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Stenzinger, Albrecht ; Endris, Volker ; Pfarr, Nicole ; Andrulis, Mindaugas ; Jöhrens, Korinna ; Klauschen, Frederick ; Siebolts, Udo ; Wolf, Thomas ; Koch, Philipp-Sebastian ; Schulz, Miriam ; Hartschuh, Wolfgang ; Goerdt, Sergij ; Lennerz, Jochen K. ; Wickenhauser, Claudia ; Klapper, Wolfram ; Anagnostopoulos, Ioannis ; Weichert, Wilko
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1% each), as well as in VHL, BRAF, MLH1, TP53 and RET (3% each). Moreover, NRAS, KRAS and ATM mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored.
Meyer, Hartwig ; Stöver, Timo ; Fouchet, Florian ; Bastiat, Guillaume ; Saulnier, Patrick ; Bäumer, Wolfgang ; Lenarz, Thomas ; Scheper, Verena
Objective: Sensorineural hearing loss leads to the progressive degeneration of spiral ganglion cells (SGC). Next to postoperative fibrous tissue growth, which should be suppressed to assure a close nerve–electrode interaction, the density of healthy SGC is one factor that influences the efficiency of cochlear implants (CI), the choice of treatment for affected patients. Rolipram, a phosphodiesterase-4 inhibitor, has proven neuroprotective and anti-inflammatory effects and might also reduce SGC degeneration and fibrosis, but it has to pass the cellular membrane to be biologically active.
Methods: Lipidic nanocapsules (LNC) can be used as biodegradable drug carriers to increase the efficacy of conventional application methods. We examined the biological effects of rolipram and LNC's core encapsulated rolipram on SGC and dendritic cell (DC) tumor necrosis factor-α (TNF-α) production in vitro and on SGC survival in systemically-deafened guinea pigs in vivo.
Results: Our results prove that rolipram does not have a beneficial effect on cultured SGC. Incorporation of rolipram in LNC increased the survival of SGC significantly. In the DC study, rolipram significantly inhibited TNF-α in a dose-dependent manner. The rolipram-loaded LNC provided a significant cytokine inhibition as well. In vivo data do not confirm the in vitro results.
Conclusion: By transporting rolipram into the SGC cytoplasm, LNC enabled the neuroprotective effect of rolipram in vitro, but not in vivo. This might be due to dilution of test substances by perilymph or an inadequate release of rolipram based on differing in vivo and in vitro conditions. Nevertheless, based on in vitro results, proving a significantly increased neuronal survival when using LNC-rolipram compared to pure rolipram and pure LNC application, we believe that the combination of rolipram and LNC can potentially reduce neuronal degeneration and fibrosis after CI implantation. We conclude that rolipram is a promising drug that can be used in inner ear therapy and that LNC have potential as an inner ear drug-delivery system. Further experiments with modified conditions might reveal in vivo biological effects.
Medema, Marnix H. ; Kottmann, Renzo ; Yilmaz, Pelin ; Cummings, Matthew ; Biggins, John B. ; Kai, Blin ; de Bruijn, Irene ; Chooi, Yit Heng ; Claesen, Jan ; Coates, R. Cameron ; Cruz-Morales, Pablo ; Duddela, Srikanth ; Düsterhus, Stephanie ; Edwards, Daniel J. ; Fewer, David P. ; Garg, Neha ; Geiger, Christoph ; Gomez-Escribano, Juan Pablo ; Greule, Anja ; Hadjithomas, Michalis ; Haines, Anthony S. ; Helfrich, Eric J. N. ; Hillwig, Matthew L. ; Ishida, Keishi ; Jones, Adam C. ; Jones, Carla S. ; Jungmann, Katrin ; Kegler, Carsten ; Kim, Hyun Uk ; Kötter, Peter ; Krug, Daniel ; Masschelein, Joleen ; Melnik, Alexey V. ; Mantovan, Simone M. ; Monroe, Emily A. ; Moore, Marcus ; Moss, Nathan ; Nützmann, Hans-Wilhelm ; Pan, Guohui ; Pati, Amrita ; Petras, Daniel ; Reen, F. Jerry ; Rosconi, Federico ; Rui, Zhe ; Tian, Zhenhua ; Tobias, Nicholas J. ; Tsunematsu, Yuta ; Wiemann, Philipp ; Wyckoff, Elizabeth ; Yan, Xiaohui ; Yim, Grace ; Yu, Fengan ; Xie, Yunchang ; Aigle, Bertrand ; Apel, Alexander K. ; Balibar, Carl J. ; Balskus, Emily P. ; Barona-Gómez, Francisco ; Bechthold, Andreas ; Bode, Helge Björn ; Borriss, Rainer ; Brady, Sean F. ; Brakhage, Axel A. ; Caffrey, Patrick ; Cheng, Yi-Qiang ; Clardy, Jon ; Cox, Russell J. ; De Mot, René ; Donadio, Stefano ; Donia, Mohamed S. ; van der Donk, Wilfred A. ; Dorrestein, Pieter C. ; Doyle, Sean ; Driessen, Arnold J. M. ; Ehling-Schulz, Monika ; Entian, Karl-Dieter ; Fischbach, Michael A. ; Gerwick, Lena ; Gerwick, William H. ; Gross, Harald ; Gust, Bertolt ; Hertweck, Christian ; Höfte, Monica ; Jensen, Susan E. ; Ju, Jianhua ; Katz, Leonard ; Kaysser, Leonard ; Klassen, Jonathan L. ; Keller, Nancy P. ; Kormanec, Jan ; Kuipers, Oscar P. ; Kuzuyama, Tomohisa ; Kyrpides, Nikos C. ; Kwon, Hyung-Jin ; Lautru, Sylvie ; Lavigne, Rob ; Lee, Chia Y. ; Linquan, Bai ; Liu, Xinyu ; Liu, Wen ; Luzhetskyy, Andriy ; Mahmud, Taifo ; Mast, Yvonne ; Méndez, Carmen ; Metsä-Ketelä, Mikko ; Micklefield, Jason ; Mitchell, Douglas A. ; Moore, Bradley S. ; Moreira, Leonilde M. ; Müller, Rolf ; Neilan, Brett A. ; Nett, Markus ; Nielsen, Jens ; O’Gara, Fergal ; Oikawa, Hideaki ; Osbourn, Anne ; Osburne, Marcia S. ; Ostash, Bohdan ; Payne, Shelley M. ; Pernodet, Jean-Luc ; Petricek, Miroslav ; Piel, Jörn ; Ploux, Olivier ; Raaijmakers, Jos M. ; Salas, José A. ; Schmitt, Esther K. ; Scott, Barry ; Seipke, Ryan F. ; Shen, Ben ; Sherman, David H. ; Sivonen, Kaarina ; Smanski, Michael J. ; Sosio, Margherita ; Stegmann, Evi ; Süssmuth, Roderich D. ; Tahlan, Kapil ; Thomas, Christopher M. ; Tang, Yi ; Truman, Andrew W. ; Viaud, Muriel ; Walton, Jonathan D. ; Walsh, Christopher T. ; Weber, Tilmann ; van Wezel, Gilles P. ; Wilkinson, Barrie ; Willey, Joanne M. ; Wohlleben, Wolfgang ; Wright, Gerard D. ; Ziemert, Nadine ; Zhang, Changsheng ; Zotchev, Sergey B. ; Breitling, Rainer ; Takano, Eriko ; Glöckner, Frank Oliver
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Löser, Heike ; Krämer, Max ; Gebauer, Florian ; Bruns, Christiane ; Schröder, Wolfgang ; Zander, Thomas ; Persa, Oana-Diana ; Alakus, Hakan ; Hölscher, Arnulf H. ; Büttner, Reinhard ; Lohneis, Philipp ; Quaas, Alexander
Immune checkpoint modulation in cancer has been demonstrated as a high-value therapeutic strategy in many tumor entities. VISTA is an immune checkpoint receptor regulating T-cell function. To the best of our knowledge, nothing is known about the expression and prognostic impact of VISTA on tumor infiltrating lymphocytes (TILs) in the tumor microenvironment of esophageal adenocarcinoma (EAC). We analyzed in total 393 EACs within a test-cohort (n = 165) and a validation-cohort (n = 228) using a monoclonal antibody (clone D1L2G). These data were statistically correlated with clinical as well as molecular data. 22.2% of the tumor cohort presented with a VISTA expression on TILs. These patients demonstrated an improved median overall survival compared to patients without VISTA expression (202.2 months vs. 21.6 months; p < 0.0001). The favorable outcome of VISTA positive tumors is significant in the entire cohort but mainly driven by the general better prognosis of T1/T2 tumors. However, in the pT1/2 group, VISTA positive tumors show a tremendous survival benefit compared to VISTA negative tumors revealing real long-term survivors in this particular subgroup. The survival difference is independent of the T-stage. This unique characteristic could influence neoadjuvant therapy concepts for EAC, since a profit of therapy could be reduced in the already favorable subgroup of VISTA positive tumors. VISTA emerges as a prognostic biomarker for long-term survival especially in the group of early TNM-stages. Future studies have to show the relevance of VISTA positive TILs within a tumor concerning response to specific immune checkpoint inhibition.
Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Behnke, Claudia ; Belounnas, Amel ; Belyaev, A. ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Chlad, Lukáš ; Deveaux, Christina Anna ; Dreyer, J. ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Filip, Peter ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gernhäuser, Roman ; Golubeva, Marina ; Greifenhagen, Robert ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Heinz, Tobias ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, W. ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Kühn, Wolfgang ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Lourenco Vaz Gil ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Maurus, Steffen ; Metag, Volker ; Michel, Jan ; Mihaylov, Dimitar ; Morozov, Sergey ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Nowakowski, K.N. ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petukhov, Oleg ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramos, S. ; Ramstein, Béatrice ; Reshetin, Andrey ; Rodriguez Ramos, Pablo ; Rosier, Philippe ; Rost, Adrian ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Schwab, Erwin ; Scozzi, Federico ; Seck, Florian ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, L. ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Szala, Melanie ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Usenko, Evgeny A. ; Wagner, Vladimir ; Wendisch, Christian ; Wiebusch, Michael ; Wirth, Joana ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
We present data on charged kaons (K±) and ϕ mesons in Au(1.23A GeV)+Au collisions. It is the first simultaneous measurement of K− and ϕ mesons in central heavy-ion collisions below a kinetic beam energy of 10A GeV. The ϕ/K− multiplicity ratio is found to be surprisingly high with a value of 0.52±0.16 and shows no dependence on the centrality of the collision. Consequently, the different slopes of the K+ and K− transverse-mass spectra can be explained solely by feed-down, which substantially softens the spectra of K− mesons. Hence, in contrast to the commonly adapted argumentation in literature, the different slopes do not necessarily imply diverging freeze-out temperatures of K+ and K− mesons caused by different couplings to baryons.
Burmeister, Thomas ; Molkentin, Mara ; Meyer, Claus ; Lachmann, Nils ; Schwartz, Stefan ; Friedrichs, Birte ; Beyer, Jörg ; Blau, Igor Wolfgang ; Lohm, Gunnar ; Tietze-Bürger, Carola ; Marschalek, Rolf ; Uharek, Lutz
This report describes the clinical courses of two acute myeloid leukemia patients. Both had MLL translocations, the first a t(10;11)(p11.2;q23) with MLL-AF10 and the second a t(11;19)(q23;p13.1) with MLL-ELL fusion. They achieved a clinical remission under conventional chemotherapy but relapsed shortly after end of therapy. Both had a history of invasive mycoses (one had possible pulmonary mycosis, one systemic candidiasis). Because no HLA-identical donor was available, a haploidentical transplantation was performed in both cases. Using a specially designed PCR method for the assessment of minimal residual disease (MRD), based on the quantitative detection of the individual chromosomal breakpoint in the MLL gene, all patients achieved complete and persistent molecular remission after transplantation. The immune reconstitution after transplantation is described in terms of total CD3+/CD4+, CD3+/CD8+, CD19+, and CD16+/CD56+ cell numbers over time. The KIR and HLA genotypes of donors and recipients are reported and the possibility of a KIR-mediated alloreactivity is discussed. This report illustrates that haploidentical transplantation may offer a chance of cure without chronic graft-versus-host disease in situations where no suitable HLA-identical donor is available even in a high-risk setting and shows the value of MRD monitoring in the pre- and posttransplant setting.
Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Behnke, Claudia ; Belounnas, Amel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Chlad, Lukáš ; Deveaux, Christina Anna ; Dreyer, Jörg ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Filip, Peter ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gernhäuser, Roman ; Golubeva, Marina ; Greifenhagen, Robert ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Heinz, Tobias ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Maurus, Steffen ; Metag, Volker ; Michel, Jan ; Mihaylov, Dimitar ; Morozov, Sergey ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Nowakowski, Krzysztof ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petukhov, Oleg ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramos, Sérgio ; Ramstein, Béatrice ; Reshetin, Andrey ; Rodriguez Ramos, Pablo ; Rosier, Philippe ; Rost, Adrian ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Schwab, Erwin ; Scozzi, Federico ; Seck, Florian ; Sellheim, Patrick ; Selyuzhenkov, Ilya ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Spies, Simon ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Szala, Melanie ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Usenko, Evgeny A. ; Wagner, Vladimir ; Wendisch, Christian ; Wiebusch, Michael ; Wirth, Joana ; Zanevsky, Yuri V. ; Zumbruch, Peter W. ; Leifels, Yvonne
We present first data on sub-threshold production of Ks0 mesons and Λ hyperons in Au+Au collisions at sNN=2.4 GeV. We observe an universal 〈Apart〉 scaling of hadrons containing strangeness, independent of their corresponding production thresholds. Comparing the yields, their 〈Apart〉 scaling, and the shapes of the rapidity and the pt spectra to state-of-the-art transport model (UrQMD, HSD, IQMD) predictions, we find that none of them can simultaneously describe these observables with reasonable χ2 values.
No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors
(2019)
Hopfner, Franziska ; Müller, Stefanie H. ; Steppat, Dagmar ; Miller, Joanna ; Schmidt, Nele ; Wandinger, Klaus-Peter ; Leypoldt, Frank ; Berg, Daniela ; Franke, Andre ; Lieb, Wolfgang ; Tittmann, Lukas ; Balzer-Geldsetzer, Monika ; Baudrexel, Simon ; Dodel, Richard ; Hilker-Roggendorf, Rüdiger ; Kalbe, Elke ; Kassubek, Jan ; Klockgether, Thomas ; Liepelt-Scarfone, Inga ; Mollenhauer, Brit ; Neuser, Petra ; Reetz, Kathrin ; Riedel, Oliver ; Schulte, Claudia ; Schulz, Jörg B. ; Spottke, Annika ; Storch, Alexander ; Trenkwalder, Claudia ; Wittchen, Hans-Ulrich ; Witt, Karsten ; Wüllner, Ullrich ; Deuschl, Günther ; Kuhlenbäumer, Gregor
Background: IgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment (n = 296) and controls (n = 295) free of neuropsychiatric disease. Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.
Methods: NMDA antibodies were analysed in the serum of patients and controls using well established validated assays. We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.
Results: The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients (13%) than in controls (22%) and higher than in previous studies in both groups. NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment, nor with quantitative indicators of disease severity and cognitive impairment. A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.
Conclusion: It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g. to Parkinson disease with dementia, while NMDA IgG antibodies define a separate disease of its own.
Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Behnke, Claudia ; Belounnas, Amel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Chlad, Lukáš ; Deveaux, Christina Anna ; Dreyer, Jörn ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Filip, Peter ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gernhäuser, Roman ; Golubeva, Marina ; Greifenhagen, Robert ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Heinz, Tobias ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Matulewicz, Tomasz ; Maurus, Steffen ; Metag, Volker ; Michel, Jan ; Mihaylov, Dimitar ; Morozov, Sergey ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Nowakowski, K. ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petukhov, Oleg ; Piasecki, Krzysztof ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramos, Sérgio ; Ramstein, Béatrice ; Reshetin, Andrey ; Rodriguez Ramos, Pablo ; Rosier, Philippe ; Rost, Adrian ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Schwab, Erwin ; Scozzi, Federico ; Seck, Florian ; Sellheim, Patrick ; Selyuzhenkov, Ilya ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Spies, Simon ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Szala, Melanie ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Usenko, Evgeny A. ; Wagner, Vladimir ; Wendisch, Christian ; Wiebusch, Michael ; Wirth, Joana ; Wójcik, Daniel Krzysztof ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
We investigate identical pion HBT intensity interferometry in central Au+Au collisions at 1.23A GeV. High-statistics π−π− and π+π+ data are measured with HADES at SIS18/GSI. The radius parameters, derived from the correlation function depending on relative momenta in the longitudinally comoving system and parametrized as three-dimensional Gaussian distribution, are studied as function of transverse momentum. A substantial charge-sign difference of the source radii is found, particularly pronounced at low transverse momentum. The extracted source parameters agree well with a smooth extrapolation of the center-of-mass energy dependence established at higher energies, extending the corresponding excitation functions down towards a very low energy.
Dantas de Paula, Mateus ; Forrest, Matthew ; Langan, Liam ; Bendix, Jörg ; Homeier, Jürgen ; Velescu, Andre ; Wilcke, Wolfgang ; Hickler, Thomas
Community trait assembly in highly diverse tropical rainforests is still poorly understood. Based on more than a decade of field measurements in a biodiversity hotspot of southern Ecuador, we implemented plant trait variation and improved soil organic matter dynamics in a widely used dynamic vegetation model (the Lund-Potsdam-Jena General Ecosystem Simulator, LPJ-GUESS) to explore the main drivers of community assembly along an elevational gradient. In the model used here (LPJ-GUESS-NTD, where NTD stands for nutrient-trait dynamics), each plant individual can possess different trait combinations, and the community trait composition emerges via ecological sorting. Further model developments include plant growth limitation by phosphorous (P) and mycorrhizal nutrient uptake. The new model version reproduced the main observed community trait shift and related vegetation processes along the elevational gradient, but only if nutrient limitations to plant growth were activated. In turn, when traits were fixed, low productivity communities emerged due to reduced nutrient-use efficiency. Mycorrhizal nutrient uptake, when deactivated, reduced net primary production (NPP) by 61–72% along the gradient. Our results strongly suggest that the elevational temperature gradient drives community assembly and ecosystem functioning indirectly through its effect on soil nutrient dynamics and vegetation traits. This illustrates the importance of considering these processes to yield realistic model predictions.
Dietrich, Sascha ; Oleś, Małgorzata ; Lu, Junyan ; Sellner, Leopold ; Anders, Simon ; Velten, Britta ; Wu, Bian ; Hüllein, Jennifer ; Silva Liberio, Michelle da ; Walther, Tatjana ; Wagner, Lena ; Rabe, Sophie ; Ghidelli-Disse, Sonja ; Bantscheff, Marcus ; Oleś, Andrzej K. ; Słabicki, Mikołaj ; Mock, Andreas ; Oakes, Christopher C. ; Wang, Shihui ; Oppermann, Sina ; Lukas, Marina ; Kim, Vladislav ; Sill, Martin ; Benner, Axel ; Jauch, Anna ; Sutton, Lesley-Ann ; Young, Emma ; Rosenquist, Richard ; Liu, Xiyang ; Jethwa, Alexander ; Lee, Kwang Seok ; Lewis, Joe ; Putzker, Kerstin ; Lutz, Christoph ; Rossi, Davide ; Mokhir, Andriy ; Oellerich, Thomas ; Zirlik, Katja ; Herling, Marco ; Nguyen-Khac, Florence ; Plass, Christoph ; Andersson, Emma ; Mustjoki, Satu ; Kalle, Christof von ; Ho, Anthony Dick ; Hensel, Manfred ; Dürig, Jan ; Ringshausen, Ingo ; Zapatka, Marc ; Huber, Wolfgang ; Zenz, Thorsten
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
De-Zolt, Silke ; Schnütgen, Frank ; Seisenberger, Claudia ; Hansen, Jens ; Hollatz, Melanie ; Floss, Thomas ; Ruiz, Patricia ; Wurst, Wolfgang ; Melchner, Harald von
High-throughput gene trapping is a random approach for inducing insertional mutations across the mouse genome. This approach uses gene trap vectors that simultaneously inactivate and report the expression of the trapped gene at the insertion site, and provide a DNA tag for the rapid identification of the disrupted gene. Gene trapping has been used by both public and private institutions to produce libraries of embryonic stem (ES) cells harboring mutations in single genes. Presently,~ 66% of the protein coding genes in the mouse genome have been disrupted by gene trap insertions. Among these, however, genes encoding signal peptides or transmembrane domains (secretory genes) are underrepresented because they are not susceptible to conventional trapping methods. Here, we describe a high-throughput gene trapping strategy that effectively targets secretory genes. We used this strategy to assemble a library of ES cells harboring mutations in 716 unique secretory genes, of which 61% were not trapped by conventional trapping, indicating that the two strategies are complementary. The trapped ES cell lines, which can be ordered from the International Gene Trap Consortium (http://www.genetrap.org), are freely available to the scientific community.
Nord, Alex S. ; Chang, Patricia J. ; Conklin, Bruce R. ; Cox, Antony V. ; Harper, Courtney A. ; Hicks, Geoffrey G. ; Huang, Conrad C. ; Johns, Susan J. ; Kawamoto, Michiko ; Liu, Songyan ; Meng, Elaine C. ; Morris, John H. ; Rossant, Janet ; Ruiz, Patricia ; Skarnes, William C. ; Soriano, Philippe ; Stanford, William L. ; Stryke, Doug ; Melchner, Harald von ; Wurst, Wolfgang ; Yamamura, Ken-ichi ; Young, Stephen G. ; Babbitt, Patricia C. ; Ferrin, Thomas E.
Gene trapping is a method of generating murine embryonic stem (ES) cell lines containing insertional mutations in known and novel genes. A number of international groups have used this approach to create sizeable public cell line repositories available to the scientific community for the generation of mutant mouse strains. The major gene trapping groups worldwide have recently joined together to centralize access to all publicly available gene trap lines by developing a user-oriented Website for the International Gene Trap Consortium (IGTC). This collaboration provides an impressive public informatics resource comprising ~45 000 well-characterized ES cell lines which currently represent ~40% of known mouse genes, all freely available for the creation of knockout mice on a non-collaborative basis. To standardize annotation and provide high confidence data for gene trap lines, a rigorous identification and annotation pipeline has been developed combining genomic localization and transcript alignment of gene trap sequence tags to identify trapped loci. This information is stored in a new bioinformatics database accessible through the IGTC Website interface. The IGTC Website (www.genetrap.org) allows users to browse and search the database for trapped genes, BLAST sequences against gene trap sequence tags, and view trapped genes within biological pathways. In addition, IGTC data have been integrated into major genome browsers and bioinformatics sites to provide users with outside portals for viewing this data. The development of the IGTC Website marks a major advance by providing the research community with the data and tools necessary to effectively use public gene trap resources for the large-scale characterization of mammalian gene function.
