobe; Fred Stroh; Paul Konopka; C.-Michael Volk article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29258 Thu, 21 Mar 2013 08:28:33 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29193 Significant reductions in stratospheric ozone occur inside the polar vortices each spring when chlorine radicals produced by heterogeneous reactions on cold particle surfaces in winter destroy ozone mainly in two catalytic cycles, the ClO dimer cycle and the ClO/BrO cycle. Chlorofluorocarbons (CFCs), which are responsible for most of the chlorine currently present in the stratosphere, have been banned by the Montreal Protocol and its amendments, and the ozone layer is predicted to recover to 1980 levels within the next few decades. During the same period, however, climate change is expected to alter the temperature, circulation patterns and chemical composition in the stratosphere, and possible geo-engineering ventures to mitigate climate change may lead to additional changes. To realistically predict the response of the ozone layer to such influences requires the correct representation of all relevant processes. The European project RECONCILE has comprehensively addressed remaining questions in the context of polar ozone depletion, with the objective to quantify the rates of some of the most relevant, yet still uncertain physical and chemical processes. To this end RECONCILE used a broad approach of laboratory experiments, two field missions in the Arctic winter 2009/10 employing the high altitude research aircraft M55-Geophysica and an extensive match ozone sonde campaign, as well as microphysical and chemical transport modelling and data assimilation. Some of the main outcomes of RECONCILE are as follows: (1) vortex meteorology: the 2009/10 Arctic winter was unusually cold at stratospheric levels during the six-week period from mid-December 2009 until the end of January 2010, with reduced transport and mixing across the polar vortex edge; polar vortex stability and how it is influenced by dynamic processes in the troposphere has led to unprecedented, synoptic-scale stratospheric regions with temperatures below the frost point; in these regions stratospheric ice clouds have been observed, extending over >106km2 during more than 3 weeks. (2) Particle microphysics: heterogeneous nucleation of nitric acid trihydrate (NAT) particles in the absence of ice has been unambiguously demonstrated; conversely, the synoptic scale ice clouds also appear to nucleate heterogeneously; a variety of possible heterogeneous nuclei has been characterised by chemical analysis of the non-volatile fraction of the background aerosol; substantial formation of solid particles and denitrification via their sedimentation has been observed and model parameterizations have been improved. (3) Chemistry: strong evidence has been found for significant chlorine activation not only on polar stratospheric clouds (PSCs) but also on cold binary aerosol; laboratory experiments and field data on the ClOOCl photolysis rate and other kinetic parameters have been shown to be consistent with an adequate degree of certainty; no evidence has been found that would support the existence of yet unknown chemical mechanisms making a significant contribution to polar ozone loss. (4) Global modelling: results from process studies have been implemented in a prognostic chemistry climate model (CCM); simulations with improved parameterisations of processes relevant for polar ozone depletion are evaluated against satellite data and other long term records using data assimilation and detrended fluctuation analysis. Finally, measurements and process studies within RECONCILE were also applied to the winter 2010/11, when special meteorological conditions led to the highest chemical ozone loss ever observed in the Arctic. In addition to quantifying the 2010/11 ozone loss and to understand its causes including possible connections to climate change, its impacts were addressed, such as changes in surface ultraviolet (UV) radiation in the densely populated northern mid-latitudes. Marc von Hobe; Slimane Bekki; Stephan Borrmann; Francesco Cairo; Francesco D'Amato; Guido Di Donfrancesco; Andreas Dörnbrack; Andreas Ebersoldt; Martin Ebert; C. Emde; Ines Engel; Manfred Ern; Wiebke Frey; S. Griessbach; Jens-Uwe Grooß; Thomas Gulde; Gebhard Günther; Elisabeth Hösen; L. Hoffmann; Viktoria Homonnai; Christopher R. Hoyle; Ivar S.A. Isaksen; David R Jackson; Imre M. Jánosi; Konrad Kandler; Christoph Kalicinsky; Andrea Keil; Sergey M. Khaykin; Farahnaz Khosrawi; Rigel Kivi; Jayan Kuttippurath; Johannes Christian Laube; Franck Lefèvre; R. Lehmann; S. Ludmann; Beiping P. Luo; Marion Marchand; Jessica Meyer; Valentin Mitev; Sergej Molleker; Rolf Müller; Hermann Oelhaf; Friedhelm Olschewski; Yvan Orsolini; Thomas Peter; Klaus Pfeilsticker; Christof Piesch; Michael C. Pitts; Lamont R. Poole; Francis D. Pope; Fabrizio Ravegnani; Markus Rex; Martin Riese; Thomas Röckmann; Bjørg Rognerud; Anke Roiger; C. Rolf; M. L. Santee; M. Scheibe; Cornelius Schiller; H. Schlager; Matteo Siciliani de Cumis; Nikolay Sitnikov; Ole Amund Søvde; Reinhold Spang; Nicole Spelten; F. Stordal; Olga Sumińska-Ebersoldt; Silvia Viciani; C.