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    Natürliche Sprachverarbeitung für das Expertensystem ScienceAtlas 

    Funk, Stefan E.
    Georg-August-Universität Göttingen, 2004
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    bFGF-mediated pluripotency maintenance in human induced pluripotent stem cells is associated with NRAS-MAPK signaling 

    Haghighi, Fereshteh; Dahlmann, Julia; Nakhaei-Rad, Saeideh; Lang, Alexander; Kutschka, Ingo; Zenker, Martin; Kensah, George; Piekorz, Roland P; Ahmadian, Mohammad R
    2018; 16(1): Art. 96
    Abstract Background Human pluripotent stem cells (PSCs) open new windows for basic research and regenerative medicine due to their remarkable properties, i.e. their ability to self-renew indefinitely and being pluripotent. There are different, conflicting data related to the role of basic fibroblast growth factor (bFGF) in intracellular signal transduction and the regulation of pluripotency of PSCs. Here, we investigated the effect of bFGF and its downstream pathways in pluripotent vs. differentiated human induced (hi) PSCs. Methods bFGF downstream signaling pathways were investigated in long-term culture of hiPSCs from pluripotent to differentiated state (withdrawing bFGF) using immunoblotting, immunocytochemistry and qPCR. Subcellular distribution of signaling components were investigated by simple fractionation and immunoblotting upon bFGF stimulation. Finally, RAS activity and RAS isoforms were studied using RAS assays both after short- and long-term culture in response to bFGF stimulation. Results Our results revealed that hiPSCs were differentiated into the ectoderm lineage upon withdrawing bFGF as an essential pluripotency mediator. Pluripotency markers OCT4, SOX2 and NANOG were downregulated, following a drastic decrease in MAPK pathway activity levels. Notably, a remarkable increase in phosphorylation levels of p38 and JAK/STAT3 was observed in differentiated hiPSCs, while the PI3K/AKT and JNK pathways remained active during differentiation. Our data further indicate that among the RAS paralogs, NRAS predominantly activates the MAPK pathway in hiPSCs. Conclusion Collectively, the MAPK pathway appears to be the prime signaling pathway downstream of bFGF for maintaining pluripotency in hiPSCs and among the MAPK pathways, the activity of NRAS-RAF-MEK-ERK is decreased during differentiation, whereas p38 is activated and JNK remains constant.
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    A two-step immunoassay for the simultaneous assessment of Aβ38, Aβ40 and Aβ42 in human blood plasma supports the Aβ42/Aβ40 ratio as a promising biomarker candidate of Alzheimer’s disease 

    Shahpasand-Kroner, Hedieh; Klafki, Hans-W.; Bauer, Chris; Schuchhardt, Johannes; Hüttenrauch, Melanie; Stazi, Martina; Bouter, Caroline; Wirths, Oliver; Vogelgsang, Jonathan; Wiltfang, Jens
    2018; 10(1): Art. 121
    Abstract Background The quantification of amyloid-beta (Aβ) peptides in blood plasma as potential biomarkers of Alzheimer’s disease (AD) is hampered by very low Aβ concentrations and the presence of matrix components that may interfere with the measurements. Methods We developed a two-step immunoassay for the simultaneous measurement of the relative levels of Aβ38, Aβ40 and Aβ42 in human EDTA plasma. The assay was employed for the study of 23 patients with dementia of the Alzheimer’s type (AD-D) and 17 patients with dementia due to other reasons (OD). We examined relationships with the clinical diagnosis, cerebral Aβ load as quantified by amyloid-positron emission tomography, apolipoprotein E genotype, Aβ levels and Tau protein in cerebrospinal fluid. Results Preconcentration of plasma Aβ peptides by immunoprecipitation substantially facilitated their immunological measurements. The Aβ42/Aβ40 and Aβ42/Aβ38 ratios were statistically significantly lower in the AD-D patients than in the OD group. The areas under the receiver operating characteristic curves reached 0.87 for the Aβ42/Aβ40 ratio and 0.80 for the Aβ42/Aβ38 ratio. Conclusions The measurement of plasma Aβ peptides with an immunological assay can be improved by preconcentration via immunoprecipitation with an antibody against the Aβ amino-terminus and elution of the captured peptides by heating in a mild detergent-containing buffer. Our findings support the Aβ42/Aβ40 ratio in blood plasma as a promising AD biomarker candidate which correlates significantly with the validated core biomarkers of AD. Further studies will be needed for technical advancement of the assay and validation of the biomarker findings.
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    RAD-seq reveals genetic structure of the F2-generation of natural willow hybrids (Salix L.) and a great potential for interspecific introgression 

