TY  - JOUR
A1  - El-Helou, Sabine M.
A1  - Biegner, Anika-Kerstin
A1  - Bode, Sebastian
A1  - Ehl, Stephan R.
A1  - Heeg, Maximilian
A1  - Maccari, Maria E.
A1  - Ritterbusch, Henrike
A1  - Speckmann, Carsten
A1  - Rusch, Stephan
A1  - Scheible, Raphael
A1  - Warnatz, Klaus
A1  - Atschekzei, Faranaz
A1  - Beider, Renata
A1  - Ernst, Diana
A1  - Gerschmann, Stev
A1  - Jablonka, Alexandra
A1  - Mielke, Gudrun
A1  - Schmidt, Reinhold E.
A1  - Schürmann, Gesine
A1  - Sogkas, Georgios
A1  - Baumann, Ulrich H.
A1  - Klemann, Christian
A1  - Viemann, Dorothee
A1  - Bernuth, Horst von
A1  - Krüger, Renate
A1  - Hanitsch, Leif G.
A1  - Scheibenbogen, Carmen M.
A1  - Wittke, Kirsten
A1  - Albert, Michael H.
A1  - Eichinger, Anna
A1  - Hauck, Fabian
A1  - Klein, Christoph
A1  - Rack-Hoch, Anita
A1  - Sollinger, Franz M.
A1  - Avila, Anne
A1  - Borte, Michael
A1  - Borte, Stephan
A1  - Fasshauer, Maria
A1  - Hauenherm, Anja
A1  - Kellner, Nils
A1  - Müller, Anna H.
A1  - Ülzen, Anett
A1  - Bader, Peter
A1  - Bakhtiar, Shahrzad
A1  - Lee, Jae-Yun
A1  - Heß, Ursula
A1  - Schubert, Ralf
A1  - Wölke, Sandra
A1  - Zielen, Stefan
A1  - Ghosh, Sujal
A1  - Laws, Hans-Juergen
A1  - Neubert, Jennifer
A1  - Oommen, Prasad T.
A1  - Hönig, Manfred
A1  - Schulz, Ansgar
A1  - Steinmann, Sandra
A1  - Klaus, Schwarz
A1  - Dückers, Gregor
A1  - Lamers, Beate
A1  - Langemeyer, Vanessa
A1  - Niehues, Tim
A1  - Shai, Sonu
A1  - Graf, Dagmar
A1  - Müglich, Carmen
A1  - Schmalzing, Marc T.
A1  - Schwaneck, Eva C.
A1  - Tony, Hans-Peter
A1  - Dirks, Johannes
A1  - Haase, Gabriele
A1  - Liese, Johannes G.
A1  - Morbach, Henner
A1  - Foell, Dirk
A1  - Hellige, Antje
A1  - Wittkowski, Helmut
A1  - Masjosthusmann, Katja
A1  - Mohr, Michael
A1  - Geberzahn, Linda
A1  - Hedrich, Christian M.
A1  - Müller, Christiane
A1  - Rösen-Wolff, Angela
A1  - Roesler, Joachim
A1  - Zimmermann, Antje
A1  - Behrends, Uta
A1  - Rieber, Nikolaus
A1  - Schauer, Uwe
A1  - Handgretinger, Rupert
A1  - Holzer, Ursula
A1  - Henes, Jörg
A1  - Kanz, Lothar
A1  - Boesecke, Christoph
A1  - Rockstroh, Jürgen K.
A1  - Schwarze-Zander, Carolynne
A1  - Wasmuth, Jan-Christian
A1  - Dilloo, Dagmar
A1  - Hülsmann, Brigitte
A1  - Schönberger, Stefan
A1  - Schreiber, Stefan
A1  - Zeuner, Rainald
A1  - Ankermann, Tobias
A1  - Bismarck, Philipp von
A1  - Huppertz, Hans-Iko
A1  - Kaiser-Labusch, Petra
A1  - Greil, Johann
A1  - Jakoby, Donate
A1  - Kulozik, Andreas E.
A1  - Metzler, Markus
A1  - Naumann-Bartsch, Nora
A1  - Sobik, Bettina
A1  - Graf, Norbert
A1  - Heine, Sabine
A1  - Kobbe, Robin
A1  - Lehmberg, Kai
A1  - Müller, Ingo
A1  - Herrmann, Friedrich
A1  - Horneff, Gerd
A1  - Klein, Ariane
A1  - Peitz, Joachim
A1  - Schmidt, Nadine
A1  - Bielack, Stefan
A1  - Groß-Wieltsch, Ute
A1  - Classen, Carl F.
A1  - Klasen, Jessica
A1  - Deutz, Peter
A1  - Kamitz, Dirk
A1  - Lassy, Lisa
A1  - Tenbrock, Klaus
A1  - Wagner, Norbert
A1  - Bernbeck, Benedikt
A1  - Brummel, Bastian
A1  - Lara-Villacanas, Eusebia
A1  - Münstermann, Esther
A1  - Schneider, Dominik T.
A1  - Tietsch, Nadine
A1  - Westkemper, Marco
A1  - Weiß, Michael
A1  - Kramm, Christof
A1  - Kühnle, Ingrid
A1  - Kullmann, Silke
A1  - Girschick, Hermann
A1  - Specker, Christof
A1  - Vinnemeier-Laubenthal, Elisabeth
A1  - Haenicke, Henriette
A1  - Schulz, Claudia
A1  - Schweigerer, Lothar
A1  - Müller, Thomas G.
A1  - Stiefel, Martina
A1  - Belohradsky, Bernd H.
A1  - Soetedjo, Veronika
A1  - Kindle, Gerhard
A1  - Grimbacher, Bodo
T1  - The German national registry of primary immunodeficiencies (2012-2017)
JF  - Frontiers in Immunology
N2  - Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. 

Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. 

Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. 

Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
KW  - registry for primary immunodeficiency
KW  - primary immunodeficiency (PID)
KW  - German PID-NET registry
KW  - PID prevalence
KW  - European Society for Immunodeficiencies (ESID)
KW  - IgG substitution therapy
KW  - CVID
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629
VL  - 10
ER  - 
TY  - JOUR
A1  - Hopp, Sarah
A1  - Albert-Weissenberger, Christiane
A1  - Mencl, Stine
A1  - Bieber, Michael
A1  - Schuhmann, Michael K.
