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Spieles, Christian ; Dumitru, Adrian Bogdan ; Bass, Steffen A. ; Bleicher, Marcus ; Brachmann, Jörg ; Brandstetter, Mathias ; Ernst, Christoph ; Gerland, Lars ; Konopka, Jens ; Soff, Sven ; Weber, Henning ; Winckelmann, Luke Andreas ; Maruhn, Joachim ; Stöcker, Horst ; Greiner, Walter
We study the thermodynamic properties of infinite nuclear matter with the Ultrarelativistic Quantum Molecular Dynamics (URQMD), a semiclassical transport model, running in a box with periodic boundary conditions. It appears that the energy density rises faster than T4 at high temperatures of T approx. 200 - 300 MeV. This indicates an increase in the number of degrees of freedom. Moreover, We have calculated direct photon production in Pb+Pb collisions at 160 GeV/u within this model. The direct photon slope from the microscopic calculation equals that from a hydrodynamical calculation without a phase transition in the equation of state of the photon source.
Scherer, Stefan ; Bass, Steffen A. ; Belkacem, Mohamed ; Bleicher, Marcus ; Brachmann, Jörg ; Dumitru, Adrian Bogdan ; Ernst, Christoph ; Gerland, Lars ; Hammon, Nils ; Hofmann, Markus ; Konopka, Jens ; Neise, Ludwig ; Reiter, Manuel ; Schramm, Stefan ; Soff, Sven ; Spieles, Christian ; Weber, Henning ; Zschiesche, Detlef ; Maruhn, Joachim ; Stöcker, Horst ; Greiner, Walter
Nonequilibrium models (three-fluid hydrodynamics, UrQMD, and quark molecular dynamics) are used to discuss the uniqueness of often proposed experimental signatures for quark matter formation in relativistic heavy ion collisions from the SPS via RHIC to LHC. It is demonstrated that these models - although they do treat the most interesting early phase of the collisions quite differently (thermalizing QGP vs. coherent color fields with virtual particles) -- all yield a reasonable agreement with a large variety of the available heavy ion data. Hadron/hyperon yields, including J/Psi meson production/suppression, strange matter formation, dileptons, and directed flow (bounce-off and squeeze-out) are investigated. Observations of interesting phenomena in dense matter are reported. However, we emphasize the need for systematic future measurements to search for simultaneous irregularities in the excitation functions of several observables in order to come close to pinning the properties of hot, dense QCD matter from data. The role of future experiments with the STAR and ALICE detectors is pointed out.
Pérez-Palma, Eduardo ; Helbig, Ingo ; Klein, Karl Martin ; Anttila, Verneri ; Horn, Heiko ; Reinthaler, Eva Maria ; Gormley, Padhraig ; Ganna, Andrea ; Byrnes, Andrea ; Pernhorst, Katharina ; Toliat, Mohammad Reza ; Saarentaus, Elmo ; Howrigan, Daniel P. ; Hoffman, Per ; Miquel, Juan Francisco ; De Ferrari, Giancarlo V. ; Nürnberg, Peter ; Lerche, Holger ; Zimprich, Fritz ; Neubauer, Bern A. ; Becker, Albert John ; Rosenow, Felix ; Perucca, Emilio ; Zara, Federico ; Weber, Yvonne G. ; Lal, Dennis
Background: Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement ‘hotspot’ loci. However, microdeletion burden not overlapping these regions or within different epilepsy subtypes has not been ascertained.
Objective: To decipher the role of microdeletions outside hotspots loci and risk assessment by epilepsy subtype.
Methods: We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1366 patients with genetic generalised epilepsy (GGE) in addition to two sets of additional unpublished genome-wide microdeletions found in 281 patients with rolandic epilepsy (RE) and 807 patients with adult focal epilepsy (AFE), totalling 2454 cases. Microdeletions were assessed in a combined and subtype-specific approaches against 6746 controls.
Results: When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted p=1.06×10−6,OR 1.89, 95% CI 1.51 to 2.35). Epilepsy subtype-specific analyses showed that hotspot microdeletions in the GGE subgroup contribute most of the overall signal (adjusted p=9.79×10−12, OR 7.45, 95% CI 4.20–13.5). Outside hotspots , microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted p=9.13×10−3,OR 2.85, 95% CI 1.62–4.94). No additional signal was observed for RE and AFE. Still, gene-content analysis identified known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes across epilepsy subtypes that were not deleted in controls.
Conclusions: Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor contribution in the aetiology of RE and AFE.