    Gramlich, Susanne; Wagner, Natascha D; Hörandl, Elvira
    2018; 18(1): Art. 317
    Abstract Background Hybridization of species with porous genomes can eventually lead to introgression via repeated backcrossing. The potential for introgression between species is reflected by the extent of segregation distortion in later generation hybrids. Here we studied a population of hybrids between Salix purpurea and S. helvetica that has emerged within the last 30 years on a glacier forefield in the European Alps due to secondary contact of the parental species. We used 5758 biallelic SNPs produced by RAD sequencing with the aim to ascertain the predominance of backcrosses (F1 hybrid x parent) or F2 hybrids (F1 hybrid x F1 hybrid) among hybrid offspring. Further, the SNPs were used to study segregation distortion in the second hybrid generation. Results The analyses in structure and NewHybrids revealed that the population consisted of parents and F1 hybrids, whereas hybrid offspring consisted mainly of backcrosses to either parental species, but also some F2 hybrids. Although there was a clear genetic differentiation between S. purpurea and S. helvetica (FST = 0.24), there was no significant segregation distortion in the backcrosses or the F2 hybrids. Plant height of the backcrosses resembled the respective parental species, whereas F2 hybrids were more similar to the subalpine S. helvetica. Conclusions The co-occurrence of the parental species and the hybrids on the glacier forefield, the high frequency of backcrossing, and the low resistance to gene flow via backcrossing make a scenario of introgression in this young hybrid population highly likely, potentially leading to the transfer of adaptive traits. We further suggest that this willow hybrid population may serve as a model for the evolutionary processes initiated by recent global warming.
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    Trace element delivery for biogas production enhanced by alternative energy crops: results from two-year field trials 

    Fahlbusch, Wiebke; Hey, Katharina; Sauer, Benedikt; Ruppert, Hans
    2018; 8(1): Art. 38
    Abstract Background Energy crop production for biogas still relies mainly on maize, but the co-digestion of alternative energy crops (legumes, amaranth, ryegrass, flower mixtures) with maize can have several advantages. First, a greater biodiversity in the fields; second, an enrichment of essential trace elements in biogas substrates (cobalt, nickel, manganese, and molybdenum); and third, less use of artificial trace element additives. Methods In two randomized field trials, 12 different variants of field crops in sole, double and intercropping were tested over a 2-year period. Dry matter yield, trace element content of the crops, and soil parameters like soil texture, pH, and soil element concentration were determined. The trace element concentrations in biogas plants resulting from input mixtures of energy crops (legumes, amaranth, faba bean, and ryegrass) and maize are calculated. Results High dry matter yields were obtained for ryegrass, maize, winter faba bean maize, intercropping winter faba bean/triticale-maize, and intercropping rye/vetch-maize. The double croppings with maize reached highest total yields (ca. 30 t DM ha−1). Total element deliveries from the harvest reveal large differences between the variants and the trace elements. Cobalt is provided most by summer faba bean maize and intercropping of winter faba bean/triticale-maize. Ryegrass can deliver the greatest amounts of Manganese and Molybdenum to biogas plants. When these energy crops are added to conventional maize input for biogas production, the trace element concentration in the fermenter can be raised significantly, e.g., 0.03 g Co t−1 FM can be attained compared to 0.003 g t−1 with maize silage input only. Sufficient Co can be provided by addition of manure to the input mixture. Conclusions Alternative energy crops in combination with maize ensure a good dry matter yield per year and provide significantly more trace elements. However, these substrate mixtures alone do not provide enough trace elements, particularly Co. However, enough Co can be supplied by a small addition of manure.
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    The type 2 acyl-CoA:diacylglycerol acyltransferase family of the oleaginous microalga Lobosphaera incisa 