A1  - Stetter, Christian
A1  - Nieswandt, Bernhard
A1  - Schmidt, Peter M.
A1  - Monoranu, Camelia-Maria
A1  - Alafuzoff, Irina
A1  - Marklund, Niklas
A1  - Nolte, Marc W.
A1  - Sirén, Anna-Leena
A1  - Kleinschnitz, Christoph
T1  - Targeting coagulation factor XII as a novel therapeutic option in brain trauma
JF  - Annals of Neurology
N2  - Objective: 
Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use. The aim of this study was to obtain preclinical evidence supporting the hypothesis that targeting factor XII prevents thrombus formation and has a beneficial effect on outcome after traumatic brain injury. 

Methods: 
We investigated the impact of genetic deficiency of factor XII and acute inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular thrombus formation and the subsequent outcome in 2 mouse models of traumatic brain injury. 

Results: 
Our study showed that both genetic deficiency of factor XII and an inhibition of activated factor XII in mice minimize trauma-induced microvascular thrombus formation and improve outcome, as reflected by better motor function, reduced brain lesion volume, and diminished neurodegeneration. Administration of human factor XII in factor XII-deficient mice fully restored injury-induced microvascular thrombus formation and brain damage. 

Interpretation: 
The robust protective effect of rHA-Infestin-4 points to a novel treatment option that can decrease ischemic injury after traumatic brain injury without increasing bleeding tendencies.
KW  - Molecular-weight heparin
KW  - Thrombus formation
KW  - Cerebral-ischemia
KW  - in-vivo
KW  - Intravascular coagulation
KW  - Hemodynamic depression
KW  - Head-injury
KW  - Rats
KW  - Model
KW  - Mice
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188800
VL  - 79
IS  - 6
ER  - 
TY  - JOUR
A1  - Carsten A., Böger
A1  - Gorski, Mathias
A1  - Li, Man
A1  - Hoffmann, Michael M.
A1  - Huang, Chunmei
A1  - Yang, Qiong
A1  - Teumer, Alexander
A1  - Krane, Vera
A1  - O'Seaghdha, Conall M.
A1  - Kutalik, Zoltán
A1  - Wichmann, H.-Erich
A1  - Haak, Thomas
A1  - Boes, Eva
A1  - Coassin, Stefan
A1  - Coresh, Josef
A1  - Kollerits, Barbara
A1  - Haun, Margot
A1  - Paulweber, Bernhard
A1  - Köttgen, Anna
A1  - Li, Guo
A1  - Shlipak, Michael G.
A1  - Powe, Neil
A1  - Hwang, Shih-Jen
A1  - Dehghan, Abbas
A1  - Rivadeneira, Fernando
A1  - Uitterlinden, André
A1  - Hofman, Albert
A1  - Beckmann, Jacques S.
A1  - Krämer, Bernhard K.
A1  - Witteman, Jacqueline
A1  - Bochud, Murielle
A1  - Siscovick, David
A1  - Rettig, Rainer
A1  - Kronenberg, Florian
A1  - Wanner, Christoph
A1  - Thadhani, Ravi I.
A1  - Heid, Iris M.
A1  - Fox, Caroline S.
A1  - Kao, W.H.
T1  - Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD
JF  - PLoS Genetics
N2  - Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR < 60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.
KW  - Chronic Kidney-disease
KW  - Stage renal-disease
KW  - Glomerular-filtration-rate
KW  - Diabetic-nephropathy
KW  - General-population
KW  - African-americans
KW  - Risk
KW  - Progression
KW  - Mortality
KW  - Variants
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133758
VL  - 7
IS  - 9
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Ageron, M.
A1  - Aharonian, F.
A1  - Aiello, S.
A1  - Albert, A.
A1  - Ameli, F.
A1  - Annasontzis, E.
A1  - Andre, M.
A1  - Androulakis, G.
A1  - Anghinolfi, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Avgitas, T.
A1  - Barbarino, G.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Belhorma, B.
A1  - Belias, A.
A1  - Berbee, A.
A1  - van den Berg, A.
A1  - Bertin, V.
A1  - Beurthey, S.
A1  - van Beeveren, V.
A1  - Beverini, N.
A1  - Biagi, S.
A1  - Biagioni, A.
A1  - Billault, M.
A1  - Bondì, M.
A1  - Bormuth, R.
A1  - Bouhadef, B.
A1  - Bourlis, G.
A1  - Bourret, S.
A1  - Boutonnet, C.
A1  - Bouwhuis, M.
A1  - Bozza, C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Buis, E.
A1  - Busto, J.
A1  - Cacopardo, G.
A1  - Caillat, L.
A1  - Calmai, M.
A1  - Calvo, D.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Cecchini, S.
A1  - Celli, S.
A1  - Champion, C.
A1  - Cherkaoui El Moursli, R.
A1  - Cherubini, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Classen, L.
A1  - Cocimano, R.
A1  - Coelho, J. A. B.
A1  - Coleiro, A.
A1  - Colonges, S.
A1  - Coniglione, R.
A1  - Cordelli, M.
A1  - Cosquer, A.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Cuttone, G.
A1  - D'Amico, A.
A1  - De Bonis, G.
A1  - De Rosa, G.
A1  - De Sio, C.
A1  - Di Capua, F.
A1  - Di Palma, I.
A1  - Díaz García, A. F.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Dorosti-Hasankiadeh, Q.
A1  - Drakopoulou, E.
A1  - Drouhin, D.
A1  - Drury, L.
A1  - Durocher, M.
A1  - Eberl, T.
A1  - Eichie, S.
A1  - van Eijk, D.
A1  - El Bojaddaini, I.
A1  - El Khayati, N.
A1  - Elsaesser, D.
A1  - Enzenhöfer, A.
A1  - Fassi, F.
A1  - Favali, P.
A1  - Fermani, P.
A1  - Ferrara, G.
A1  - Filippidis, C.
A1  - Frascadore, G.
A1  - Fusco, L. A.
A1  - Gal, T.
A1  - Galatà, S.
A1  - Garufi, F.
A1  - Gay, P.
A1  - Gebyehu, M.
A1  - Giordano, V.
A1  - Gizani, N.
A1  - Gracia, R.
A1  - Graf, K.
A1  - Grégoire, T.
A1  - Grella, G.
A1  - Habel, R.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Harissopulos, S.
A1  - Heid, T.
A1  - Heijboer, A.
A1  - Heine, E.
