@article{JahnSchmidtMock2014, author = {Jahn, Martin T. and Schmidt, Katrin and Mock, Thomas}, title = {A novel cost effective and high-throughput isolation and identification method for marine microalgae}, series = {Plant Methods}, volume = {10}, journal = {Plant Methods}, number = {26}, doi = {10.1186/1746-4811-10-26}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121255}, year = {2014}, abstract = {BACKROUND: Marine microalgae are of major ecologic and emerging economic importance. Biotechnological screening schemes of microalgae for specific traits and laboratory experiments to advance our knowledge on algal biology and evolution strongly benefit from culture collections reflecting a maximum of the natural inter- and intraspecific diversity. However, standard procedures for strain isolation and identification, namely DNA extraction, purification, amplification, sequencing and taxonomic identification still include considerable constraints increasing the time required to establish new cultures. RESULTS: In this study, we report a cost effective and high-throughput isolation and identification method for marine microalgae. The throughput was increased by applying strain isolation on plates and taxonomic identification by direct PCR (dPCR) of phylogenetic marker genes in combination with a novel sequencing electropherogram based screening method to assess the taxonomic diversity and identity of the isolated cultures. For validation of the effectiveness of this approach, we isolated and identified a range of unialgal cultures from natural phytoplankton communities sampled in the Arctic Ocean. These cultures include the isolate of a novel marine Chlorophyceae strain among several different diatoms. CONCLUSIONS: We provide an efficient and effective approach leading from natural phytoplankton communities to isolated and taxonomically identified algal strains in only a few weeks. Validated with sensitive Arctic phytoplankton, this approach overcomes the constraints of standard molecular characterisation and establishment of unialgal cultures."}, language = {en} } @article{BornHolmbergGoernetetal.2014, author = {Born, Dennis-Peter and Holmberg, Hans-Christer and Goernet, Florian and Sperlich, Billy}, title = {A novel compression garment with adhesive silicone stripes improves repeated sprint performance - a multi-experimental approach on the underlying mechanisms}, series = {BMC Sports Science, Medicine and Rehabilitation}, volume = {6}, journal = {BMC Sports Science, Medicine and Rehabilitation}, number = {21}, issn = {2052-1847}, doi = {10.1186/2052-1847-6-21}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120591}, year = {2014}, abstract = {Background Repeated sprint performance is determined by explosive production of power, as well as rapid recovery between successive sprints, and there is evidence that compression garments and sports taping can improve both of these factors. Methods In each of two sub-studies, female athletes performed two sets of 30 30-m sprints (one sprint per minute), one set wearing compression garment with adhesive silicone stripes (CGSS) intended to mimic taping and the other with normal clothing, in randomized order. Sub-study 1 (n = 12) focused on cardio-respiratory, metabolic, hemodynamic and perceptual responses, while neuronal and biomechanical parameters were examined in sub-study 2 (n = 12). Results In both sub-studies the CGSS improved repeated sprint performance during the final 10 sprints (best P < 0.01, d = 0.61). None of the cardio-respiratory or metabolic variables monitored were altered by wearing this garment (best P = 0.06, d = 0.71). Also during the final 10 sprints, rating of perceived exertion by the upper leg muscles was reduced (P = 0.01, d = 1.1), step length increased (P = 0.01, d = 0.91) and activation of the m. rectus femoris elevated (P = 0.01, d = 1.24), while the hip flexion angle was lowered throughout the protocol (best P < 0.01, d = 2.28) and step frequency (best P = 0.34, d = 0.2) remained unaltered. Conclusion Although the physiological parameters monitored were unchanged, the CGSS appears to improve performance during 30 30-m repeated sprints by reducing perceived exertion and altering running technique.}, language = {en} } @article{BornHolmbergGoernertetal.2014, author = {Born, Dennis-Peter and Holmberg, Hans-Christer and Goernert, Florian and Sperlich, Billy}, title = {A novel compression garment with adhesive silicone stripes improves repeated sprint performance - a multi-experimental approach on the underlying mechanisms}, series = {BMC Sports Science, Medicine and Rehabilitation}, volume = {6}, journal = {BMC Sports Science, Medicine and Rehabilitation}, number = {21}, doi = {doi:10.1186/2052-1847-6-21}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116995}, year = {2014}, abstract = {Background Repeated sprint performance is determined by explosive production of power, as well as rapid recovery between successive sprints, and there is evidence that compression garments and sports taping can improve both of these factors. Methods In each of two sub-studies, female athletes performed two sets of 30 30-m sprints (one sprint per minute), one set wearing compression garment with adhesive silicone stripes (CGSS) intended to mimic taping and the other with normal clothing, in randomized order. Sub-study 1 (n = 12) focused on cardio-respiratory, metabolic, hemodynamic and perceptual responses, while neuronal and biomechanical parameters were examined in sub-study 2 (n = 12). Results In both sub-studies the CGSS improved repeated sprint performance during the final 10 sprints (best P < 0.01, d = 0.61). None of the cardio-respiratory or metabolic variables monitored were altered by wearing this garment (best P = 0.06, d = 0.71). Also during the final 10 sprints, rating of perceived exertion by the upper leg muscles was reduced (P = 0.01, d = 1.1), step length increased (P = 0.01, d = 0.91) and activation of the m. rectus femoris elevated (P = 0.01, d = 1.24), while the hip flexion angle was lowered throughout the protocol (best P < 0.01, d = 2.28) and step frequency (best P = 0.34, d = 0.2) remained unaltered. Conclusion Although the physiological parameters monitored were unchanged, the CGSS appears to improve performance during 30 30-m repeated sprints by reducing perceived exertion and altering running technique.}, language = {en} } @article{DirksHaaseCantaertetal.2022, author = {Dirks, Johannes and Haase, Gabriele and Cantaert, Tineke and Frey, Lea and Klaas, Moritz and Rickert, Christian H. and Girschick, Hermann and Meffre, Eric and Morbach, Henner}, title = {A novel AICDA splice-site mutation in two siblings with HIGM2 permits somatic hypermutation but abrogates mutational targeting}, series = {Journal of Clinical Immunology}, volume = {42}, journal = {Journal of Clinical Immunology}, number = {4}, doi = {10.1007/s10875-022-01233-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324253}, pages = {771-782}, year = {2022}, abstract = {Hyper-IgM syndrome type 2 (HIGM2) is a B cell intrinsic primary immunodeficiency caused by mutations in AICDA encoding activation-induced cytidine deaminase (AID) which impair immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). Whereas autosomal-recessive AID-deficiency (AR-AID) affects both CSR and SHM, the autosomal-dominant form (AD-AID) due to C-terminal heterozygous variants completely abolishes CSR but only partially affects SHM. AR-AID patients display enhanced germinal center (GC) reactions and autoimmune manifestations, which are not present in AD-AID, suggesting that SHM but not CSR regulates GC reactions and peripheral B cell tolerance. Herein, we describe two siblings with HIGM2 due to a novel homozygous AICDA mutation (c.428-1G > T) which disrupts the splice acceptor site of exon 4 and results in the sole expression of a truncated AID variant that lacks 10 highly conserved amino acids encoded by exon 4 (AID-ΔE4a). AID-ΔE4a patients suffered from defective CSR and enhanced GC reactions and were therefore indistinguishable from other AR-AID patients. However, the AID-ΔE4a variant only partially affected SHM as observed in AD-AID patients. In addition, AID-ΔE4a but not AD-AID patients revealed impaired targeting of mutational hotspot motives and distorted mutational patterns. Hence, qualitative defects in AID function and altered SHM rather than global decreased SHM activity may account for the disease phenotype in these patients.}, language = {en} } @article{Koelligan2021, author = {K{\"o}lligan, Daniel}, title = {A note on Vedic cīti-}, series = {Indogermanische Forschungen}, volume = {126}, journal = {Indogermanische Forschungen}, number = {1}, issn = {1613-0405}, doi = {10.1515/if-2021-007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250986}, pages = {135 -- 140}, year = {2021}, abstract = {Vedic cīti-, attested in the Atharvaveda, is argued to be related to Av. ṣ̌āitī-, OP šiyāti- 'happiness' built to PIE *kʷi̯eh₁- 'to (come to) rest'.}, language = {en} } @article{SanchoVandersmissenCrapsetal.2017, author = {Sancho, Ana and Vandersmissen, Ine and Craps, Sander and Luttun, Aernout and Groll, J{\"u}rgen}, title = {A new strategy to measure intercellular adhesion forces in mature cell-cell contacts}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {46152}, doi = {10.1038/srep46152}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170999}, year = {2017}, abstract = {Intercellular adhesion plays a major role in tissue development and homeostasis. Yet, technologies to measure mature cell-cell contacts are not available. We introduce a methodology based on fluidic probe force microscopy to assess cell-cell adhesion forces after formation of mature intercellular contacts in cell monolayers. With this method we quantify that L929 fibroblasts exhibit negligible cell-cell adhesion in monolayers whereas human endothelial cells from the umbilical artery (HUAECs) exert strong intercellular adhesion forces per cell. We use a new in vitro model based on the overexpression of Muscle Segment Homeobox 1 (MSX1) to induce Endothelial-to-Mesenchymal Transition (EndMT), a process involved in cardiovascular development and disease. We reveal how intercellular adhesion forces in monolayer decrease significantly at an early stage of EndMT and we show that cells undergo stiffening and flattening at this stage. This new biomechanical insight complements and expands the established standard biomolecular analyses. Our study thus introduces a novel tool for the assessment of mature intercellular adhesion forces in a physiological setting that will be of relevance to biological processes in developmental biology, tissue regeneration and diseases like cancer and fibrosis.}, language = {en} } @article{SchartlSchroeder1987, author = {Schartl, Manfred and Schr{\"o}der, Johannes Horst}, title = {A new species of the genus Xiphophorus Heckel 1848, endemic to northern Coahuila, Mexico (Pisces: Poeciliidae)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87117}, year = {1987}, abstract = {Xiphophorus meyeri n. sp. is described as an endemic to Muzquiz, Coahuila, Mexico. It appears to be the northernmost species of the genus. The new species is related to X. couchianus and X. gordoni, but differs morphologically from those by dorsal fin ray number, by the expression of some gonopodial features and most markedly by the appearance of macromelanophores or tr-melanophores.}, subject = {Schwertkr{\"a}pfling}, language = {en} } @article{BraeuerBurchardtMunkeltBleieretal.2022, author = {Br{\"a}uer-Burchardt, Christian and Munkelt, Christoph and Bleier, Michael and Heinze, Matthias and Gebhart, Ingo and K{\"u}hmstedt, Peter and Notni, Gunther}, title = {A new sensor system for accurate 3D surface measurements and modeling of underwater objects}, series = {Applied Sciences}, volume = {12}, journal = {Applied Sciences}, number = {9}, issn = {2076-3417}, doi = {10.3390/app12094139}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270792}, year = {2022}, abstract = {A new underwater 3D scanning device based on structured illumination and designed for continuous capture of object data in motion for deep sea inspection applications is introduced. The sensor permanently captures 3D data of the inspected surface and generates a 3D surface model in real time. Sensor velocities up to 0.7 m/s are directly compensated while capturing camera images for the 3D reconstruction pipeline. The accuracy results of static measurements of special specimens in a water basin with clear water show the high accuracy potential of the scanner in the sub-millimeter range. Measurement examples with a moving sensor show the significance of the proposed motion compensation and the ability to generate a 3D model by merging individual scans. Future application tests in offshore environments will show the practical potential of the sensor for the desired inspection tasks.}, language = {en} } @article{MatsudaUnoKondoetal.2015, author = {Matsuda, Yoichi and Uno, Yoshinobu and Kondo, Mariko and Gilchrist, Michael J. and Zorn, Aaron M. and Rokhsar, Daniel S. and Schmid, Michael and Taira, Masanori}, title = {A New Nomenclature of Xenopus laevis Chromosomes Based on the Phylogenetic Relationship to Silurana/Xenopus tropicalis}, series = {Cytogenetic and Genome Research}, volume = {145}, journal = {Cytogenetic and Genome Research}, number = {3-4}, issn = {1424-8581}, doi = {10.1159/000381292}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196748}, pages = {187-191}, year = {2015}, abstract = {Xenopus laevis (XLA) is an allotetraploid species which appears to have undergone whole-genome duplication after the interspecific hybridization of 2 diploid species closely related to Silurana/Xenopus tropicalis (XTR). Previous cDNA fluorescence in situ hybridization (FISH) experiments have identified 9 sets of homoeologous chromosomes in X. laevis, in which 8 sets correspond to chromosomes 1-8 of X. tropicalis (XTR1-XTR8), and the last set corresponds to a fusion of XTR9 and XTR10. In addition, recent X. laevis genome sequencing and BAC-FISH experiments support this physiological relationship and show no gross chromosome translocation in the X. laevis karyotype. Therefore, for the benefit of both comparative cytogenetics and genome research, we here propose a new chromosome nomenclature for X. laevis based on the phylogenetic relationship and chromosome length, i.e. XLA1L, XLA1S, XLA2L, XLA2S, and so on, in which the numbering of XLA chromosomes corresponds to that in X. tropicalis and the postfixes 'L' and 'S' stand for 'long' and 'short' chromosomes in the homoeologous pairs, which can be distinguished cytologically by their relative size. The last chromosome set is named XLA9L and XLA9S, in which XLA9 corresponds to both XTR9 and XTR10, and hence, to emphasize the phylogenetic relationship to X. tropicalis, XLA9_10L and XLA9_10S are also used as synonyms.