    Zienkiewicz, Krzysztof; Benning, Urs; Siegler, Heike; Feussner, Ivo
    2018; 18(1): Art. 298
    Abstract Background Oleaginous microalgae are promising sources of energy-rich triacylglycerols (TAGs) for direct use for food, feed and industrial applications. Lobosphaera incisa is a fresh water unicellular alga, which in response to nutrient stress accumulates a high amount of TAGs with a high proportion of arachidonic acid (ARA). The final committed step of de novo TAG biosynthesis is catalyzed by acyl-CoA:diacylglycerol acyltransferases (DGATs), which add a fatty acid (FA) to the final sn-3 position of diacylglycerol (DAG). Results Genome analysis revealed the presence of five putative DGAT isoforms in L. incisa, including one DGAT of type 1, three DGATs of type 2 and a single isoform of a type 3 DGAT. For LiDGAT1, LiDGAT2.1, LiDGAT2.2 and LiDGAT2.3 enzyme activity was confirmed by expressing them in the TAG-deficient yeast strain H1246. Feeding experiments of yeast transformants with fatty acids suggest a broad substrate specificity spectrum for LiDGAT1. A significant TAG production in response to exogenous ARA was found for LiDGAT2.2. Cellular localization of the four type 1 and type 2 DGATs expressed in yeast revealed that they all localize to distinct ER domains. A prominent association of LiDGAT1 with ER domains in close proximity to forming lipid droplets (LDs) was also observed. Conclusions The data revealed a distinct molecular, functional and cellular nature of type 1 and type 2 DGATs from L. incisa, with LiDGAT1 being a major contributor to the TAG pool. LiDGATs of type 2 might be in turn involved in the incorporation of unusual fatty acids into TAG and thus regulate the composition of TAG. This report provides a valuable resource for the further research of microalgae DGATs oriented towards production of fresh-water strains with higher oil content of valuable composition, not only for oil industry but also for human and animal nutrition.
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    Sample size calculation in multi-centre clinical trials 

    Harden, Markus; Friede, Tim
    2018; 18(1): Art. 156
    Abstract Background Multi-centre randomized controlled clinical trials play an important role in modern evidence-based medicine. Advantages of collecting data from more than one site are numerous, including accelerated recruitment and increased generalisability of results. Mixed models can be applied to account for potential clustering in the data, in particular when many small centres contribute patients to the study. Previously proposed methods on sample size calculation for mixed models only considered balanced treatment allocations which is an unlikely outcome in practice if block randomisation with reasonable choices of block length is used. Methods We propose a sample size determination procedure for multi-centre trials comparing two treatment groups for a continuous outcome, modelling centre differences using random effects and allowing for arbitrary sample sizes. It is assumed that block randomisation with fixed block length is used at each study site for subject allocation. Simulations are used to assess operation characteristics such as power of the sample size approach. The proposed method is illustrated by an example in disease management systems. Results A sample size formula as well as a lower and upper boundary for the required overall sample size are given. We demonstrate the superiority of the new sample size formula over the conventional approach of ignoring the multi-centre structure and show the influence of parameters such as block length or centre heterogeneity. The application of the procedure on the example data shows that large blocks require larger sample sizes, if centre heterogeneity is present. Conclusion Unbalanced treatment allocation can result in substantial power loss when centre heterogeneity is present but not considered at the planning stage. When only few patients by centre will be recruited, one has to weigh the risk of imbalance between treatment groups due to large blocks and the risk of unblinding due to small blocks. The proposed approach should be considered when planning multi-centre trials.
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    Importance of operator training and rest perfusion on the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance 