Martinelli, Paola ; Schaaf, Otmar ; Mantoulidis, Andreas ; Martin, Laetitia J. ; Fuchs, Julian E. ; Bader, Gerd ; Gollner, Andreas ; Wolkerstorfer, Bernhard ; Rogers, Catherine ; Balıkçı, Esra ; Lipp, Jesse J. ; Mischerikow, Nikolai ; Doebel, Sandra ; Gerstberger, Thomas ; Sommergruber, Wolfgang ; Huber, Kilian ; Böttcher, Jark
The bromodomain and PHD-finger containing transcription factor (BPTF) is part of the nucleosome remodeling factor (NURF) complex and has been implicated in multiple cancer types. Here, we report the discovery of a potent and selective chemical probe targeting the bromodomain of BPTF with an attractive pharmacokinetic profile enabling cellular and in vivo experiments in mice. Microarray-based transcriptomics in presence of the probe in two lung cancer cell lines revealed only minor effects on the transcriptome. Profiling against a panel of cancer cell lines revealed that the antiproliferative effect does not correlate with BPTF dependency score in depletion screens. Both observations and the multi-domain architecture of BPTF suggest that depleting the protein by proteolysis targeting chimeras (PROTACs) could be a promising strategy to target cancer cell proliferation. We envision that the presented chemical probe and the related negative control will enable the research community to further explore scientific hypotheses with respect to BPTF bromodomain inhibition.
Hinze, Claas Heinrich ; Oommen, Prasad Thomas ; Dressler, Frank ; Urban, Andreas ; Weller-Heinemann, Frank ; Speth, Fabian ; Lainka, Elke Maria ; Brunner, Jürgen ; Fesq, Heike ; Föll, Dirk ; Müller-Felber, Wolfgang ; Neudorf, Ulrich ; Rietschel, Christoph Georg ; Schwarz, Tobias ; Schara, Ulrike ; Haas, Johannes-Peter
Background: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in childhood and a major cause of morbidity among children with pediatric rheumatic diseases. The management of JDM is very heterogeneous. The JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define consensus- and practice-based strategies in order to harmonize diagnosis, treatment and monitoring of JDM.
Methods: The JDM working group was established in 2015 consisting of 23 pediatric rheumatologists, pediatric neurologists and dermatologists with expertise in the management of JDM. Current practice patterns of management in JDM had previously been identified via an online survey among pediatric rheumatologists and neurologists. Using a consensus process consisting of online surveys and a face-to-face consensus conference statements were defined regarding the diagnosis, treatment and monitoring of JDM. During the conference consensus was achieved via nominal group technique. Voting took place using an electronic audience response system, and at least 80% consensus was required for individual statements.
Results: Overall 10 individual statements were developed, finally reaching a consensus of 92 to 100% regarding (1) establishing a diagnosis, (2) case definitions for the application of the strategies (moderate and severe JDM), (3) initial diagnostic testing, (4) monitoring and documentation, (5) treatment targets within the context of a treat-to-target strategy, (6) supportive therapies, (7) explicit definition of a treat-to-target strategy, (8) various glucocorticoid regimens, including intermittent intravenous methylprednisolone pulse and high-dose oral glucocorticoid therapies with tapering, (9) initial glucocorticoid-sparing therapy and (10) management of refractory disease.
Conclusion: Using a consensus process among JDM experts, statements regarding the management of JDM were defined. These statements and the strategies aid in the management of patients with moderate and severe JDM.
Stangl, Stefan ; Tontcheva, Nikoletta ; Sievert, Wolfgang ; Shevtsov, Maxim ; Niu, Minli ; Schmid, Thomas E. ; Pigorsch, Steffi ; Combs, Stephanie ; Haller, Bernhard ; Balermpas, Panagiotis ; Rödel, Franz ; Rödel, Claus ; Fokas, Emmanouil ; Krause, Mechthild ; Linge, Annett ; Lohaus, Fabian ; Baumann, Michael ; Tinhofer, Inge ; Budach, Volker ; Stuschke, Martin ; Grosu, Anca-Ligia ; Abdollahi, Amir ; Debus, Jürgen ; Belka, Claus ; Maihöfer, Cornelius ; Mönnich, David ; Zips, Daniel ; Multhoff, Gabriele
Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56+ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56+ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers.
The Fire Modeling Intercomparison Project (FireMIP), phase 1: experimental and analytical protocols
(2016)
Rabin, Sam S. ; Melton, Joe R. ; Lasslop, Gitta ; Bachelet, Dominique ; Forrest, Matthew ; Hantson, Stijn ; Li, Fang ; Mangeon, Stephane ; Yue, Chao ; Arora, Vivek ; Hickler, Thomas ; Kloster, Silvia ; Knorr, Wolfgang ; Nieradzik, Lars ; Spessa, Allan ; Folberth, Gerd A. ; Sheehan, Tim ; Voulgarakis, Apostolos ; Prentice, I. Colin ; Sitch, Stephen ; Kaplan, Jed O. ; Harrison, Sandy P. ; Arneth, Almut
The important role of fire in regulating vegetation community composition and contributions to emissions of greenhouse gases and aerosols make it a critical component of dynamic global vegetation models and Earth system models. Over two decades of development, a wide variety of model structures and mechanisms have been designed and incorporated into global fire models, which have been linked to different vegetation models. However, there has not yet been a systematic examination of how these different strategies contribute to model performance. Here we describe the structure of the first phase of the Fire Model Intercomparison Project (FireMIP), which for the first time seeks to systematically compare a number of models. By combining a standardized set of input data and model experiments with a rigorous comparison of model outputs to each other and to observations, we will improve the understanding of what drives vegetation fire, how it can best be simulated, and what new or improved observational data could allow better constraints on model behavior. Here we introduce the fire models used in the first phase of FireMIP, the simulation protocols applied, and the benchmarking system used to evaluate the models. The works published in this journal are distributed under the Creative Commons Attribution 3.0 License. This license does not affect the Crown copy-right work, which is re-usable under the Open Government Licence (OGL). The Creative Commons Attribution 3.0 License and the OGL are interoperable and do not conflict with, reduce, or limit each other.
Hantson, Stijn ; Arneth, Almut ; Harrison, Sandy P. ; Kelley, Douglas I. ; Prentice, I. Colin ; Rabin, Sam S. ; Archibald, Sally ; Mouillot, Florent ; Arnold, Steve R. ; Artaxo, Paulo ; Bachelet, Dominique ; Ciais, Philippe ; Forrest, Matthew ; Friedlingstein, Pierre ; Hickler, Thomas ; Kaplan, Jed O. ; Kloster, Silvia ; Knorr, Wolfgang ; Lasslop, Gitta ; Li, Fang ; Mangeon, Stephane ; Melton, Joe R. ; Meyn, Andrea ; Sitch, Stephen ; Spessa, Allan ; Werf, Guido R. van der ; Voulgarakis, Apostolos ; Yue, Chao
Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. We indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.
Hantson, Stijn ; Arneth, Almut ; Harrison, Sandy P. ; Kelley, Douglas I. ; Prentice, I. Colin ; Rabin, Sam S. ; Archibald, Sally ; Mouillot, Florent ; Arnold, Steve R. ; Artaxo, Paulo ; Bachelet, Dominique ; Ciais, Philippe ; Forrest, Matthew ; Friedlingstein, Pierre ; Hickler, Thomas ; Kaplan, Jed O. ; Kloster, Silvia ; Knorr, Wolfgang ; Lasslop, Gitta ; Li, Fang ; Mangoen, Stephane ; Melton, Joe R. ; Meyn, Andrea ; Sitch, Stephen ; Spessa, Allan ; Werf, Guido R. van der ; Voulgarakis, Apostolos ; Yue, Chao
Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, either using well-founded empirical relationships or process-based models with good predictive skill. A large variety of models exist today and it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project - FireMIP, an international project to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we summarise the current state-of-the-art in fire regime modelling and model evaluation, and outline what lessons may be learned from FireMIP.