A1  - Henry, S.
A1  - Hernández-Rey, J. J.
A1  - Hevinga, M.
A1  - Hofestädt, J.
A1  - Hugon, C. M. F.
A1  - Illuminati, G.
A1  - James, C. W.
A1  - Jansweijer, P.
A1  - Jongen, M.
A1  - de Jong, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Kappes, A.
A1  - Katz, U. F.
A1  - Keller, P.
A1  - Kieft, G.
A1  - Kießling, D.
A1  - Koffeman, E. N.
A1  - Kooijman, P.
A1  - Kouchner, A.
A1  - Kulikovskiy, V.
A1  - Lahmann, R.
A1  - Lamare, P.
A1  - Leisos, A.
A1  - Leonora, E.
A1  - Lindsey Clark, M.
A1  - Liolios, A.
A1  - Llorenz Alvarez, C. D.
A1  - Lo Presti, D.
A1  - Löhner, H.
A1  - Lonardo, A.
A1  - Lotze, M.
A1  - Loucatos, S.
A1  - Maccioni, E.
A1  - Mannheim, K.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Mariş, O.
A1  - Markou, C.
A1  - Martínez-Mora, J. A.
A1  - Martini, A.
A1  - Mele, R.
A1  - Melis, K. W.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Migneco, E.
A1  - Mijakowski, P.
A1  - Miraglia, A.
A1  - Mollo, C. M.
A1  - Mongelli, M.
A1  - Morganti, M.
A1  - Moussa, A.
A1  - Musico, P.
A1  - Musumeci, M.
A1  - Navas, S.
A1  - Nicoleau, C. A.
A1  - Olcina, I.
A1  - Olivetto, C.
A1  - Orlando, A.
A1  - Papaikonomou, A.
A1  - Papaleo, R.
A1  - Păvălaş, G. E.
A1  - Peek, H.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Pfutzner, M.
A1  - Piattelli, P.
A1  - Pikounis, K.
A1  - Poma, G. E.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Pratolongo, F.
A1  - Pühlhofer, G.
A1  - Pulvirenti, S.
A1  - Quinn, L.
A1  - Racca, C.
A1  - Raffaelli, F.
A1  - Randazzo, N.
A1  - Rapidis, P.
A1  - Razis, P.
A1  - Real, D.
A1  - Resvanis, L.
A1  - Reubelt, J.
A1  - Riccobene, G.
A1  - Rossi, C.
A1  - Rovelli, A.
A1  - Saldaña, M.
A1  - Salvadori, I.
A1  - Samtleben, D. F. E.
A1  - Sánchez García, A.
A1  - Sánchez Losa, A.
A1  - Sanguineti, M.
A1  - Santangelo, A.
A1  - Santonocito, D.
A1  - Sapienza, P.
A1  - Schimmel, F.
A1  - Schmelling, J.
A1  - Sciacca, V.
A1  - Sedita, M.
A1  - Seitz, T.
A1  - Sgura, I.
A1  - Simeone, F.
A1  - Siotis, I.
A1  - Sipala, V.
A1  - Spisso, B.
A1  - Spurio, M.
A1  - Stavropoulos, G.
A1  - Steijger, J.
A1  - Stellacci, S. M.
A1  - Stransky, D.
A1  - Taiuti, M.
A1  - Tayalati, Y.
A1  - Tézier, D.
A1  - Theraube, S.
A1  - Thompson, L.
A1  - Timmer, P.
A1  - Tönnis, C.
A1  - Trasatti, L.
A1  - Trovato, A.
A1  - Tsirigotis, A.
A1  - Tzamarias, S.
A1  - Tzamariudaki, E.
A1  - Vallage, B.
A1  - Van Elewyk, V.
A1  - Vermeulen, J.
A1  - Vicini, P.
A1  - Viola, S.
A1  - Vivolo, D.
A1  - Volkert, M.
A1  - Voulgaris, G.
A1  - Wiggers, L.
A1  - Wilms, J.
A1  - de Wolf, E.
A1  - Zachariadou, K.
A1  - Zornoza, J. D.
A1  - Zúñiga, J.
T1  - Letter of intent for KM3NeT 2.0
JF  - Journal of Physics G-Nuclear and Particle Physics
N2  - The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and
KW  - neutrino astronomy
KW  - eutrino physics
KW  - deep sea neutrino telescope
KW  - neutrino mass hierarchy
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188050
VL  - 43
IS  - 8
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Albert, A.
A1  - André, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Avgitas, T.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Basa, S.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Bou-Cabo, M.
A1  - Bouwhuis, M.C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Busto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Celli, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coleiro, A.
A1  - Coniglione, R.
A1  - Costantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Deschamps, A.
A1  - De Bonis, G.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Drouhin, D.
A1  - Eberl, T.
A1  - El Bojaddaini, I.
A1  - Elsässer, D.
A1  - Enzenhöfer, A.
A1  - Fehn, K.
A1  - Felis, I.
A1  - Fusco, L.A.
A1  - Galatà, S.
A1  - Gay, P.
A1  - Geißelsöder, S.
A1  - Geyer, K.
A1  - Giordano, V.
A1  - Gleixner, A.
A1  - Glotin, H.
A1  - Gracia-Ruiz, R.
A1  - Graf, K.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Heijboer, A.J.
A1  - Hello, Y.
A1  - Hernández-Rey, J.-J.
A1  - Hößl, J.
A1  - Hofestädt, J.
A1  - Hugon, C.
A1  - Illuminati, G.
A1  - James, C.W.
A1  - de Jong, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Katz, U.
A1  - Kießling, D.
A1  - Kouchner, A.
A1  - Kreter, M.
A1  - Kreykenbohm, I.
A1  - Kulikovskiy, V.
A1  - Lachaud, C.
A1  - Lahmann, R.
A1  - Lefèvre, D.
A1  - Leonora, E.
A1  - Loucatos, S.
A1  - Marcelin, M.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Martínez-Mora, J.A.
A1  - Mathieu, A.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Moussa, A.
A1  - Mueller, C.
A1  - Nezri, E.
A1  - Păvălaș, G.E.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Piattelli, P.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Racca, C.
A1  - Riccobene, G.
A1  - Roensch, K.
A1  - Saldaña, M.
A1  - Samtleben, D.F.E.
A1  - Sanguineti, M.
A1  - Sapienza, P.
A1  - Schnabel, J.
A1  - Schüssler, F.