-Michael Volk; Marcel vom Scheidt; Alexey Ulanovski; Peter von der Gathen; Kaley A. Walker; Tobias Wegner; Ralf Weigel; S. Weinbuch; G. Wetzel; Franck G. Wienhold; Johannes Wintel; I. Wohltmann; Wolfgang Woiwode; Isla A. K. Young; Vladimir Yushkov; B. Zobrist; Fred Stroh article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29193 Wed, 20 Mar 2013 11:28:26 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28854 High-throughput protein localization studies require multiple strategies. Mass spectrometric analysis of defined cellular fractions is one of the complementary approaches to a diverse array of cell biological methods. In recent years, the protein content of different cellular (sub-)compartments was approached. Despite of all the efforts made, the analysis of membrane fractions remains difficult, in that the dissection of the proteomes of the envelope membranes of chloroplasts or mitochondria is often not reliable because sample purity is not always warranted. Moreover, proteomic studies are often restricted to single (model) species, and therefore limited in respect to differential individual evolution. In this study we analyzed the chloroplast envelope proteomes of different plant species, namely, the individual proteomes of inner and outer envelope (OE) membrane of Pisum sativum and the mixed envelope proteomes of Arabidopsis thaliana and Medicago sativa. The analysis of all three species yielded 341 identified proteins in total, 247 of them being unique. 39 proteins were genuine envelope proteins found in at least two species. Based on this and previous envelope studies we defined the core envelope proteome of chloroplasts. Comparing the general overlap of the available six independent studies (including ours) revealed only a number of 27 envelope proteins. Depending on the stringency of applied selection criteria we found 231 envelope proteins, while less stringent criteria increases this number to 649 putative envelope proteins. Based on the latter we provide a map of the outer and inner envelope core proteome, which includes many yet uncharacterized proteins predicted to be involved in transport, signaling, and response. Furthermore, a foundation for the functional characterization of yet unidentified functions of the inner and OE for further analyses is provided. Stefan Simm; Dimitrios G. Papasotiriou; Mohamed Ibrahim; Matthias Leisegang; Bernd Müller; Tobias Schorge; Michael Karas; Oliver Mirus; Maik S. Sommer; Enrico Schleiff article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28854 Tue, 12 Feb 2013 10:59:46 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28316 The project focuses on the efficiency of combined technologies to reduce the release of micropollutants and bacteria into surface waters via sewage treatment plants of different size and via stormwater overflow basins of different types. As a model river in a highly populated catchment area, the river Schussen and, as a control, the river Argen, two tributaries of Lake Constance, Southern Germany, are under investigation in this project. The efficiency of the different cleaning technologies is monitored by a wide range of exposure and effect analyses including chemical and microbiological techniques as well as effect studies ranging from molecules to communities. Rita Triebskorn; Klaus Amler; Ludek Blaha; Claudia Gallert; Sabrina Giebner; Hans Güde; Anja Henneberg; Stefanie Hess; Harald Hetzenauer; Klaus Jedele; Ralph-Michael Jung; Sven Kneipp; Heinz-R. Köhler; Stefanie Krais; Bertram Kuch; Claudia Lange; Herbert Löffler; Diana Maier; Jörg Metzger; Michael Müller; Jörg Oehlmann; Raphaela Osterauer; Katharina Peschke; Jürgen Raizner; Peter Rey; Magali Rault; Doreen Richter; Frank Sacher; Marco Scheurer; Jutta Schneider-Rapp; Merav Seifan; Markus Spieth; Hans-Joachim Vogel; Michael Weyhmüller; Josef Winter; Karl Wurm article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28316 Wed, 06 Feb 2013 15:29:35 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27285 We report progress in our exploration of the finite-temperature phase structure of two-flavour lattice QCD with twisted-mass Wilson fermions and a tree-level Symanzik-improved gauge action