}, language = {en} } @article{HerrmannHappMoellmannetal.1993, author = {Herrmann, K. H. and Happ, M. and M{\"o}llmann, K.-P. and Tomm, J. W. and Becker, Charles R. and Kraus, M. M. and Yuan, S. and Landwehr, G.}, title = {A new model for the absorption coefficient of narrow gap (Hg,Cd)Te that simultaneously considers band tails and band filling}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-37894}, year = {1993}, abstract = {A semiempirical model is presented that correlates the broadening of the absorption edge with both transitions below the energy gap and with transitions by the Kane band model. This model correctly fits both the absorption and luminescence spectra of narrow-gap (Hg,Cd)Te samples that have been grown by the traveling heater method as well as by molecular-beam epitaxy. The accuracy of the band-gap determination is enhanced by this model.}, language = {en} } @article{WalterDegenPfeifferetal.2021, author = {Walter, Thomas and Degen, Jacqueline and Pfeiffer, Keram and St{\"o}ckl, Anna and Montenegro, Sergio and Degen, Tobias}, title = {A new innovative real-time tracking method for flying insects applicable under natural conditions}, series = {BMC Zoology}, volume = {6}, journal = {BMC Zoology}, doi = {10.1186/s40850-021-00097-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265716}, year = {2021}, abstract = {Background Sixty percent of all species are insects, yet despite global efforts to monitor animal movement patterns, insects are continuously underrepresented. This striking difference between species richness and the number of species monitored is not due to a lack of interest but rather to the lack of technical solutions. Often the accuracy and speed of established tracking methods is not high enough to record behavior and react to it experimentally in real-time, which applies in particular to small flying animals. Results Our new method of real-time tracking relates to frequencies of solar radiation which are almost completely absorbed by traveling through the atmosphere. For tracking, photoluminescent tags with a peak emission (1400 nm), which lays in such a region of strong absorption through the atmosphere, were attached to the animals. The photoluminescent properties of passivated lead sulphide quantum dots were responsible for the emission of light by the tags and provide a superb signal-to noise ratio. We developed prototype markers with a weight of 12.5 mg and a diameter of 5 mm. Furthermore, we developed a short wave infrared detection system which can record and determine the position of an animal in a heterogeneous environment with a delay smaller than 10 ms. With this method we were able to track tagged bumblebees as well as hawk moths in a flight arena that was placed outside on a natural meadow. Conclusion Our new method eliminates the necessity of a constant or predictable environment for many experimental setups. Furthermore, we postulate that the developed matrix-detector mounted to a multicopter will enable tracking of small flying insects, over medium range distances (>1000m) in the near future because: a) the matrix-detector equipped with an 70 mm interchangeable lens weighs less than 380 g, b) it evaluates the position of an animal in real-time and c) it can directly control and communicate with electronic devices.}, language = {en} } @article{UllmannMoellerBaumhaueretal.2022, author = {Ullmann, Tobias and M{\"o}ller, Eric and Baumhauer, Roland and Lange-Athinodorou, Eva and Meister, Julia}, title = {A new Google Earth Engine tool for spaceborne detection of buried palaeogeographical features - examples from the Nile Delta (Egypt)}, series = {E\&G Quaternary Science Journal}, volume = {71}, journal = {E\&G Quaternary Science Journal}, number = {2}, doi = {10.5194/egqsj-71-243-2022}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300164}, pages = {243-247}, year = {2022}, abstract = {No abstract available.}, language = {en} } @article{vanUnenStumpfSchmidetal.2016, author = {van Unen, Jakobus and Stumpf, Anette D. and Schmid, Benedikt and Reinhard, Nathalie R. and Hordijk, Peter L. and Hoffmann, Carsten and Gadella, Theodorus W. J. and Goedhart, Joachim}, title = {A New Generation of FRET Sensors for Robust Measurement of Gα\(_{i1}\), Gα\(_{i2}\) and Gα\(_{i3}\) Activation Kinetics in Single Cells}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0146789}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167387}, pages = {e0146789}, year = {2016}, abstract = {G-protein coupled receptors (GPCRs) can activate a heterotrimeric G-protein complex with subsecond kinetics. Genetically encoded biosensors based on F{\"o}rster resonance energy transfer (FRET) are ideally suited for the study of such fast signaling events in single living cells. Here we report on the construction and characterization of three FRET biosensors for the measurement of Gα\(_{i1}\), Gα\(_{i2}\) and Gα\(_{i3}\) activation. To enable quantitative long-term imaging of FRET biosensors with high dynamic range, fluorescent proteins with enhanced photophysical properties are required. Therefore, we use the currently brightest and most photostable CFP variant, mTurquoise2, as donor fused to Gα\(_{i}\) subunit, and cp173Venus fused to the Gγ\(_{2}\) subunit as acceptor. The Gα\(_{i}\) FRET biosensors constructs are expressed together with Gβ\(_{1}\) from a single plasmid, providing preferred relative expression levels with reduced variation in mammalian cells. The Gα\(_{i}\) FRET sensors showed a robust response to activation of endogenous or over-expressed alpha-2A-adrenergic receptors, which was inhibited by pertussis toxin. Moreover, we observed activation of the Gα\(_{i}\) FRET sensor in single cells upon stimulation of several GPCRs, including the LPA\(_{2}\), M\(_{3}\) and BK\(_{2}\) receptor. Furthermore, we show that the sensors are well suited to extract kinetic parameters from fast measurements in the millisecond time range. This new generation of FRET biosensors for Gα\(_{i1}\), Gα\(_{i2}\) and Gα\(_{i3}\) activation will be valuable for live-cell measurements that probe Gα\(_{i}\) activation.}, language = {en} } @article{BeerSteffanDewenterHaerteletal.2016, author = {Beer, Katharina and Steffan-Dewenter, Ingolf and H{\"a}rtel, Stephan and Helfrich-F{\"o}rster, Charlotte}, title = {A new device for monitoring individual activity rhythms of honey bees reveals critical effects of the social environment on behavior}, series = {Journal of Comparative Physiology A}, volume = {202}, journal = {Journal of Comparative Physiology A}, number = {8}, doi = {10.1007/s00359-016-1103-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188030}, pages = {555-565}, year = {2016}, abstract = {Chronobiological studies of individual activity rhythms in social insects can be constrained by the artificial isolation of individuals from their social context. We present a new experimental set-up that simultaneously measures the temperature rhythm in a queen-less but brood raising mini colony and the walking activity rhythms of singly kept honey bees that have indirect social contact with it. Our approach enables monitoring of individual bees in the social context of a mini colony under controlled laboratory conditions. In a pilot experiment, we show that social contact with the mini colony improves the survival of monitored young individuals and affects locomotor activity patterns of young and old bees. When exposed to conflicting Zeitgebers consisting of a light-dark (LD) cycle that is phase-delayed with respect to the mini colony rhythm, rhythms of young and old bees are socially synchronized with the mini colony rhythm, whereas isolated bees synchronize to the LD cycle. We conclude that the social environment is a stronger Zeitgeber than the LD cycle and that our new experimental set-up is well suited for studying the mechanisms of social entrainment in honey bees.}, language = {en} } @article{RogersGilesDraperetal.2021, author = {Rogers, Bruce and Giles, David and Draper, Nick and Hoos, Olaf and Gronwald, Thomas}, title = {A New Detection Method Defining the Aerobic Threshold for Endurance Exercise and Training Prescription Based on Fractal Correlation Properties of Heart Rate Variability}, series = {Frontiers in Physiology}, volume = {11}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2020.596567}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222601}, year = {2021}, abstract = {The short-term scaling exponent alpha1 of detrended fluctuation analysis (DFA a1), a nonlinear index of heart rate variability (HRV) based on fractal correlation properties, has been shown to steadily change with increasing exercise intensity. To date, no study has specifically examined using the behavior of this index as a method for defining a low intensity exercise zone. The aim of this report is to compare both oxygen intake (VO\(_{2}\)) and heart rate (HR) reached at the first ventilatory threshold (VT1), a well-established delimiter of low intensity exercise, to those derived from a predefined DFA a1 transitional value. Gas exchange and HRV data were obtained from 15 participants during an incremental treadmill run. Comparison of both VO\(_{2}\) and HR reached at VT1 defined by gas exchange (VT1 GAS) was made to those parameters derived from analysis of DFA a1 reaching a value of 0.75 (HRVT). Based on Bland Altman analysis, linear regression, intraclass correlation (ICC) and t testing, there was strong agreement between VT1 GAS and HRVT as measured by both HR and VO\(_{2}\). Mean VT1 GAS was reached at 39.8 ml/kg/min with a HR of 152 bpm compared to mean HRVT which was reached at 40.1 ml/kg/min with a HR of 154 bpm. Strong linear relationships were seen between test modalities, with Pearson's r values of 0.99 (p < 0.001) and.97 (p < 0.001) for VO\(_{2}\) and HR comparisons, respectively. Intraclass correlation between VT1 GAS and HRVT was 0.99 for VO\(_{2}\) and 0.96 for HR. In addition, comparison of VT1 GAS and HRVT showed no differences by t testing, also supporting the method validity. In conclusion, it appears that reaching a DFA a1 value of 0.75 on an incremental treadmill test is closely associated with crossing the first ventilatory threshold. As training intensity below the first ventilatory threshold is felt to have great importance for endurance sport, utilization of DFA a1 activity may provide guidance for a valid low training zone.}, language = {en} } @article{WenzArndtSamnick2022, author = {Wenz, Jan and Arndt, Felix and Samnick, Samuel}, title = {A new concept for the production of \(^{11}\)C-labelled radiotracers}, series = {EJNMMI Radiopharmacy and Chemistry}, volume = {7}, journal = {EJNMMI Radiopharmacy and Chemistry}, doi = {10.1186/s41181-022-00159-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300731}, year = {2022}, abstract = {Background The GMP-compliant production of radiopharmaceuticals has been performed using disposable units (cassettes) with a dedicated synthesis module. To expand this "plug 'n' synthesize" principle to a broader scope of modules we developed a pressure controlled setup that offers an alternative to the usual stepper motor controlled rotary valves. The new concept was successfully applied to the synthesis of N-methyl-[\(^{11}\)C]choline, L-S-methyl-[\(^{11}\)C]methionine and [11C]acetate. Results The target gas purification of cyclotron produced [\(^{11}\)C]CO\(_2\) and subsequent conversion to [\(^{11}\)C]MeI was carried out on a TRACERlab Fx C Pro module. The labelling reactions were controlled with a TRACERlab Fx FE module. With the presented modular principle we were able to produce N-methyl-[\(^{11}\)C]choline and L-S-methyl-[\(^{11}\)C]methionine by loading a reaction loop with neat N,N'-dimethylaminoethanol (DMAE) or an ethanol/water mixture of NaOH and L-homocysteine (L-HC), respectively and a subsequent reaction with [\(^{11}\)C]MeI. After 18 min N-methyl-[\(^{11}\)C]choline was isolated with 52\% decay corrected yield and a radiochemical purity of > 99\%. For L-S-methyl-[\(^{11}\)C]methionine the total reaction time was 19 min reaction, yielding 25\% of pure product (> 97\%). The reactor design was used as an exemplary model for the technically challenging [\(^{11}\)C]acetate synthesis. The disposable unit was filled with 1 mL MeMgCl (0.75 M) in tetrahydrofuran (THF) bevore [\(^{11}\)C]CO\(_2\) was passed through. After complete release of [\(^{11}\)C]CO\(_2\) the reaction mixture was quenched with water and guided through a series of ion exchangers (H\(^+\), Ag\(^+\) and OH\(^-\)). The product was retained on a strong anion exchanger, washed with water and finally extracted with saline. The product mixture was acidified and degassed to separate excess [\(^{11}\)C]CO\(_2\) before dispensing. Under these conditions the total reaction time was 18 ± 2 min and pure [\(^{11}\)C]acetate (n = 10) was isolated with a decay corrected yield of 51 ± 5\%. Conclusion Herein, we described a novel single use unit for the synthesis of carbon-11 labelled tracers for preclinical and clinical applications of N-methyl-[\(^{11}\)C]choline, L-S-methyl-[\(^{11}\)C]methionine and [11C]acetate.