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- Bianchi, Nicola (20)
- Cai, Xiao (20)
- Hayrapetyan, A. (20)
- Kisel, Ivan (20)
- Koch, Alexander (20)
- Schmidt, Christian Joachim (20)
- Vasiliev, Andrey (20)
- Wang, Y. (20)
- Zhang, X. (20)
- Adamová, Dagmar (19)
- Aggarwal, Madan Mohan (19)
- Aglieri Rinella, Gianluca (19)
- Aguilar Salazar, S. (19)
- Ahammed, Zubayer (19)
- Ahmad, Nazeer (19)
- Ahn, Sang Un (19)
- Akindinov, Alexander (19)
- Aleksandrov, Dmitry (19)
- Alessandro, Bruno (19)
- Alfaro Molina, Jose Ruben (19)
- Alici, Andrea (19)
- Alt, Torsten (19)
- Altini, V. (19)
- Andrei, Cristian (19)
- Andronic, Anton (19)
- Antinori, Federico (19)
- Antičić, Tome (19)
- Antonioli, Pietro (19)
- Aphecetche, Laurent Bernard (19)
- Appelshäuser, Harald (19)
- Arcelli, Silvia (19)
- Armesto, Néstor (19)
- Arnaldi, Roberta (19)
- Aronsson, Tomas Robert (19)
- Arsene, Ionut Cristian (19)
- Augustinus, Andre (19)
- Averbeck, Ralf Peter (19)
- Azmi, Mohd Danish (19)
- Bach, Matthias (19)
- Badalà, Angela (19)
- Baek, Yong Wook (19)
- Bailhache, Raphaëlle (19)
- Bala, Remu (19)
- Baldini Ferroli, Rinaldo (19)
- Baldisseri, Alberto (19)
- Barbera, Roberto (19)
- Barile, Francesco (19)
- Barnaföldi, Gergely Gábor (19)
- Barret, Valerie (19)
- Bartke, Jerzy (19)
- Basile, Maurizio (19)
- Bastid, Nicole (19)
- Bathen, Bastian (19)
- Batigne, Guillaume (19)
- Batyunya, Boris (19)
- Baumann, C. (19)
- Bearden, Ian Gardner (19)
- Belikov, Iouri (19)
- Bellwied, Rene (19)
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- Berceanu, Ionela (19)
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- Betev, Latchezar (19)
- Bhasin, Anju (19)
- Bhati, Ashok Kumar (19)
- Bianchi, Livio (19)
- Bianchin, Chiara (19)
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- Kalweit, Alexander Philipp (19)
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- Kim, M. (19)
- Kim, S. (19)
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- Koch, K. (19)
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- Kour, R. (19)
- Kowalski, Marek (19)
- Kox, Serge (19)
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- Ma, R. (19)
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Institut
Ortega-Andrade, H. Mauricio ; Bentley, Alexander ; Koch, Claudia ; Yánez-Muñoz, Mario H. ; Entiauspe-Neto, Omar Machado
The amerophidian snake radiation is a Late Cretaceous superfamily that encompasses two families: Aniliidae, pipe snakes, and Tropidophiidae, dwarf boas. We describe a new dwarf boa snake species, from the Tropidophiidae family, from the cloud forest in northeastern Ecuador. Tropidophis cacuangoae sp. nov. can be diagnosed from its congeners based on external and osteological morphology. The new species inhabits eastern tropical piedmont and lower evergreen montane forests, in the Amazon Tropical Rainforest biome, and is likely to be an Ecuadorian endemic. We also discuss the relationships of the new species with South American tropidophiids and provide a key to the identification of mainland South American dwarf boas.
Koch, Agnes Antonia Sophie ; Sponholz, Stefan ; Trainer, Stephan ; Stratmann, Jan Alexander ; Sebastian, Martin ; Rauch, Maximilian ; Wolff, Robert ; Steinbach, Joachim Peter ; Ronellenfitsch, Michael Wilfried ; Urban, Hans
Brain metastases are a common finding upon initial diagnosis of otherwise locally limited non-small cell lung cancer. We present a retrospective case series describing three cases of patients with symptomatic, synchronous brain metastases and resectable lung tumors. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab. Afterwards, resection of the pulmonary lesion with curative intent was performed. One patient showed progressive disease 12 months after initial diagnosis, and passed away 31 months after initial diagnosis. Two of the patients are still alive and maintain a good quality of life with a progression-free survival and overall survival of 28 and 35 months, respectively, illustrating the potential of novel combinatorial treatment approaches.
