TY  - JOUR
A1  - Zahnert, Thomas
A1  - Löwenheim, Hubert
A1  - Beutner, Dirk
A1  - Hagen, Rudolf
A1  - Ernst, Arneborg
A1  - Pau, Hans-Wilhelm
A1  - Zehlicke, Thorsten
A1  - Kühne, Hilke
A1  - Friese, Natascha
A1  - Tropitzsch, Anke
A1  - Lüers, Jan-Christoffer
A1  - Mlynski, Robert
A1  - Todt, Ingo
A1  - Hüttenbrink, Karl-Bernd
T1  - Multicenter Clinical Trial of Vibroplasty Couplers to Treat Mixed/Conductive Hearing Loss: First Results
JF  - Audiology and Neurotology
N2  - Objective: To evaluate the safety and effectiveness of round window (RW), oval window (OW), CliP and Bell couplers for use with an active middle ear implant. Methods: This is a multicenter, long-term, prospective trial with consecutive enrollment, involving 6 university hospitals in Germany. Bone conduction, air conduction, implant-aided warble-tone thresholds and Freiburger monosyllable word recognition scores were compared with unaided preimplantation results in 28 moderate-to-profound hearing-impaired patients after 12 months of follow-up. All patients had previously undergone failed reconstruction surgeries (up to 5 or more). In a subset of patients, additional speech tests at 12 months postoperatively were used to compare the aided with the unaided condition after implantation with the processor switched off. An established quality-of-life questionnaire for hearing aids was used to determine patient satisfaction. Results: Postoperative bone conduction remained stable. Mean functional gain for all couplers was 37 dB HL (RW = 42 dB, OW = 35 dB, Bell = 38 dB, CliP = 27 dB). The mean postoperative Freiburger monosyllable score was 71% at 65 dB SPL. The postimplantation mean SRT<sub>50</sub> (speech reception in quiet for 50% understanding of words in sentences) improved on average by 23 dB over unaided testing and signal-to-noise ratios also improved in all patients. The International Outcome Inventory for Hearing Aids (IOI-HA)quality-of-life questionnaire was scored very positively by all patients. Conclusion: A significant improvement was seen with all couplers, and patients were satisfied with the device at 12 months postoperatively. These results demonstrate that an active implant is an advantage in achieving good hearing benefit in patients with prior failed reconstruction surgery.
KW  - conductive hearing loss
KW  - mixed hearing loss
KW  - vibroplasty
KW  - couplers
KW  - middle ear implant
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199129
SN  - 1420-3030
SN  - 1421-9700
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 21
IS  - 4
ER  - 
TY  - JOUR
A1  - Dengler, Julius
A1  - Maldaner, Nicolai
A1  - Gläsker, Sven
A1  - Endres, Matthias
A1  - Wagner, Martin
A1  - Malzahn, Uwe
A1  - Heuschmann, Peter U.
A1  - Vajkoczy, Peter
T1  - Outcome of Surgical or Endovascular Treatment of Giant Intracranial Aneurysms, with Emphasis on Age, Aneurysm Location, and Unruptured Aneuryms - A Systematic Review and Meta-Analysis
JF  - Cerebrovascular Diseases
N2  - Background: Designing treatment strategies for unruptured giant intracranial aneurysms (GIA) is difficult as evidence of large clinical trials is lacking. We examined the outcome following surgical or endovascular GIA treatment focusing on patient age, GIA location and unruptured GIA. Methods: Medline and Embase were searched for studies reporting on GIA treatment outcome published after January 2000. We calculated the proportion of good outcome (PGO) for all included GIA and for unruptured GIA by meta-analysis using a random effects model. Results: We included 54 studies containing 64 study populations with 1,269 GIA at a median follow-up time (FU-T) of 26.4 months (95% CI 10.8-42.0). PGO was 80.9% (77.4-84.4) in the analysis of all GIA compared to 81.2% (75.3-86.1) in the separate analysis of unruptured GIA. For each year added to patient age, PGO decreased by 0.8%, both for all GIA and unruptured GIA. For all GIA, surgical treatment resulted in a PGO of 80.3% (95% CI 76.0-84.6) compared to 84.2% (78.5-89.8, p = 0.27) after endovascular treatment. In unruptured GIA, PGO was 79.7% (95% CI 71.5-87.8) after surgical treatment and 84.9% (79.1-90.7, p = 0.54) after endovascular treatment. PGO was lower in high quality studies and in studies presenting aggregate instead of individual patient data. In unruptured GIA, the OR for good treatment outcome was 5.2 (95% CI 2.0-13.0) at the internal carotid artery compared to 0.1 (0.1-0.3, p < 0.1) in the posterior circulation. Patient sex, FU-T and prevalence of ruptured GIA were not associated with PGO. Conclusions: We found that the chances of good outcome after surgical or endovascular GIA treatment mainly depend on patient age and aneurysm location rather than on the type of treatment conducted. Our analysis may inform future research on GIA.