}, language = {en} } @article{BalasubramanianSkafHolzgrabeetal.2018, author = {Balasubramanian, Srikkanth and Skaf, Joseph and Holzgrabe, Ulrike and Bharti, Richa and F{\"o}rstner, Konrad U. and Ziebuhr, Wilma and Humeida, Ute H. and Abdelmohsen, Usama R. and Oelschlaeger, Tobias A.}, title = {A new bioactive compound from the marine sponge-derived Streptomyces sp. SBT348 inhibits staphylococcal growth and biofilm formation}, series = {Frontiers in Microbiology}, volume = {9}, journal = {Frontiers in Microbiology}, doi = {10.3389/fmicb.2018.01473}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221408}, year = {2018}, abstract = {Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients carrying surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms leads to refractory and persistent device-related infections (DRIs). Staphylococci organized in biofilms are more tolerant to antibiotics and immune responses, and thus are difficult-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm-based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal, and silicone surfaces. A bioassay-guided fractionation was performed to isolate the active compound (SKC3) from the crude SBT348 extract. Our results demonstrated that SKC3 effectively inhibits the growth (MIC: 31.25 \(\mu\)g/ml) and biofilm formation (sub-MIC range: 1.95-<31.25 \(\mu\)g/ml) of S. epidermidis RP62A in vitro. Chemical characterization of SKC3 by heat and enzyme treatments, and mass spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258.3 Da). Cytotoxicity profiling of SKC3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria mellonella revealed its non-toxic nature at the effective dose. Transcriptome analysis of SKC3 treated S. epidermidis RP62A has further unmasked its negative effect on central metabolism such as carbon flux as well as, amino acid, lipid, and energy metabolism. Taken together, these findings suggest a potential of SKC3 as a putative drug to prevent staphylococcal DRIs.}, language = {en} } @article{MaschwitzFialaLinsenmair1992, author = {Maschwitz, Ulrich and Fiala, Brigitte and Linsenmair, K. Eduard}, title = {A new ant-tree from SE Asia: Zanthoxylum myriacanthum (Rutaceae), the Thorny Ivy-Rue}, isbn = {0025-1291}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42967}, year = {1992}, abstract = {Zanthoxylum myriacanthum, a small Rutaceous tree growing mainly in secondary hill forests in SE Asia, is a true myrmecophyte. It possesses stem domatia in the form of hollow branches with slitlike openings. Branch hollows and entrance slits are produced by the plant itself through pith degene~.tion ?u.d growth proceSses. If the entrance is not kept open by ants it closes again by growth ol the surrounding tissue after some time. The domatia are colonized opportunistic ally by different arboreous ants, e.g. Crematogaster and Campono tus. Additionally many small extrafloral nectaries are found on the leaflets of Zanthoxylum myriacanthum. Judging from herbarium studies and literature records at least four more true ant trees are found in the genus Zanthoxylum namely Z. rhetsa in SE Asia, Z. conspersipunctatum, Z. pluviatile and Z. vinkii in New Guinea. We could not confirm ant inhabitation in Drypetes pendula (Euphorbiaceae) on the Malay Peninsula, which has also been recorded to be an anttree.}, language = {en} } @article{CzernetzkiArrowsmithFantuzzietal.2021, author = {Czernetzki, Corinna and Arrowsmith, Merle and Fantuzzi, Felipe and G{\"a}rtner, Annalena and Tr{\"o}ster, Tobias and Krummenacher, Ivo and Schorr, Fabian and Braunschweig, Holger}, title = {A neutral beryllium(I) radical}, series = {Angewandte Chemie International Edition}, volume = {60}, journal = {Angewandte Chemie International Edition}, number = {38}, doi = {10.1002/anie.202108405}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256529}, pages = {20776-20780}, year = {2021}, abstract = {The reduction of a cyclic alkyl(amino)carbene (CAAC)-stabilized organoberyllium chloride yields the first neutral beryllium radical, which was characterized by EPR, IR, UV/Vis spectroscopy and X-ray crystallography. DFT calculations show significant spin density at beryllium and confirm donor-acceptor bonding between an alkylberyllium radical fragment and a neutral CAAC ligand.}, language = {en} } @article{MusselHewig2019, author = {Mussel, Patrick and Hewig, Johannes}, title = {A neural perspective on when and why trait greed comes at the expense of others}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-47372-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231652}, year = {2019}, abstract = {Depending on the point of view, conceptions of greed range from being a desirable and inevitable feature of a well-regulated, well-balanced economy to the root of all evil - radix omnium malorum avaritia (Tim 6.10). Regarding the latter, it has been proposed that greedy individuals strive for obtaining desired goods at all costs. Here, we show that trait greed predicts selfish economic decisions that come at the expense of others in a resource dilemma. This effect was amplified when individuals strived for obtaining real money, as compared to points, and when their revenue was at the expense of another person, as compared to a computer. On the neural level, we show that individuals high, compared to low in trait greed showed a characteristic signature in the EEG, a reduced P3 effect to positive, compared to negative feedback, indicating that they may have a lack of sensitivity to adjust behavior according to positive and negative stimuli from the environment. Brain-behavior relations further confirmed this lack of sensitivity to behavior adjustment as a potential underlying neuro-cognitive mechanism which explains selfish and reckless behavior that may come at the expense of others.}, language = {en} } @article{PeseschkianCordtsGuentheretal.2021, author = {Peseschkian, Tara and Cordts, Isabell and G{\"u}nther, Ren{\´e} and Stolte, Benjamin and Zeller, Daniel and Schr{\"o}ter, Carsten and Weyen, Ute and Regensburger, Martin and Wolf, Joachim and Schneider, Ilka and Hermann, Andreas and Metelmann, Moritz and Kohl, Zacharias and Linker, Ralf A. and Koch, Jan Christoph and B{\"u}chner, Boriana and Weiland, Ulrike and Sch{\"o}nfelder, Erik and Heinrich, Felix and Osmanovic, Alma and Klopstock, Thomas and Dorst, Johannes and Ludolph, Albert C. and Boentert, Matthias and Hagenacker, Tim and Deschauer, Marcus and Lingor, Paul and Petri, Susanne and Schreiber-Katz, Olivia}, title = {A nation-wide, multi-center study on the quality of life of ALS patients in Germany}, series = {Brain Sciences}, volume = {11}, journal = {Brain Sciences}, number = {3}, issn = {2076-3425}, doi = {10.3390/brainsci11030372}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234147}, year = {2021}, abstract = {Improving quality of life (QoL) is central to amyotrophic lateral sclerosis (ALS) treatment. This Germany-wide, multicenter cross-sectional study analyses the impact of different symptom-specific treatments and ALS variants on QoL. Health-related QoL (HRQoL) in 325 ALS patients was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) and EuroQol Five Dimension Five Level Scale (EQ-5D-5L), together with disease severity (captured by the revised ALS Functional Rating Scale (ALSFRS-R)) and the current care and therapies used by our cohort. At inclusion, the mean ALSAQ-5 total score was 56.93 (max. 100, best = 0) with a better QoL associated with a less severe disease status (β = -1.96 per increase of one point in the ALSFRS-R score, p < 0.001). "Limb-onset" ALS (lALS) was associated with a better QoL than "bulbar-onset" ALS (bALS) (mean ALSAQ-5 total score 55.46 versus 60.99, p = 0.040). Moreover, with the ALSFRS-R as a covariate, using a mobility aid (β = -7.60, p = 0.001), being tracheostomized (β = -14.80, p = 0.004) and using non-invasive ventilation (β = -5.71, p = 0.030) were associated with an improved QoL, compared to those at the same disease stage who did not use these aids. In contrast, antidepressant intake (β = 5.95, p = 0.007), and increasing age (β = 0.18, p = 0.023) were predictors of worse QoL. Our results showed that the ALSAQ-5 was better-suited for ALS patients than the EQ-5D-5L. Further, the early and symptom-specific clinical management and supply of assistive devices can significantly improve the individual HRQoL of ALS patients. Appropriate QoL questionnaires are needed to monitor the impact of treatment to provide the best possible and individualized care.}, language = {en} } @article{HermSteinbachWanneretal.2022, author = {Herm, Lukas-Valentin and Steinbach, Theresa and Wanner, Jonas and Janiesch, Christian}, title = {A nascent design theory for explainable intelligent systems}, series = {Electronic Markets}, volume = {32}, journal = {Electronic Markets}, number = {4}, issn = {1019-6781}, doi = {10.1007/s12525-022-00606-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323809}, pages = {2185-2205}, year = {2022}, abstract = {Due to computational advances in the past decades, so-called intelligent systems can learn from increasingly complex data, analyze situations, and support users in their decision-making to address them. However, in practice, the complexity of these intelligent systems renders the user hardly able to comprehend the inherent decision logic of the underlying machine learning model. As a result, the adoption of this technology, especially for high-stake scenarios, is hampered. In this context, explainable artificial intelligence offers numerous starting points for making the inherent logic explainable to people. While research manifests the necessity for incorporating explainable artificial intelligence into intelligent systems, there is still a lack of knowledge about how to socio-technically design these systems to address acceptance barriers among different user groups. In response, we have derived and evaluated a nascent design theory for explainable intelligent systems based on a structured literature review, two qualitative expert studies, a real-world use case application, and quantitative research. Our design theory includes design requirements, design principles, and design features covering the topics of global explainability, local explainability, personalized interface design, as well as psychological/emotional factors.}, language = {en} } @article{BaurRautenbergFaulstichetal.2014, author = {Baur, Stefanie and Rautenberg, Maren and Faulstich, Manuela and Grau, Timo and Severin, Yannik and Unger, Clemens and Hoffmann, Wolfgang H. and Rudel, Thomas and Autenrieth, Ingo B. and Weidenmaier, Christopher}, title = {A Nasal Epithelial Receptor for Staphylococcus aureus WTA Governs Adhesion to Epithelial Cells and Modulates Nasal Colonization}, series = {PLOS PATHOGENS}, volume = {10}, journal = {PLOS PATHOGENS}, number = {5}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1004089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116280}, pages = {e1004089}, year = {2014}, abstract = {Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization.}, language = {en} } @article{SuterHuangEngels1994, author = {Suter, H. U. and Huang, M.-B. and Engels, Bernd}, title = {A Multireference Configuration Interaction Study of the Hyperfine Structure of the Molecules CCO, CNN and NCN in their triplet ground states}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59108}, year = {1994}, abstract = {The hyperfine structures of the isoelectronic molecules CCO. CNN, and NCN in their triplet ground states (X\(^3 \sum ^-\)) are investigated by means of ab initio methods. The infrared frequencies and geometries are detennined and compared with experiment. Configuration selected multireference configuration interaction calculations in combination with perturbation theory to correct the wave function (MRD-CI/B\(_K\)) employing extended atomic orbital (AO) basis sets yielded very accurate hyperfine properties. The theoretical values for CCO are in excellent agreement with the experimental values determined by Smith and Weltner [J. Chem. Phys. 62,4592 (1975)]. For CNN, the first assignment of Smith and Weltner for the two nitrogen atoms has to be changed. A qualitative discussion of the electronic structure discloses no simple relation between the structure of the singly occupied orbitals and the measured hyperfine coupling constants. Vibrational effects were found to be of little importance.}, subject = {Organische Chemie}, language = {en} } @article{RadakovicReboredoHelmetal.2017, author = {Radakovic, D. and Reboredo, J. and Helm, M. and Weigel, T. and Sch{\"u}rlein, S. and Kupczyk, E. and Leyh, R. G. and Walles, H. and Hansmann, J.}, title = {A multilayered electrospun graft as vascular access for hemodialysis}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0185916}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159102}, pages = {e0185916}, year = {2017}, abstract = {Despite medical achievements, the number of patients with end-stage kidney disease keeps steadily raising, thereby entailing a high number of surgical and interventional procedures to establish and maintain arteriovenous vascular access for hemodialysis. Due to vascular disease, aneurysms or infection, the preferred access—an autogenous arteriovenous fistula—is not always available and appropriate. Moreover, when replacing small diameter blood vessels, synthetic vascular grafts possess well-known disadvantages. A continuous multilayered gradient electrospinning was used to produce vascular grafts made of collagen type I nanofibers on luminal and adventitial graft side, and poly-ɛ-caprolactone as medial layer. Therefore, a custom-made electrospinner with robust environmental control was developed. The morphology of electrospun grafts was characterized by scanning electron microscopy and measurement of mechanical properties. Human microvascular endothelial cells were cultured in the graft under static culture conditions and compared to cultures obtained from dynamic continuous flow bioreactors. Immunofluorescent analysis showed that endothelial cells form a continuous luminal layer and functional characteristics were confirmed by uptake of acetylated low-density-lipoprotein. Incorporation of vancomycin and gentamicin to the medial graft layer allowed antimicrobial inhibition without exhibiting an adverse impact on cell viability. Most striking a physiological hemocompatibility was achieved for the multilayered grafts.