for a temporal lattice size Nt = 8. Extending our investigations to a wider region of parameter space we gain a global view of the rich phase structure. We identify the finite temperature transition/ crossover for a non-vanishing twisted-mass parameter in the neighbourhood of the zerotemperature critical line at sufficiently high b . Our findings are consistent with Creutz’s conjecture of a conical shape of the finite temperature transition surface. Comparing with NLO lattice cPT we achieve an improved understanding of this shape. Ernst-Michael Ilgenfritz; Karl Jansen; Maria Paola Lombardo; Michael Müller-Preussker; Marcus Petschlies; Owe Philipsen; Lars Zeidlewicz conferenceobject http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27285 Mon, 17 Dec 2012 15:33:45 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27283 We discuss the use of Wilson fermions with twisted mass for simulations of QCD thermodynamics. As a prerequisite for a future analysis of the finite-temperature transition making use of automatic O(a) improvement, we investigate the phase structure in the space spanned by the hopping parameter k , the coupling b , and the twisted mass parameter m. We present results for Nf = 2 degenerate quarks on a 163×8 lattice, for which we investigate the possibility of an Aoki phase existing at strong coupling and vanishing m, as well as of a thermal phase transition at moderate gauge couplings and non-vanishing m. Ernst-Michael Ilgenfritz; Michael Müller-Preußker; Marcus Petschlies; Karl Jansen; Maria Paola Lombardo; Owe Philipsen; Lars Zeidlewicz; André Sternbeck conferenceobject http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27283 Mon, 17 Dec 2012 15:24:59 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27437 We present the current status of lattice simulations with Nf = 2 maximally twisted mass Wilson fermions at finite temperature. In particular, the determination of the thermal transition tempera- ture is discussed. Florian Burger; Malik Kirchner; Michael Müller-Preussker; Ernst-Michael Ilgenfritz; Maria Paola Lombardo; Owe Philipsen; Lars Zeidlewicz; Carsten Urbach conferenceobject http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27437 Fri, 14 Dec 2012 15:10:56 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27441 We report about the current status of our ongoing study of the chiral limit of two-flavor QCD at finite temperature with twisted mass quarks. We estimate the pseudo-critical temperature Tc for three values of the pion mass in the range of mPS ~ 300 and 500 MeV and discuss different chiral scenarios. Furthermore, we present first preliminary results for the trace anomaly, pressure and energy density. We have studied several discretizations of Euclidean time up to Nt = 12 in order to assess the continuum limit of the trace anomaly. From its interpolation we evaluate the pressure and energy density employing the integral method. Here, we have focussed on two pion masses with mPS ~ 400 and 700 MeV. Florian Burger; Malik Kirchner; Michael Müller-Preussker; Ernst-Michael Ilgenfritz; Maria-Paola Lombardo; Owe Philipsen; Christopher Pinke; Lars Zeidlewicz conferenceobject http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27441 Fri, 14 Dec 2012 13:05:21 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27776 The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as “streaks” which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these “streaks” also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively. Marcus Bleicher; Lucas Burigo; Marco Durante; Maren Herrlitz; Michael Krämer; Igor Mishustin; Iris Müller; Francesco Natale; Igor Pshenichnov; Stefan Schramm; Gisela Taucher-Scholz; Cathrin Wälzlein article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27776 Thu, 13 Dec 2012 16:28:23 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/26383 Riboswitches reflect a novel concept in gene regulation that is particularly suited for technological adaptation. Therefore, we characterized thermodynamically the ligand binding properties of a synthetic, tetracycline (tc)-binding RNA aptamer, which regulates gene expression in a dose-dependent manner when inserted into the untranslated region of an mRNA. In vitro, one molecule of tc is bound by one molecule of partially pre-structured and conformationally homogeneous apo-RNA. The dissociation constant of 770 pM, as determined by fluorimetry, is the lowest reported so far for a small molecule-binding RNA aptamer. Additional calorimetric analysis of RNA point mutants and tc derivatives identifies functional groups crucial for the interaction and including their respective enthalpic and entropic contributions we can propose detailed