DGK and DZHK position paper on genome editing: basic science applications and future perspective
(2021)
Brandes, Ralf ; Dueck, Anne ; Engelhardt, Stefan ; Kaulich, Manuel ; Kupatt, Christian ; De Angelis, Maria Teresa ; Leisegang, Matthias ; Le Noble, Ferdinand ; Moretti, Alessandra ; Müller, Oliver J. ; Skryabin, Boris V. ; Thum, Thomas ; Wurst, Wolfgang
For a long time, gene editing had been a scientific concept, which was limited to a few applications. With recent developments, following the discovery of TALEN zinc-finger endonucleases and in particular the CRISPR/Cas system, gene editing has become a technique applicable in most laboratories. The current gain- and loss-of function models in basic science are revolutionary as they allow unbiased screens of unprecedented depth and complexity and rapid development of transgenic animals. Modifications of CRISPR/Cas have been developed to precisely interrogate epigenetic regulation or to visualize DNA complexes. Moreover, gene editing as a clinical treatment option is rapidly developing with first trials on the way. This article reviews the most recent progress in the field, covering expert opinions gathered during joint conferences on genome editing of the German Cardiac Society (DGK) and the German Center for Cardiovascular Research (DZHK). Particularly focusing on the translational aspect and the combination of cellular and animal applications, the authors aim to provide direction for the development of the field and the most frequent applications with their problems.
Przygoda, Witold ; Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Atomssa, Ermias T. ; Behnke, Claudia ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Deveaux, Christina Anna ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petousis, Vlasios ; Pietraszko, Jerzy ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
Pietraszko, Jerzy ; Agakishiev, Geydar ; Behnke, Claudia ; Belver, Daniel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Cabanelas Eiras, Pablo ; Chernenko, Sergey P. ; Dritsa, Christina ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; González-Díaz, Diégo ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Höhne, Claudia ; Holzmann, Romain ; Huck, Patrick ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Krizek, Filip ; Kuc, Hubert ; Kugler, Andrej ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lang, Simon Martin ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Siebenson, Johannes Stephan ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Weber, Michael ; Wendisch, Christian ; Wüstenfeld, Jörn ; Yurevich, Sergey ; Zanevsky, Yuri V.
Many QCD based and phenomenological models predict changes of hadron properties in a strongly interacting environment. The results of these models differ significantly and the experimental determination of hadron properties in nuclear matter is essential. In this paper we present a review of selected physics results obtained at GSI Helmholtzzentrum für Schwerionenforschung GmbH by HADES (High-Acceptance Di-Electron Spectrometer). The e+e− pair emission measured for proton and heavy-ion induced collisions is reported together with results on strangeness production. The future HADES activities at the planned FAIR facility are also discussed.
Lorenz, Manuel ; Agakishiev, Geydar ; Behnke, Claudia ; Belver, Daniel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Cabanelas Eiras, Pablo ; Dritsa, Christina ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fonte, Paulo ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; González-Díaz, Diégo ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Holzmann, Romain ; Huck, Patrick ; Höhne, Claudia ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Krizek, Filip ; Kuc, Hubert ; Kugler, Andrej ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lang, Simon Martin ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Siebenson, Johannes Stephan ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Weber, Michael ; Wendisch, Christian ; Wüstenfeld, Jörn ; Yurevich, Sergey ; Zanevsky, Yuri V.
The knowledge of baryonic resonance properties and production cross sections plays an important role for the extraction and understanding of medium modifications of mesons in hot and/or dense nuclear matter. We present and discuss systematics on dielectron and strangeness production obtained with HADES on p+p, p+A and A+A collisions in the few GeV energy regime with respect to these resonances.
Epple, Eliane ; Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Atomssa, Ermias T. ; Behnke, Claudia ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Deveaux, Christina Anna ; Dybczak, Adrian ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petousis, Vlasios ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
his contribution aims to give a basic overview of the latest results regarding the production of resonances in different collision systems. The results were extracted from experimental data collected with HADES that is a multipurpose detector located at the GSI Helmholtzzentrum, Darmstadt. The main points discussed here are: the properties of the strange resonances Λ(1405) and Σ(1385), the role of Δ’s as a source of pions in the final state, the production dynamics reflected in form of differential cross sections, and the role of the ϕ meson as a source for K− particles.
Ramstein, Béatrice ; Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Atomssa, Ermias T. ; Behnke, Claudia ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Deveaux, Christina Anna ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petousis, Vlasios ; Pietraszko, Jerzy ; Przygoda, Witold ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
Lorenz, Manuel ; Agakishiev, Geydar ; Behnke, Claudia ; Belver, Daniel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Cabanelas Eiras, Pablo ; Chernenko, Sergey P. ; Dritsa, Christina ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; González-Díaz, Diégo ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Höhne, Claudia ; Holzmann, Romain ; Huck, Patrick ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Krizek, Filip ; Kuc, Hubert ; Kugler, Andrej ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lang, Simon Martin ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Siebenson, Johannes Stephan ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Weber, Michael ; Wendisch, Christian ; Wüstenfeld, Jörn ; Yurevich, Sergey ; Zanevsky, Yuri V.
The High Acceptance DiElectron Spectrometer HADES [1] is installed at the Helmholtzzentrum für Schwerionenforschung (GSI) accelerator facility in Darmstadt. It investigates dielectron emission and strangeness production in the 1-3 AGeV regime. A recent experiment series focusses on medium-modifications of light vector mesons in cold nuclear matter. In two runs, p+p and p+Nb reactions were investigated at 3.5 GeV beam energy; about 9·109 events have been registered. In contrast to other experiments the high acceptance of the HADES allows for a detailed analysis of electron pairs with low momenta relative to nuclear matter, where modifications of the spectral functions of vector mesons are predicted to be most prominent. Comparing these low momentum electron pairs to the reference measurement in the elementary p+p reaction, we find in fact a strong modification of the spectral distribution in the whole vector meson region.
Kurilkin, Pavel ; Agakishiev, Geydar ; Behnke, Claudia ; Belver, Daniel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Cabanelas Eiras, Pablo ; Chernenko, Sergey P. ; Dritsa, Christina ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo J. R. ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; González-Díaz, Diégo ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Holzmann, Romain ; Huck, Patrick ; Höhne, Claudia ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Krizek, Filip ; Kuc, Hubert ; Kugler, Andrej ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lang, Simon Martin ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Siebenson, Johannes Stephan ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Weber, Michael ; Wendisch, Christian ; Wüstenfeld, Jörn ; Yurevich, Sergey ; Zanevsky, Yuri V.
New results on the differential cross section in deuteron-proton elastic scattering are obtained at the deuteron kinetic energy of 2.5 GeV with the HADES spectrometer. The angular range of 69° – 125° in the center of mass system is covered. The obtained results are compared with the relativistic multiple scattering model calculation using the CD-Bonn deuteron wave function. The data at fixed scattering angles in the c.m. are in qualitative agreement with the constituent counting rules prediction.
Hollenbach, Marcus ; Prettin, Christiane ; Gundling, Felix ; Schepp, Wolfgang ; Seufert, Jochen ; Stein, Jürgen ; Rösch, Thomas ; Aberle, Jens ; Feisthammel, Jürgen ; Petrof, David ; Hoffmeister, Albrecht
Background: Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure.
Methods: We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated.
Discussion: This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment.
Trial registration: 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).
Rabin, Sam S. ; Melton, Joe R. ; Lasslop, Gitta ; Bachelet, Dominique ; Forrest, Matthew ; Hantson, Stijn ; Kaplan, Jed O. ; Li, Fang ; Mangeon, Stephane ; Ward, Daniel S. ; Yue, Chao ; Arora, Vivek ; Hickler, Thomas ; Kloster, Silvia ; Knorr, Wolfgang ; Nieradzik, Lars ; Spessa, Allan ; Folberth, Gerd A. ; Sheehan, Tim ; Voulgarakis, Apostolos ; Kelley, Douglas I. ; Prentice, I. Colin ; Sitch, Stephen ; Harrison, Sandy P. ; Arneth, Almut
The important role of fire in regulating vegetation community composition and contributions to emissions of greenhouse gases and aerosols make it a critical component of dynamic global vegetation models and Earth system models. Over 2 decades of development, a wide variety of model structures and mechanisms have been designed and incorporated into global fire models, which have been linked to different vegetation models. However, there has not yet been a systematic examination of how these different strategies contribute to model performance. Here we describe the structure of the first phase of the Fire Model Intercomparison Project (FireMIP), which for the first time seeks to systematically compare a number of models. By combining a standardized set of input data and model experiments with a rigorous comparison of model outputs to each other and to observations, we will improve the understanding of what drives vegetation fire, how it can best be simulated, and what new or improved observational data could allow better constraints on model behavior. In this paper, we introduce the fire models used in the first phase of FireMIP, the simulation protocols applied, and the benchmarking system used to evaluate the models. We have also created supplementary tables that describe, in thorough mathematical detail, the structure of each model.
