TY - JOUR A1 - Estrada, Veronica A1 - Krebbers, Julia A1 - Voss, Christian A1 - Brazda, Nicole A1 - Blazyca, Heinrich A1 - Illgen, Jennifer A1 - Seide, Klaus A1 - Jürgens, Christian A1 - Müller, Jörg A1 - Martini, Rudolf A1 - Trieu, Hoc Khiem A1 - Müller, Hans Werner T1 - Low-pressure micro-mechanical re-adaptation device sustainably and effectively improves locomotor recovery from complete spinal cord injury JF - Communications Biology N2 - Traumatic spinal cord injuries result in impairment or even complete loss of motor, sensory and autonomic functions. Recovery after complete spinal cord injury is very limited even in animal models receiving elaborate combinatorial treatments. Recently, we described an implantable microsystem (microconnector) for low-pressure re-adaption of severed spinal stumps in rat. Here we investigate the long-term structural and functional outcome following microconnector implantation after complete spinal cord transection. Re-adaptation of spinal stumps supports formation of a tissue bridge, glial and vascular cell invasion, motor axon regeneration and myelination, resulting in partial recovery of motor-evoked potentials and a thus far unmet improvement of locomotor behaviour. The recovery lasts for at least 5 months. Despite a late partial decline, motor recovery remains significantly superior to controls. Our findings demonstrate that microsystem technology can foster long-lasting functional improvement after complete spinal injury, providing a new and effective tool for combinatorial therapies. KW - implants KW - preclinical research KW - spinal cord injury Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227357 VL - 1 ER - TY - JOUR A1 - Dunce, James M. A1 - Milburn, Amy E. A1 - Gurusaran, Manickam A1 - da Cruz, Irene A1 - Sen, Lee T. A1 - Benavente, Ricardo A1 - Davies, Owen R. T1 - Structural basis of meiotic telomere attachment to the nuclear envelope by MAJIN-TERB2-TERB1 JF - Nature Communications N2 - Meiotic chromosomes undergo rapid prophase movements, which are thought to facilitate the formation of inter-homologue recombination intermediates that underlie synapsis, crossing over and segregation. The meiotic telomere complex (MAJIN, TERB1, TERB2) tethers telomere ends to the nuclear envelope and transmits cytoskeletal forces via the LINC complex to drive these rapid movements. Here, we report the molecular architecture of the meiotic telomere complex through the crystal structure of MAJIN-TERB2, together with light and X-ray scattering studies of wider complexes. The MAJIN-TERB2 2:2 hetero-tetramer binds strongly to DNA and is tethered through long flexible linkers to the inner nuclear membrane and two TRF1-binding 1:1 TERB2-TERB1 complexes. Our complementary structured illumination microscopy studies and biochemical findings reveal a telomere attachment mechanism in which MAJIN-TERB2-TERB1 recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA and form a mature attachment plate. KW - DNA KW - meiosis KW - proteins KW - super-resolution microscopy KW - X-ray crystallography Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226416 VL - 9 ER - TY - JOUR A1 - Dubail, Johanne A1 - Huber, Céline A1 - Chantepie, Sandrine A1 - Sonntag, Stephan A1 - Tüysüz, Beyhan A1 - Mihci, Ercan A1 - Gordon, Christopher T. A1 - Steichen-Gersdorf, Elisabeth A1 - Amiel, Jeanne A1 - Nur, Banu A1 - Stolte-Dijkstra, Irene A1 - van Eerde, Albertien M. A1 - van Gassen, Koen L. A1 - Breugem, Corstiaan C. A1 - Stegmann, Alexander A1 - Lekszas, Caroline A1 - Maroofian, Reza A1 - Karimiani, Ehsan Ghayoor A1 - Bruneel, Arnaud A1 - Seta, Nathalie A1 - Munnich, Arnold A1 - Papy-Garcia, Dulce A1 - De La Dure-Molla, Muriel A1 - Cormier-Daire, Valérie T1 - SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects JF - Nature Communications N2 - Skeletal dysplasia with multiple dislocations are severe disorders characterized by dislocations of large joints and short stature. The majority of them have been linked to pathogenic variants in genes encoding glycosyltransferases, sulfotransferases or epimerases required for glycosaminoglycan synthesis. Using exome sequencing, we identify homozygous mutations in SLC10A7 in six individuals with skeletal dysplasia with multiple dislocations and amelogenesis imperfecta. SLC10A7 encodes a 10-transmembrane-domain transporter located at the plasma membrane. Functional studies in vitro demonstrate that SLC10A7 mutations reduce SLC10A7 protein expression. We generate a