Eckes, Timon Sebastian ; Patyna, Ralf Sammy ; Koch, Alexander ; Oftring, Anke ; Gauer, Stefan ; Obermüller, Nicholas ; Schwalm, Stephanie ; Schäfer, Liliana ; Chun, Jerold ; Gröne, Hermann-Josef ; Pfeilschifter, Josef
S1P and its receptors have been reported to play important roles in the development of renal fibrosis. Although S1P5 has barely been investigated so far, there are indications that it can influence inflammatory and fibrotic processes. Here, we report the role of S1P5 in renal inflammation and fibrosis. Male S1P5 knockout mice and wild-type mice on a C57BL/6J background were fed with an adenine-rich diet for 7 days or 14 days to induce tubulointerstitial fibrosis. The kidneys of untreated mice served as respective controls. Kidney damage, fibrosis, and inflammation in kidney tissues were analyzed by real-time PCR, Western blot, and histological staining. Renal function was assessed by plasma creatinine ELISA. The S1P5 knockout mice had better renal function and showed less kidney damage, less proinflammatory cytokine release, and less fibrosis after 7 days and 14 days of an adenine-rich diet compared to wild-type mice. S1P5 knockout ameliorates tubular damage and tubulointerstitial fibrosis in a model of adenine-induced nephropathy in mice. Thus, targeting S1P5 might be a promising goal for the pharmacological treatment of kidney diseases.
Glück, Melanie ; Koch, Alexander ; Brunkhorst, Robert ; Ferreiros Bouzas, Nerea ; Trautmann, Sandra ; Schäfer, Liliana ; Pfeilschifter, Waltraud ; Pfeilschifter, Josef ; Vutukuri, Rajkumar
Sphingosine 1-phosphate (S1P) is a lipid mediator with numerous biological functions. The term ‘S1P’ mainly refers to the sphingolipid molecule with a long-chain sphingoid base of 18 carbon atoms, d18:1 S1P. The enzyme serine palmitoyltransferase catalyses the first step of the sphingolipid de novo synthesis using palmitoyl-CoA as the main substrate. After further reaction steps, d18:1 S1P is generated. However, also stearyl-CoA or myristoyl-CoA can be utilised by the serine palmitoyltransferase, which at the end of the S1P synthesis pathway, results in the production of d20:1 S1P and d16:1 S1P respectively. We measured these S1P homologues in mice and renal tissue of patients suffering from renal cell carcinoma (RCC). Our experiments highlight the relevance of d16:1 S1P for the induction of connective tissue growth factor (CTGF) in the human renal clear cell carcinoma cell line A498 and human RCC tissue. We show that d16:1 S1P versus d18:1 and d20:1 S1P leads to the highest CTGF induction in A498 cells via S1P2 signalling and that both d16:1 S1P and CTGF levels are elevated in RCC compared to adjacent healthy tissue. Our data indicate that d16:1 S1P modulates conventional S1P signalling by acting as a more potent agonist at the S1P2 receptor than d18:1 S1P. We suggest that elevated plasma levels of d16:1 S1P might play a pro-carcinogenic role in the development of RCC via CTGF induction.
Crowdfunding platforms offer project initiators the opportunity to acquire funds from the Internet crowd and, therefore, have become a valuable alternative to traditional sources of funding. However, some processes on crowdfunding platforms cause undesirable external effects that influence the funding success of projects. In this context, we focus on the phenomenon of project overfunding. Massively overfunded projects have been discussed to overshadow other crowdfunding projects which in turn receive less funding. We propose a funding redistribution mechanism to internalize these overfunding externalities and to improve overall funding results. To evaluate this concept, we develop and deploy an agent-based model (ABM). This ABM is based on a multi-attribute decision-making approach and is suitable to simulate the dynamic funding processes on a crowdfunding platform. Our evaluation provides evidence that possible modifications of the crowdfunding mechanisms bear the chance to optimize funding results and to alleviate existing flaws.