Griesinger, Frank ; Eberhardt, Wilfried E. E. ; Nusch, Arnd ; Reiser, Marcel ; Zahn, Mark-Oliver ; Maintz, Christoph ; Bernhardt, Christiane ; Losem, Christoph ; Stenzinger, Albrecht ; Heukamp, Lukas ; Büttner, Reinhard ; Marschner, Sebastian ; Jänicke, Martina ; Fleitz, Annette ; Spring, Lisa ; Sahlmann, Jörg ; Karatas, Aysun ; Hipper, Annette ; Weichert, Wilko ; Heilmann, Monika ; Sadjadian, Parvis ; Gleiber, Wolfgang ; Grah, Christian ; Waller, Cornelius ; Reck, Martin ; Rittmeyer, Achim ; Christopoulos, Petros ; Sebastian, Martin ; Thomas, Michael
Pati, Sarthak ; Baid, Ujjwal ; Edwards, Brandon ; Sheller, Micah ; Wang, Shih-Han ; Reina, G. Anthony ; Foley, Patrick ; Gruzdev, Alexey ; Karkada, Deepthi ; Davatzikos, Christos ; Sako, Chiharu ; Ghodasara, Satyam ; Bilello, Michel ; Mohan, Suyash ; Vollmuth, Philipp ; Brugnara, Gianluca ; Jayachandran Preetha, Chandrakanth ; Sahm, Felix ; Maier-Hein, Klaus ; Zenk, Maximilian ; Bendszus, Martin ; Wick, Wolfgang ; Calabrese, Evan ; Rudie, Jeffrey ; Villanueva-Meyer, Javier ; Cha, Soonmee ; Ingalhalikar, Madhura ; Jadhav, Manali ; Pandey, Umang ; Saini, Jitender ; Garrett, John ; Larson, Matthew ; Jeraj, Robert ; Currie, Stuart ; Frood, Russell ; Fatania, Kavi ; Huang, Raymond Y. ; Chang, Ken ; Balaña, Carmen ; Capellades, Jaume ; Puig, Josep ; Trenkler, Johannes ; Pichler, Josef ; Necker, Georg ; Haunschmidt, Andreas ; Meckel, Stephan ; Shukla, Gaurav ; Liem, Spencer ; Alexander, Gregory S. ; Lombardo, Joseph ; Palmer, Joshua D. ; Flanders, Adam E. ; Dicker, Adam P. ; Sair, Haris I. ; Jones, Craig K. ; Venkataraman, Archana ; Jiang, Meirui ; So, Tiffany Y. ; Chen, Cheng ; Heng, Pheng Ann ; Dou, Qi ; Kozubek, Michal ; Lux, Filip ; Michálek, Jan ; Matula, Petr ; Keřkovský, Miloš ; Kopřivová, Tereza ; Dostál, Marek ; Vybíhal, Václav ; Vogelbaum, Michael A. ; Mitchell, J. Ross ; Farinhas, Joaquim ; Maldjian, Joseph A. ; Bangalore Yogananda, Chandan Ganesh ; Pinho, Marco C. ; Reddy, Divya ; Holcomb, James ; Wagner, Benjamin C. ; Ellingson, Benjamin M. ; Cloughesy, Timothy F. ; Raymond, Catalina ; Oughourlian, Talia ; Hagiwara, Akifumi ; Wang, Chencai ; To, Minh-Son ; Bhardwaj, Sargam ; Chong, Chee ; Agzarian, Marc ; Falcão, Alexandre Xavier ; Martins, Samuel B. ; Teixeira, Bernardo Corrêa de Almeida ; Sprenger, Flávia ; Menotti, David ; Lucio, Diego R. ; LaMontagne, Pamela ; Marcus, Daniel ; Wiestler, Benedikt ; Kofler, Florian ; Ezhov, Ivan ; Metz, Marie ; Jain, Rajan ; Lee, Matthew ; Lui, Yvonne W. ; McKinley, Richard ; Slotboom, Johannes ; Radojewski, Piotr ; Meier, Raphael ; Wiest, Roland Gerhard Rudi ; Murcia, Derrick ; Fu, Eric ; Haas, Rourke ; Thompson, John ; Ormond, David Ryan ; Badve, Chaitra ; Sloan, Andrew E. ; Vadmal, Vachan ; Waite, Kristin ; Colen, Rivka R. ; Pei, Linmin ; Ak, Murat ; Srinivasan, Ashok ; Bapuraj, Jayapalli Rajiv ; Rao, Arvind ; Wang, Nicholas ; Yoshiaki, Ota ; Moritani, Toshio ; Turk, Sevcan ; Lee, Joonsang ; Prabhudesai, Snehal ; Morón, Fanny ; Mandel, Jacob ; Kamnitsas, Konstantinos ; Glocker, Ben ; Dixon, Luke V. M. ; Williams, Matthew ; Zampakis, Peter ; Panagiotopoulos, Vasileios ; Tsiganos, Panagiotis ; Alexiou, Sotiris ; Haliassos, Ilias ; Zacharaki, Evangelia I. ; Moustakas, Konstantinos ; Kalogeropoulou, Christina ; Kardamakis, Dimitrios M. ; Choi, Yoon Seong ; Lee, Seung-Koo ; Chang, Jong Hee ; Ahn, Sung Soo ; Luo, Bing ; Poisson, Laila ; Wen, Ning ; Tiwari, Pallavi ; Verma, Ruchika ; Bareja, Rohan ; Yadav, Ipsa ; Chen, Jonathan ; Kumar, Neeraj ; Smits, Marion ; Voort, Sebastian R. van der ; Alafandi, Ahmed ; Incekara, Fatih ; Wijnenga, Maarten M. J. ; Kapsas, Georgios ; Gahrmann, Renske ; Schouten, Joost W. ; Dubbink, Hendrikus J. ; Vincent, Arnaud J. P. E. ; Van den Bent, Martin J. ; French, Pim J. ; Klein, Stefan ; Yuan, Yading ; Sharma, Sonam ; Tseng, Tzu-Chi ; Adabi, Saba ; Niclou, Simone P. ; Keunen, Olivier ; Hau, Ann-Christin ; Vallières, Martin ; Fortin, David ; Lepage, Martin ; Landman, Bennett ; Ramadass, Karthik ; Xu, Kaiwen ; Chotai, Silky ; Chambless, Lola B. ; Mistry, Akshitkumar ; Thompson, Reid C. ; Gusev, Yuriy ; Bhuvaneshwar, Krithika ; Sayah, Anousheh ; Bencheqroun, Camelia ; Belouali, Anas ; Madhavan, Subha ; Booth, Thomas C. ; Chelliah, Alysha ; Modat, Marc ; Shuaib, Haris ; Dragos, Carmen ; Abayazeed, Aly ; Kolodziej, Kenneth ; Hill, Michael ; Abbassy, Ahmed ; Gamal, Shady ; Mekhaimar, Mahmoud ; Qayati, Mohamed ; Reyes, Mauricio ; Park, Ji Eun ; Yun, Jihye ; Kim, Ho Sung ; Mahajan, Abhishek ; Muzi, Mark ; Benson, Sean ; Beets-Tan, Regina G. H. ; Teuwen, Jonas ; Herrera-Trujillo, Alejandro ; Trujillo, Maria ; Escobar, William ; Abello, Ana Lorena ; Bernal, Jose ; Gómez, Jhon ; Choi, Joseph ; Baek, Stephen ; Kim, Yusung ; Ismael, Heba ; Allen, Bryan ; Buatti, John M. ; Kotrotsou, Aikaterini ; Li, Hongwei ; Weiss, Tobias ; Weller, Michael ; Bink, Andrea ; Pouymayou, Bertrand ; Shaykh, Hassan F. ; Saltz, Joel ; Prasanna, Prateek ; Shrestha, Sampurna ; Mani, Kartik M. ; Payne, David ; Kurc, Tahsin ; Pelaez, Enrique ; Franco-Maldonado, Heydy ; Loayza, Francis ; Quevedo Sacoto, Andrés Sebastián ; Guevara, Pamela ; Torche, Esteban ; Mendoza, Cristobal ; Vera, Franco ; Ríos, Elvis ; López, Eduardo ; Velastin, Sergio Alejandro ; Ogbole, Godwin ; Soneye, Mayowa ; Oyekunle, Dotun ; Odafe-Oyibotha, Olubunmi ; Osobu, Babatunde ; Shu’aibu, Mustapha ; Dorcas, Adeleye ; Dako, Farouk ; Simpson, Amber L. ; Hamghalam, Mohammad ; Peoples, Jacob J. ; Hu, Ricky ; Tran, Anh ; Cutler, Danielle ; Moraes, Fabio Y. ; Boss, Michael A. ; Gimpel, James ; Kattil Veettil, Deepak ; Schmidt, Kendall ; Bialecki, Brian ; Marella, Sailaja ; Price, Cynthia ; Cimino, Lisa ; Apgar, Charles ; Shah, Prashant ; Menze, Bjoern Holger ; Barnholtz-Sloan, Jill S. ; Martin, Jason ; Bakas, Spyridon