Slc10a7−/− mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype. Furthermore, we identify decreased heparan sulfate levels in Slc10a7−/− mouse cartilage and patient fibroblasts. Finally, we find an abnormal N-glycoprotein electrophoretic profile in patient blood samples. Together, our findings support the involvement of SLC10A7 in glycosaminoglycan synthesis and specifically in skeletal development. KW - bone development KW - disease genetics KW - medical genetics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226377 VL - 9 ER - TY - JOUR A1 - Dostál, Jakub A1 - Fennel, Franziska A1 - Koch, Federico A1 - Herbst, Stefanie A1 - Würthner, Frank A1 - Brixner, Tobias T1 - Direct observation of exciton–exciton interactions JF - Nature Communications N2 - Natural light harvesting as well as optoelectronic and photovoltaic devices depend on efficient transport of energy following photoexcitation. Using common spectroscopic methods, however, it is challenging to discriminate one-exciton dynamics from multi-exciton interactions that arise when more than one excitation is present in the system. Here we introduce a coherent two-dimensional spectroscopic method that provides a signal only in case that the presence of one exciton influences the behavior of another one. Exemplarily, we monitor exciton diffusion by annihilation in a perylene bisimide-based J-aggregate. We determine quantitatively the exciton diffusion constant from exciton–exciton-interaction 2D spectra and reconstruct the annihilation-free dynamics for large pump powers. The latter enables for ultrafast spectroscopy at much higher intensities than conventionally possible and thus improves signal-to-noise ratios for multichromophore systems; the former recovers spatio–temporal dynamics for a broad range of phenomena in which exciton interactions are present. KW - energy transfer KW - self-assembly KW - optical spectroscopy Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226271 VL - 9 ER - TY - JOUR A1 - Dindas, Julian A1 - Scherzer, Sönke A1 - Roelfsema, M. Rob G. A1 - Meyer, Katharina von A1 - Müller, Heike M. A1 - Al-Rasheid, K. A. S. A1 - Palme, Klaus A1 - Dietrich, Petra A1 - Becker, Dirk A1 - Bennett, Malcolm J. A1 - Hedrich, Rainer T1 - AUX1-mediated root hair auxin influx governs SCFTIR1/AFB-type Ca2+ signaling JF - Nature Communications N2 - Auxin is a key regulator of plant growth and development, but the causal relationship between hormone transport and root responses remains unresolved. Here we describe auxin uptake, together with early steps in signaling, in Arabidopsis root hairs. Using intracellular microelectrodes we show membrane depolarization, in response to IAA in a concentration- and pH-dependent manner. This depolarization is strongly impaired in aux1 mutants, indicating that AUX1 is the major transporter for auxin uptake in root hairs. Local intracellular auxin application triggers Ca2+ signals that propagate as long-distance waves between root cells and modulate their auxin responses. AUX1-mediated IAA transport, as well as IAA- triggered calcium signals, are blocked by treatment with the SCFTIR1/AFB - inhibitor auxinole. Further, they are strongly reduced in the tir1afb2afb3 and the cngc14 mutant. Our study reveals that the AUX1 transporter, the SCFTIR1/AFB receptor and the CNGC14 Ca2+ channel, mediate fast auxin signaling in roots. KW - auxin KW - permeation and transport Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225368 VL - 9 ER - TY - JOUR A1 - de Jong, Simone A1 - Diniz, Mateus Jose Abdalla A1 - Saloma, Andiara A1 - Gadelha, Ary A1 - Santoro, Marcos L. A1 - Ota, Vanessa K. A1 - Noto, Cristiano A1 - Curtis, Charles A1 - Newhouse, Stephen J. A1 - Patel, Hamel A1 - Hall, Lynsey S. A1 - O'Reilly, Paul F. A1 - Belangero, Sintia I. A1 - Bressan, Rodrigo A. A1 - Breen, Gerome T1 - Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder JF - Communications Biology N2 - Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders. KW - bipolar disorder KW - depression KW - genetic association study KW - genetic linkage study Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223622 VL - 1 ER - TY - JOUR A1 - Ciuchi, Sergio A1 - Di Sante, Domenico A1 - Dobrosavljević, Vladimir A1 - Fratini, Simone T1 - The origin of Mooij correlations in disordered metals JF - npj Quantum Materials N2 - Sufficiently disordered metals display systematic deviations from the behavior predicted by semi-classical Boltzmann transport theory. Here the scattering events from