Yotova, Anna Y. ; O'Leary, Aet ; Fernàndez-Castillo, Noèlia ; Gan, Gabriela ; Antón-Galindo, Ester ; Cabana-Domínguez, Judit ; Kranz, Thorsten M. ; Grünewald, Lena ; Mota, Nina Roth ; Franke, Barbara ; Straube, Benjamin ; Lueken, Ulrike ; Weber, Heike ; Pauli, Paul ; Freudenberg, Florian ; Cormand, Bru ; Slattery, David A. ; Reif, Andreas
Ziegler, Georg Christoph ; Ehlis, Ann-Christine ; Weber, Heike ; Vitale, Maria Rosaria ; Zöller, Johanna E. M. ; Ku, Hsing-Ping ; Schiele, Miriam A. ; Kürbitz, Laura I. ; Romanos, Marcel ; Pauli, Paul ; Kalisch, Raffael ; Zwanzger, Peter M. ; Domschke, Katharina ; Fallgatter, Andreas J. ; Reif, Andreas ; Lesch, Klaus-Peter J.
The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
Schrade, Katharina ; Tröger, Jessica ; Eldahshan, Adeeb ; Zühlke, Kerstin ; Abdul Azeez, Kamal R. ; Elkins, Jonathan M. ; Neuenschwander, Martin ; Oder, Andreas ; Elkewedi, Mohamed ; Jaksch, Sarah ; Andrae, Karsten ; Li, Jinliang ; Fernandes, Joao ; Müller, Paul Markus ; Grunwald, Stephan ; Marino, Stephen A. ; Vukićević, Tanja ; Eichhorst, Jenny ; Wiesner, Burkhard ; Weber, Marcus ; Kapiloff, Michael ; Rocks, Oliver ; Daumke, Oliver ; Wieland, Thomas ; Knapp, Stefan ; Kries, Jens Peter von ; Klussmann, Enno
Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking.
Pérez-Palma, Eduardo ; Helbig, Ingo ; Klein, Karl Martin ; Anttila, Verneri ; Horn, Heiko ; Maria Reinthaler, Eva ; Gormley, Padhraig ; Ganna, Andrea ; Byrnes, Andrea ; Pernhorst, Katharina ; Toliat, Mohammad Reza ; Saarentaus, Elmo ; Howrigan, Daniel P. ; Hoffman, Per ; Miquel, Juan Francisco ; De Ferrari, Giancarlo ; Nürnberg, Peter ; Lerche, Holger ; Zimprich, Fritz ; Neubauer, Bern A. ; Becker, Albert J. ; Rosenow, Felix ; Perucca, Emilio ; Zara, Federico ; Weber, Yvonne G. ; Lal, Dennis
Background Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement “hotspot” loci. However, deciphering their role outside hotspots and risk assessment by epilepsy sub-type has not been conducted.
Methods We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1,366 patients with Genetic Generalized Epilepsy (GGE) plus two sets of additional unpublished genome-wide microdeletions found in 281 Rolandic Epilepsy (RE) and 807 Adult Focal Epilepsy (AFE) patients, totaling 2,454 cases. These microdeletion sets were assessed in a combined analysis and in sub-type specific approaches against 6,746 ethnically matched controls.
Results When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted-P= 2.00×10-7; OR = 1.89; 95%-CI: 1.51-2.35), where the implicated microdeletions overlapped with rarely deleted genes and those involved in neurodevelopmental processes. Sub-type specific analyses showed that hotspot deletions in the GGE subgroup contribute most of the signal (adjusted-P = 1.22×10-12; OR = 7.45; 95%-CI = 4.20-11.97). Outside hotspot loci, microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted-P = 4.78×10-3; OR = 2.30; 95%-CI = 1.42-3.70), whereas no additional signal was observed for RE and AFE. Still, gene content analysis was able to identify known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes affected in more than one epilepsy sub-type but not in controls.
Conclusions Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor to negligible contribution in the etiology of RE and AFE.
Gaßner, Tobias ; Trassinelli, Martino ; Heß, Regina ; Spillmann, Uwe ; Banaś, Dariusz ; Blumenhagen, Karl-Heinz ; Bosch, Fritz ; Brandau, Carsten ; Chen, Weidong ; Dimopoulou, Christina ; Förster, Eckhart ; Grisenti, Robert Evaristo ; Gumberidze, Alexandre ; Hagmann, Siegbert ; Hillenbrand, Pierre-Michel ; Indelicato, Paul ; Jagodziński, Paweł ; Kämpfer, Tino ; Kozhuharov, Christophor ; Lestinsky, Michael ; Liesen, Heinz-Dieter ; Litvinov, Yuri A. ; Loetzsch, Robert ; Manil, Bruno ; Märtin, Renate ; Nolden, Fritz ; Petridis, Nikolaos ; Sanjari, Mohammad Shahab ; Schulze, Kai-Sven ; Schwemlein, Max ; Simionovici, Alexandre S. ; Steck, Markus ; Stöhlker, Thomas ; Szabo, Csilla I. ; Trotsenko, Sergiy ; Uschmann, Ingo ; Weber, Günter ; Wehrhan, Ortrud ; Winckler, Nicolas ; Winters, Danyal Ferdinant Alexander ; Winters, Natalya ; Ziegler, Eric ; Beyer, Heinrich F.