A1  - Seitz, T.
A1  - Sieger, C.
A1  - Spurio, M.
A1  - Stolarczyk, Th.
A1  - Sánchez-Losa, A.
A1  - Taiuti, M.
A1  - Trovato, A.
A1  - Tselengidou, M.
A1  - Turpin, D.
A1  - Tönnis, C.
A1  - Vallage, B.
A1  - Vallée, C.
A1  - Van Elewyck, V.
A1  - Vivolo, D.
A1  - Wagner, S.
A1  - Wilms, J.
A1  - Zornoza, J.D.
A1  - Zúñiga, J.
T1  - A search for Secluded Dark Matter in the Sun with the ANTARES neutrino telescope
JF  - Journal of Cosmology and Astroparticle Physics
N2  - A search for Secluded Dark Matter annihilation in the Sun using 2007-2012 data of the ANTARES neutrino telescope is presented. Three different cases are considered: a) detection of dimuons that result from the decay of the mediator, or neutrino detection from: b) mediator that decays into a dimuon and, in turn, into neutrinos, and c) mediator that decays directly into neutrinos. As no significant excess over background is observed, constraints are derived on the dark matter mass and the lifetime of the mediator.
KW  - dark matter experiments
KW  - neutrino detectors
KW  - dark matter detectors
KW  - neutrino astronomy
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189035
VL  - 2016
IS  - 5
ER  - 
TY  - THES
A1  - Albert, Michael
T1  - Intelligent analysis of medical data in a generic telemedicine infrastructure
T1  - Intelligente Datenanalyse in einer generischen Telemedizinumgebung
N2  - Telemedicine uses telecommunication and information technology to provide health care services over spatial distances. In the upcoming demographic changes towards an older average population age, especially rural areas suffer from a decreasing doctor to patient ratio as well as a limited amount of available medical specialists in acceptable distance. These areas could benefit the most from telemedicine applications as they are known to improve access to medical services, medical expertise and can also help to mitigate critical or emergency situations. Although the possibilities of telemedicine applications exist in the entire range of healthcare, current systems focus on one specific disease while using dedicated hardware to connect the patient with the supervising telemedicine center.

This thesis describes the development of a telemedical system which follows a new generic design approach. This bridges the gap of existing approaches that only tackle one specific application. The proposed system on the contrary aims at supporting as many diseases and use cases as possible by taking all the stakeholders into account at the same time. To address the usability and acceptance of the system it is designed to use standardized hardware like commercial medical sensors and smartphones for collecting medical data of the patients and transmitting them to the telemedical center. The smartphone can also act as interface to the patient for health questionnaires or feedback.
The system can handle the collection and transport of medical data, analysis and visualization of the data as well as providing a real time communication with video and audio between the users.
On top of the generic telemedical framework the issue of scalability is addressed by integrating a rule-based analysis tool for the medical data. Rules can be easily created by medical personnel via a visual editor and can be personalized for each patient. The rule-based analysis tool is extended by multiple options for visualization of the data, mechanisms to handle complex rules and options for performing actions like raising alarms or sending automated messages.

It is sometimes hard for the medical experts to formulate their knowledge into rules and there may be information in the medical data that is not yet known. This is why a machine learning module was integrated into the system. It uses the incoming medical data of the patients to learn new rules that are then presented to the medical personnel for inspection. This is in line with European legislation where the human still needs to be in charge of such decisions.
Overall, we were able to show the benefit of the generic approach by evaluating it in three completely different medical use cases derived from specific application needs: monitoring of COPD (chronic obstructive pulmonary disease) patients, support of patients performing dialysis at home and councils of intensive-care experts. In addition the system was used for a non-medical use case: monitoring and optimization of industrial machines and robots. In all of the mentioned cases, we were able to prove the robustness of the generic approach with real users of the corresponding domain. This is why we can propose this approach for future development of telemedical systems.
N2  - Telemedizin nutzt Telekommunikation und Informationstechnologie, um medizinische Dienstleistungen über räumliche Distanzen hinweg zu ermöglichen. Durch den demographischen Wandel hin zu einer älteren Bevölkerung, verschlechtert sich vor allem im ländlichen Raum der Betreuungsschlüssel zwischen (Fach-)ärzten und Patienten, während Experten in den jeweiligen medizinischen Spezialgebieten sehr weit verteilt sind und Anfahrtswege immer weiter werden.
Gerade der ländliche Raum profitiert von der Telemedizin. Anfahrtswege entfallen, wenn Untersuchungen oder ärztliche Konzile über Telemedizinsysteme abgewickelt werden. Kritische Situationen können entschärft oder vermieden werden, wenn Spezialisten durch Telemedizin frühzeitig eingebunden werden. Aktuelle Telemedizinsysteme sind allerdings generell auf ein bestimmtes Krankheitsbild beschränkt und verwenden dedizierte Hardware, um den Patienten mit dem telemedizinischen Zentrum zu verbinden, obwohl ein breiteres Anwendungsspektrum in der gesamten Gesundheitsversorgung denkbar ist.
Diese Arbeit beschreibt die Entwicklung eines Telemedizinsystems, das darauf ausgelegt ist das System so generisch zu planen und zu entwickeln, dass möglichst viele Krankheitsbilder und Anwendungsfälle abgebildet werden können. Dafür werden alle möglichen Beteiligten des Systems mit berücksichtigt und einbezogen. Um das Telemedizinsystem bedienerfreundlich zu gestalten und die Akzeptanz zu erhöhen, wurde auf den Einsatz von Standardhardware, wie kommerzielle medizinische Sensorik oder Smartphones, hoher Wert gelegt. Das Smartphone dient dabei unter anderem als Patientengerät, das die Daten verschiedenster Sensorik auslesen, aggregieren und an das zentrale System weiterleiten kann. Es kann interaktive Fragebögen anzeigen und verwendet werden, um dem Patienten Feedback zu den Daten zu geben. Das Telemedizinsystem unterstützt die komplette Kette der telemedizinischen Datenverarbeitung, von der Aufnahme der Daten über den abgesicherten Transport bis hin zur Analyse und Visualisierung der Daten. Zusätzlich wird eine Kommunikationsmöglichkeit der Beteiligten über Audio- oder Videotelefonie zur Verfügung gestellt.