impurities or thermal excitations can no longer be considered as additive-independent processes, as asserted by Matthiessen’s rule following from this picture. In the intermediate region between the regime of good conduction and that of insulation, one typically finds a change of sign of the temperature coefficient of resistivity, even at elevated temperature spanning ambient conditions, a phenomenology that was first identified by Mooij in 1973. Traditional weak coupling approaches to identify relevant corrections to the Boltzmann picture focused on long-distance interference effects such as “weak localization”, which are especially important in low dimensions (1D and 2D) and close to the zero-temperature limit. Here we formulate a strong-coupling approach to tackle the interplay of strong disorder and lattice deformations (phonons) in bulk three-dimensional metals at high temperatures. We identify a polaronic mechanism of strong disorder renormalization, which describes how a lattice locally responds to the relevant impurity potential. This mechanism, which quantitatively captures the Mooij regime, is physically distinct and unrelated to Anderson localization, but realizes early seminal ideas of Anderson himself, concerning the interplay of disorder and lattice deformations. KW - electronic properties and materials KW - phase transitions and critical phenomena KW - theory and computation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223148 VL - 3 ER - TY - JOUR A1 - China, Swarup A1 - Burrows, Susannah M. A1 - Wang, Bingbing A1 - Harder, Tristan H. A1 - Weis, Johannes A1 - Tanarhte, Meryem A1 - Rizzo, Luciana V. A1 - Brito, Joel A1 - Cirino, Glauber G. A1 - Ma, Po-Lun A1 - Cliff, John A1 - Artaxo, Paulo A1 - Gilles, Mary K. A1 - Laskin, Alexander T1 - Fungal spores as a source of sodium salt particles in the Amazon basin JF - Nature Communications N2 - In the Amazon basin, particles containing mixed sodium salts are routinely observed and are attributed to marine aerosols transported from the Atlantic Ocean. Using chemical imaging analysis, we show that, during the wet season, fungal spores emitted by the forest biosphere contribute at least 30% (by number) to sodium salt particles in the central Amazon basin. Hydration experiments indicate that sodium content in fungal spores governs their growth factors. Modeling results suggest that fungal spores account for ~69% (31–95%) of the total sodium mass during the wet season and that their fractional contribution increases during nighttime. Contrary to common assumptions that sodium-containing aerosols originate primarily from marine sources, our results suggest that locally-emitted fungal spores contribute substantially to the number and mass of coarse particles containing sodium. Hence, their role in cloud formation and contribution to salt cycles and the terrestrial ecosystem in the Amazon basin warrant further consideration. KW - atmospheric chemistry KW - biogeochemistry KW - environmental sciences Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222492 VL - 9 ER - TY - JOUR A1 - Castilho, Miguel A1 - Hochleitner, Gernot A1 - Wilson, Wouter A1 - van Rietbergen, Bert A1 - Dalton, Paul D. A1 - Groll, Jürgen A1 - Malda, Jos A1 - Ito, Keita T1 - Mechanical behavior of a soft hydrogel reinforced with three-dimensional printed microfibre scaffolds JF - Scientific Reports N2 - Reinforcing hydrogels with micro-fibre scaffolds obtained by a Melt-Electrospinning Writing (MEW) process has demonstrated great promise for developing tissue engineered (TE) constructs with mechanical properties compatible to native tissues. However, the mechanical performance and reinforcement mechanism of the micro-fibre reinforced hydrogels is not yet fully understood. In this study, FE models, implementing material properties measured experimentally, were used to explore the reinforcement mechanism of fibre-hydrogel composites. First, a continuum FE model based on idealized scaffold geometry was used to capture reinforcement effects related to the suppression of lateral gel expansion by the scaffold, while a second micro-FE model based on micro-CT images of the real construct geometry during compaction captured the effects of load transfer through the scaffold interconnections. Results demonstrate that the reinforcement mechanism at higher scaffold volume fractions was dominated by the load carrying-ability of the fibre scaffold interconnections, which was much higher than expected based on testing