Barucca, Gianni ; Davì, F. ; Lancioni, G. ; Mengucci, P. ; Montalto, L. ; Natali, P. P. ; Paone, N. ; Rinaldi, D. ; Scalise, L. ; Erni, W. ; Krusche, B. ; Steinacher, M. ; Walford, N. ; Cao, N. ; Liu, Z. ; Liu, C. ; Liu, B. ; Shen, X. ; Sun, S. ; Tao, J. ; Xiong, X. A. ; Zhao, G. ; Zhao, J. ; Albrecht, Malte ; Alkakhi, W. ; Bökelmann, S. ; Coen, S. ; Feldbauer, Florian ; Fink, M. ; Frech, J. ; Freudenreich, V. ; Fritsch, Miriam ; Grochowski, J. ; Hagdorn, R. ; Heinsius, Fritz-Herbert ; Held, T. ; Holtmann, Tobias ; Keshk, I. ; Koch, H. ; Kopf, Bertram ; Kuhlmann, M. ; Kümmel, M. ; Küßner, M. ; Li, J. ; Linzen, L. ; Maldaner, Stephan ; Oppotsch, J. ; Pankonin, S. ; Pelizäus, Marc ; Pflüger, S. ; Pitka, A. ; Reher, J. ; Reicherz, G. ; Schnier, Claudius ; Steinke, M. ; Triffterer, T. ; Wenzel, C. ; Wiedner, Ulrich ; Denizli, H. ; Er, N. ; Keskin, U. ; Olgun, A. T. ; Yerlikaya, S. ; Yilmaz, A. ; Beck, R. ; Hammann, C. ; Hartmann, J. ; Ketzer, Bernhard ; Müllers, J. ; Rossbach, M. ; Salisbury, B. ; Schmidt, Christian Joachim ; Thoma, U. ; Urban, M. ; Bianconi, A. ; Bragadireanu, Mario ; Pantea, D. ; Domagala, M. ; Filo, G. ; Lisowski, E. ; Lisowski, F. ; Michałek, M. ; Poznański, P. ; Płażek, J. ; Korcyl, K. ; Kozela, A. ; Lebiedowicz, P. ; Pysz, K. ; Schäfer, W. ; Szczurek, A. ; Firlej, M. ; Fiutowski, T. ; Idzik, M. ; Moron, J. ; Swientek, K. ; Terlecki, P. ; Korcyl, G. ; Lalik, R. ; Malige, A. ; Moskal, P. ; Nowakowski, K. ; Przygoda, W. ; Rathod, N. ; Rudy, Z. ; Salabura, P. ; Smyrski, J. ; Augustin, I. ; Böhm, R. ; Lehmann, I. ; Schmitt, L. ; Varentsov, V. ; Al-Turany, Mohammad ; Belias, A. ; Deppe, H. ; Dzhygadlo, R. ; Flemming, H. ; Gerhardt, A. ; Götzen, Klaus ; Heinz, Andreas ; Jiang, P. ; Karabowicz, R. ; Koch, S. ; Kurilla, U. ; Lehmann, D. ; Lühning, J. ; Lynen, U. ; Orth, H. ; Peters, Klaus ; Saito, T. ; Schepers, G. ; Schmidt, C. J. ; Schwarz, C. ; Schwiening, J. ; Täschner, Alexander ; Traxler, M. ; Voss, B. ; Wieczorek, P. ; Abazov, V. ; Alexeev, G. ; Arefiev, V. A. ; Astakhov, V. ; Barabanov, M. Yu. ; Batyunya, B. V. ; Dodokhov, V. Kh. ; Efremov, A. ; Fechtchenko, A. ; Galoyan, A. ; Golovanov, G. ; Koshurnikov, E. K. ; Lobanov, Y. Yu. ; Olshevskiy, A. G. ; Piskun, A. A. ; Samartsev, A. ; Shimanski, S. ; Skachkov, N. B. ; Skachkova, A. N. ; Strokovsky, E. A. ; Tokmenin, V. ; Uzhinsky, V. ; Verkheev, A. ; Vodopianov, A. ; Zhuravlev, N. I. ; Branford, D. ; Watts, D. ; Böhm, M. ; Eyrich, W. ; Lehmann, A. ; Miehling, D. ; Pfaffinger, M. ; Quin, N. ; Robison, L. ; Seth, K. ; Xiao, T. ; Bettoni, Diego ; Ali, A. ; Hamdi, A. ; Himmelreich, Mathilde ; Krebs, M. ; Nakhoul, S. ; Nerling, Frank ; Belousov, A. ; Kisel, Ivan ; Kozlov, Grigory ; Pugach, M. ; Zyzak, Maksym ; Bianchi, Nicola ; Gianotti, Paola ; Lucherini, V. ; Bracco, G. ; Bettner, Y. ; Bodenschatz, S. ; Brinkmann, K. T. ; Brück, L. ; Diehl, S. ; Dormenev, V. ; Düren, M. ; Erlen, T. ; Föhl, K. ; Hahn, C. ; Hayrapetyan, A. ; Hofmann, J. ; Kegel, S. ; Kesselkaul, M. ; Köseoglu, I. ; Kripko, A. ; Kühn, Wolfgang ; Lange, Jens Sören ; Metag, V. ; Moritz, M. ; Nanova, M. ; Novotny, R. ; Orsich, P. ; Pereira-de-Lira, J. ; Peter, M. ; Sachs, M. ; Schmidt, M. ; Schubert, R. ; Stenzel, H. ; Straube, M. ; Strickert, M. ; Thöring, U. ; Wasem, T. ; Wohlfahrt, B. ; Zaunick, H. G. ; Tomasi-Gustafsson, E. ; Glazier, D. ; Ireland, D. ; Seitz, B. ; Deepak, P. N. ; Kulkarni, A. ; Kappert, R. ; Kavatsyuk, Myroslav O. ; Loehner, H. ; Messchendorp, J. ; Rodin, Viktor ; Schakel, P. ; Vejdani, S. ; Dutta, K. ; Kalita, K. ; Huang, G. ; Liu, D. ; Peng, H. ; Qi, H. ; Sun, Y. ; Zhou, X. ; Kunze, M. ; Azizi, K. ; Tavukoglu, Z. ; Derichs, A. ; Dosdall, R. ; Esmail, W. ; Gillitzer, A. ; Goldenbaum, F. ; Grunwald, D. ; Jokhovets, L. ; Kannika, J. ; Kulessa, P. ; Orfanitski, S. ; Pérez Andrade, G. ; Prasuhn, D. ; Prencipe, E. ; Pütz, J. ; Ritman, J. ; Rosenthal, E. ; Schadmand, S. ; Schmitz, R. ; Scholl, A. ; Sefzick, T. ; Serdyuk, V. ; Stockmanns, T. ; Veretennikov, D. ; Wintz, P. ; Wüstner, P. ; Xu, H. ; Zhou, Y. ; Cao, X. ; Hu, Q. ; Li, Z. ; Li, H. ; Liang, Y. ; Ma, X. ; Rigato, V. ; Isaksson, L. ; Achenbach, P. ; Corell, O. ; Denig, Achim ; Distler, M. ; Hoek, M. ; Lauth, W. ; Leithoff, H. H. ; Liu, Z. ; Merkel, H. ; Müller, U. ; Pochodzalla, J. ; Schlimme, S. ; Sfienti, C. ; Thiel, M. ; Zambrana, M. ; Ahmed, Samer ; Bleser, S. ; Bölting, M. ; Capozza, L. ; Dbeyssi, A. ; Ehret, A. ; Klasen, R. ; Kliemt, Ralf ; Maas, F. ; Motzko, C. ; Noll, O. ; Piñeiro, D. Rodríguez ; Schupp, F. ; Steinen, M. ; Wolff, S. ; Zimmermann, I. ; Fedorov, A. ; Kazlou, D. ; Korzhik, M. ; Missevitch, O. ; Balanutsa, P. ; Chernetsky, V. ; Demekhin, A. ; Dolgolenko, A. ; Fedorets, P. ; Gerasimov, A. ; Golubev, A. ; Goryachev, V. ; Kantsyrev, A. ; Kirin, D. Y. ; Kristi, N. ; Ladygina, E. ; Luschevskaya, E. ; Matveev, V. A. ; Panjushkin, V. ; Stavinskiy, A. V. ; Balashoff, A. ; Boukharov, A. ; Malyshev, O. ; Basant, K. N. ; Kumawat, H. ; Roy, B. ; Saxena, Alok ; Yogesh, S. ; Bonaventura, D. ; Brand, P. ; Fritzsch, C. ; Grieser, S. ; Hargens, C. ; Hergemöller, A. K. ; Hetz, B. ; Hüsken, Nils ; Kellers, J. ; Khoukaz, Alfons ; Mannweiler, C. ; Vestrick, S. ; Bumrungkoh, D. ; Herold, Christoph ; Khosonthongkee, K. ; Kobdaj, Chinorat ; Limphirat, A. ; Manasatitpong, K. ; Nasawad, T. ; Pongampai, S. ; Simantathammakul, T. ; Srisawad, P. ; Wongprachanukul, N. ; Yan, Y. ; Yu, C. ; Zhang, X. ; Zhu, W. ; Blinov, A. E. ; Kononov, S. ; Kravchenko, E. A. ; Antokhin, E. ; Barnyakov, A. Yu. ; Beloborodov, K. ; Blinov, V. E. ; Kuyanov, I. A. ; Pivovarov, S. ; Pyata, E. ; Tikhonov, Y. ; Hunter, G. ; Lattery, M. ; Pace, H. ; Boca, Gianluigi ; Duda, D. ; Finger, M. ; Finger, M. ; Kveton, A. ; Pesek, M. ; Peskova, M. ; Prochazka, I. ; Slunecka, M. ; Volf, M. ; Gallus, P. ; Jary, V. ; Korchak, O. ; Marcisovsky, M. ; Neue, G. ; Novy, J. ; Tomasek, L. ; Tomasek, M. ; Virius, M. ; Vrba, V. ; Abramov, V. ; Bukreeva, S. ; Chernichenko, S. ; Derevschikov, A. ; Ferapontov, V. ; Goncharenko, Y. ; Levin, A. ; Maslova, E. ; Melnik, Y. ; Meščanin, Aleksei P. ; Minaev, N. ; Mochalov, V. ; Moiseev, V. ; Morozov, D. ; Nogach, L. ; Poslavskiy, S. ; Ryazantsev, A. ; Ryzhikov, S. ; Semenov, P. ; Shein, I. ; Uzunian, A. ; Vasiliev, Andrey ; Yakutin, A. ; Roy, U. ; Yabsley, B. ; Belostotski, S. ; Fedotov, G. ; Gavrilov, G. ; Izotov, A. ; Manaenkov, S. ; Miklukho, O. ; Zhdanov, A. ; Atac, A. ; Bäck, T. ; Cederwall, B. ; Makonyi, K. ; Preston, M. ; Tegner, P. E. ; Wölbing, D. ; Gandhi, K. ; Rai, A. K. ; Godre, S. ; Crede, V. ; Dobbs, S. ; Eugenio, P. ; Lersch, D. ; Calvo, D. ; De Remigis, P. ; Filippi, A. ; Mazza, G. ; Rivetti, Angelo ; Wheadon, R. ; Bussa, M. P. ; Spataro, Stefano ; Iazzi, F. ; Lavagno, A. ; Martin, A. ; Akram, A. ; Calen, H. ; Andersson, W. Ikegami ; Johansson, Tord ; Kupsc, Andrzej ; Marciniewski, P. ; Papenbrock, Michael ; Regina, J. ; Rieger, J. ; Schönning, K. ; Wolke, M. ; Pothodi Chackara, V. ; Chlopik, A. ; Kesik, G. ; Melnychuk, D. ; Tarasiuk, J. ; Wojciechowski, M. ; Wronka, S. ; Zwieglinski, B. ; Amsler, C. ; Bühler, Paul ; Marton, J. ; Nalti, W. ; Steinschaden, D. ; Widmann, Eberhard ; Zimmermann, S. ; Zmeskal, Johann
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
Wilhelm, Raphael ; Eckes, Timon Sebastian ; Imre, Gergely ; Kippenberger, Stefan ; Meissner, Markus ; Thomas, Dominique Jeanette ; Trautmann, Sandra ; Merlio, Jean-Philippe ; Chevret, Edith ; Kaufmann, Roland ; Pfeilschifter, Josef ; Koch, Alexander ; Jäger, Manuel Alexander
Cutaneous T cell lymphomas (CTCLs) represent a heterogeneous group of T cell lymphomas that primarily affect the skin. The most frequent forms of CTCL are mycosis fungoides and Sézary syndrome. Both are characterized by frequent recurrence, developing chronic conditions and high mortality with a lack of a curative treatment. In this study, we evaluated the effect of short-chain, cell-permeable C6 Ceramide (C6Cer) on CTCL cell lines and keratinocytes. C6Cer significantly reduced cell viability of CTCL cell lines and induced cell death via apoptosis and necrosis. In contrast, primary human keratinocytes and HaCaT keratinocytes were less affected by C6Cer. Both keratinocyte cell lines showed higher expressions of ceramide catabolizing enzymes and HaCaT keratinocytes were able to metabolize C6Cer faster and more efficiently than CTCL cell lines, which might explain the observed protective effects. Along with other existing skin-directed therapies, C6Cer could be a novel well-tolerated drug for the topical treatment of CTCL.