}, language = {en} } @article{ZahoGhirlandoAlfonsoetal.2015, author = {Zaho, Huaying and Ghirlando, Rodolfo and Alfonso, Carlos and Arisaka, Fumio and Attali, Ilan and Bain, David L. and Bakhtina, Marina M. and Becker, Donald F. and Bedwell, Gregory J. and Bekdemir, Ahmet and Besong, Tabot M. D. and Birck, Catherine and Brautigam, Chad A. and Brennerman, William and Byron, Olwyn and Bzowska, Agnieszka and Chaires, Jonathan B. and Chaton, Catherine T. and Coelfen, Helmbut and Connaghan, Keith D. and Crowley, Kimberly A. and Curth, Ute and Daviter, Tina and Dean, William L. and Diez, Ana I. and Ebel, Christine and Eckert, Debra M. and Eisele, Leslie E. and Eisenstein, Edward and England, Patrick and Escalante, Carlos and Fagan, Jeffrey A. and Fairman, Robert and Finn, Ron M. and Fischle, Wolfgang and Garcia de la Torre, Jose and Gor, Jayesh and Gustafsson, Henning and Hall, Damien and Harding, Stephen E. and Hernandez Cifre, Jose G. and Herr, Andrew B. and Howell, Elizabeth E. and Isaac, Richard S. and Jao, Shu-Chuan and Jose, Davis and Kim, Soon-Jong and Kokona, Bashkim and Kornblatt, Jack A. and Kosek, Dalibor and Krayukhina, Elena and Krzizike, Daniel and Kusznir, Eric A. and Kwon, Hyewon and Larson, Adam and Laue, Thomas M. and Le Roy, Aline and Leech, Andrew P. and Lilie, Hauke and Luger, Karolin and Luque-Ortega, Juan R. and Ma, Jia and May, Carrie A. and Maynard, Ernest L. and Modrak-Wojcik, Anna and Mok, Yee-Foong and M{\"u}cke, Norbert and Nagel-Steger, Luitgard and Narlikar, Geeta J. and Noda, Masanori and Nourse, Amanda and Obsil, Thomas and Park, Chad K and Park, Jin-Ku and Pawelek, Peter D. and Perdue, Erby E. and Perkins, Stephen J. and Perugini, Matthew A. and Peterson, Craig L. and Peverelli, Martin G. and Piszczek, Grzegorz and Prag, Gali and Prevelige, Peter E. and Raynal, Bertrand D. E. and Rezabkova, Lenka and Richter, Klaus and Ringel, Alison E. and Rosenberg, Rose and Rowe, Arthur J. and Rufer, Arne C. and Scott, David J. and Seravalli, Javier G. and Solovyova, Alexandra S. and Song, Renjie and Staunton, David and Stoddard, Caitlin and Stott, Katherine and Strauss, Holder M. and Streicher, Werner W. and Sumida, John P. and Swygert, Sarah G. and Szczepanowski, Roman H. and Tessmer, Ingrid and Toth, Ronald T. and Tripathy, Ashutosh and Uchiyama, Susumu and Uebel, Stephan F. W. and Unzai, Satoru and Gruber, Anna Vitlin and von Hippel, Peter H. and Wandrey, Christine and Wang, Szu-Huan and Weitzel, Steven E and Wielgus-Kutrowska, Beata and Wolberger, Cynthia and Wolff, Martin and Wright, Edward and Wu, Yu-Sung and Wubben, Jacinta M. and Schuck, Peter}, title = {A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0126420}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151903}, pages = {e0126420}, year = {2015}, abstract = {Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304\(\pm\)0.188) S (4.4\%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of \(\pm\)0.030 S (0.7\%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.}, language = {en} } @article{PetersKnoepperGrafenetal.2022, author = {Peters, Annika E. and Kn{\"o}pper, Konrad and Grafen, Anika and Kastenm{\"u}ller, Wolfgang}, title = {A multifunctional mouse model to study the role of Samd3}, series = {European Journal of Immunology}, volume = {52}, journal = {European Journal of Immunology}, number = {2}, doi = {10.1002/eji.202149469}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257362}, pages = {328-337}, year = {2022}, abstract = {The capacity to develop immunological memory is a hallmark of the adaptive immune system. To investigate the role of Samd3 for cellular immune responses and memory development, we generated a conditional knock-out mouse including a fluorescent reporter and a huDTR cassette for conditional depletion of Samd3-expressing cells. Samd3 expression was observed in NK cells and CD8 T cells, which are known for their specific function against intracellular pathogens like viruses. After acute viral infections, Samd3 expression was enriched within memory precursor cells and the frequency of Samd3-expressing cells increased during the progression into the memory phase. Similarly, during chronic viral infections, Samd3 expression was predominantly detected within precursors of exhausted CD8 T cells that are critical for viral control. At the functional level however, Samd3-deficient CD8 T cells were not compromised in the context of acute infection with Vaccinia virus or chronic infection with Lymphocytic choriomeningitis virus. Taken together, we describe a novel multifunctional mouse model to study the role of Samd3 and Samd3-expressing cells. We found that Samd3 is specifically expressed in NK cells, memory CD8 T cells, and precursor exhausted T cells during viral infections, while the molecular function of this enigmatic gene remains further unresolved.}, language = {en} } @article{KaethnerHalderHintermuelleretal.2017, author = {K{\"a}thner, Ivo and Halder, Sebastian and Hinterm{\"u}ller, Christoph and Espinosa, Arnau and Guger, Christoph and Miralles, Felip and Vargiu, Eloisa and Dauwalder, Stefan and Rafael-Palou, Xavier and Sol{\`a}, Marc and Daly, Jean M. and Armstrong, Elaine and Martin, Suzanne and K{\"u}bler, Andrea}, title = {A Multifunctional Brain-Computer Interface Intended for Home Use: An Evaluation with Healthy Participants and Potential End Users with Dry and Gel-Based Electrodes}, series = {Frontiers in Neuroscience}, volume = {11}, journal = {Frontiers in Neuroscience}, number = {286}, doi = {10.3389/fnins.2017.00286}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157925}, year = {2017}, abstract = {Current brain-computer interface (BCIs) software is often tailored to the needs of scientists and technicians and therefore complex to allow for versatile use. To facilitate home use of BCIs a multifunctional P300 BCI with a graphical user interface intended for non-expert set-up and control was designed and implemented. The system includes applications for spelling, web access, entertainment, artistic expression and environmental control. In addition to new software, it also includes new hardware for the recording of electroencephalogram (EEG) signals. The EEG system consists of a small and wireless amplifier attached to a cap that can be equipped with gel-based or dry contact electrodes. The system was systematically evaluated with a healthy sample, and targeted end users of BCI technology, i.e., people with a varying degree of motor impairment tested the BCI in a series of individual case studies. Usability was assessed in terms of effectiveness, efficiency and satisfaction. Feedback of users was gathered with structured questionnaires. Two groups of healthy participants completed an experimental protocol with the gel-based and the dry contact electrodes (N = 10 each). The results demonstrated that all healthy participants gained control over the system and achieved satisfactory to high accuracies with both gel-based and dry electrodes (average error rates of 6 and 13\%). Average satisfaction ratings were high, but certain aspects of the system such as the wearing comfort of the dry electrodes and design of the cap, and speed (in both groups) were criticized by some participants. Six potential end users tested the system during supervised sessions. The achieved accuracies varied greatly from no control to high control with accuracies comparable to that of healthy volunteers. Satisfaction ratings of the two end-users that gained control of the system were lower as compared to healthy participants. The advantages and disadvantages of the BCI and its applications are discussed and suggestions are presented for improvements to pave the way for user friendly BCIs intended to be used as assistive technology by persons with severe paralysis.}, language = {en} } @article{TomaszkiewiczChalopinSchartletal.2014, author = {Tomaszkiewicz, Marta and Chalopin, Domitille and Schartl, Manfred and Galiana, Delphine and Volff, Jean-Nicolas}, title = {A multicopy Y-chromosomal SGNH hydrolase gene expressed in the testis of the platyfish has been captured and mobilized by a Helitron transposon}, series = {BMC Genetics}, volume = {15}, journal = {BMC Genetics}, number = {44}, doi = {10.1186/1471-2156-15-44}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116746}, year = {2014}, abstract = {Background: Teleost fish present a high diversity of sex determination systems, with possible frequent evolutionary turnover of sex chromosomes and sex-determining genes. In order to identify genes involved in male sex determination and differentiation in the platyfish Xiphophorus maculatus, bacterial artificial chromosome contigs from the sex-determining region differentiating the Y from the X chromosome have been assembled and analyzed. Results: A novel three-copy gene called teximY (for testis-expressed in Xiphophorus maculatus on the Y) was identified on the Y but not on the X chromosome. A highly related sequence called texim1, probably at the origin of the Y-linked genes, as well as three more divergent texim genes were detected in (pseudo) autosomal regions of the platyfish genome. Texim genes, for which no functional data are available so far in any organism, encode predicted esterases/lipases with a SGNH hydrolase domain. Texim proteins are related to proteins from very different origins, including proteins encoded by animal CR1 retrotransposons, animal platelet-activating factor acetylhydrolases (PAFah) and bacterial hydrolases. Texim gene distribution is patchy in animals. Texim sequences were detected in several fish species including killifish, medaka, pufferfish, sea bass, cod and gar, but not in zebrafish. Texim-like genes are also present in Oikopleura (urochordate), Amphioxus (cephalochordate) and sea urchin (echinoderm) but absent from mammals and other tetrapods. Interestingly, texim genes are associated with a Helitron transposon in different fish species but not in urochordates, cephalochordates and echinoderms, suggesting capture and mobilization of an ancestral texim gene in the bony fish lineage. RT-qPCR analyses showed that Y-linked teximY genes are preferentially expressed in testis, with expression at late stages of spermatogenesis (late spermatids and spermatozeugmata). Conclusions: These observations suggest either that TeximY proteins play a role in Helitron transposition in the male germ line in fish, or that texim genes are spermatogenesis genes mobilized and spread by transposable elements in fish genomes.}, language = {en} } @article{TranGiaDenisBacelarFerreiraetal.2021, author = {Tran-Gia, Johannes and Denis-Bacelar, Ana M. and Ferreira, Kelley M. and Robinson, Andrew P. and Calvert, Nicholas and Fenwick, Andrew J. and Finocchiaro, Domenico and Fioroni, Federica and Grassi, Elisa and Heetun, Warda and Jewitt, Stephanie J. and Kotzassarlidou, Maria and Ljungberg, Michael and McGowan, Daniel R. and Scott, Nathaniel and Scuffham, James and Gleisner, Katarina Sj{\"o}green and Tipping, Jill and Wevrett, Jill and Lassmann, Michael}, title = {A multicentre and multi-national evaluation of the accuracy of quantitative Lu-177 SPECT/CT imaging performed within the MRTDosimetry project}, series = {EJNMMI Physics}, volume = {8}, journal = {EJNMMI Physics}, doi = {10.1186/s40658-021-00397-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270380}, year = {2021}, abstract = {Purpose Patient-specific dosimetry is required to ensure the safety of molecular radiotherapy and to predict response. Dosimetry involves several steps, the first of which is the determination of the activity of the radiopharmaceutical taken up by an organ/lesion over time. As uncertainties propagate along each of the subsequent steps (integration of the time-activity curve, absorbed dose calculation), establishing a reliable activity quantification is essential. The MRTDosimetry project was a European initiative to bring together expertise in metrology and nuclear medicine research, with one main goal of standardizing quantitative \(^{177}\)Lu SPECT/CT imaging based on a calibration protocol developed and tested in a multicentre inter-comparison. This study presents the setup and results of this comparison exercise. Methods The inter-comparison included nine SPECT/CT systems. Each site performed a set of three measurements with the same setup (system, acquisition and reconstruction): (1) Determination of an image calibration for conversion from counts to activity concentration (large cylinder phantom), (2) determination of recovery coefficients for partial volume correction (IEC NEMA PET body phantom with sphere inserts), (3) validation of the established quantitative imaging setup using a 3D printed two-organ phantom (ICRP110-based kidney and spleen). In contrast to previous efforts, traceability of the activity measurement was required for each participant, and all participants were asked to calculate uncertainties for their SPECT-based activities. Results Similar combinations of imaging system and reconstruction lead to similar image calibration factors. The activity ratio results of the anthropomorphic phantom validation demonstrate significant harmonization of quantitative imaging performance between the sites with all sites falling within one standard deviation of the mean values for all inserts. Activity recovery was underestimated for total kidney, spleen, and kidney cortex, while it was overestimated for the medulla. Conclusion This international comparison exercise demonstrates that harmonization of quantitative SPECT/CT is feasible when following very specific instructions of a dedicated calibration protocol, as developed within the MRTDosimetry project. While quantitative imaging performance demonstrates significant harmonization, an over- and underestimation of the activity recovery highlights the limitations of any partial volume correction in the presence of spill-in and spill-out between two adjacent volumes of interests.