Um die Skalierbarkeit des Systems zu erhöhen, wurde ein regelbasiertes Auswertesystem für die Patientendaten implementiert. Das medizinische Personal kann über ein einfach zu bedienendes grafisches Interface patientenindividuelle Regeln anlegen. Das Regelsystem ist in der Lage die Daten anhand komplexer Regeln zu analysieren, Visualisierungen zu erzeugen oder Aktionen auszulösen, wie beispielsweise einen Alarm zu geben, wenn die Werte des Patienten sich verschlechtern.
Es kommt vor, dass die Experten ihr Wissen nicht in konkrete Regeln formulieren können oder dass Wissen in den Daten steckt, das den Experten selbst nicht bekannt ist. Deshalb kommt ein weiteres Modul zum Einsatz, das anhand der eingehenden Daten mittels maschinellem Lernen neue Regeln erzeugt und dem Fachpersonal zur Überprüfung vorschlägt. Die letzte Entscheidung liegt immer bei dem jeweiligen Fachpersonal, so dass das System konform zu aktuellem europäischem Recht arbeitet.
Der generische Ansatz des Telemedizinsystems wurde in drei verschiedenen medizinischen Anwendungsszenarien mit den entsprechenden Anwendern getestet: Langzeitmonitoring von COPD (chronisch obstruktive Lungenerkrankung) Patienten, Unterstützung von Heimdialyse Patienten und intensivmedizinische Konsile. Zusätzlich wurde das System im industriellen Anwendungskontext zum Überwachen und Optimieren von Industrieanlagen und Industrierobotern eingesetzt. In allen Anwendungsfällen konnten wir die Machbarkeit des Systems zeigen und mit Anwendern aus dem jeweiligen Fachbereich evaluieren. Das System kann somit als robuste Grundlage für die Entwicklung weiterer Telemedizinsysteme und Anwendungen dienen.
T3  - Forschungsberichte in der Robotik = Research Notes in Robotics - 17 
KW  - Telemedizin
KW  - Regelbasiertes Modell
KW  - telemedicine
KW  - rulebased analysis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174213
SN  - 978-3-945459-26-3 (Online)
ER  - 
TY  - JOUR
A1  - Albert-Weissenberger, Christiane
A1  - Mencl, Stine
A1  - Schuhmann, Michael K.
A1  - Salur, Irmak
A1  - Göb, Eva
A1  - Langhauser, Friederike
A1  - Hopp, Sarah
A1  - Hennig, Nelli
A1  - Meuth, Sven G.
A1  - Nolte, Marc W.
A1  - Sirén, Anna-Leena
A1  - Kleinschnitz, Christoph
T1  - C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation
JF  - Frontiers in Cellular Neuroscience
N2  - Traumatic brain injury (TBI) induces a strong inflammatory response which includes blood-brain barrier damage, edema formation and infiltration of different immune cell subsets. More recently, microvascular thrombosis has been identified as another pathophysiological feature of TBI. The contact-kinin system represents an interface between inflammatory and thrombotic circuits and is activated in different neurological diseases. C1-Inhibitor counteracts activation of the contact-kinin system at multiple levels. We investigated the therapeutic potential of C1-Inhibitor in a model of TBI. Male and female C57BL/6 mice were subjected to cortical cryolesion and treated with C1-Inhibitor after 1 h. Lesion volumes were assessed between day 1 and day 5 and blood-brain barrier damage, thrombus formation as well as the local inflammatory response were determined post TBI. Treatment of male mice with 15.0 IU C1-Inhibitor, but not 7.5 IU, 1 h after cryolesion reduced lesion volumes by ~75% on day 1. This protective effect was preserved in female mice and at later stages of trauma. Mechanistically, C1-Inhibitor stabilized the blood-brain barrier and decreased the invasion of immune cells into the brain parenchyma. Moreover, C1-Inhibitor had strong antithrombotic effects. C1-Inhibitor represents a multifaceted anti-inflammatory and antithrombotic compound that prevents traumatic neurodegeneration in clinically meaningful settings.
KW  - thrombosis
KW  - traumatic brain injury
KW  - C1-inhibitor
KW  - blood-brain barrier
KW  - contact-kinin system
KW  - edema
KW  - inflammation
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119263
SN  - 1662-5102
VL  - 8
ER  - 
TY  - JOUR
A1  - Albert-Weissenberger, Christiane
A1  - Stetter, Christian
A1  - Meuth, Sven G.
A1  - Göbel, Kerstin
A1  - Bader, Michael
A1  - Sirén, Anna-Leena
A1  - Kleinschnitz, Christoph
T1  - Blocking of Bradykinin Receptor B1 Protects from Focal Closed Head Injury in Mice by Reducing Axonal Damage and Astroglia Activation
JF  - Journal of Cerebral Blood Flow and Metabolism
N2  - The two bradykinin receptors B1R and B2R are central components of the kallikrein–kinin system with different expression kinetics and binding characteristics. Activation of these receptors by kinins triggers inflammatory responses in the target organ and in most situations enhances tissue damage. We could recently show that blocking of B1R, but not B2R, protects from cortical cryolesion by reducing inflammation and edema formation. In the present study, we investigated the role of B1R and B2R in a closed head model of focal traumatic brain injury (TBI; weight drop). Increased expression of B1R in the injured hemispheres of wild-type mice was restricted to the later stages after brain trauma, i.e. day 7 (P<0.05), whereas no significant induction could be observed for the B2R (P>0.05). Mice lacking the B1R, but not the B2R, showed less functional deficits on day 3 (P<0.001) and day 7 (P<0.001) compared with controls. Pharmacological blocking of B1R in wild-type mice had similar effects. Reduced axonal injury and astroglia activation could be identified as underlying mechanisms, while inhibition of B1R had only little influence on the local inflammatory response in this model. Inhibition of B1R may become a novel strategy to counteract trauma-induced neurodegeneration.
KW  - R-715
KW  - kinin receptors
KW  - closed head injury
KW  - β-APP
KW  - astrocytes
KW  - TNF-α
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125903
VL  - 32
IS  - 9
ER  - 
TY  - JOUR
A1  - Dupuis, Luc
A1  - Dengler, Reinhard
A1  - Heneka, Michael T.
A1  - Meyer, Thomas
A1  - Zierz, Stephan
A1  - Kassubek, Jan
A1  - Fischer, Wilhelm
A1  - Steiner, Franziska
A1  - Lindauer, Eva
A1  - Otto, Markus
A1  - Dreyhaupt, Jens
A1  - Grehl, Torsten
A1  - Hermann, Andreas
A1  - Winkler, Andrea S.