KW  - surgical aneurysm treatment
KW  - giant intracranial aneurysm
KW  - endovascular treatment
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196792
SN  - 1015-9770
SN  - 1421-9786
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 41
IS  - 3-4
ER  - 
TY  - RPRT
A1  - Metzger, Florian
A1  - Rafetseder, Albert
A1  - Schröder, Svenja
A1  - Zwickl, Patrick
T1  - The Prospects of Cloud Gaming: Do the Benefits Outweigh the Costs?
N2  - In recent years, cloud gaming has become a popular research topic and has claimed many benefits in the commercial domain over conventional gaming. While, cloud gaming platforms have frequently failed in the past, they have received a new impetus over the last years that brought it to the edge of commercial breakthrough. The fragility of the cloud gaming market may be caused by the high investment costs, offered pricing models or competition from existing "à la carte" platforms. This paper aims at investigating the costs and benefits of both platform types through a twofold approach. We first take on the perspective of the customers, and investigate several cloud gaming platforms and their pricing models in comparison to the costs of other gaming platforms. Then, we explore engagement metrics in order to assess the enjoyment of playing the offered games. Lastly, coming from the perspective of the service providers, we aim to identify challenges in cost-effectively operating a large-scale cloud gaming service while maintaining high QoE values. Our analysis provides initial, yet still comprehensive reasons and models for the prospects of cloud gaming in a highly competitive market.
KW  - Cloud Computing
KW  - Videospiel
KW  - Kosten-Nutzen-Analyse
KW  - Cloud Gaming
KW  - Video Game QoS
KW  - Cost-benefit analysis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242452
N1  - Originally written in 2016, but never published.
ER  - 
TY  - JOUR
A1  - Van Haute, Lindsey
A1  - Dietmann, Sabine
A1  - Kremer, Laura
A1  - Hussain, Shobbir
A1  - Pearce, Sarah F.
A1  - Powell, Christopher A.
A1  - Rorbach, Joanna
A1  - Lantaff, Rebecca
A1  - Blanco, Sandra
A1  - Sauer, Sascha
A1  - Kotzaeridou, Urania
A1  - Hoffmann, Georg F.
A1  - Memari, Yasin
A1  - Kolb-Kokocinski, Anja
A1  - Durbin, Richard
A1  - Mayr, Johannes A.
A1  - Frye, Michaela
A1  - Prokisch, Holger
A1  - Minczuk, Michal
T1  - Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3
JF  - Nature Communications
N2  - Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m5C) methyltransferase NSun3 and link m5C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. We show that NSun3 is required for deposition of m5C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNAMet). Further, we demonstrate that m5C deficiency in mt-tRNAMet results in the lack of 5-formylcytosine (f5C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f5C in human mitochondrial RNA is generated by oxidative processing of m5C.
KW  - Methylation
KW  - RNA
KW  - Transferases
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165998
VL  - 7
ER  - 
TY  - JOUR
A1  - Mitchell, Jonathan S.
A1  - Li, Ni
A1  - Weinhold, Niels
A1  - Försti, Asta
A1  - Ali, Mina
A1  - van Duin, Mark
A1  - Thorleifsson, Gudmar
A1  - Johnson, David C.
A1  - Chen, Bowang
A1  - Halvarsson, Britt-Marie
A1  - Gudbjartsson, Daniel F.
A1  - Kuiper, Rowan
A1  - Stephens, Owen W.
A1  - Bertsch, Uta
A1  - Broderick, Peter
A1  - Campo, Chiara
A1  - Einsele, Hermann
A1  - Gregory, Walter A.
A1  - Gullberg, Urban
A1  - Henrion, Marc
A1  - Hillengass, Jens
A1  - Hoffmann, Per
A1  - Jackson, Graham H.
A1  - Johnsson, Ellinor
A1  - Jöud, Magnus
A1  - Kristinsson, Sigurdur Y.
A1  - Lenhoff, Stig
A1  - Lenive, Oleg
A1  - Mellqvist, Ulf-Henrik
A1  - Migliorini, Gabriele
A1  - Nahi, Hareth
A1  - Nelander, Sven
A1  - Nickel, Jolanta
A1  - Nöthen, Markus M.