structural and functional roles for certain groups. The conclusions are consistent with mutational analyses in vivo and support the hypothesis that tc-binding reinforces the structure of the RNA aptamer, preventing the scanning ribosome from melting it efficiently. Michael Müller; Julia E. Weigand; Oliver Weichenrieder; Beatrix Süß article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/26383 Thu, 20 Sep 2012 13:31:22 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24273 This paper introduces a new methodology for the fabrication of strain-sensor elements for MEMS and NEMS applications based on the tunneling effect in nano-granular metals. The strain-sensor elements are prepared by the maskless lithography technique of focused electron-beam-induced deposition (FEBID) employing the precursor trimethylmethylcyclopentadienyl platinum [MeCpPt(Me)3]. We use a cantilever-based deflection technique to determine the sensitivity (gauge factor) of the sensor element. We find that its sensitivity depends on the electrical conductivity and can be continuously tuned, either by the thickness of the deposit or by electron-beam irradiation leading to a distinct maximum in the sensitivity. This maximum finds a theoretical rationale in recent advances in the understanding of electronic charge transport in nano-granular metals. Christian H. Schwalb; Christina Grimm; Markus Baranowski; Roland Sachser; Fabrizio Porrati; Heiko Reith; Pintu Das; Jens Müller; Friedemann Völklein; Alexander Kaya; Michael Huth article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24273 Wed, 13 Jun 2012 11:27:45 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25013 Background. Data on the economic impact of Lyme borreliosis (LB) on European health care systems is scarce. This project focused on the epidemiology and costs for laboratory testing in LB patients in Germany. Materials and Methods. We performed a sentinel analysis of epidemiological and medicoeconomic data for 2007 and 2008. Data was provided by a German statutory health insurance (DAK) company covering approx. 6.04 million members. In addition, the quality of diagnostic testing for LB in Germany was studied. Results. In 2007 and 2008, the incident diagnosis LB was coded on average for 15,742 out of 6.04 million insured members (0.26%). 20,986 EIAs and 12,558 immunoblots were ordered annually for these patients. For all insured members in the outpatient sector, a total of 174,820 EIAs and 52,280 immunoblots were reimbursed annually to health care providers (cost: 2,600,850€). For Germany, the overall expected cost is estimated at 51,215,105€. However, proficiency testing data questioned test quality and standardization of diagnostic assays used. Conclusion. Findings from this study suggest ongoing issues related to care for LB and may help to improve future LB disease management. Iris Müller; Michael H. Freitag; Gabriele Poggensee; Elke Scharnetzky; Eberhard Straube; Christof Schoerner; Harald Hlobil; Hans-Jochen Hagedorn; Gerold Stanek; Alexandra Schubert-Unkmeir; Douglas E. Norris; Jochen Gensichen; Klaus-Peter Hunfeld article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25013 Mon, 04 Jun 2012 13:07:43 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24643 Synthesis of acetate from carbon dioxide and molecular hydrogen is considered to be the first carbon assimilation pathway on earth. It combines carbon dioxide fixation into acetyl-CoA with the production of ATP via an energized cell membrane. How the pathway is coupled with the net synthesis of ATP has been an enigma. The anaerobic, acetogenic bacterium Acetobacterium woodii uses an ancient version of this pathway without cytochromes and quinones. It generates a sodium ion potential across the cell membrane by the sodium-motive ferredoxin:NAD oxidoreductase (Rnf). The genome sequence of A. woodii solves the enigma: it uncovers Rnf as the only ion-motive enzyme coupled to the pathway and unravels a metabolism designed to produce reduced ferredoxin and overcome energetic barriers by virtue of electron-bifurcating, soluble enzymes. Anja Poehlein; Silke Schmidt; Anne-Kristin Kaster; Meike Goenrich; John Vollmers; Andrea Thürmer; Johannes Bertsch; Kai Schuchmann; Birgit Voigt; Michael Hecker; Rolf Daniel; Rudolf K. Thauer; Gerhard Gottschalk; Volker Müller article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24643 Wed, 25 Apr 2012 17:38:07 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22143 Introduction Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard of care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard of care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods Patients who received rituximab having