}, language = {en} } @article{CanuPuglisiBerchiallaetal.2021, author = {Canu, Letizia and Puglisi, Soraya and Berchialla, Paola and De Filpo, Giuseppina and Brignardello, Francesca and Schiavi, Francesca and Ferrara, Alfonso Massimiliano and Zovato, Stefania and Luconi, Michaela and Pia, Anna and Appetecchia, Marialuisa and Arvat, Emanuela and Letizia, Claudio and Maccario, Mauro and Parasiliti-Caprino, Mirko and Altieri, Barbara and Faggiano, Antongiulio and Modica, Roberta and Morelli, Valentina and Arosio, Maura and Verga, Uberta and Pellegrino, Micaela and Petramala, Luigi and Concistr{\`e}, Antonio and Razzore, Paola and Ercolino, Tonino and Rapizzi, Elena and Maggi, Mario and Stigliano, Antonio and Burrello, Jacopo and Terzolo, Massimo and Opocher, Giuseppe and Mannelli, Massimo and Reimondo, Giuseppe}, title = {A multicenter epidemiological study on second malignancy in non-syndromic pheochromocytoma/paraganglioma patients in Italy}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {22}, issn = {2072-6694}, doi = {10.3390/cancers13225831}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250148}, year = {2021}, abstract = {No studies have carried out an extensive analysis of the possible association between non-syndromic pheochromocytomas and paragangliomas (PPGLs) and other malignancies. To assess >the risk of additional malignancy in PPGL, we retrospectively evaluated 741 patients with PPGLs followed-up in twelve referral centers in Italy. Incidence of second malignant tumors was compared between this cohort and Italian patients with two subsequent malignancies. Among our patients, 95 (12.8\%) developed a second malignant tumor, which were mainly prostate, colorectal and lung/bronchial cancers in males, breast cancer, differentiated thyroid cancer and melanoma in females. The standardized incidence ratio was 9.59 (95\% CI 5.46-15.71) in males and 13.21 (95\% CI 7.52-21.63) in females. At multivariable analysis, the risk of developing a second malignant tumor increased with age at diagnosis (HR 2.50, 95\% CI 1.15-5.44, p = 0.021 for 50-59 vs. <50-year category; HR 3.46, 95\% CI 1.67-7.15, p < 0.001 for >60- vs. <50-year). In patients with available genetic evaluation, a positive genetic test was inversely associated with the risk of developing a second tumor (HR 0.25, 95\% CI 0.10-0.63, p = 0.003). In conclusion, PPGLs patients have higher incidence of additional malignant tumors compared to the general population who had a first malignancy, which could have an impact on the surveillance strategy.}, language = {en} } @article{GersztenSahgalSheehanetal.2013, author = {Gerszten, Peter C. and Sahgal, Arjun and Sheehan, Jason P. and Kersh, Ronald and Chen, Stephanie and Flickinger, John C. and Quader, Mubina and Fahim, Daniel and Grills, Inga and Shin, John H. and Winey, Brian and Oh, Kevin and Sweeney, Reinhart A. and Guckenberger, Matthias}, title = {A multi-national report on methods for institutional credentialing for spine radiosurgery}, series = {Radiation Oncology}, volume = {8}, journal = {Radiation Oncology}, number = {158}, doi = {10.1186/1748-717X-8-158}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131485}, year = {2013}, abstract = {Background: Stereotactic body radiotherapy and radiosurgery are rapidly emerging treatment options for both malignant and benign spine tumors. Proper institutional credentialing by physicians and medical physicists as well as other personnel is important for the safe and effective adoption of spine radiosurgery. This article describes the methods for institutional credentialing for spine radiosurgery at seven highly experienced international institutions. Methods: All institutions (n = 7) are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided spine radiosurgery. A questionnaire consisting of 24 items covering various aspects of institutional credentialing for spine radiosurgery was completed by all seven institutions. Results: Close agreement was observed in most aspects of spine radiosurgery credentialing at each institution. A formal credentialing process was believed to be important for the implementation of a new spine radiosurgery program, for patient safety and clinical outcomes. One institution has a written policy specific for spine radiosurgery credentialing, but all have an undocumented credentialing system in place. All institutions rely upon an in-house proctoring system for the training of both physicians and medical physicists. Four institutions require physicians and medical physicists to attend corporate sponsored training. Two of these 4 institutions also require attendance at a non-corporate sponsored academic society radiosurgery course. Corporate as well as non-corporate sponsored training were believed to be complimentary and both important for training. In 5 centers, all cases must be reviewed at a multidisciplinary conference prior to radiosurgery treatment. At 3 centers, neurosurgeons are not required to be involved in all cases if there is no evidence for instability or spinal cord compression. Backup physicians and physicists are required at only 1 institution, but all institutions have more than one specialist trained to perform spine radiosurgery. All centers believed that credentialing should also be device specific, and all believed that professional societies should formulate guidelines for institutions on the requirements for spine radiosurgery credentialing. Finally, in 4 institutions radiation therapists were required to attend corporate-sponsored device specific training for credentialing, and in only 1 institution were radiation therapists required to also attend academic society training for credentialing. Conclusions: This study represents the first multi-national report of the current practice of institutional credentialing for spine radiosurgery. Key methodologies for safe implementation and credentialing of spine radiosurgery have been identified. There is strong agreement among experienced centers that credentialing is an important component of the safe and effective implementation of a spine radiosurgery program.}, language = {en} } @article{HardcastleTomeCannonetal.2012, author = {Hardcastle, Nicholas and Tom{\´e}, Wolfgang A. and Cannon, Donald M. and Brouwer, Charlotte L. and Wittendorp, Paul W. H. and Dogan, Nesrin and Guckenberger, Matthias and Allaire, St{\´e}phane and Mallya, Yogish and Kumar, Prashant and Oechsner, Markus and Richter, Anne and Song, Shiyu and Myers, Michael and Polat, B{\"u}lent and Bzdusek, Karl}, title = {A multi-institution evaluation of deformable image registration algorithms for automatic organ delineation in adaptive head and neck radiotherapy}, series = {Radiation Oncology}, volume = {7}, journal = {Radiation Oncology}, number = {90}, doi = {10.1186/1748-717X-7-90}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134756}, year = {2012}, abstract = {Background: Adaptive Radiotherapy aims to identify anatomical deviations during a radiotherapy course and modify the treatment plan to maintain treatment objectives. This requires regions of interest (ROIs) to be defined using the most recent imaging data. This study investigates the clinical utility of using deformable image registration (DIR) to automatically propagate ROIs. Methods: Target (GTV) and organ-at-risk (OAR) ROIs were non-rigidly propagated from a planning CT scan to a per-treatment CT scan for 22 patients. Propagated ROIs were quantitatively compared with expert physician-drawn ROIs on the per-treatment scan using Dice scores and mean slicewise Hausdorff distances, and center of mass distances for GTVs. The propagated ROIs were qualitatively examined by experts and scored based on their clinical utility. Results: Good agreement between the DIR-propagated ROIs and expert-drawn ROIs was observed based on the metrics used. 94\% of all ROIs generated using DIR were scored as being clinically useful, requiring minimal or no edits. However, 27\% (12/44) of the GTVs required major edits. Conclusion: DIR was successfully used on 22 patients to propagate target and OAR structures for ART with good anatomical agreement for OARs. It is recommended that propagated target structures be thoroughly reviewed by the treating physician.}, language = {en} } @article{WinkelbeinerWandtEbertetal.2020, author = {Winkelbeiner, Nicola and Wandt, Viktoria K. and Ebert, Franziska and Lossow, Kristina and Bankoglu, Ezgi E. and Martin, Maximilian and Mangerich, Aswin and Stopper, Helga and Bornhorst, Julia and Kipp, Anna P. and Schwerdtle, Tanja}, title = {A multi-endpoint approach to base excision repair incision activity augmented by PARylation and DNA damage levels in mice: impact of sex and age}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {18}, issn = {1422-0067}, doi = {10.3390/ijms21186600}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285706}, year = {2020}, abstract = {Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2'-deoxyguanosine (8-oxodG), 5-hydroxy-2'-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.}, language = {en} } @article{DorschKrieterLemkeetal.2012, author = {Dorsch, Oliver and Krieter, Detlef H. and Lemke, Horst-Dieter and Fischer, Stefan and Melzer, Nima and Sieder, Christian and Bramlage, Peter and Harenberg, Job}, title = {A multi-center, prospective, open-label, 8-week study of certoparin for anticoagulation during maintenance hemodialysis - the membrane study}, series = {BMC Nephrology}, volume = {13}, journal = {BMC Nephrology}, number = {50}, doi = {10.1186/1471-2369-13-50}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124052}, year = {2012}, abstract = {Background Adequate anticoagulation is prerequisite for effective hemodialysis to prevent clotting in the extracorporeal circuit. We aimed providing first data on the efficacy and safety of the low-molecular-weight heparin certoparin in this setting. Methods Multicenter, open-label, 8-week trial. Patients received a single dose of 3,000 IU certoparin i.v. with additional titration steps of 600 IU and/or continuous infusion if necessary. Results 120 patients were screened, 109 enrolled (median age 71; range 26-90 years) and 106 available for efficacy analyses. The percentage of unsatisfactory dialysis results at 8 weeks due to clotting or bleeding, was 1.9\% (n = 2/106; 95\% confidence interval [CI] 0.23-6.65\%); no major bleeding. 1.9\% had moderate/severe clotting in the lines/bubble catcher and 2.8\% in the dialyser at week 8. 15.7 ± 14.3\% of the dialysis filters' visual surface area was showing redness. In subgroups of patients receiving median doses of 3000 ± 0, 3000 (2400-6000) and 4200 (3000-6600) IU, plasma aXa levels at baseline, 4 and 8 weeks were 0.24 [95\%CI 0.21-0.27], 0.33 [0.27-0.40] and 0.38 [0.33-0.45] aXa IU/ml at 2 h. \(C_{48h}\) was 0.01 [0.01-0.02] aXa IU at all visits. At baseline and 4 weeks \(AUC_{0-48h}\) was 2.66 [2.19-3.24] and 3.66 [3.00-4.45] aXa IU*h/ml. In 3.0\% of dialyses (n = 83/2724) prolonged fistula compression times were documented. Eight patients (7.34\%) had at least one episode of minor bleeding. 4) 85.3\% of patients had any adverse event, 9.2\% were serious without suspected drug relation; and in 32 patients a drug-relation was suspected. Conclusions Certoparin appears effective and safe for anticoagulation in patients undergoing maintenance hemodialysis.}, language = {en} } @article{DorschKrieterLemkeetal.2012, author = {Dorsch, Oliver and Krieter, Detlef H. and Lemke, Horst-Dieter and Fischer, Stefan and Melzer, Nima and Sieder, Christian and Bramlage, Peter and Harenberg, Job}, title = {A multi-center, prospective, open-label, 8-week study of certoparin for anticoagulation during maintenance hemodialysis - the membrane study}, series = {BMC Nephrology}, volume = {13}, journal = {BMC Nephrology}, number = {50}, doi = {10.1186/1471-2369-13-50}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134845}, year = {2012}, abstract = {Background: Adequate anticoagulation is prerequisite for effective hemodialysis to prevent clotting in the extracorporeal circuit. We aimed providing first data on the efficacy and safety of the low-molecular-weight heparin certoparin in this setting. Methods: Multicenter, open-label, 8-week trial. Patients received a single dose of 3,000 IU certoparin i.v. with additional titration steps of 600 IU and/or continuous infusion if necessary. Results: 120 patients were screened, 109 enrolled (median age 71; range 26-90 years) and 106 available for efficacy analyses. The percentage of unsatisfactory dialysis results at 8 weeks due to clotting or bleeding, was 1.9\% (n = 2/106; 95\% confidence interval [CI] 0.23-6.65\%); no major bleeding. 1.9\% had moderate/severe clotting in the lines/bubble catcher and 2.8\% in the dialyser at week 8.15.7 +/- 14.3\% of the dialysis filters' visual surface area was showing redness. In subgroups of patients receiving median doses of 3000 +/- 0, 3000 (2400-6000) and 4200 (3000-6600) IU, plasma aXa levels at baseline, 4 and 8 weeks were 0.24 [ 95\% CI 0.21-0.27], 0.33 [0.27-0.40] and 0.38 [0.33-0.45] aXa IU/ml at 2 h. C-48h was 0.01 [0.01-0.02] aXa IU at all visits. At baseline and 4 weeks AUC(0-48h) was 2.66 [2.19-3.24] and 3.66 [3.00-4.45] aXa IU*h/ml. In 3.0\% of dialyses (n = 83/2724) prolonged fistula compression times were documented. Eight patients (7.34\%) had at least one episode of minor bleeding. 4) 85.3\% of patients had any adverse event, 9.2\% were serious without suspected drug relation; and in 32 patients a drug-relation was suspected. Conclusions: Certoparin appears effective and safe for anticoagulation in patients undergoing maintenance hemodialysis.