scaffolds alone because the hydrogel provides resistance against buckling of the scaffold. We propose that the theoretical understanding presented in this work will assist the design of more effective composite constructs with potential applications in a wide range of TE conditions. KW - biomedical engineering KW - biomedical materials KW - gels and hydrogels Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222280 VL - 8 ER - TY - JOUR A1 - Carradec, Quentin A1 - Pelletier, Eric A1 - Da Silva, Corinne A1 - Alberti, Adriana A1 - Seeleuthner, Yoann A1 - Blanc-Mathieu, Romain A1 - Lima-Mendez, Gipsi A1 - Rocha, Fabio A1 - Tirichine, Leila A1 - Labadie, Karine A1 - Kirilovsky, Amos A1 - Bertrand, Alexis A1 - Engelen, Stefan A1 - Madoui, Mohammed-Amin A1 - Méheust, Raphaël A1 - Poulain, Julie A1 - Romac, Sarah A1 - Richter, Daniel J. A1 - Yoshikawa, Genki A1 - Dimier, Céline A1 - Kandels-Lewis, Stefanie A1 - Picheral, Marc A1 - Searson, Sarah A1 - Jaillon, Olivier A1 - Aury, Jean-Marc A1 - Karsenti, Eric A1 - Sullivan, Matthew B. A1 - Sunagawa, Shinichi A1 - Bork, Peer A1 - Not, Fabrice A1 - Hingamp, Pascal A1 - Raes, Jeroen A1 - Guidi, Lionel A1 - Ogata, Hiroyuki A1 - de Vargas, Colomban A1 - Iudicone, Daniele A1 - Bowler, Chris A1 - Wincker, Patrick T1 - A global ocean atlas of eukaryotic gene JF - Nature Communications N2 - While our knowledge about the roles of microbes and viruses in the ocean has increased tremendously due to recent advances in genomics and metagenomics, research on marine microbial eukaryotes and zooplankton has benefited much less from these new technologies because of their larger genomes, their enormous diversity, and largely unexplored physiologies. Here, we use a metatranscriptomics approach to capture expressed genes in open ocean Tara Oceans stations across four organismal size fractions. The individual sequence reads cluster into 116 million unigenes representing the largest reference collection of eukaryotic transcripts from any single biome. The catalog is used to unveil functions expressed by eukaryotic marine plankton, and to assess their functional biogeography. Almost half of the sequences have no similarity with known proteins, and a great number belong to new gene families with a restricted distribution in the ocean. Overall, the resource provides the foundations for exploring the roles of marine eukaryotes in ocean ecology and biogeochemistry. KW - genomics KW - marine biology KW - microbial ecology KW - water microbiology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222250 VL - 9 ER - TY - JOUR A1 - Brunk, Michael A1 - Sputh, Sebastian A1 - Doose, Sören A1 - van de Linde, Sebastian A1 - Terpitz, Ulrich T1 - HyphaTracker: An ImageJ toolbox for time-resolved analysis of spore germination in filamentous fungi JF - Scientific Reports N2 - The dynamics of early fungal development and its interference with physiological signals and environmental factors is yet poorly understood. Especially computational analysis tools for the evaluation of the process of early spore germination and germ tube formation are still lacking. For the time-resolved analysis of conidia germination of the filamentous ascomycete Fusarium fujikuroi we developed a straightforward toolbox implemented in ImageJ. It allows for processing of microscopic acquisitions (movies) of conidial germination starting with drift correction and data reduction prior to germling analysis. From the image time series germling related region of interests (ROIs) are extracted, which are analysed for their area, circularity, and timing. ROIs originating from germlings crossing other hyphae or the image boundaries are omitted during analysis. Each conidium/hypha is identified and related to its origin, thus allowing subsequent categorization. The efficiency of HyphaTracker was proofed and the accuracy was tested on simulated germlings at different signal-to-noise ratios. Bright-field microscopic images of conidial germination of rhodopsin-deficient F. fujikuroi mutants and their respective control strains were analysed with HyphaTracker. Consistent with our observation in earlier studies the CarO deficient mutant germinated earlier and grew faster than other, CarO expressing strains. KW - bioinformatics KW - cell growth KW - fungal biology KW - microscopy Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221691 VL - 8 ER - TY - JOUR A1 - Bruchhagen, Christin A1 - Jarick, Marcel A1 - Mewis, Carolin A1 - Hertlein, Tobias A1 - Niemann, Silke A1 - Ohlsen, Knut A1 - Peters, Georg A1 - Planz, Oliver A1 - Ludwig, Stephan A1 - Ehrhardt, Christina T1 - Metabolic conversion of CI-1040 turns a cellular MEK-inhibitor into an antibacterial compound JF - Scientific Reports N2 - Influenza virus (IV) infections cause severe respiratory illnesses that can be complicated by bacterial super-infections. Previously, we identified the cellular Raf-MEK-ERK cascade as a promising antiviral target. Inhibitors of MEK, such as CI-1040, showed potent antiviral activity. However, it remained unclear if this inhibitor and its active form, ATR-002, might sensitize host cells to either IV or secondary bacterial infections. To address these questions, we studied the anti-pathogen activity of ATR-002 in comparison to CI-1040, particularly, its impact on Staphylococcus aureus (S. aureus), which is a major cause of IV super-infections. We analysed IV and S. aureus titres in vitro during super-infection in the presence and absence of the drugs and characterized the direct impact of ATR-002 on bacterial growth and phenotypic changes. Importantly, neither CI-1040 nor ATR-002 treatment led to increased bacterial titres during super-infection, indicating that the drug does not sensitize cells for bacterial infection. In contrast, we rather observed reduced bacterial titres in presence of ATR-002. Surprisingly, ATR-002 also led to reduced bacterial growth in suspension cultures, reduced stress- and antibiotic tolerance without resistance induction. Our data identified for the first time that a particular MEK-inhibitor metabolite exhibits direct antibacterial activity, which is likely due to interference with the bacterial PknB kinase/Stp phosphatase signalling system. KW - antimicrobials KW - pathogens Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221648 VL - 8 ER - TY - JOUR A1 - Anany, Mohamed A. A1 - Kreckel, Jennifer A1 - Füllsack, Simone A1 - Rosenthal, Alevtina A1 - Otto, Christoph A1 - Siegmund, Daniela A1 - Wajant, Harald T1 - Soluble TNF-like weak inducer of apoptosis (TWEAK) enhances poly(I:C)-induced RIPK1-mediated necroptosis JF - Cell Death & Disease N2 - TNF-like weak inducer of apoptosis (TWEAK) and inhibition of protein synthesis with cycloheximide (CHX) sensitize for poly(I:C)-induced cell death. Notably, although CHX preferentially enhanced poly(I:C)-induced apoptosis, TWEAK enhanced primarily poly(I:C)-induced necroptosis. Both sensitizers of poly(I:C)-induced cell death, however, showed no major effect on proinflammatory poly(I:C) signaling. Analysis of a panel of HeLa-RIPK3 variants lacking TRADD, RIPK1, FADD, or caspase-8 expression revealed furthermore similarities and differences in the way how poly(I:C)/TWEAK, TNF, and TRAIL utilize these molecules for signaling. RIPK1 turned out to be essential for poly(I:C)/TWEAK-induced caspase-8-mediated apoptosis but was dispensable for this response in TNF and TRAIL signaling. TRADD-RIPK1-double deficiency differentially affected poly(I:C)-triggered gene induction but abrogated gene induction by TNF completely. FADD deficiency abrogated TRAIL- but not TNF- and poly(I:C)-induced necroptosis, whereas TRADD elicited protective activity against all three death inducers. A general protective activity against poly(I:C)-, TRAIL-, and TNF-induced cell death was also observed in FLIPL and FLIPS transfectrants. Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221104 VL - 9 ER - TY - JOUR A1 - Albrecht, Jörg A1 - Classen, Alice A1 - Vollstädt, Maximilian G.R. A1 - Mayr, Antonia A1 - Mollel, Neduvoto P. A1 - Schellenberger Costa, David A1 - Dulle, Hamadi I. A1 - Fischer, Markus A1 - Hemp, Andreas A1 - Howell, Kim M. A1 - Kleyer, Michael A1 - Nauss, Thomas A1 - Peters, Marcell K. A1 - Tschapka, Marco A1 - Steffan-Dewenter, Ingolf A1 - Böhning-Gaese, Katrin A1 - Schleuning, Matthias T1 - Plant and animal functional diversity drive mutualistic network assembly across an elevational gradient JF - Nature Communications N2 - Species' functional traits set the blueprint for pair-wise interactions in ecological networks. Yet, it is unknown to what extent the functional diversity of plant and animal communities controls network assembly along environmental gradients in real-world ecosystems. Here we address this question with a unique dataset of mutualistic bird-fruit, bird-flower and insect-flower interaction networks and associated functional traits of 200 plant and 282 animal species sampled along broad climate and land-use gradients on Mt. Kilimanjaro. We