A1  - Bogdahn, Ulrich
A1  - Benecke, Reiner
A1  - Schrank, Bertold
A1  - Wessig, Carsten
A1  - Grosskreutz, Julian
A1  - Ludolph, Albert C.
T1  - A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis
JF  - PLoS One
N2  - Background: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). 
Methods/Principal Findings: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. 
Conclusion/Significance: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole.
KW  - ALS
KW  - transgenic mouse model
KW  - central nervous system
KW  - nonalcoholic steatohepatitis
KW  - PPAR-gamme
KW  - hexanucleotide repeat
KW  - disease progression
KW  - delays progression
KW  - SOD1 mutations
KW  - monocycline
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130255
VL  - 7
IS  - 6
ER  - 
TY  - JOUR
A1  - Stetter, Christian
A1  - Lopez-Caperuchipi, Simon
A1  - Hopp-Krämer, Sarah
A1  - Bieber, Michael
A1  - Kleinschnitz, Christoph
A1  - Sirén, Anna-Leena
A1  - Albert-Weißenberger, Christiane
T1  - Amelioration of cognitive and behavioral deficits after traumatic brain injury in coagulation factor XII deficient mice
JF  - International Journal of Molecular Sciences
N2  - Based on recent findings that show that depletion of factor XII (FXII) leads to better posttraumatic neurological recovery, we studied the effect of FXII-deficiency on post-traumatic cognitive and behavioral outcomes in female and male mice. In agreement with our previous findings, neurological deficits on day 7 after weight-drop traumatic brain injury (TBI) were significantly reduced in FXII\(^{−/−}\) mice compared to wild type (WT) mice. Also, glycoprotein Ib (GPIb)-positive platelet aggregates were more frequent in brain microvasculature of WT than FXII\(^{−/−}\) mice 3 months after TBI. Six weeks after TBI, memory for novel object was significantly reduced in both female and male WT but not in FXII\(^{−/−}\) mice compared to sham-operated mice. In the setting of automated home-cage monitoring of socially housed mice in IntelliCages, female WT mice but not FXII\(^{−/−}\) mice showed decreased exploration and reacted negatively to reward extinction one month after TBI. Since neuroendocrine stress after TBI might contribute to trauma-induced cognitive dysfunction and negative emotional contrast reactions, we measured peripheral corticosterone levels and the ration of heart, lung, and spleen weight to bodyweight. Three months after TBI, plasma corticosterone levels were significantly suppressed in both female and male WT but not in FXII\(^{−/−}\) mice, while the relative heart weight increased in males but not in females of both phenotypes when compared to sham-operated mice. Our results indicate that FXII deficiency is associated with efficient post-traumatic behavioral and neuroendocrine recovery.
KW  - closed head injury
KW  - contact-kinin system
KW  - object recognition memory
KW  - IntelliCage
KW  - Crespi effect
KW  - stress
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284959
SN  - 1422-0067
VL  - 22
IS  - 9
ER  - 
TY  - JOUR
A1  - Lawitschka, Anita
A1  - Brunmair, Matthias
A1  - Bauer, Dorothea
A1  - Zubarovskaya, Natalia
A1  - Felder-Puig, Rosemarie
A1  - Strahm, Brigitte
A1  - Bader, Peter
A1  - Strauss, Gabriele
A1  - Albert, Michael
A1  - Luettichau, Irene von
A1  - Greinix, Hildegard
A1  - Wolff, Daniel
A1  - Peters, Christina
T1  - Psychometric properties of the Activities Scale for Kids-performance after allogeneic hematopoietic stem cell transplantation in adolescents and children
BT  - Results of a prospective study on behalf of the German-Austrian-Swiss GVHD Consortium
JF  - Wiener klinische Wochenschrift
N2  - Background
The psychometric properties of an instrument, the Activity Scale for Kids-performance (ASKp), were assessed which was proposed to capture physical functioning after allogeneic hematopoietic stem cell transplantation (HSCT). Additionally, this multicenter observational prospective study investigated the influence of clinical correlates focusing on chronic graft-versus-host disease (cGVHD).

Methods
Patient-reported ASKp, clinician-reported Karnofsky/Lansky status (KPS/PSS), patient characteristics and cGVHD details were assessed of 55 patients with a median age of 12 years at baseline after day +100 post-HSCT and every 3 months during the next 18 months. The psychometric properties were evaluated and ASKp and KPS/PSS status was compared using ANOVAS and multiple regression models.

Results
The German version of the ASKp showed good psychometric properties except for ceiling effects. Discrimination ability of the ASKp was good regarding the need for devices but failed to predict cGVHD patients. Both the ASKp and the KPS/PSS were associated with patients after adoptive cell therapy being in need for devices, suffering from overlap cGVHD and from steroid side effects but not with patients’ age and gender. In contrast to the KPS/PSS the ASKp only showed significant differences after merging moderate and severe cGHVD patients when comparing them to No-cGVHD (F = 4.050; p = 0.049), being outperformed by the KPS/PSS (F = 20.082; p < 0.001).

Conclusion
The ASKp showed no clear advantages compared to KPS/PSS even though economical and patients’ effort was higher. Further application range may be limited through ceiling effects. Both should be taken into consideration. Therefore, the results may not support the usage of ASKp after HSCT and rather suggest KPS/PSS, both patient and clinician reported.
KW  - physical functioning
KW  - cancer patients
KW  - AYAs
KW  - GVHD
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281100
VL  - 133
IS  - 1-2
ER  - 
TY  - JOUR
A1  - Kölbel, Heike
A1  - Roos, Andreas
A1  - van der Ven, Peter F. M.
A1  - Evangelista, Teresinha
A1  - Nolte, Kay
A1  - Johnson, Katherine
A1  - Töpf, Ana
A1  - Wilson, Michael
A1  - Kress, Wolfram
A1  - Sickmann, Albert
A1  - Straub, Volker
A1  - Kollipara, Laxmikanth
A1  - Weis, Joachim
A1  - Fürst, Dieter O.