}, language = {en} } @article{PalamidesJodeleitFoehlingeretal.2016, author = {Palamides, Pia and Jodeleit, Henrika and F{\"o}hlinger, Michael and Beigel, Florian and Herbach, Nadja and Mueller, Thomas and Wolf, Eckhard and Siebeck, Matthias and Gropp, Roswitha}, title = {A mouse model for ulcerative colitis based on NOD-scid IL2R gamma(null) mice reconstituted with peripheral blood mononuclear cells from affected individuals}, series = {Disease Models \& Mechanisms}, volume = {9}, journal = {Disease Models \& Mechanisms}, doi = {10.1242/dmm.025452}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164946}, pages = {985-997}, year = {2016}, abstract = {Animal models reflective of ulcerative colitis (UC) remain a major challenge, and yet are crucial to understand mechanisms underlying the onset of disease and inflammatory characteristics of relapses and remission. Mouse models in which colitis-like symptoms are induced through challenge with toxins such as oxazolone, dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) have been instrumental in understanding the inflammatory processes of UC. However, these neither reflect the heterogeneous symptoms observed in the UC-affected population nor can they be used to test the efficacy of inhibitors developed against human targets where high sequence and structural similarity of the respective ligands is lacking. In an attempt to overcome these problems, we have developed a mouse model that relies on NOD-scid IL2R γnull mice reconstituted with peripheral blood mononuclear cells derived from UC-affected individuals. Upon challenge with ethanol, mice developed colitis-like symptoms and changes in the colon architecture, characterized by influx of inflammatory cells, edema, crypt loss, crypt abscesses and epithelial hyperplasia, as previously observed in immune-competent mice. TARC, TGFβ1 and HGF expression increased in distal parts of the colon. Analysis of human leucocytes isolated from mouse spleen revealed an increase in frequencies of CD1a+, CD64+, CD163+ and TSLPR+ CD14+ monocytes, and antigen-experienced CD44+ CD4+ and CD8+ T-cells in response to ethanol. Analysis of human leucocytes from the colon of challenged mice identified CD14+ monocytes and CD11b+ monocytes as the predominant populations. Quantitative real-time PCR (RT-PCR) analysis from distal parts of the colon indicated that IFNγ might be one of the cytokines driving inflammation. Treatment with infliximab ameliorated symptoms and pathological manifestations, whereas pitrakinra had no therapeutic benefit. Thus, this model is partially reflective of the human disease and might help to increase the translation of animal and clinical studies.}, language = {en} } @article{SchneiderSeebauerBeuerleetal.2024, author = {Schneider, Tilman and Seebauer, Florian and Beuerle, Florian and W{\"u}rthner, Frank}, title = {A monodisperse, end-capped Ru(bda) oligomer with outstanding performance in heterogeneous electrochemical water oxidation}, series = {Advanced Materials Technologies}, volume = {9}, journal = {Advanced Materials Technologies}, number = {11}, issn = {2365-709X}, doi = {10.1002/admt.202301721}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363133}, year = {2024}, abstract = {AbstractWater oxidation catalysis is a key step for sustainable fuel production by water splitting into hydrogen and oxygen. The synthesis of a novel coordination oligomer based on four Ru(bda) (bda = 2,2′-bipyridine-6,6′-dicarboxylate) centers, three 4,4′-bipyridine (4,4′-bpy) linkers, and two 4-picoline (4-pic) end caps is reported. The monodispersity of this tetranuclear compound is characterized by NMR techniques. Heterogeneous electrochemical water oxidation after immobilization on multi-walled carbon nanotubes (MWCNTs) shows catalytic performance unprecedented for this compound class, with a turnover frequency (TOF) of 133 s\(^{-1}\) and a turnover number (TON) of 4.89 × 10\(^6\), at a current density of 43.8 mA cm\(^{-2}\) and a potential of 1.45 V versus normal hydrogen electrode (NHE).}, language = {en} } @article{MolochnikovRabeyDobronevskyetal.2012, author = {Molochnikov, Leonid and Rabey, Jose M. and Dobronevsky, Evgenya and Bonuccelli, Ubaldo and Ceravolo, Roberto and Frosini, Daniela and Gr{\"u}nblatt, Edna and Riederer, Peter and Jacob, Christian and Aharon-Peretz, Judith and Bashenko, Yulia and Youdim, Moussa B. H. and Mandel, Silvia A.}, title = {A molecular signature in blood identifies early Parkinson's disease}, series = {Molecular Neurodegeneration}, volume = {7}, journal = {Molecular Neurodegeneration}, number = {26}, doi = {10.1186/1750-1326-7-26}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134508}, year = {2012}, abstract = {Background: The search for biomarkers in Parkinson's disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD. Results: The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95\% confidence interval [CI] 0.60-0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08-1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95\% CI 0.75-0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95\% CI 0.60-0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95\% CI 1.14-1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. The performance of the five-gene classifier on the de novo PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100\% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22)), suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer's disease (n = 29). Conclusions: The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.}, language = {en} } @article{MergetWolf2010, author = {Merget, Benjamin and Wolf, Matthias}, title = {A molecular phylogeny of Hypnales (Bryophyta) inferred from ITS2 sequence-structure data}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67997}, year = {2010}, abstract = {Background: Hypnales comprise over 50\% of all pleurocarpous mosses. They provide a young radiation complicating phylogenetic analyses. To resolve the hypnalean phylogeny, it is necessary to use a phylogenetic marker providing highly variable features to resolve species on the one hand and conserved features enabling a backbone analysis on the other. Therefore we used highly variable internal transcribed spacer 2 (ITS2) sequences and conserved secondary structures, as deposited with the ITS2 Database, simultaneously. Findings: We built an accurate and in parts robustly resolved large scale phylogeny for 1,634 currently available hypnalean ITS2 sequence-structure pairs. Conclusions: Profile Neighbor-Joining revealed a possible hypnalean backbone, indicating that most of the hypnalean taxa classified as different moss families are polyphyletic assemblages awaiting taxonomic changes.}, subject = {Moose}, language = {en} } @article{LoefflerWirthKreuzHoppetal.2019, author = {Loeffler-Wirth, Henry and Kreuz, Markus and Hopp, Lydia and Arakelyan, Arsen and Haake, Andrea and Cogliatti, Sergio B. and Feller, Alfred C. and Hansmann, Martin-Leo and Lenze, Dido and M{\"o}ller, Peter and M{\"u}ller-Hermelink, Hans Konrad and Fortenbacher, Erik and Willscher, Edith and Ott, German and Rosenwald, Andreas and Pott, Christiane and Schwaenen, Carsten and Trautmann, Heiko and Wessendorf, Swen and Stein, Harald and Szczepanowski, Monika and Tr{\"u}mper, Lorenz and Hummel, Michael and Klapper, Wolfram and Siebert, Reiner and Loeffler, Markus and Binder, Hans}, title = {A modular transcriptome map of mature B cell lymphomas}, series = {Genome Medicine}, volume = {11}, journal = {Genome Medicine}, doi = {10.1186/s13073-019-0637-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237262}, year = {2019}, abstract = {Background Germinal center-derived B cell lymphomas are tumors of the lymphoid tissues representing one of the most heterogeneous malignancies. Here we characterize the variety of transcriptomic phenotypes of this disease based on 873 biopsy specimens collected in the German Cancer Aid MMML (Molecular Mechanisms in Malignant Lymphoma) consortium. They include diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt's lymphoma, mixed FL/DLBCL lymphomas, primary mediastinal large B cell lymphoma, multiple myeloma, IRF4-rearranged large cell lymphoma, MYC-negative Burkitt-like lymphoma with chr. 11q aberration and mantle cell lymphoma. Methods We apply self-organizing map (SOM) machine learning to microarray-derived expression data to generate a holistic view on the transcriptome landscape of lymphomas, to describe the multidimensional nature of gene regulation and to pursue a modular view on co-expression. Expression data were complemented by pathological, genetic and clinical characteristics. Results We present a transcriptome map of B cell lymphomas that allows visual comparison between the SOM portraits of different lymphoma strata and individual cases. It decomposes into one dozen modules of co-expressed genes related to different functional categories, to genetic defects and to the pathogenesis of lymphomas. On a molecular level, this disease rather forms a continuum of expression states than clearly separated phenotypes. We introduced the concept of combinatorial pattern types (PATs) that stratifies the lymphomas into nine PAT groups and, on a coarser level, into five prominent cancer hallmark types with proliferation, inflammation and stroma signatures. Inflammation signatures in combination with healthy B cell and tonsil characteristics associate with better overall survival rates, while proliferation in combination with inflammation and plasma cell characteristics worsens it. A phenotypic similarity tree is presented that reveals possible progression paths along the transcriptional dimensions. Our analysis provided a novel look on the transition range between FL and DLBCL, on DLBCL with poor prognosis showing expression patterns resembling that of Burkitt's lymphoma and particularly on 'double-hit' MYC and BCL2 transformed lymphomas. Conclusions The transcriptome map provides a tool that aggregates, refines and visualizes the data collected in the MMML study and interprets them in the light of previous knowledge to provide orientation and support in current and future studies on lymphomas and on other cancer entities.}, language = {en} } @article{SommerRichterRogauschetal.2011, author = {Sommer, Claudia and Richter, Helmut and Rogausch, Jan P. and Frettloh, Jule and Lungenhausen, Margitta and Maier, Christoph}, title = {A modified score to identify and discriminate neuropathic pain: a study on the German version of the neuropathic pain symptom inventory (NPSI)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68716}, year = {2011}, abstract = {Background: Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain. Methods: We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles. Results: Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91\%) and acceptable specificity (70\%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct. Conclusions: The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain.}, subject = {Neuralgie}, language = {en} } @article{YeWilhelmGentschevetal.2021, author = {Ye, Mingyu and Wilhelm, Martina and Gentschev, Ivaylo and Szalay, Alad{\´a}r}, title = {A modified limiting dilution method for monoclonal stable cell line selection using a real-time fluorescence imaging system: A practical workflow and advanced applications}, series = {Methods and Protocols}, volume = {4}, journal = {Methods and Protocols}, number = {1}, doi = {10.3390/mps4010016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228896}, year = {2021}, abstract = {Stable cell lines are widely used in laboratory research and pharmaceutical industry. They are mainly applied in recombinant protein and antibody productions, gene function studies, drug screens, toxicity assessments, and for cancer therapy investigation. There are two types of cell lines, polyclonal and monoclonal origin, that differ regarding their homogeneity and heterogeneity. Generating a high-quality stable cell line, which can grow continuously and carry a stable genetic modification without alteration is very important for most studies, because polyclonal cell lines of multicellular origin can be highly variable and unstable and lead to inconclusive experimental results. The most commonly used technologies of single cell originate monoclonal stable cell isolation in laboratory are fluorescence-activated cell sorting (FACS) sorting and limiting dilution cloning. Here, we describe a modified limiting dilution method of monoclonal stable cell line selection using the real-time fluorescence imaging system IncuCyte\(^®\)S3.}, language = {en} } @article{RaslanAlbertWeissenbergerWestermaieretal.2012, author = {Raslan, Furat and Albert-Weißenberger, Christiane and Westermaier, Thomas and Saker, Saker and Kleinschmitz, Christoph and Lee, Jin-Yul}, title = {A modified double injection model of cisterna magna for the study of delayed cerebral vasospasm following subarachnoid hemorrhage in rats}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76038}, year = {2012}, abstract = {Delayed cerebral vasospasm following subarachnoid hemorrhage (SAH) is a serious medical complication, characterized by constriction of cerebral arteries leading to varying degrees of cerebral ischemia. Numerous clinical and experimental studies have been performed in the last decades; however, the pathophysiologic mechanism of cerebral vasospasm after SAH still remains unclear. Among a variety of experimental SAH models, the double hemorrhage rat model involving direct injection of autologous arterial blood into the cisterna magna has been used most frequently for the study of delayed cerebral vasospasm following SAH in last years. Despite the simplicity of the technique, the second blood injection into the cisterna magna may result in brainstem injury leading to high mortality. Therefore, a modified double hemorrhage model of cisterna magna has been developed in rat recently. We describe here step by step the surgical technique to induce double SAH and compare the degree of vasospasm with other cisterna magna rat models using histological assessment of the diameter and cross-sectional area of the basilar artery}, subject = {Medizin}, language = {en} } @article{BrillSchwab2019, author = {Brill, Michael and Schwab, Frank}, title = {A mixed-methods approach using self-report, observational time series data, and content analysis for process analysis of a media reception phenomenon}, series = {Frontiers in Psychology}, volume = {10}, journal = {Frontiers in Psychology}, doi = {10.3389/fpsyg.2019.01666}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201380}, pages = {1666}, year = {2019}, abstract = {Due to the complexityof research objects, theoretical concepts, and stimuli in media research, researchers in psychology and communications presumably need sophisticated measures beyond self-report scales to answer research questions on media use processes. The present study evaluates stimulus-dependent structure in spontaneous eye-blink behavior as an objective, corroborative measure for the media use phenomenon of spatial presence. To this end, a mixed methods approach is used in an experimental setting to collect, combine, analyze, and interpret data from standardized participant self-report, observation of participant behavior, and content analysis of the media stimulus. T-pattern detection is used to analyze stimulus-dependent blinking behavior, and this structural data is then contrasted with self-report data. The combined results show that behavioral indicators yield the predicted results, while self-report data shows unpredicted results that are not predicted by the underlying theory. The use of a mixed methods approach offered insights that support further theory development and theory testing beyond a traditional, mono-method experimental approach.