A1  - Rafnar, Thorunn
A1  - Ross, Fiona M.
A1  - da Silva Filho, Miguel Inacio
A1  - Swaminathan, Bhairavi
A1  - Thomsen, Hauke
A1  - Turesson, Ingemar
A1  - Vangsted, Annette
A1  - Vogel, Ulla
A1  - Waage, Anders
A1  - Walker, Brian A.
A1  - Wihlborg, Anna-Karin
A1  - Broyl, Annemiek
A1  - Davies, Faith E.
A1  - Thorsteinsdottir, Unnur
A1  - Langer, Christian
A1  - Hansson, Markus
A1  - Kaiser, Martin
A1  - Sonneveld, Pieter
A1  - Stefansson, Kari
A1  - Morgan, Gareth J.
A1  - Goldschmidt, Hartmut
A1  - Hemminki, Kari
A1  - Nilsson, Björn
A1  - Houlston, Richard S.
T1  - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
JF  - Nature Communications
N2  - Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 10−13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
KW  - Cancer genetics
KW  - Genome-wide association studies
KW  - Myeloma
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165983
VL  - 7
ER  - 
TY  - JOUR
A1  - Hanzelmann, Dennis
A1  - Joo, Hwang-Soo
A1  - Franz-Wachtel, Mirita
A1  - Hertlein, Tobias
A1  - Stevanovic, Stefan
A1  - Macek, Boris
A1  - Wolz, Christiane
A1  - Götz, Friedrich
A1  - Otto, Michael
A1  - Kretschmer, Dorothee
A1  - Peschel, Andreas
T1  - Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants
JF  - Nature Communications
N2  - Sepsis caused by Gram-positive bacterial pathogens is a major fatal disease but its molecular basis remains elusive. Toll-like receptor 2 (TLR2) has been implicated in the orchestration of inflammation and sepsis but its role appears to vary for different pathogen species and clones. Accordingly, Staphylococcus aureus clinical isolates differ substantially in their capacity to activate TLR2. Here we show that strong TLR2 stimulation depends on high-level production of phenol-soluble modulin (PSM) peptides in response to the global virulence activator Agr. PSMs are required for mobilizing lipoproteins, the TLR2 agonists, from the staphylococcal cytoplasmic membrane. Notably, the course of sepsis caused by PSM-deficient S. aureus is similar in wild-type and TLR2-deficient mice, but TLR2 is required for protection of mice against PSM-producing S. aureus. Thus, a crucial role of TLR2 depends on agonist release by bacterial surfactants. Modulation of this process may lead to new therapeutic strategies against Gram-positive infections.
KW  - Pathogens
KW  - Toll-like receptors
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165975
VL  - 7
ER  - 
TY  - JOUR
A1  - Baptista, Marisa A.P.
A1  - Keszei, Marton
A1  - Oliveira, Mariana
A1  - Sunahara, Karen K.S.
A1  - Andersson, John
A1  - Dahlberg, Carin I.M.
A1  - Worth, Austen J.
A1  - Liedén, Agne
A1  - Kuo, I-Chun
A1  - Wallin, Robert P.A.
A1  - Snapper, Scott B.
A1  - Eidsmo, Liv
A1  - Scheynius, Annika
A1  - Karlsson, Mikael C.I.
A1  - Bouma, Gerben
A1  - Burns, Siobhan O.
A1  - Forsell, Mattias N.E.
A1  - Thrasher, Adrian J.
A1  - Nylén, Susanne
A1  - Westerberg, Lisa S.
T1  - Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells
JF  - Nature Communications
N2  - Wiskott–Aldrich syndrome (WAS) is caused by loss-of-function mutations in theWASp gene.
Decreased cellular responses in WASp-deficient cells have been interpreted to mean that
WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an
exception to this concept and show that WASp-deficient dendritic cells have increased
activation of Rac2 that support cross-presentation to CD8þ T cells. Using two different skin
pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin
and increased expansion of IFNg-producing CD8þ T cells in the draining lymph node and
spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8þ
T cells at the expense of CD4þ T cells. WASp-deficient dendritic cells induce increased
cross-presentation to CD8þ T cells by activating Rac2 that maintains a near neutral pH of
phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2
signalling pathways in dendritic cells.