A1  - Schara, Ulrike
T1  - First clinical and myopathological description of a myofibrillar myopathy with congenital onset and homozygous mutation in FLNC
JF  - Human Mutation
N2  - Filamin C (encoded by the FLNC gene) is a large actin‐cross‐linking protein involved in shaping the actin cytoskeleton in response to signaling events both at the sarcolemma and at myofibrillar Z‐discs of cross‐striated muscle cells. Multiple mutations in FLNC are associated with myofibrillar myopathies of autosomal‐dominant inheritance. Here, we describe for the first time a boy with congenital onset of generalized muscular hypotonia and muscular weakness, delayed motor development but no cardiac involvement associated with a homozygous FLNC mutation c.1325C>G (p.Pro442Arg). We performed ultramorphological, proteomic, and functional investigations as well as immunological studies of known marker proteins for dominant filaminopathies. We show that the mutant protein is expressed in similar quantities as the wild‐type variant in control skeletal muscle fibers. The proteomic signature of quadriceps muscle is altered and ultrastructural perturbations are evident. Moreover, filaminopathy marker proteins are comparable both in our homozygous and a dominant control case (c.5161delG). Biochemical investigations demonstrate that the recombinant mutant protein is less stable and more prone to degradation by proteolytic enzymes than the wild‐type variant. The unusual congenital presentation of the disease clearly demonstrates that homozygosity for mutations in FLNC severely aggravates the phenotype.
KW  - congenital myopathy
KW  - filamin C
KW  - myofibrillar myopathy
KW  - proteomic signature
KW  - recessive inheritance
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215481
VL  - 41
IS  - 9
SP  - 1600
EP  - 1614
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Albert, A.
A1  - André, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Avgitas, T.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Basa, S.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Bouwhuis, M.C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Busto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Celli, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coleiro, A.
A1  - Coniglione, R.
A1  - Costantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Deschamps, A.
A1  - De Bonis, G.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Drouhin, D.
A1  - Eberl, T.
A1  - El Bojaddaini, I.
A1  - Elsässer, D.
A1  - Enzenhöfer, A.
A1  - Fehn, K.
A1  - Felis, I.
A1  - Fusco, L.A.
A1  - Galatà, S.
A1  - Gay, P.
A1  - Geißelsöder, S.
A1  - Geyer, K.
A1  - Giordano, V.
A1  - Gleixner, A.
A1  - Glotin, H.
A1  - Gracia-Ruiz, R.
A1  - Graf, K.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Heijboer, A.J.
A1  - Hello, Y.
A1  - Hernández-Rey, J.J.
A1  - Hößl, J.
A1  - Hofestädt, J.
A1  - Hugon, C.
A1  - Illuminati, G.
A1  - James, C.W.
A1  - de Jong, M.
A1  - Jongen, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Katz, U.
A1  - Kießling, D.
A1  - Kouchner, A.
A1  - Kreter, M.
A1  - Kreykenbohm, I.
A1  - Kulikovskiy, V.
A1  - Lachaud, C.
A1  - Lahmann, R.
A1  - Lefèvre, D.
A1  - Leonora, E.
A1  - Loucatos, S.
A1  - Marcelin, M.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Martínez-Mora, J.A.
A1  - Mathieu, A.
A1  - Melis, K.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Moussa, A.
A1  - Mueller, C.
A1  - Nezri, E.
A1  - Pavalas, G.E.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Piattelli, P.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Racca, C.
A1  - Riccobene, G.
A1  - Roensch, K.
A1  - Saldaña, M.
A1  - Samtleben, D.F.E.
A1  - Sánchez-Losa, A.
A1  - Sanguineti, M.
A1  - Sapienza, P.
A1  - Schnabel, J.
A1  - Schüssler, F.
A1  - Seitz, T.
A1  - Sieger, C.
A1  - Spurio, M.
A1  - Stolarczyk, Th.
A1  - Taiuti, M.
A1  - Tönnis, C.
A1  - Trovato, A.
A1  - Tselengidou, M.
A1  - Turpin, D.
A1  - Vallage, B.
A1  - Vallée, C.
A1  - Van Elewyck, V.
A1  - Vivolo, D.
A1  - Wagner, S.
A1  - Wilms, J.
A1  - Zornoza, J.D.
A1  - Zúñiga, J.
T1  - Limits on dark matter annihilation in the sun using the ANTARES neutrino telescope
JF  - Physics Letters B
N2  - A search for muon neutrinos originating from dark matter annihilations in the Sun is performed using the data recorded by the ANTARES neutrino telescope from 2007 to 2012. In order to obtain the best possible sensitivities to dark matter signals, an optimisation of the event selection criteria is performed taking into account the background of atmospheric muons, atmospheric neutrinos and the energy spectra of the expected neutrino signals. No significant excess over the background is observed and 90% C.L. upper limits on the neutrino flux, the spin-dependent and spin-independent WIMP-nucleon cross-sections are derived for WIMP masses ranging from 50 GeV to 5 TeV for the annihilation channels WIMP + WIMP→ b\(\overline{b}\), W\(^{+}\)W\(^{−}\) and τ\(^{+}\)τ\(^{−}\).
KW  - dark matter
KW  - WIMP
KW  - neutralino
KW  - indirect detection
KW  - neutrino telescope
KW  - sun
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166642
VL  - 759
ER  - 
TY  - JOUR
A1  - Schanbacher, Constanze
A1  - Bieber, Michael
A1  - Reinders, Yvonne
A1  - Cherpokova, Deya
A1  - Teichert, Christina
A1  - Nieswandt, Bernhard
A1  - Sickmann, Albert
A1  - Kleinschnitz, Christoph
A1  - Langhauser, Friederike
A1  - Lorenz, Kristina
T1  - ERK1/2 activity is critical for the outcome of ischemic stroke
JF  - International Journal of Molecular Sciences
N2  - Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2\(^{wt}\)) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood–brain barrier (BBB) leakiness, inflammation, and the number of apoptotic neurons. To compare ERK1/2 activation and inhibition side-by-side, we also used mice with ubiquitous overexpression of the Raf-kinase inhibitor protein (RKIP\(^{wt}\)) and its phosphorylation-deficient mutant RKIP\(^{S153A}\), known inhibitors of the ERK1/2 signaling cascade. RKIP\(^{wt}\) and RKIP\(^{S153A}\) attenuated ischemia-induced damages, in particular via anti-inflammatory signaling. Taken together, our data suggest that stimulation of the Raf/MEK/ERK1/2-cascade is severely detrimental and its inhibition is rather protective. Thus, a tight control of the ERK1/2 signaling is essential for the outcome in response to ischemic stroke.