}, language = {en} } @article{Lin2011, author = {Lin, Hang}, title = {A Mixed Bag of Results: Village Elections in Contemporary China}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68684}, year = {2011}, abstract = {While there is only little transformation to the absolute power of the party-state to be detected, some grassroots democratic experiments, however, are receiving enormous attention of the world, especially village elections. Nevertheless, this preliminary exercise of democracy is widely characterized as a mixed bag of results. Since its first conduction, it has experienced immense development and bought great impact not only on different rural political institutions, but also on common mass villagers, as well as changes to the local governance. But at the same time, the limitations of the factual effectiveness of these elections can hardly be underestimated and such aspects as the standardization of electoral procedures are still to be further improved. Moreover, given the wide variations across Chinese countryside and the strong oppositions from all levels, the future of China's village elections remain hard to gauge.}, subject = {China}, language = {en} } @article{SchusterJohannsenRoewer2013, author = {Schuster, Frank and Johannsen, Stephan and Roewer, Norbert}, title = {A Minimal-Invasive Metabolic Test Detects Malignant Hyperthermia Susceptibility in a Patient after Sevoflurane-Induced Metabolic Crisis}, series = {Case Reports in Anesthesiology}, journal = {Case Reports in Anesthesiology}, doi = {10.1155/2013/953859}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97080}, year = {2013}, abstract = {Malignant hyperthermia is a rare but life-threatening complication of general anesthesia in predisposed patients usually triggered by potent inhalation anesthetics and/or the depolarizing muscle relaxant succinylcholine. The authors present a case of delayed sevoflurane-induced malignant hyperthermia in a 21-year-old male patient that was sufficiently treated by discontinuation of trigger agent application and dantrolene infusion. After surviving an MH episode diagnostic procedures are indicated to increase patient safety. In the presented case, the use of a novel minimal-invasive metabolic test with intramuscular injection of halothane and caffeine successfully confirmed MH susceptibility and hence might be an alternative for invasive in vitro contracture testing in selected cases.}, language = {en} } @article{RotherKraftSmithetal.2021, author = {Rother, Lisa and Kraft, Nadine and Smith, Dylan B. and El Jundi, Basil and Gill, Richard J. and Pfeiffer, Keram}, title = {A micro-CT-based standard brain atlas of the bumblebee}, series = {Cell and Tissue Research}, volume = {386}, journal = {Cell and Tissue Research}, number = {1}, issn = {1432-0878}, doi = {10.1007/s00441-021-03482-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267783}, pages = {29-45}, year = {2021}, abstract = {In recent years, bumblebees have become a prominent insect model organism for a variety of biological disciplines, particularly to investigate learning behaviors as well as visual performance. Understanding these behaviors and their underlying neurobiological principles requires a clear understanding of brain anatomy. Furthermore, to be able to compare neuronal branching patterns across individuals, a common framework is required, which has led to the development of 3D standard brain atlases in most of the neurobiological insect model species. Yet, no bumblebee 3D standard brain atlas has been generated. Here we present a brain atlas for the buff-tailed bumblebee Bombus terrestris using micro-computed tomography (micro-CT) scans as a source for the raw data sets, rather than traditional confocal microscopy, to produce the first ever micro-CT-based insect brain atlas. We illustrate the advantages of the micro-CT technique, namely, identical native resolution in the three cardinal planes and 3D structure being better preserved. Our Bombus terrestris brain atlas consists of 30 neuropils reconstructed from ten individual worker bees, with micro-CT allowing us to segment neuropils completely intact, including the lamina, which is a tissue structure often damaged when dissecting for immunolabeling. Our brain atlas can serve as a platform to facilitate future neuroscience studies in bumblebees and illustrates the advantages of micro-CT for specific applications in insect neuroanatomy.}, language = {en} } @article{SexauerBhasinSchoenetal.2023, author = {Sexauer, Moritz and Bhasin, Hemal and Sch{\"o}n, Maria and Roitsch, Elena and Wall, Caroline and Herzog, Ulrike and Markmann, Katharina}, title = {A micro RNA mediates shoot control of root branching}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-43738-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357472}, year = {2023}, abstract = {Plants extract mineral nutrients from the soil, or from interactions with mutualistic soil microbes via their root systems. Adapting root architecture to nutrient availability enables efficient resource utilization, particularly in patchy and dynamic environments. Root growth responses to soil nitrogen levels are shoot-mediated, but the identity of shoot-derived mobile signals regulating root growth responses has remained enigmatic. Here we show that a shoot-derived micro RNA, miR2111, systemically steers lateral root initiation and nitrogen responsiveness through its root target TML (TOO MUCH LOVE) in the legume Lotus japonicus, where miR2111 and TML were previously shown to regulate symbiotic infections with nitrogen fixing bacteria. Intriguingly, systemic control of lateral root initiation by miR2111 and TML/HOLT (HOMOLOGUE OF LEGUME TML) was conserved in the nonsymbiotic ruderal Arabidopsis thaliana, which follows a distinct ecological strategy. Thus, the miR2111-TML/HOLT regulon emerges as an essential, conserved factor in adaptive shoot control of root architecture in dicots.}, language = {en} } @article{SalmanHaiderSchreinerKendletal.2019, author = {Salman Haider, Malik and Schreiner, Jochen and Kendl, Sabine and Kroiss, Matthias and Luxenhofer, Robert}, title = {A Micellar Mitotane Formulation with High Drug-Loading and Solubility: Physico-Chemical Characterization and Cytotoxicity Studies in 2D and 3D In Vitro Tumor Models}, series = {Macromolecular Bioscience}, volume = {20}, journal = {Macromolecular Bioscience}, number = {1}, doi = {10.1002/mabi.201900178}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206224}, pages = {1900178}, year = {2019}, abstract = {Adrenocortical carcinoma (ACC) is a rare tumor and prognosis is overall poor but heterogeneous. Mitotane (MT) has been used for treatment of ACC for decades, either alone or in combination with cytotoxic chemotherapy. Even at doses up to 6 g per day, more than half of the patients do not achieve targeted plasma concentration (14-20 mg L\(^{-1}\)) even after many months of treatment due to low water solubility, bioavailability, and unfavorable pharmacokinetic profile. Here a novel MT nanoformulation with very high MT concentrations in physiological aqueous media is reported. The MT-loaded nanoformulations are characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction which confirms the amorphous nature of the drug. The polymer itself does not show any cytotoxicity in adrenal and liver cell lines. By using the ACC model cell line NCI-H295 both in monolayers and tumor cell spheroids, micellar MT is demonstrated to exhibit comparable efficacy to its ethanol solution. It is postulated that this formulation will be suitable for i.v. application and rapid attainment of therapeutic plasma concentrations. In conclusion, the micellar formulation is considered a promising tool to alleviate major drawbacks of current MT treatment while retaining bioactivity toward ACC in vitro.}, language = {en} } @article{NazzalHowariYaslametal.2022, author = {Nazzal, Yousef and Howari, Fares M. and Yaslam, Aya and Iqbal, Jibran and Maloukh, Lina and Ambika, Lakshmi Kesari and Al-Taani, Ahmed A. and Ali, Ijaz and Othman, Eman M. and Jamal, Arshad and Naseem, Muhammad}, title = {A methodological review of tools that assess dust microbiomes, metatranscriptomes and the particulate chemistry of indoor dust}, series = {Atmosphere}, volume = {13}, journal = {Atmosphere}, number = {8}, issn = {2073-4433}, doi = {10.3390/atmos13081276}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285957}, year = {2022}, abstract = {Indoor house dust is a blend of organic and inorganic materials, upon which diverse microbial communities such as viruses, bacteria and fungi reside. Adequate moisture in the indoor environment helps microbial communities multiply fast. The outdoor air and materials that are brought into the buildings by airflow, sandstorms, animals pets and house occupants endow the indoor dust particles with extra features that impact human health. Assessment of the health effects of indoor dust particles, the type of indoor microbial inoculants and the secreted enzymes by indoor insects as allergens merit detailed investigation. Here, we discuss the applications of next generation sequencing (NGS) technology which is used to assess microbial diversity and abundance of the indoor dust environments. Likewise, the applications of NGS are discussed to monitor the gene expression profiles of indoor human occupants or their surrogate cellular models when exposed to aqueous solution of collected indoor dust samples. We also highlight the detection methods of dust allergens and analytical procedures that quantify the chemical nature of indoor particulate matter with a potential impact on human health. Our review is thus unique in advocating the applications of interdisciplinary approaches that comprehensively assess the health effects due to bad air quality in built environments.}, language = {en} } @article{KunzAzadEngelHolmbergetal.2019, author = {Kunz, Philipp and Azad Engel, Florian and Holmberg, Hans-Christer and Sperlich, Billy}, title = {A meta-comparison of the effects of high-intensity interval training to those of small-sided games and other training protocols on parameters related to the physiology and performance of youth soccer players}, series = {Sports Medicine - Open}, volume = {5}, journal = {Sports Medicine - Open}, doi = {10.1186/s40798-019-0180-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200332}, pages = {7}, year = {2019}, abstract = {Background High-intensity interval training (HIIT) is frequently employed to improve the endurance of various types of athletes. To determine whether youth soccer players may benefit from the intermittent load and time efficiency of HIIT, we performed a meta-analysis of the relevant scientific literature. Objectives Our primary objective was to compare changes in various physiological parameters related to the performance of youth soccer players in response to running-based HIIT to the effects of other common training protocols (i.e., small-sided games, technical training and soccer-specific training, or high-volume endurance training). A secondary objective was to compare specifically running-based HIIT to a soccer-specific form of HIIT known as small-sided games (SSG) in this same respect, since this latter type of training is being discussed extensively by coaches. Method A systematic search of the PubMed, SPORTDiscus, and Web of Science databases was performed in August of 2017 and updated during the review process in December of 2018. The criteria for inclusion of articles for analysis were as follows: (1) comparison of HIIT to SSG or some other training protocol employing a pre-post design, (2) involvement of healthy young athletes (≤ 18 years old), and (3) assessment of variables related to endurance or soccer performance. Hedges' g effect size (dppc2) and associated 95\% confidence intervals for the comparison of the responses to HIIT and other interventions were calculated. Results Nine studies, involving 232 young soccer players (mean age 16.2 ± 1.6 years), were examined. Endurance training in the form of HIIT or SSG produced similar positive effects on most parameters assessed, including peak oxygen uptake and maximal running performance during incremental running (expressed as Vmax or maximal aerobic speed (MAS)), shuttle runs (expressed as the distance covered or time to exhaustion), and time-trials, as well as submaximal variables such as running economy and running velocity at the lactate threshold. HIIT induced a moderate improvement in soccer-related tests involving technical exercises with the soccer ball and other game-specific parameters (i.e., total distance covered, number of sprints, and number of involvements with the ball). Neuromuscular parameters were largely unaffected by HIIT or SSG. Conclusion The present meta-analysis indicates that HIIT and SSG have equally beneficial impacts on variables related to the endurance and soccer-specific performance of youth soccer players, but little influence on neuromuscular performance.