KW  - Cell signalling
KW  - Dendritic cells
KW  - Disease genetics
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165966
VL  - 7
ER  - 
TY  - JOUR
A1  - Knorr, Johannes
A1  - Sokkar, Pandian
A1  - Schott, Sebastian
A1  - Costa, Paolo
A1  - Thiel, Walter
A1  - Sander, Wolfram
A1  - Sanchez-Garcia, Elsa
A1  - Nuernberger, Patrick
T1  - Competitive solvent-molecule interactions govern primary processes of diphenylcarbene in solvent mixtures
JF  - Nature Communications
N2  - Photochemical reactions in solution often proceed via competing reaction pathways
comprising intermediates that capture a solvent molecule. A disclosure of the underlying
reaction mechanisms is challenging due to the rapid nature of these processes and the
intricate identification of how many solvent molecules are involved. Here combining
broadband femtosecond transient absorption and quantum mechanics/molecular mechanics
simulations, we show for one of the most reactive species, diphenylcarbene, that the
decision-maker is not the nearest solvent molecule but its neighbour. The hydrogen bonding
dynamics determine which reaction channels are accessible in binary solvent mixtures at
room temperature. In-depth analysis of the amount of nascent intermediates corroborates
the importance of a hydrogen-bonded complex with a protic solvent molecule, in striking
analogy to complexes found at cryogenic temperatures. Our results show that adjacent
solvent molecules take the role of key abettors rather than bystanders for the fate of the
reactive intermediate.
KW  - Reaction kinetics and dynamics
KW  - Photochemistry
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165954
VL  - 7
ER  - 
TY  - JOUR
A1  - Wawra, Stephan
A1  - Fesel, Philipp
A1  - Widmer, Heidi
A1  - Timm, Malte
A1  - Seibel, Jürgen
A1  - Leson, Lisa
A1  - Kesseler, Leona
A1  - Nostadt, Robin
A1  - Hilbert, Magdalena
A1  - Langen, Gregor
A1  - Zuccaro, Alga
T1  - The fungal-specific beta-glucan-binding lectin FGB1 alters cell-wall composition and suppresses glucan-triggered immunity in plants
JF  - Nature Communications
N2  - β-glucans are well-known modulators of the immune system in mammals but little is known about β-glucan triggered immunity in planta. Here we show by isothermal titration calorimetry, circular dichroism spectroscopy and nuclear magnetic resonance spectroscopy that the FGB1 gene from the root endophyte Piriformospora indica encodes for a secreted fungal-specific β-glucan-binding lectin with dual function. This lectin has the potential to both alter fungal cell wall composition and properties, and to efficiently suppress β-glucan-triggered immunity in different plant hosts, such as Arabidopsis, barley and Nicotiana benthamiana. Our results hint at the existence of fungal effectors that deregulate innate sensing of β-glucan in plants.
KW  - Effectors in plant pathology
KW  - Fungal host response
KW  - Lectins
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165945
VL  - 7
ER  - 
TY  - JOUR
A1  - Goméz-H, Laura
A1  - Felipe-Medina, Natalia
A1  - Sánchez-Martín, Manuel
A1  - Davies, Owen R.
A1  - Ramos, Isabel
A1  - García-Tuñón, Ignacio
A1  - de Rooij, Dirk G.
A1  - Dereli, Ihsan
A1  - Tóth, Attila
A1  - Barbero, José Luis
A1  - Benavente, Ricardo
A1  - Llano, Elena
A1  - Pendas, Alberto M.
T1  - C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility
JF  - Nature Communications
N2  - Meiotic recombination generates crossovers between homologous chromosomes that are essential for genome haploidization. The synaptonemal complex is a ‘zipper’-like protein assembly that synapses homologue pairs together and provides the structural framework for processing recombination sites into crossovers. Humans show individual differences in the number of crossovers generated across the genome. Recently, an anonymous gene variant in C14ORF39/SIX6OS1 was identified that influences the recombination rate in humans. Here we show that C14ORF39/SIX6OS1 encodes a component of the central element of the synaptonemal complex. Yeast two-hybrid analysis reveals that SIX6OS1 interacts with the well-established protein synaptonemal complex central element 1 (SYCE1). Mice lacking SIX6OS1 are defective in chromosome synapsis at meiotic prophase I, which provokes an arrest at the pachytene-like stage and results in infertility. In accordance with its role as a modifier of the human recombination rate, SIX6OS1 is essential for the appropriate processing of intermediate recombination nodules before crossover formation.
KW  - Chromosomes
KW  - Meiosis
KW  - Spermatogenesis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165907
VL  - 7
ER  -