Pati, Sarthak ; Baid, Ujjwal ; Edwards, Brandon ; Sheller, Micah ; Wang, Shih-Han ; Reina, G. Anthony ; Foley, Patrick ; Gruzdev, Alexey ; Karkada, Deepthi ; Davatzikos, Christos ; Sako, Chiharu ; Ghodasara, Satyam ; Bilello, Michel ; Mohan, Suyash ; Vollmuth, Philipp ; Brugnara, Gianluca ; Jayachandran Preetha, Chandrakanth ; Sahm, Felix ; Maier-Hein, Klaus ; Zenk, Maximilian ; Bendszus, Martin ; Wick, Wolfgang ; Calabrese, Evan ; Rudie, Jeffrey ; Villanueva-Meyer, Javier ; Cha, Soonmee ; Ingalhalikar, Madhura ; Jadhav, Manali ; Pandey, Umang ; Saini, Jitender ; Garrett, John ; Larson, Matthew ; Jeraj, Robert ; Currie, Stuart ; Frood, Russell ; Fatania, Kavi ; Huang, Raymond Y. ; Chang, Ken ; Balaña, Carmen ; Capellades, Jaume ; Puig, Josep ; Trenkler, Johannes ; Pichler, Josef ; Necker, Georg ; Haunschmidt, Andreas ; Meckel, Stephan ; Shukla, Gaurav ; Liem, Spencer ; Alexander, Gregory S. ; Lombardo, Joseph ; Palmer, Joshua D. ; Flanders, Adam E. ; Dicker, Adam P. ; Sair, Haris I. ; Jones, Craig K. ; Venkataraman, Archana ; Jiang, Meirui ; So, Tiffany Y. ; Chen, Cheng ; Heng, Pheng Ann ; Dou, Qi ; Kozubek, Michal ; Lux, Filip ; Michálek, Jan ; Matula, Petr ; Keřkovský, Miloš ; Kopřivová, Tereza ; Dostál, Marek ; Vybíhal, Václav ; Vogelbaum, Michael A. ; Mitchell, J. Ross ; Farinhas, Joaquim ; Maldjian, Joseph A. ; Bangalore Yogananda, Chandan Ganesh ; Pinho, Marco C. ; Reddy, Divya ; Holcomb, James ; Wagner, Benjamin C. ; Ellingson, Benjamin M. ; Cloughesy, Timothy F. ; Raymond, Catalina ; Oughourlian, Talia ; Hagiwara, Akifumi ; Wang, Chencai ; To, Minh-Son ; Bhardwaj, Sargam ; Chong, Chee ; Agzarian, Marc ; Falcão, Alexandre Xavier ; Martins, Samuel B. ; Teixeira, Bernardo Corrêa de Almeida ; Sprenger, Flávia ; Menotti, David ; Lucio, Diego R. ; LaMontagne, Pamela ; Marcus, Daniel ; Wiestler, Benedikt ; Kofler, Florian ; Ezhov, Ivan ; Metz, Marie ; Jain, Rajan ; Lee, Matthew ; Lui, Yvonne W. ; McKinley, Richard ; Slotboom, Johannes ; Radojewski, Piotr ; Meier, Raphael ; Wiest, Roland Gerhard Rudi ; Murcia, Derrick ; Fu, Eric ; Haas, Rourke ; Thompson, John ; Ormond, David Ryan ; Badve, Chaitra ; Sloan, Andrew E. ; Vadmal, Vachan ; Waite, Kristin ; Colen, Rivka R. ; Pei, Linmin ; Ak, Murat ; Srinivasan, Ashok ; Bapuraj, Jayapalli Rajiv ; Rao, Arvind ; Wang, Nicholas ; Yoshiaki, Ota ; Moritani, Toshio ; Turk, Sevcan ; Lee, Joonsang ; Prabhudesai, Snehal ; Morón, Fanny ; Mandel, Jacob ; Kamnitsas, Konstantinos ; Glocker, Ben ; Dixon, Luke V. M. ; Williams, Matthew ; Zampakis, Peter ; Panagiotopoulos, Vasileios ; Tsiganos, Panagiotis ; Alexiou, Sotiris ; Haliassos, Ilias ; Zacharaki, Evangelia I. ; Moustakas, Konstantinos ; Kalogeropoulou, Christina ; Kardamakis, Dimitrios M. ; Choi, Yoon Seong ; Lee, Seung-Koo ; Chang, Jong Hee ; Ahn, Sung Soo ; Luo, Bing ; Poisson, Laila ; Wen, Ning ; Tiwari, Pallavi ; Verma, Ruchika ; Bareja, Rohan ; Yadav, Ipsa ; Chen, Jonathan ; Kumar, Neeraj ; Smits, Marion ; Voort, Sebastian R. van der ; Alafandi, Ahmed ; Incekara, Fatih ; Wijnenga, Maarten M. J. ; Kapsas, Georgios ; Gahrmann, Renske ; Schouten, Joost W. ; Dubbink, Hendrikus J. ; Vincent, Arnaud J. P. E. ; Van den Bent, Martin J. ; French, Pim J. ; Klein, Stefan ; Yuan, Yading ; Sharma, Sonam ; Tseng, Tzu-Chi ; Adabi, Saba ; Niclou, Simone P. ; Keunen, Olivier ; Hau, Ann-Christin ; Vallières, Martin ; Fortin, David ; Lepage, Martin ; Landman, Bennett ; Ramadass, Karthik ; Xu, Kaiwen ; Chotai, Silky ; Chambless, Lola B. ; Mistry, Akshitkumar ; Thompson, Reid C. ; Gusev, Yuriy ; Bhuvaneshwar, Krithika ; Sayah, Anousheh ; Bencheqroun, Camelia ; Belouali, Anas ; Madhavan, Subha ; Booth, Thomas C. ; Chelliah, Alysha ; Modat, Marc ; Shuaib, Haris ; Dragos, Carmen ; Abayazeed, Aly ; Kolodziej, Kenneth ; Hill, Michael ; Abbassy, Ahmed ; Gamal, Shady ; Mekhaimar, Mahmoud ; Qayati, Mohamed ; Reyes, Mauricio ; Park, Ji Eun ; Yun, Jihye ; Kim, Ho Sung ; Mahajan, Abhishek ; Muzi, Mark ; Benson, Sean ; Beets-Tan, Regina G. H. ; Teuwen, Jonas ; Herrera-Trujillo, Alejandro ; Trujillo, Maria ; Escobar, William ; Abello, Ana Lorena ; Bernal, Jose ; Gómez, Jhon ; Choi, Joseph ; Baek, Stephen ; Kim, Yusung ; Ismael, Heba ; Allen, Bryan ; Buatti, John M. ; Kotrotsou, Aikaterini ; Li, Hongwei ; Weiss, Tobias ; Weller, Michael ; Bink, Andrea ; Pouymayou, Bertrand ; Shaykh, Hassan F. ; Saltz, Joel ; Prasanna, Prateek ; Shrestha, Sampurna ; Mani, Kartik M. ; Payne, David ; Kurc, Tahsin ; Pelaez, Enrique ; Franco-Maldonado, Heydy ; Loayza, Francis ; Quevedo Sacoto, Andrés Sebastián ; Guevara, Pamela ; Torche, Esteban ; Mendoza, Cristobal ; Vera, Franco ; Ríos, Elvis ; López, Eduardo ; Velastin, Sergio Alejandro ; Ogbole, Godwin ; Soneye, Mayowa ; Oyekunle, Dotun ; Odafe-Oyibotha, Olubunmi ; Osobu, Babatunde ; Shu’aibu, Mustapha ; Dorcas, Adeleye ; Dako, Farouk ; Simpson, Amber L. ; Hamghalam, Mohammad ; Peoples, Jacob J. ; Hu, Ricky ; Tran, Anh ; Cutler, Danielle ; Moraes, Fabio Y. ; Boss, Michael A. ; Gimpel, James ; Kattil Veettil, Deepak ; Schmidt, Kendall ; Bialecki, Brian ; Marella, Sailaja ; Price, Cynthia ; Cimino, Lisa ; Apgar, Charles ; Shah, Prashant ; Menze, Bjoern Holger ; Barnholtz-Sloan, Jill S. ; Martin, Jason ; Bakas, Spyridon
Muth, Daniel Rudolf ; Priglinger, Siegfried Georg ; Shajari, Mehdi ; Kreutzer, Thomas Christian ; Mayer, Wolfgang Johann
Purpose: To describe a novel surgical technique of a combined implantation of an artificial iris and a scleral fixated intraocular lens (IOL) using flanged IOL haptics (“Yamane” technique).
Observations: The suturelessly implanted artificial iris-IOL-sandwich was stable with good functional as well as aesthetic results. However, our case showed a postoperative intraocular pressure rise.
Conclusions: The presented case demonstrates that a visual as well as cosmetical rehabilitation seems to be possible even after severe, penetrating ocular trauma with profound iris defects.
Importance: The sutureless IOL scleral fixation technique can also be used in combination with a sutureless artificial iris implantation. Further studies are needed to evaluate the long-term safety profile and rates of postoperative complications.
Settelmeier, Stephan ; Kessler, Lukas ; Varasteh, Zohreh ; Mahabadi, Amir Abbas ; Michel, Christian Lars ; Papathanasiou, Maria ; Laschinsky, Christina ; Rischpler, Christoph ; Fendler, Wolfgang P. ; Schlosser, Thomas Wilfried ; Umutlu, Lale ; Herrmann, Ken ; Rassaf, Tienush ; Kersting, David
Lal, Dennis ; Ruppert, Ann-Kathrin ; Trucks, Holger ; Schulz, Herbert ; Kovel, Carolien G. de ; Kasteleijn-Nolst Trenité, Dorothée G. ; Sonsma, Anja C. M. ; Koeleman, Bobby P. ; Lindhout, Dick ; Weber, Yvonne G. ; Lerche, Holger ; Kapser, Claudia ; Schankin, Christoph Josef ; Kunz, Wolfram S. ; Surges, Rainer ; Elger, Christian Erich ; Gaus, Verena ; Schmitz, Bettina ; Helbig, Ingo ; Muhle, Hiltrud ; Stephani, Ulrich ; Klein, Karl Martin ; Rosenow, Felix ; Neubauer, Bernd Axel ; Reinthaler, Eva Maria ; Zimprich, Fritz ; Feucht, Martha ; Møller, Rikke S. ; Hjalgrim, Helle ; Jonghe, Peter De ; Suls, Arvid ; Lieb, Wolfgang ; Franke, Andre ; Strauch, Konstantin ; Gieger, Christian ; Schurmann, Claudia ; Schminke, Ulf ; Nürnberg, Peter ; Sander, Thomas
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
Russotto, Paolo ; Chartier, Marielle ; Cozma, Mircea Dan ; De Filippo, Enrico ; Le Fèvre, Arnaud ; Gannon, S. ; Gašparić, Igor ; Kis, M. ; Kupny, S. ; Leifels, Yvonne ; Lemmon, Roy Crawford ; Li, Q. ; Lukasik, J. ; Marini, P. ; Pawlowski, P. ; Trautmann, Wolfgang ; Acosta, L. ; Adamczyk, M. ; Al-Ajlan, A. ; Al-Garawi, M. ; Al-Homaidhi, S. ; Amorini, Francesca ; Auditore, Lucrezia ; Aumann, Thomas ; Ayyad, Y. ; Baran, V. ; Basrak, Z. ; Bassini, R. ; Benlliure Anaya, Jose Fernando ; Boiano, Ciro ; Boisjoli, M. ; Boretzky, Konstanze ; Brzychczyk, Janusz ; Budzanowski, Andrzej ; Cardella, Giuseppe ; Chajecki, Zbigniew ; Chbihi, A. ; Colonna, Maria ; Czech, Bronislaw ; Di Toro, Massimo ; Famiano, Michael A. ; Greco, V. ; Grassi, L. ; Guazzoni, Chiara ; Guazzoni, P. ; Heil, Michael ; Heilborn, L. ; Introzzi, Riccardo ; Isobe, Tadaaki ; Kezzar, K. ; Krasznahorkay, Attila ; Kurz, Nikolaus ; La Guidara, E. ; Lanzalone, Gaetano ; Lasko, P. ; Lombardo, Ivano ; Lynch, William G. ; Matthews, Z. ; May, L. ; Minniti, T. ; Mostazo, M. ; Pagano, A. ; Papa, M. ; Pirrone, Sara ; Pleskac, Radek ; Politi, Giuseppe ; Porto, Francesco ; Reifarth, René ; Reisdorf, Willibrord ; Riccio, F. ; Rizzo, Francesca ; Rosato, E. ; Rossi, Dominic M. ; Santoro, S. ; Simon, Haik ; Skwirczynska, I. ; Sosin, Zbigniew ; Stuhl, László ; Trifirò, Antonio ; Trimarchi, Marina ; Tsang, M. Betty ; Verde, Giuseppe ; Veselsky, M. ; Vigilante, Mariano ; Wieloch, A. ; Wigg, P. ; Wolter, Hermann ; Wu, P. ; Yennello, Sherry J. ; Zambon, P. ; Zetta, L. ; Zoric, Maja
The elliptic-flow ratio of neutrons with respect to protons or light complex particles in reactions of heavy ions at pre-relativistic energies has been proposed as an observable sensitive to the strength of the symmetry term of the nuclear equation of state at supra-saturation densities. In the ASY-EOS experiment at the GSI laboratory, flows of neutrons and light charged particles were measured for 197Au+197Au collisions at 400 MeV/nucleon. Flow results obtained for the Au+Au system, in comparison with predictions of the UrQMD transport model, confirm the moderately soft to linear density dependence of the symmetry energy deduced from the earlier FOPI-LAND data.