show that plant functional diversity is mainly limited by precipitation, while animal functional diversity is primarily limited by temperature. Furthermore, shifts in plant and animal functional diversity along the elevational gradient control the niche breadth and partitioning of the respective other trophic level. These findings reveal that climatic constraints on the functional diversity of either plants or animals determine the relative importance of bottom-up and top-down control in plant-animal interaction networks. KW - Traits-Environment Relationships KW - Species Traits KW - Ecological Networks KW - 4TH-Corner Problem KW - Multiple Traits KW - Bottom-up KW - Biodiversity KW - Community ecology KW - Ecological networks KW - Ecology KW - Ecosystem ecology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221056 VL - 9 ER - TY - JOUR T1 - Long-term monitoring of the ANTARES optical module efficiencies using \(^{40}\)K decays in sea water JF - European Physical Journal C N2 - Cherenkov light induced by radioactive decay products is one of the major sources of background light for deep-sea neutrino telescopes such as ANTARES. These decays are at the same time a powerful calibration source. Using data collected by the ANTARES neutrino telescope from mid 2008 to 2017, the time evolution of the photon detection efficiency of optical modules is studied. A modest loss of only 20% in 9 years is observed. The relative time calibration between adjacent modules is derived as well. KW - Neutrino Telescope KW - Dark-Matter KW - Calibration KW - System KW - Light Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227815 VL - 78 ER - TY - JOUR T1 - Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials JF - Lancet Oncology N2 - Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21.4% for NACT versus 15.9% for adjuvant chemotherapy (5.5% increase [95% CI 2.4-8.6]; rate ratio 1.37 [95% CI 1.17-1.61]; p = 0.0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38.2% for NACT vs 38.0% for adjuvant chemotherapy; rate ratio 1.02 [95% CI 0.92-1.14]; p = 0.66), breast cancer mortality (34.4% vs 33.7%; 1.06 [0.95-1.18]; p = 0.31), or death from any cause (40.9% vs 41.2%; 1.04 [0.94-1.15]; p = 0.45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. Copyright (c) The Author(s). Published by Elsevier Ltd. KW - Stimulating factor KW - Therapy KW - Methotrexate KW - Radiotherapy KW - Survival KW - Surgery Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227782 VL - 19 IS - 1 ER - TY - JOUR T1 - Characterisation of the Hamamatsu photomultipliers for the KM3NeT Neutrino Telescope JF - Journal of Instrumentation N2 - The Hamamatsu R12199-023-inch photomultiplier tube is the photodetector chosen for the first phase of the KM3NeT neutrino telescope. About 7000 photomultipliers have been characterised for dark count rate, timing spread and spurious pulses. The quantum efficiency, the gain and the peak-to-valley ratio have also been measured for a sub-sample in order to determine parameter values needed as input to numerical simulations of the detector. KW - Cherenkov detectors KW - Large detector systems for particle and astroparticle physics KW - Neutrino detectors KW - Photon detectors for UV, visible and IR photons (vacuum) KW - Prototype Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227744 VL - 13 ER - TY - JOUR A1 - Abt, Raimond A1 - Erdmenger, Johanna T1 - Properties of modular Hamiltonians on entanglement plateaux JF - Journal of High Energy Physics N2 - The modular Hamiltonian of reduced states, given essentially by the logarithm of the reduced density matrix, plays an important role within the AdS/CFT correspondence in view of its relation to quantum information. In particular, it is an essential ingredient for quantum information measures of distances between states, such as the relative entropy and the Fisher information metric. However, the modular Hamiltonian is known explicitly only for a few examples. For a family of states rho(lambda) that is parametrized by a scalar lambda, the first order contribution in (lambda) over tilde = lambda-lambda(0) of the modular Hamiltonian to the relative entropy between rho(lambda) and a reference state rho(lambda 0) is completely determined by the entanglement entropy, via the first law of entanglement. For several examples, e.g. for ball-shaped regions in the ground state of CFTs, higher order contributions are known to vanish. In these cases the modular Hamiltonian contributes to the