    Villa, Adriana D M; Corsinovi, Laura; Ntalas, Ioannis; Milidonis, Xenios; Scannell, Cian; Di Giovine, Gabriella; Child, Nicholas; Ferreira, Catarina; Nazir, Muhummad S; Karady, Julia; et al.
    Eshja, EsmeraldaDe Francesco, ViolaBettencourt, NunoSchuster, AndreasIsmail, Tevfik FRazavi, RezaChiribiri, Amedeo
    2018; 20(1): Art. 74
    Abstract Background Clinical evaluation of stress perfusion cardiovascular magnetic resonance (CMR) is currently based on visual assessment and has shown high diagnostic accuracy in previous clinical trials, when performed by expert readers or core laboratories. However, these results may not be generalizable to clinical practice, particularly when less experienced readers are concerned. Other factors, such as the level of training, the extent of ischemia, and image quality could affect the diagnostic accuracy. Moreover, the role of rest images has not been clarified. The aim of this study was to assess the diagnostic accuracy of visual assessment for operators with different levels of training and the additional value of rest perfusion imaging, and to compare visual assessment and automated quantitative analysis in the assessment of coronary artery disease (CAD). Methods We evaluated 53 patients with known or suspected CAD referred for stress-perfusion CMR. Nine operators (equally divided in 3 levels of competency) blindly reviewed each case twice with a 2-week interval, in a randomised order, with and without rest images. Semi-automated Fermi deconvolution was used for quantitative analysis and estimation of myocardial perfusion reserve as the ratio of stress to rest perfusion estimates. Results Level-3 operators correctly identified significant CAD in 83.6% of the cases. This percentage dropped to 65.7% for Level-2 operators and to 55.7% for Level-1 operators (p < 0.001). Quantitative analysis correctly identified CAD in 86.3% of the cases and was non-inferior to expert readers (p = 0.56). When rest images were available, a significantly higher level of confidence was reported (p = 0.022), but no significant differences in diagnostic accuracy were measured (p = 0.34). Conclusions Our study demonstrates that the level of training is the main determinant of the diagnostic accuracy in the identification of CAD. Level-3 operators performed at levels comparable with the results from clinical trials. Rest images did not significantly improve diagnostic accuracy, but contributed to higher confidence in the results. Automated quantitative analysis performed similarly to level-3 operators. This is of increasing relevance as recent technical advances in image reconstruction and analysis techniques are likely to permit the clinical translation of robust and fully automated quantitative analysis into routine clinical practice.
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    Classifying development stages of primeval European beech forests: is clustering a useful tool? 

    Glatthorn, Jonas; Feldmann, Eike; Tabaku, Vath; Leuschner, Christoph; Meyer, Peter
    2018; 18(1): Art. 47
    Abstract Background Old-growth and primeval forests are passing through a natural development cycle with recurring stages of forest development. Several methods for assigning patches of different structure and size to forest development stages or phases do exist. All currently existing classification methods have in common that a priori assumptions about the characteristics of certain stand structural attributes such as deadwood amount are made. We tested the hypothesis that multivariate datasets of primeval beech forest stand structure possess an inherent, aggregated configuration of data points with individual clusters representing forest development stages. From two completely mapped primeval beech forests in Albania, seven ecologically important stand structural attributes characterizing stand density, regeneration, stem diameter variation and amount of deadwood are derived at 8216 and 9666 virtual sampling points (moving window, focal filtering). K-means clustering is used to detect clusters in the datasets (number of clusters (k) between 2 and 5). The quality of the single clustering solutions is analyzed with average silhouette width as a measure for clustering quality. In a sensitivity analysis, clustering is done with datasets of four different spatial scales of observation (200, 500, 1000 and 1500 m2, circular virtual plot area around sampling points) and with two different kernels (equal weighting of all objects within a plot vs. weighting by distance to the virtual plot center). Results The clustering solutions succeeded in detecting and mapping areas with homogeneous stand structure. The areas had extensions of more than 200 m2, but differences between clusters were very small with average silhouette widths of less than 0.28. The obtained datasets had a homogeneous configuration with only very weak trends for clustering. Conclusions Our results imply that forest development takes place on a continuous scale and that discrimination between development stages in primeval beech forests is splitting continuous datasets at selected thresholds. For the analysis of the forest development cycle, direct quantification of relevant structural features or processes might be more appropriate than classification. If, however, the study design demands classification, our results can justify the application of conventional forest development stage classification schemes rather than clustering.
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    COMT Val158Met Polymorphism and Social Impairment Interactively Affect Attention-Deficit Hyperactivity Symptoms in Healthy Adolescents 