Ablikim, Medina ; Achasov, Mikhail N. ; Adlarson, Patrik ; Ahmed, Samer ; Albrecht, Malte ; Aliberti, Riccardo ; Amoroso, Antonio ; An, M. R. ; An, Qi ; Bai, X. H. ; Bai, Yu ; Bakina, Olga ; Baldini Ferroli, Rinaldo ; Balossino, Ilaria ; Ban, Yong ; Begzsuren, Khurelbaatar ; Berger, Niklaus ; Bertani, Monica ; Bettoni, Diego ; Bianchi, Fabrizio ; Bloms, Johannes ; Bortone, Alberto ; Boyko, Igor R. ; Briere, Roy A. ; Cai, Hao ; Cai, Xiao ; Calcaterra, Alessandro ; Cao, G. F. ; Cao, N. ; Çetin, Serkant Ali ; Chang, J. F. ; Chang, W. L. ; Chelkov, G. ; Chen, D. Y. ; Chen, G. ; Chen, H. S. ; Chen, M. L. ; Chen, S. J. ; Chen, X. R. ; Chen, Y. B. ; Chen, Z. J. ; Cheng, W. S. ; Cibinetto, Gianluigi ; Cossio, Fabio ; Cui, X. F. ; Dai, Hongliang ; Dai, Xinchen ; Dbeyssi, Alaa ; Boer, Remco E. de ; Dedovich, Dmitri V. ; Deng, Z. Y. ; Denig, Achim ; Denysenko, Igor ; Destefanis, Marco Giovanni Maria ; De Mori, Francesca ; Ding, Yanchun ; Dong, C. ; Dong, J. ; Dong, L. Y. ; Dong, M. Y. ; Dong, X. ; Du, S. X. ; Fan, Y. L. ; Fang, J. ; Fang, S. S. ; Fang, Y. ; Farinelli, R. ; Fava, Luciano ; Feldbauer, Florian ; Felici, Giulietto ; Feng, C. Q. ; Feng, J. H. ; Fritsch, Miriam ; Fu, Chengdong ; Gao, Y. ; Gao, Y. ; Gao, Y. ; Gao, Y. G. ; Garzia, Isabella ; Ge, P. T. ; Geng, C. ; Gersabeck, Evelina ; Gilman, Alexander ; Götzen, Klaus ; Gong, L. ; Gong, W. X. ; Gradl, Wolfgang ; Greco, M. ; Gu, L. M. ; Gu, Minhao ; Gu, Y. T. ; Guan, C. Y. ; Guo, A. Q. ; Guo, L. B. ; Guo, R. P. ; Guo, Y. P. ; Guskov, Alexey ; Han, T. T. ; Han, W. Y. ; Hao, X. Q. ; Harris, Frederick Allan ; He, K. L. ; Heinsius, Fritz-Herbert ; Heinz, C. H. ; Held, T. ; Heng, Y. K. ; Herold, Christoph ; Himmelreich, Mathilde ; Holtmann, Tobias ; Hou, G. Y. ; Hou, Y. R. ; Hou, Z. L. ; Hu, H. M. ; Hu, J. F. ; Hu, T. ; Hu, Y. ; Huang, G. S. ; Huang, L. Q. ; Huang, X. T. ; Huang, Y. P. ; Huang, Z. ; Hussain, Tahir ; Hüsken, Nils ; Ikegami Andersson, Walter ; Imoehl, William ; Irshad, M. ; Jaeger, S. ; Janchiv, S. ; Ji, Q. ; Ji, Q. P. ; Ji, X. B. ; Ji, X. L. ; Ji, Y. Y. ; Jiang, H. B. ; Jiang, X. S. ; Jiao, J. B. ; Jiao, Z. ; Jin, S. ; Jin, Y. ; Jing, M. Q. ; Johansson, Tord ; Kalantar-Nayestanaki, Nasser ; Kang, X. S. ; Kappert, Rosa ; Kavatsyuk, Myroslav O. ; Ke, B. C. ; Keshk, I. K. ; Khoukaz, Alfons ; Kiese, P. ; Kiuchi, R. ; Kliemt, Ralf ; Koch, L. ; Kolcu, O. B. ; Kopf, Bertram ; Kuemmel, M. ; Küßner, Meike ; Kupsc, Andrzej ; Kurth, M. G. ; Kühn, Wolfgang ; Lane, J. J. ; Lange, Jens Sören ; Larin, Paul ; Lavania, Anita ; Lavezzi, Lia ; Lei, Z. H. ; Leithoff, Hans Heinrich ; Lellmann, Max ; Lenz, Thomas ; Li, C. ; Li, C. H. ; Li, Cheng ; Li, D. M. ; Li, F. ; Li, G. ; Li, H. ; Li, H. ; Li, H. B. ; Li, H. J. ; Li, J. L. ; Li, J. Q. ; Li, J. S. ; Li, Ke ; Li, L. K. ; Li, Lei ; Li, P. R. ; Li, S. Y. ; Li, W. D. ; Li, W. G. ; Li, X. H. ; Li, Xing Long ; Li, Xiaoyu ; Li, Z. Y. ; Liang, H. ; Liang, H. ; Liang, H. ; Liang, Y. F. ; Liang, Y. T. ; Liao, G. R. ; Liao, L. Z. ; Libby, J. ; Lin, C. X. ; Liu, B. J. ; Liu, C. X. ; Liu, D. ; Liu, F. H. ; Liu, Fang ; Liu, Feng ; Liu, H. B. ; Liu, H. M. ; Liu, Huanhuan ; Liu, Huihui ; Liu, J. B. ; Liu, J. L. ; Liu, J. Y. ; Liu, K. ; Liu, K. Y. ; Liu, L. ; Liu, M. H. ; Liu, P. L. ; Liu, Q. ; Liu, Q. ; Liu, S. B. ; Liu, Shuai ; Liu, T. ; Liu, W. M. ; Liu, X. ; Liu, Y. ; Liu, Y. B. ; Liu, Z. A. ; Liu, Z. Q. ; Lou, X. C. ; Lu, F. X. ; Lu, H. J. ; Lu, J. D. ; Lu, J. G. ; Lu, X. L. ; Lu, Y. ; Lu, Y. P. ; Luo, C. L. ; Luo, M. X. ; Luo, P. W. ; Luo, Tao ; Luo, X. L. ; Lyu, X. R. ; Ma, F. C. ; Ma, Hailong ; Ma, L. L. ; Ma, M. M. ; Ma, Q. M. ; Ma, R. Q. ; Ma, R. T. ; Ma, X. X. ; Ma, X. Y. ; Maas, Frank E. ; Maggiora, Marco ; Maldaner, Stephan ; Malde, Sneha ; Malik, Qadeer Afzal ; Mangoni, Alessio ; Mao, Y. J. ; Mao, Z. P. ; Marcello, S. ; Meng, Z. X. ; Messchendorp, Johannes Gerhardus ; Mezzadri, Giulio ; Min, T. J. ; Mitchell, Ryan Edward ; Mo, X. H. ; Mo, Y. J. ; Muchnoi, Nikolai Yu. ; Muramatsu, Hajime ; Nakhoul, S. ; Nefedov, Yury ; Nerling, Frank ; Nikolaev, Ivan Borisovich ; Ning, Z. ; Nisar, Shabana ; Ouyang, Q. ; Pacetti, Simone ; Pan, Xiang ; Pan, Y. ; Pathak, A. ; Pathak, A. ; Patteri, Piero ; Pelizäus, Marc ; Peng, H. P. ; Peters, Klaus ; Pettersson, J. ; Ping, J. L. ; Ping, R. G. ; Pogodin, S. ; Poling, Ronald ; Prasad, Vindhyawasini ; Qi, H. ; Qi, H. R. ; Qi, K. H. ; Qi, M. ; Qi, T. Y. ; Qian, S. ; Qian, W. B. ; Qian, Z. ; Qiao, C. F. ; Qin, L. Q. ; Qin, X. P. ; Qin, X. S. ; Qin, Z. H. ; Qiu, J. F. ; Qu, S. Q. ; Rashid, K. H. ; Ravindran, Krishnakumar ; Redmer, Christoph Florian ; Rivetti, Angelo ; Rodin, Viktor ; Da Rocha Rolo, Manuel Dionisio ; Rong, Gang ; Rosner, Christoph ; Rump, Marcel Andre ; Sang, H. S. ; Sarantsev, Andrei V. ; Schelhaas, Yasemin ; Schnier, Claudius ; Schönning, Karin ; Scodeggio, Marco ; Shan, D. C. ; Shan, W. ; Shan, X. Y. ; Shangguan, J. F. ; Shao, M. ; Shen, C. P. ; Shen, H. F. ; Shen, P. X. ; Shen, X. Y. ; Shi, H. C. ; Shi, R. S. ; Shi, X. ; Shi, X. D. ; Song, J. J. ; Song, W. M. ; Song, Y. X. ; Sosio, Stefano ; Spataro, Stefano ; Su, K. X. ; Su, P. P. ; Sui, F. F. ; Sun, G. X. ; Sun, H. K. ; Sun, J. F. ; Sun, L. ; Sun, S. S. ; Sun, T. ; Sun, W. Y. ; Sun, W. Y. ; Sun, X. ; Sun, Y. J. ; Sun, Y. K. ; Sun, Y. Z. ; Sun, Z. T. ; Tan, Y. H. ; Tan, Y. X. ; Tang, C. J. ; Tang, G. Y. ; Tang, J. ; Teng, J. X. ; Thoren, Viktor ; Tian, W. H. ; Tian, Y. T. ; Uman, Ismail ; Wang, B. ; Wang, C. W. ; Wang, D. Y. ; Wang, H. J. ; Wang, H. P. ; Wang, K. ; Wang, L. L. ; Wang, M. ; Wang, M. Z. ; Wang, Meng ; Wang, W. ; Wang, W. H. ; Wang, W. P. ; Wang, X. ; Wang, X. F. ; Wang, X. L. ; Wang, Y. ; Wang, Y. ; Wang, Y. D. ; Wang, Y. F. ; Wang, Y. Q. ; Wang, Y. 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We measure the inclusive semielectronic decay branching fraction of the D+s meson. A double-tag technique is applied to e+e− annihilation data collected by the BESIII experiment at the BEPCII collider, operating in the center-of-mass energy range 4.178–4.230 GeV. We select positrons fromD+s→Xe+νe with momenta greater than 200 MeV/c and determine the laboratory momentum spectrum, accounting for the effects of detector efficiency and resolution. The total positron yield and semielectronic branching fraction are determined by extrapolating this spectrum below the momentum cutoff. We measure the D+s semielectronic branching fraction to be(6.30±0.13(stat.)±0.09(syst.)±0.04(ext.))%, showing no evidence for unobserved exclusive semielectronic modes. We combine this result with external data taken from literature to determine the ratio of the D+s and D0 semielectronic widths, Γ(D+s→Xe+νe)Γ(D0→Xe+νe)=0.790±0.016(stat.)±0.011(syst.)±0.016(ext.). Our results are consistent with and more precise than previous measurements.