shown an inadequate response to standard of care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2440 mg of rituximab over a median (range) of 194 (180 to 1407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies. Additional file 1: Supplemental tables. Table A1. Duration of follow-up from first rituximab infusion to last control visit by diagnosis. Table A2. Number of rituximab infusions by diagnosis. Hans-Peter Tony; Gerd-Rüdiger Burmester; Hendrik Schulze-Koops; Mathias Grunke; Joerg Christoph Henes; Ina Kötter; Judith Haas; Leonore Unger; Svjetlana Lovric; Marion Haubitz; Rebecca Fischer-Betz; Gamal Chehab; Andrea Rubbert-Roth; Christof Specker; Jutta Weinerth; Julia Ulrike Holle; Ulf Müller-Ladner; Ramona König; Christoph Fiehn; Philip Burgwinkel; Klemens Budde; Helmut Sörensen; Michael Meurer; Martin Aringer; Bernd Kieseier; Cornelia Erfurt-Berge; Michael Sticherling; Roland Veelken; Ulf Ziemann; Frank Strutz; Praxis von Wussow; Florian M. P. Meier; Nico Hunzelmann; Nico Schmidt; Raoul Bergner; Andreas Schwarting; Rüdiger Eming; Michael Hertl; Rudolf Stadler; Michael Schwarz-Eywill; Siegfried Wassenberg; Martin Fleck; Claudia Metzler; Uwe Zettl; Jens Westphal; Stefan Heitmann; Anna Laura Herzog; Heinz Wiendl; Waltraud Jakob; Enno Schmidt; Enno Schmidt; Klaus Freivogel; Thomas Dörner; GRAID investigators article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22143 Fri, 22 Jul 2011 09:53:44 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22783 We present simulations with the Chemical Lagrangian Model of the Stratosphere (CLaMS) for the Arctic winter 2002/2003. We integrated a Lagrangian denitrification scheme into the three-dimensional version of CLaMS that calculates the growth and sedimentation of nitric acid trihydrate (NAT) particles along individual particle trajectories. From those, we derive the HNO3 downward flux resulting from different particle nucleation assumptions. The simulation results show a clear vertical redistribution of total inorganic nitrogen ( ), with a maximum vortex average permanent removal of over 5ppb in late December between 500 and 550K and a corresponding increase of of over 2ppb below about 450K. The simulated vertical redistribution of is compared with balloon observations by MkIV and in-situ observations from the high altitude aircraft Geophysica. Assuming a globally uniform NAT particle nucleation rate of 7.8x10-6cm-3h-1 in the model, the observed denitrification is well reproduced. In the investigated winter 2002/2003, the denitrification has only moderate impact (≤14%) on the simulated vortex average ozone loss of about 1.1ppm near the 460K level. At higher altitudes, above 600K potential temperature, the simulations show significant ozone depletion through -catalytic cycles due to the unusual early exposure of vortex air to sunlight. Jens-Uwe Grooß; Gebhard Günther; Rolf Müller; Paul Konopka; Stephan Bausch; Hans Schlager; Christiane Voigt; C.-Michael Volk; Geoffrey C. Toon article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22783 Thu, 26 May 2011 16:26:14 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/20685 Background: It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention. Methods: The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency. Discussion: This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion on psychotherapy in psychotic disorders, and to help implement psychotherapy in routine care. Furthermore, the study will allow drawing conclusions about the mediators of treatment effects of CBT of psychotic disorders. Trial Registration Current Controlled Trials ISRCTN29242879 Stefan Klingberg; Andreas Wittorf; Christoph Meisner; Wolfgang Wölwer; Georg Wiedemann; Jutta Herrlich; Andreas Bechdolf; Bernhard W. Müller; Gudrun Sartory; Michael Wagner; Tilo Kircher; Hans-Helmut König; Corinna Engel; Gerhard Buchkremer article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/20685 Tue, 18 Jan 2011 14:27:13 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/20673 HDL, through sphingosine-1-phosphate (S1P), exerts direct cardioprotective effects on ischemic myocardium. It remains unclear whether other HDL-associated sphingophospholipids have similar effects. We therefore examined if HDL-associated sphingosylphosphorylcholine (SPC) reduces infarct size in a mouse model of transient myocardial ischemia/reperfusion. Intravenously administered SPC dose-dependently reduced infarct size after 30 minutes of myocardial ischemia and 24 hours reperfusion compared to controls. Infarct size was also reduced by postischemic, therapeutical administration of SPC. Immunohistochemistry revealed reduced polymorphonuclear neutrophil recruitment to the infarcted