    Millenet, Sabina K.; Nees, Frauke; Heintz, Stefan; Bach, Christiane; Frank, Josef; Vollstädt-Klein, Sabine; Bokde, Arun; Bromberg, Uli; Büchel, Christian; Quinlan, Erin B.; et al.
    Desrivières, SylvaneFröhner, JulianeFlor, HertaFrouin, VincentGaravan, HughGowland, PennyHeinz, AndreasIttermann, BerndLemaire, HerveMartinot, Jean-LucMartinot, Marie-Laure P.Papadoulos, Dimitri O.Paus, TomášPoustka, LuiseRietschel, MarcellaSmolka, Michael N.Walter, HenrikWhelan, RobSchumann, GunterBanaschewski, TobiasHohmann, Sarah
    2018; 9
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    Expression of combinatorial immunoglobulins in macrophages in the tumor microenvironment 

    Fuchs, Tina; Hahn, Martin; Ries, Lukas; Giesler, Sophie; Busch, Svenja; Wang, Chunlin; Han, Jian; Schulze, Torsten J.; Puellmann, Kerstin; Beham, Alexander W.; et al.
    Kaminski, Wolfgang E.Neumaier, Michael
    2018; 13(9): Art. e0204108
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    Insights into permanent pacemaker implantation following TAVR in a real-world cohort 

    Tichelbäcker, Tobias; Bergau, Leonard; Puls, Miriam; Friede, Tim; Mütze, Tobias; Maier, Lars Siegfried; Frey, Norbert; Hasenfuß, Gerd; Zabel, Markus; Jacobshagen, Claudius; et al.
    Sossalla, Samuel
    2018; 13(10): Art. e0204503
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    Food cue-induced craving in individuals with bulimia nervosa and binge-eating disorder 

    Meule, Adrian; Küppers, Carolyn; Harms, Louisa; Friederich, Hans-Christoph; Schmidt, Ulrike; Blechert, Jens; Brockmeyer, Timo
    2018; 13(9): Art. e0204151
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    Newly produced synaptic vesicle proteins are preferentially used in synaptic transmission 

    Truckenbrodt, Sven; Viplav, Abhiyan; Jähne, Sebastian; Vogts, Angela; Denker, Annette; Wildhagen, Hanna; Fornasiero, Eugenio F; Rizzoli, Silvio O
    2018; 37(15): Art. e98044
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    Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis 

    Llorens, Franc; Thüne, Katrin; Martí, Eulàlia; Kanata, Eirini; Dafou, Dimitra; Díaz-Lucena, Daniela; Vivancos, Ana; Shomroni, Orr; Zafar, Saima; Schmitz, Matthias; et al.
    Michel, UweFernández-Borges, NataliaAndréoletti, Olivierdel Río, José AntonioDíez, JuanaFischer, AndreBonn, StefanSklaviadis, TheodorosTorres, Juan MariaFerrer, IsidreZerr, Inga
    2018; 14(1): Art. e1006802
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    Dissemination of Fusarium proliferatum by mealworm beetle Tenebrio molitor 

    Guo, Zhiqing; Pfohl, Katharina; Karlovsky, Petr; Dehne, Heinz-Wilhelm; Altincicek, Boran
    2018; 13(9): Art. e0204602
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    Animal TSEs and public health: What remains of past lessons? 

    Zafar, Saima; Shafiq, Mohsin; Andréoletti, Olivier; Zerr, Inga
    2018; 14(2): Art. e1006759
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    Impacts of Microplastics on the Soil Biophysical Environment 

    de Souza Machado, Anderson Abel; Lau, Chung Wai; Till, Jennifer; Kloas, Werner; Lehmann, Anika; Becker, Roland; Rillig, Matthias C.
    2018; 52(17) p.9656-9665
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    Genome-wide association studies and meta-analysis uncovers new candidate genes for growth and carcass traits in pigs 

    Blaj, Iulia; Tetens, Jens; Preuß, Siegfried; Bennewitz, Jörn; Thaller, Georg
    2018; 13(10): Art. e0205576
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