Fisher information metric in a trivial way. We investigate under which conditions the modular Hamiltonian provides a non-trivial contribution to the Fisher information metric, i.e. when the contribution of the modular Hamiltonian to the relative entropy is of higher order in (lambda) over tilde. We consider one-parameter families of reduced states on two entangling regions that form an entanglement plateau, i.e. the entanglement entropies of the two regions saturate the Araki-Lieb inequality. We show that in general, at least one of the relative entropies of the two entangling regions is expected to involve (lambda) over tilde contributions of higher order from the modular Hamiltonian. Furthermore, we consider the implications of this observation for prominent AdS/CFT examples that form entanglement plateaux in the large N limit. KW - AdS-CFT Correspondence KW - Gauge-gravity correspondence KW - Conformal Field Theory KW - Relative Entropy KW - Complexity Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227693 VL - 11 IS - 2 ER - TY - JOUR A1 - Klenke, Daniela A1 - Quast, Anja A1 - Prelog, Martina A1 - Holl-Wieden, Annette A1 - Riekert, Maximilian A1 - Stellzig-Eisenhauer, Angelika A1 - Meyer-Marcotty, Philipp T1 - TMJ pathomorphology in patients with JIA-radiographic parameters for early diagnosis- JF - Head & Face Medicine N2 - Background Juvenile idiopathic arthritis (JIA) is often accompanied by pathomorphological changes to the temporomandibular joint (TMJ). By analyzing orthodontical orthopantomograms of JIA patients the aims of the study were a) classification of condyle changes, b) quantification of bony asymmetries of condylar destruction and c) detection of relationships between disease duration and TMJ-involvement. Patients/Methods 46 caucasian JIA-patients (28 female; 18 male; < 16.0 years) were enrolled, each joint (n = 92) was morphologically assessed by means of orthopantomogram, quantitatively analysed and compared with duration of general disease. Condyle morphology was assessed using the Billiau scale for severity of destruction [1]. The quantitative analysis was based on ratios of condyle, ramus and mandible height. Results Patients were divided into groups (Group I – slightly affected, n = 36; Billiau severity 0–2; condyle findings: X-ray normal, condyle erosions, condylar flattening; Group II – severely affected, N = 10; Billiau severity 3–4; condyle findings: condylar flattenings and erosions, unilateral/bilateral complete loss of condyles), based on morphological analysis of condylar destruction. Duration of disease was significantly longer in Group II (8.9 ± 5.2 years) than in Group I (4.6 ± 4.7 years). Asymmetries of condyle, ramus and mandible height, quantitatively analysed by contralateral comparison, were significantly more marked in patients of Group II than of Group I. Conclusions Orthopantomogram imaging can be used in orthodontics clinical routine to detect TMJ-pathologies and is an important reference for monitoring progression of JIA. Classification into severe and slightly affected TMJ is possible by analysis of condylar pathomorphology. An association between degree of destruction, extent of lower jaw asymmetry and disease duration is suggested by the results. KW - juvenile idiopathic arthritis KW - TMJ KW - OPT KW - asymmetry KW - condyle pathomorphology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325882 VL - 14 ER - TY - JOUR A1 - Semler, Elisa A1 - Anderl-Straub, Sarah A1 - Uttner, Ingo A1 - Diehl-Schmid, Janine A1 - Danek, Adrian A1 - Einsiedler, Beate A1 - Fassbender, Klaus A1 - Fliessbach, Klaus A1 - Huppertz, Hans-Jürgen A1 - Jahn, Holger A1 - Kornhuber, Johannes A1 - Landwehrmeyer, Bernhard A1 - Lauer, Martin A1 - Muche, Rainer A1 - Prudlo, Johannes A1 - Schneider, Anja A1 - Schroeter, Matthias L. A1 - Ludolph, Albert C. A1 - Otto, Markus T1 - A language-based sum score for the course and therapeutic intervention in primary progressive aphasia JF - Alzheimer's Research & Therapy N2 - Background With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions. Methods We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials. Results Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures. Conclusion Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies. KW - frontotemporal dementia KW - cognitive neuropsychology in dementia KW - assessment of cognitive disorders/dementia KW - volumetric MRI KW - aphasia Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236277 VL - 10 ER -