Jakobi, Katja ; Beyer, Sandra ; Koch, Alexander ; Thomas, Dominique Jeanette ; Schwalm, Stephanie ; Zeuzem, Stefan ; Pfeilschifter, Josef ; Grammatikos, Georgios
Hepatocellular carcinoma (HCC) shows a remarkable heterogeneity and is recognized as a chemoresistant tumor with dismal prognosis. In previous studies, we observed significant alterations in the serum sphingolipids of patients with HCC. This study aimed to investigate the in vitro effects of sorafenib, which is the most widely used systemic HCC medication, on the sphingolipid pathway as well as the effects of inhibiting the sphingolipid pathway in HCC. Huh7.5 and HepG2 cells were stimulated with sorafenib, and inhibitors of the sphingolipid pathway and cell proliferation, viability, and concentrations of bioactive metabolites were assessed. We observed a significant downregulation of cell proliferation and viability and a simultaneous upregulation of dihydroceramides upon sorafenib stimulation. Interestingly, fumonisin B1 (FB1) and the general sphingosine kinase inhibitor SKI II were able to inhibit cell proliferation more prominently in HepG2 and Huh7.5 cells, whereas there were no consistent effects on the formation of dihydroceramides, thus implying an involvement of distinct metabolic pathways. In conclusion, our study demonstrates a significant downregulation of HCC proliferation upon sorafenib, FB1, and SKI II treatment, whereas it seems they exert antiproliferative effects independently from sphingolipids. Certainly, further data would be required to elucidate the potential of FB1 and SKI II as putative novel therapeutic targets in HCC.
Vutukuri, Rajkumar ; Koch, Alexander ; Trautmann, Sandra ; Schreiber, Yannick ; Thomas, Dominique Jeanette ; Mayser, Franziska ; Meyer zu Heringdorf, Dagmar ; Pfeilschifter, Josef ; Pfeilschifter, Waltraud ; Brunkhorst, Robert
Sphingosine 1-phosphate (S1P) signaling influences numerous cell biological mechanisms such as differentiation, proliferation, survival, migration, and angiogenesis. Intriguingly, our current knowledge is based solely on the role of S1P with an 18-carbon long-chain base length, S1P d18:1. Depending on the composition of the first and rate-limiting enzyme of the sphingolipid de novo metabolism, the serine palmitoyltransferase, other chain lengths have been described in vivo. While cells are also able to produce S1P d20:1, its abundance and function remains elusive so far. Our experiments are highlighting the role of S1P d20:1 in the mouse central nervous system (CNS) and human glioblastoma. We show here that S1P d20:1 and its precursors are detectable in both healthy mouse CNS-tissue and human glioblastoma. On the functional level, we focused our work on one particular, well-characterized pathway, the induction of cyclooxygenase (COX)-2 expression via the S1P receptor 2 (S1P2). Intriguingly, S1P d20:1 only fairly induces COX-2 expression and can block the S1P d18:1-induced COX-2 expression mediated via S1P2 activation in the human glioblastoma cell line LN229. This data indicates that S1P d20:1 might act as an endogenous modulator of S1P signaling via a partial agonism at the S1P2 receptor. While our findings might stimulate further research on the relevance of long-chain base lengths in sphingolipid signaling, the metabolism of S1P d20:1 has to be considered as an integral part of S1P signaling pathways in vivo.