Accurate spectroscopy of highly-charged high-Z ions in a storage ring is demonstrated to be feasible by the use of specially adapted crystal optics. The method has been applied for the measurement of the 1s Lamb shift in hydrogen-like gold (Au+78) in a storage ring through spectroscopy of the Lyman x-rays. This measurement represents the first result obtained for a high-Z element using high-resolution wavelength-dispersive spectroscopy in the hard x-ray regime, paving the way for sensitivity to higher- order QED effects.
Rastrepina, Ganna ; Aumann, Thomas ; Bishop, Shawn ; Blaum, Klaus ; Boretzky, Konstanze ; Bosch, Fritz ; Bräuning, Harald ; Brandau, Carsten ; Davinson, Thomas ; Dillmann, Iris ; Dimopoulou, Christina ; Ershova, Olga ; Fülöp, Zsolt ; Geissel, Hans ; Gyürky, György ; Heil, Michael ; Käppeler, Franz ; Kelic-Heil, Aleksandra ; Kozhuharov, Christophor ; Langer, Christoph ; Le Bleis, Tudi ; Litvinov, Yuri A. ; Lotay, Gavin ; Marganiec, Justyna ; Münzenberg, Gottfried ; Nolden, Fritz ; Petridis, Nikos ; Plag, Ralf ; Popp, Ulrich ; Reifarth, René ; Riese, Björn ; Rigollet, Catherine ; Scheidenberger, Christoph ; Simon, Haik ; Sonnabend, Kerstin ; Steck, Markus ; Stöhlker, Thomas ; Sümmerer, Klaus ; Scücs, Tamas ; Weber, Günter ; Weick, Helmut ; Winters, Danyal Ferdinant Alexander ; Winters, Natalya ; Woods, Philip John ; Zhong, Qi-Ping
8th International Conference on Nuclear Physics at Storage Rings Stori11, October 9-14, 2011 Laboratori Nazionale di Frascati, Italy.
Storage rings offer the possibility of measuring proton- and alpha-induced reactions in inverse kinematics. The combination of this approachwith a radioactive beamfacility allows, in principle, the determination of the respective cross sections for radioactive isotopes. Such data are highly desired for a better understanding of astrophysical nucleosynthesis processes like the p-process. A pioneering experiment has been performed at the Experimental Storage Ring (ESR) at GSI using a stable 96Ru beam at 9-11 AMeV and a hydrogen target. Monte-Carlo simulations of the experiment were made using the Geant4 code. In these simulations, the experimental setup is described in detail and all reaction channels can be investigated. Based on the Geant4 simulations, a prediction of the shape of different spectral components can be performed. A comparison of simulated predictions with the experimental results shows a good agreement and allows the extraction of the cross section.
Bingemer, Heinz ; Klein, Holger ; Ebert, Martin ; Haunold, Werner ; Bundke, Ulrich ; Herrmann, Thomas ; Kandler, Konrad ; Müller-Ebert, Dörthe ; Weinbruch, Stephan ; Judt, Anna ; Weber, A. ; Nillius, Björn ; Ardon-Dryer, Karin ; Levin, Zev ; Curtius, Joachim
We have sampled atmospheric ice nuclei (IN) and aerosol in Germany and in Israel during spring 2010. IN were analyzed by the static vapor diffusion chamber FRIDGE, as well as by electron microscopy. During the Eyjafjallajökull volcanic eruption of April 2010 we have measured the highest ice nucleus number concentrations (>600 l−1) in our record of 2 yr of daily IN measurements in central Germany. Even in Israel, located about 5000 km away from Iceland, IN were as high as otherwise only during desert dust storms. The fraction of aerosol activated as ice nuclei at −18 °C and 119% rhice and the corresponding area density of ice-active sites per aerosol surface were considerably higher than what we observed during an intense outbreak of Saharan dust over Europe in May 2008.
Pure volcanic ash accounts for at least 53–68% of the 239 individual ice nucleating particles that we collected in aerosol samples from the event and analyzed by electron microscopy. Volcanic ash samples that had been collected close to the eruption site were aerosolized in the laboratory and measured by FRIDGE. Our analysis confirms the relatively poor ice nucleating efficiency (at −18 °C and 119% ice-saturation) of such "fresh" volcanic ash, as it had recently been found by other workers. We find that both the fraction of the aerosol that is active as ice nuclei as well as the density of ice-active sites on the aerosol surface are three orders of magnitude larger in the samples collected from ambient air during the volcanic peaks than in the aerosolized samples from the ash collected close to the eruption site. From this we conclude that the ice-nucleating properties of volcanic ash may be altered substantially by aging and processing during long-range transport in the atmosphere, and that global volcanism deserves further attention as a potential source of atmospheric ice nuclei.