area after SPC treatment, and apoptosis was attenuated as measured by TUNEL. In vitro, SPC inhibited leukocyte adhesion to TNFα-activated endothelial cells and protected rat neonatal cardiomyocytes from apoptosis. S1P3 was identified as the lysophospholipid receptor mediating the cardioprotection by SPC, since its effect was completely absent in S1P3-deficient mice. We conclude that HDL-associated SPC directly protects against myocardial reperfusion injury in vivo via the S1P3 receptor. Christine Herzog; Martina Schmitz; Bodo Levkau; Ilka Herrgott; Jan Mersmann; Jan Larmann; Kai Johanning; Michael Winterhalter; Jerold Chun; Frank Ulrich Müller; Frank Echtermeyer; Reinhard Hildebrand; Gregor Theilmeier article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/20673 Wed, 12 Jan 2011 12:32:50 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7617 In der heutigen Zeit ist der Konsum von Drogen wie THC und Amphetaminen insbe-sondere unter Jugendlichen weit verbreitet. Vor allem durch die aufputschende Wirkung der Amphetamine und deren Ruf als Partydroge kommt es gehäuft an Wochenenden zu vermehrten Autofahrten unter Drogeneinfluss. Die vorliegende Arbeit untersucht die Auswirkungen von THC- und Amphetaminkon-sum auf verschiedene Sehleistungen. Zu diesem Zweck wurde eine Gruppe von Kraft-fahrzeugführern, die unter Drogeneinfluss standen, mit einem nicht beeinflussten Kol-lektiv verglichen. Es zeigten sich signifikante Unterschiede im Bereich der Testzeit sowie des Stereose-hens, wobei die Gruppe der Drogenkonsumenten und hier vorrangig die Amphetamin-konsumenten deutlich schlechter abschnitten. Die Beeinträchtigungen im Bereich der Testzeit dürften auf eine deutlich eingeschränkte Konzentrationsfähigkeit unter Amphetamin- und THC- Konsum zurück zu führen sein, vermutlich hervorgerufen durch Wirkungen im Bereich des Hypothalamus und Hippo-campus, welche im Bereich der Aufmerksamkeit sowie des Lernverhaltens eine wich-tige Rolle spielen. Verbindungen dieser beiden Hirnareale zur Sehbahn könnten eine Erklärung für die Einschränkungen im Bereich des Stereosehens vor allem der Amphetamingruppe sein, da diese Substanzgruppe sowohl Hippocampus, Hypothalamus als auch die Mandel-kerne beeinflusst, THC hingegen nur den Hippocampus. Insgesamt muss anhand der vorliegenden Ergebnisse von einer Beeinträchtigung der Fahrtüchtigkeit unter THC und Amphetaminen unabhängig von der konsumierten Dro-genmenge ausgegangen werden. Hieraus lässt sich ableiten, dass die Einführung eines Grenzwertes aufgrund der sehr individuellen Beeinträchtigungen auf die kognitiven und optischen Fähigkeiten einer einzelnen Person als äußerst problematisch zu bewerten ist und somit die Fahrsicherheit und Fahreignung nur bei einem völligen Verzicht auf jeg-lichen Cannabis- oder Amphetaminkonsum gewährleistet ist. Michael Müller-Trudrung doctoralthesis http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7617 Fri, 26 Mar 2010 12:53:10 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7087 Poster presentation: Background Nitric oxide (NO) is an essential vasodilator. In vascular diseases, oxidative stress attenuates NO signaling by both chemical scavenging of free NO and oxidation and down-regulation of its major intracellular receptor, the alpha/beta heterodimeric heme-containing soluble guanylate cyclase (sGC). Oxidation can also induce loss of sGC's heme and responsiveness to NO. Results sGC activators such as BAY 58-2667 bind to oxidized/heme-free sGC and reactivate the enzyme to exert disease-specific vasodilation. Here we show that oxidation-induced down-regulation of sGC protein extends to isolated blood vessels. Mechanistically, degradation was triggered through sGC ubiquitination and proteasomal degradation. The heme-binding site ligand, BAY 58-2667, prevented sGC ubiquitination and stabilized both alpha and beta subunits. Conclusion Collectively, our data establish oxidation-ubiquitination of sGC as a modulator of NO/cGMP signaling and point to a new mechanism of action for sGC activating vasodilators by stabilizing their receptor, oxidized/heme-free sGC. Sabine Meurer; Sylke Pioch; Tatjana Pabst; Nils Opitz; Peter M. Schmidt; Tobias Beckhaus; Kristina Wagner; Simone Matt; Kristina Gegenbauer; Sandra Geschka; Michael Karas; Johannes-Peter Stasch; Harald H. H. W. Schmidt; Werner Müller-Esterl article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7087 Sun, 20 Sep 2009 17:48:44 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6969 The complete molecule of the title compound, [Sn(C6H5)2Cl2(C9H21OP)2], is generated by crystallographic inversion symmetry, the Sn atom is located on a special position of site symmetry \overline{1}. The Sn atom adopts an all-trans SnC2O2Cl2 octahedral geometry. As a consequence of the bulky substituents at the O atom, the P-O-Sn bond angle is 163.9 (3)°. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.012 Å; R factor = 0.058; wR factor = 0.099; data-to-parameter ratio = 18.6. Manuela Müller; Hans-Wolfram Lerner; Michael Bolte article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6969 Mon, 14 Sep 2009 08:45:09 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6571 Background Since June 2002, revised regulations in Germany have required "Emergency Medical Care" as an interdisciplinary subject, and state that emergency treatment should be of increasing importance within the curriculum. A survey of the current status of undergraduate medical education in emergency medical care establishes the basis for further committee work. Methods Using a standardized questionnaire, all medical faculties in Germany were asked to answer questions concerning the structure of their curriculum, representation of disciplines, instructors' qualifications, teaching and assessment methods, as well as evaluation procedures. Results Data from 35 of the 38 medical schools in Germany were analysed. In 32 of 35 medical faculties, the local Department of Anaesthesiology is responsible for the teaching of emergency medical care; in two faculties, emergency medicine is taught mainly by the Department of Surgery and in another by Internal Medicine. Lectures, seminars and practical training units are scheduled in varying composition at 97% of the locations. Simulation technology is integrated at 60% (n=21); problem-based learning at 29% (n=10), e-learning at 3% (n=1), and internship in ambulance service is mandatory at 11% (n=4). In terms of assessment methods, multiple-choice exams (15 to 70 questions) are favoured (89%, n=31), partially supplemented by open questions (31%, n=11). Some faculties also perform single practical tests (43%, n=15), objective structured clinical examination (OSCE; 29%, n=10) or oral examinations (17%, n=6). Conclusion Emergency Medical Care in undergraduate medical education in Germany has a practical orientation, but is very inconsistently structured. The innovative options of simulation technology or state-of-the-art assessment methods are not consistently utilized. Therefore, an exchange of experiences and concepts between faculties and disciplines should be promoted to guarantee a standard level of education in emergency medical care. Stefan K. Beckers; Arnd Timmermann; Michael P. Müller; Matthias Angstwurm; Felix Walcher article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6571 Tue, 02 Jun 2009 15:00:03 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6262 The Match method for the quantification of polar chemical ozone loss is investigated mainly with respect to the impact of the transport of air masses across the vortex edge. For the winter 2002/03, we show that significant transport across the vortex edge occurred and was simulated by the Chemical Lagrangian Model of the Stratosphere. In-situ observations of inert tracers and ozone from HAGAR on the Geophysica aircraft and balloon-borne sondes, and remote observations from MIPAS on the ENVISAT satellite were reproduced well by CLaMS. The model even reproduced a small vortex remnant that remained a distinct feature until June 2003 and was also observed in-situ by a balloon-borne whole air sampler. We use this CLaMS simulation to quantify the impact of transport across the vortex edge on ozone loss estimates from the Match method. We show that a time integration of the determined vortex average ozone loss rates, as performed in Match, results in a larger ozone loss than the polar vortex average ozone loss in CLaMS. The determination of the Match ozone loss rates is also influenced by the transport of air across the vortex edge. We use the model to investigate how the sampling of the ozone sondes on which Match is based represents the vortex average ozone loss rate. Both the time integration of ozone loss and the determination of ozone loss rates for Match are evaluated using the winter 2002/2003 CLaMS simulation. These impacts can explain the majority of the differences between CLaMS and Match column ozone loss. While the investigated effects somewhat reduce the apparent discrepancy in January ozone loss rates reported earlier, a distinct discrepancy between simulations and Match remains. However, its contribution to the accumulated ozone loss over the winter is not large. Jens-Uwe Grooß; Rolf Müller; Paul Konopka; Hildegard-Maria Steinhorst; Andreas Engel; Tanja Möbius; C.-Michael Volk article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6262 Mon, 30 Mar 2009 09:16:25 +0200