KW  - ERK1/2
KW  - tMCAO
KW  - ischemic stroke
KW  - RKIP
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283991
SN  - 1422-0067
VL  - 23
IS  - 2
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Albert, A.
A1  - André, M.
A1  - Anghinolfi, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Avgitas, T.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Basa, S.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Bouwhuis, M.C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Busto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Celli, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coleiro, A.
A1  - Coniglione, R.
A1  - Constantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Deschamps, A.
A1  - De Bonis, G.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Drouhin, D.
A1  - Eberl, T.
A1  - El Bojaddaini, I.
A1  - Elsässer, D.
A1  - Enzenhöfer, A.
A1  - Fehn, K.
A1  - Felis, I.
A1  - Fusco, L.A.
A1  - Galatà, S.
A1  - Gay, P.
A1  - Geißelsöder, S.
A1  - Geyer, K.
A1  - Giordano, V.
A1  - Gleixner, A.
A1  - Glotin, H.
A1  - Gracia-Ruiz, R.
A1  - Graf, K.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Heijboer, A.J.
A1  - Hello, Y.
A1  - Hernández-Rey, J.J.
A1  - Hößl, J.
A1  - Hofestädt, J.
A1  - Hugon, C.
A1  - Illuminati, G.
A1  - James, C.W.
A1  - de Jong, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Katz, U.
A1  - Kießling, D.
A1  - Kouchner, A.
A1  - Kreter, M.
A1  - Kreykenbohm, I.
A1  - Kulikovskiy, V.
A1  - Lachaud, C.
A1  - Lahmann, R.
A1  - Lefèvre, D.
A1  - Leonora, E.
A1  - Loucatos, S.
A1  - Marcelin, M.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Martínez-Mora, J.A.
A1  - Mathieu, A.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Moussa, A.
A1  - Mueller, C.
A1  - Nezri, E.
A1  - Pavalas, G.E.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Piattelli, P.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Racca, C.
A1  - Riccobene, G.
A1  - Roensch, K.
A1  - Saldaña, M.
A1  - Samtleben, D.F.E.
A1  - Sánchez-Losa, A.
A1  - Sanguineti, M.
A1  - Sapienza, P.
A1  - Schnabel, J.
A1  - Schüssler, F.
A1  - Seitz, T.
A1  - Sieger, C.
A1  - Spurio, M.
A1  - Stolarczyk, Th.
A1  - Taiuti, M.
A1  - Trovato, A.
A1  - Tselengidou, M.
A1  - Turpin, D.
A1  - Tönnis, C.
A1  - Vallage, B.
A1  - Vallée, C.
A1  - Van Elewyck, V.
A1  - Visser, E.
A1  - Vivolo, D.
A1  - Wagner, S.
A1  - Wilms, J.
A1  - Zornoza, J.D.
A1  - Zúñiga, J.
T1  - Constraints on the neutrino emission from the Galactic Ridge with the ANTARES telescope
JF  - Physics Letters B
N2  - A highly significant excess of high-energy astrophysical neutrinos has been reported by the IceCube Collaboration. Some features of the energy and declination distributions of IceCube events hint at a North/South asymmetry of the neutrino flux. This could be due to the presence of the bulk of our Galaxy in the Southern hemisphere. The ANTARES neutrino telescope, located in the Mediterranean Sea, has been taking data since 2007. It offers the best sensitivity to muon neutrinos produced by galactic cosmic ray interactions in this region of the sky. In this letter a search for an extended neutrino flux from the Galactic Ridge region is presented. Different models of neutrino production by cosmic ray propagation are tested. No excess of events is observed and upper limits for different neutrino flux spectral indices Γ are set. For Γ=2.4 the 90% confidence level flux upper limit at 100 TeV for one neutrino flavour corresponds to Φ\(^{1f}_{0}\) (100 TeV) = 2.0 · 10\(^{−17}\) GeV\(^{−1}\) cm\(^{−2}\)s\(^{−1}\)sr\(^{−1}\). Under this assumption, at most two events of the IceCube cosmic candidates can originate from the Galactic Ridge. A simple power-law extrapolation of the Fermi-LAT flux to account for IceCube High Energy Starting Events is excluded at 90% confidence level.
KW  - neutrino emission
KW  - Galactic Ridge
KW  - ANTARES telescope
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166608
VL  - 760
ER  - 
TY  - JOUR
A1  - Dekker, Annelot M.
A1  - Diekstra, Frank P.
A1  - Pulit, Sara L.
A1  - Tazelaar, Gijs H. P.
A1  - van der Spek, Rick A.
A1  - van Rheenen, Wouter
A1  - van Eijk, Kristel R.
A1  - Calvo, Andrea
A1  - Brunetti, Maura
A1  - Van Damme, Philip
A1  - Robberecht, Wim
A1  - Hardiman, Orla
A1  - McLaughlin, Russell
A1  - Chiò, Adriano
A1  - Sendtner, Michael
A1  - Ludolph, Albert C.
A1  - Weishaupt, Jochen H.
A1  - Pardina, Jesus S. Mora
A1  - van den Berg, Leonard H.
A1  - Veldink, Jan H.
T1  - Exome array analysis of rare and low frequency variants in amyotrophic lateral sclerosis
JF  - Scientific Reports
N2  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 1 in ~350 individuals. Genetic association studies have established ALS as a multifactorial disease with heritability estimated at ~61%, and recent studies show a prominent role for rare variation in its genetic architecture. To identify rare variants associated with disease onset we performed exome array genotyping in 4,244 cases and 3,106 controls from European cohorts. In this largest exome-wide study of rare variants in ALS to date, we performed single-variant association testing, gene-based burden, and exome-wide individual set-unique burden (ISUB) testing to identify single or aggregated rare variation that modifies disease risk. In single-variant testing no variants reached exome-wide significance, likely due to limited statistical power. Gene-based burden testing of rare non-synonymous and loss-of-function variants showed NEK1 as the top associated gene. ISUB analysis did not show an increased exome-wide burden of deleterious variants in patients, possibly suggesting a more region-specific role for rare variation. Complete summary statistics are released publicly. This study did not implicate new risk loci, emphasizing the immediate need for future large-scale collaborations in ALS that will expand available sample sizes, increase genome coverage, and improve our ability to detect rare variants associated to ALS.
KW  - amyotrophic lateral sclerosis
KW  - genome-wide association studies
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223686
VL  - 9
ER  -