}, language = {en} } @article{PlanesNinolesRubioetal.2015, author = {Planes, Maria D. and Ni{\~n}oles, Regina and Rubio, Lourdes and Bissoli, Gaetano and Bueso, Eduardo and Garc{\´i}a-S{\´a}nchez, Mar{\´i}a J. and Alejandro, Santiago and Gonzalez-Guzm{\´a}n, Miguel and Hedrich, Rainer and Rodriguez, Pedro L. and Fern{\´a}ndez, Jos{\´e} A. and Serrano, Ram{\´o}n}, title = {A mechanism of growth inhibition by abscisic acid in germinating seeds of Arabidopsis thaliana based on inhibition of plasma membrane \(H^+\)-ATPase and decreased cytosolic pH, \(K^+\), and anions}, series = {Journal of Experimental Botany}, volume = {66}, journal = {Journal of Experimental Botany}, number = {3}, doi = {10.1093/jxb/eru442}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121221}, pages = {813-25}, year = {2015}, abstract = {The stress hormone abscisic acid (ABA) induces expression of defence genes in many organs, modulates ion homeostasis and metabolism in guard cells, and inhibits germination and seedling growth. Concerning the latter effect, several mutants of Arabidopsis thaliana with improved capability for \(H^+\) efflux (wat1-1D, overexpression of AKT1 and ost2-1D) are less sensitive to inhibition by ABA than the wild type. This suggested that ABA could inhibit \(H^+\) efflux (\(H^+\)-ATPase) and induce cytosolic acidification as a mechanism of growth inhibition. Measurements to test this hypothesis could not be done in germinating seeds and we used roots as the most convenient system. ABA inhibited the root plasma-membrane H+-ATPase measured in vitro (ATP hydrolysis by isolated vesicles) and in vivo (\(H^+\) efflux from seedling roots). This inhibition involved the core ABA signalling elements: PYR/PYL/RCAR ABA receptors, ABA-inhibited protein phosphatases (HAB1), and ABA-activated protein kinases (SnRK2.2 and SnRK2.3). Electrophysiological measurements in root epidermal cells indicated that ABA, acting through the PYR/PYL/RCAR receptors, induced membrane hyperpolarization (due to \(K^+\) efflux through the GORK channel) and cytosolic acidification. This acidification was not observed in the wat1-1D mutant. The mechanism of inhibition of the \(H^+\)-ATPase by ABA and its effects on cytosolic pH and membrane potential in roots were different from those in guard cells. ABA did not affect the in vivo phosphorylation level of the known activating site (penultimate threonine) of (\(H^+\)-ATPase in roots, and SnRK2.2 phosphorylated in vitro the C-terminal regulatory domain of (\(H^+\)-ATPase while the guard-cell kinase SnRK2.6/OST1 did not.}, language = {en} } @article{OPUS4-17369, title = {A measurement of the calorimeter response to single hadrons and determination of the jet energy scale uncertainty using LHC Run-1 \(pp\)-collision data with the ATLAS detector}, series = {European Physical Journal C}, volume = {77}, journal = {European Physical Journal C}, number = {26}, organization = {The ATLAS Collaboration}, doi = {10.1140/epjc/s10052-016-4580-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173690}, year = {2017}, abstract = {A measurement of the calorimeter response to isolated charged hadrons in the ATLAS detector at the LHC is presented. This measurement is performed with 3.2 nb\(^{-1}\) of proton-proton collision data at \(\sqrt{s}\) = 7 TeV from 2010 and 0.1 nb\(^{-1}\) of data at \(\sqrt{s}\) = 8 TeV from 2012. A number of aspects of the calorimeter response to isolated hadrons are explored. After accounting for energy deposited by neutral particles, there is a 5\% discrepancy in the modelling, using various sets of GEANT4 hadronic physics models, of the calorimeter response to isolated charged hadrons in the central calorimeter region. The description of the response to anti-protons at low momenta is found to be improved with respect to previous analyses. The electromagnetic and hadronic calorimeters are also examined separately, and the detector simulation is found to describe the response in the hadronic calorimeter well. The jet energy scale uncertainty and correlations in scale between jets of different momenta and pseudorapidity are derived based on these studies. The uncertainty is 2-5\% for jets with transverse momenta above 2 TeV, where this method provides the jet energy scale uncertainty for ATLAS.}, language = {en} } @article{AliMontenegro2014, author = {Ali, Quasim and Montenegro, Sergio}, title = {A Matlab Implementation of Differential GPS for Low-cost GPS Receivers}, doi = {10.12716/1001.08.03.03}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113618}, year = {2014}, abstract = {A number of public codes exist for GPS positioning and baseline determination in off-line mode. However, no software code exists for DGPS exploiting correction factors at base stations, without relying on double difference information. In order to accomplish it, a methodology is introduced in MATLAB environment for DGPS using C/A pseudoranges on single frequency L1 only to make it feasible for low-cost GPS receivers. Our base station is at accurately surveyed reference point. Pseudoranges and geometric ranges are compared at base station to compute the correction factors. These correction factors are then handed over to rover for all valid satellites observed during an epoch. The rover takes it into account for its own true position determination for corresponding epoch. In order to validate the proposed algorithm, our rover is also placed at a pre-determined location. The proposed code is an appropriate and simple to use tool for post-processing of GPS raw data for accurate position determination of a rover e.g. Unmanned Aerial Vehicle during post-mission analysis.}, language = {en} } @article{SchneiderSodian1991, author = {Schneider, Wolfgang and Sodian, Beate}, title = {A longitudinal study of young children's memory behavior and Performance in a sort-recall task}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62169}, year = {1991}, abstract = {No abstract available}, subject = {Psychologie}, language = {en} } @article{DashkovskiyKapustyanSchmid2020, author = {Dashkovskiy, Sergey and Kapustyan, Oleksiy and Schmid, Jochen}, title = {A local input-to-state stability result w.r.t. attractors of nonlinear reaction-diffusion equations}, series = {Mathematics of Control, Signals, and Systems}, volume = {32}, journal = {Mathematics of Control, Signals, and Systems}, number = {3}, doi = {10.1007/s00498-020-00256-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281099}, pages = {309-326}, year = {2020}, abstract = {We establish the local input-to-state stability of a large class of disturbed nonlinear reaction-diffusion equations w.r.t. the global attractor of the respective undisturbed system.}, language = {en} } @article{GerhardHartmannWiegeringBenoitetal.2021, author = {Gerhard-Hartmann, Elena and Wiegering, Verena and Benoit, Clemens and Meyer, Thomas and Rosenwald, Andreas and Maurus, Katja and Ernestus, Karen}, title = {A large retroperitoneal lipoblastoma as an incidental finding: a case report}, series = {BMC Pediatrics}, volume = {21}, journal = {BMC Pediatrics}, doi = {10.1186/s12887-021-02628-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260173}, year = {2021}, abstract = {Background Lipoblastoma is a rare benign mesenchymal neoplasm of infancy that most commonly occurs on the extremities and trunk but can arise at variable sites of the body. Retroperitoneal lipoblastomas are particularly rare but can grow to enormous size, and preoperative diagnosis is difficult with diverse, mostly malignant differential diagnoses that would lead to aggressive therapy. Since lipoblastoma is a benign tumor that has an excellent prognosis after resection, correct diagnosis is crucial. Case presentation A case of a large retroperitoneal tumor of a 24-month old infant that was clinically suspicious of a malignant tumor is presented. Due to proximity to the right kidney, clinically most probably a nephroblastoma or clear cell sarcoma of the kidney was suspected. Radiological findings were ambiguous. Therefore, the mass was biopsied, and histology revealed an adipocytic lesion. Although mostly composed of mature adipocytes, in view of the age of the patient, the differential diagnosis of a (maturing) lipoblastoma was raised, which was supported by molecular analysis demonstrating a HAS2-PLAG1 fusion. The tumor was completely resected, and further histopathological workup led to the final diagnosis of a 13 cm large retroperitoneal maturing lipoblastoma. The child recovered promptly from surgery and showed no evidence of recurrence so far. Conclusion Although rare, lipoblastoma should be included in the differential diagnoses of retroperitoneal tumors in infants and children, and molecular diagnostic approaches could be a helpful diagnostic adjunct in challenging cases.}, language = {en} } @article{SemlerAnderlStraubUttneretal.2018, author = {Semler, Elisa and Anderl-Straub, Sarah and Uttner, Ingo and Diehl-Schmid, Janine and Danek, Adrian and Einsiedler, Beate and Fassbender, Klaus and Fliessbach, Klaus and Huppertz, Hans-J{\"u}rgen and Jahn, Holger and Kornhuber, Johannes and Landwehrmeyer, Bernhard and Lauer, Martin and Muche, Rainer and Prudlo, Johannes and Schneider, Anja and Schroeter, Matthias L. and Ludolph, Albert C. and Otto, Markus}, title = {A language-based sum score for the course and therapeutic intervention in primary progressive aphasia}, series = {Alzheimer's Research \& Therapy}, volume = {10}, journal = {Alzheimer's Research \& Therapy}, organization = {FLTD consortium}, doi = {10.1186/s13195-018-0345-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236277}, year = {2018}, abstract = {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.}, language = {en} } @article{KarlNeitzelWachsmuth2020, author = {Karl, Veronika and Neitzel, Ira and Wachsmuth, Daniel}, title = {A Lagrange multiplier method for semilinear elliptic state constrained optimal control problems}, series = {Computational Optimization and Applications}, volume = {77}, journal = {Computational Optimization and Applications}, issn = {0926-6003}, doi = {10.1007/s10589-020-00223-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232811}, pages = {7831-869}, year = {2020}, abstract = {In this paper we apply an augmented Lagrange method to a class of semilinear ellip-tic optimal control problems with pointwise state constraints. We show strong con-vergence of subsequences of the primal variables to a local solution of the original problem as well as weak convergence of the adjoint states and weak-* convergence of the multipliers associated to the state constraint. Moreover, we show existence of stationary points in arbitrary small neighborhoods of local solutions of the original problem. Additionally, various numerical results are presented.}, language = {en} } @article{LatifiHolzwarthSkidmoreetal.2021, author = {Latifi, Hooman and Holzwarth, Stefanie and Skidmore, Andrew and Brůna, Josef and Červenka, Jaroslav and Darvishzadeh, Roshanak and Hais, Martin and Heiden, Uta and Homolov{\´a}, Lucie and Krzystek, Peter and Schneider, Thomas and Star{\´y}, Martin and Wang, Tiejun and M{\"u}ller, J{\"o}rg and Heurich, Marco}, title = {A laboratory for conceiving Essential Biodiversity Variables (EBVs)—The 'Data pool initiative for the Bohemian Forest Ecosystem'}, series = {Methods in Ecology and Evolution}, volume = {12}, journal = {Methods in Ecology and Evolution}, number = {11}, doi = {10.1111/2041-210X.13695}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262743}, pages = {2073-2083}, year = {2021}, abstract = {Effects of climate change-induced events on forest ecosystem dynamics of composition, function and structure call for increased long-term, interdisciplinary and integrated research on biodiversity indicators, in particular within strictly protected areas with extensive non-intervention zones. The long-established concept of forest supersites generally relies on long-term funds from national agencies and goes beyond the logistic and financial capabilities of state- or region-wide protected area administrations, universities and research institutes. We introduce the concept of data pools as a smaller-scale, user-driven and reasonable alternative to co-develop remote sensing and forest ecosystem science to validated products, biodiversity indicators and management plans. We demonstrate this concept with the Bohemian Forest Ecosystem Data Pool, which has been established as an interdisciplinary, international data pool within the strictly protected Bavarian Forest and Šumava National Parks and currently comprises 10 active partners. We demonstrate how the structure and impact of the data pool differs from comparable cases. We assessed the international influence and visibility of the data pool with the help of a systematic literature search and a brief analysis of the results. Results primarily suggest an increase in the impact and visibility of published material during the life span of the data pool, with highest visibilities achieved by research conducted on leaf traits, vegetation phenology and 3D-based forest inventory. We conclude that the data pool results in an efficient contribution to the concept of global biodiversity observatory by evolving towards a training platform, functioning as a pool of data and algorithms, directly communicating with management for implementation and providing test fields for feasibility studies on earth observation missions.}, language = {en} } @article{Ruhe1970, author = {Ruhe, Ernstpeter}, title = {A Johenne, ma dame et m'amie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-36735}, year = {1970}, abstract = {No abstract available}, language = {fr} } @article{StangeDesirKakaretal.2015, author = {Stange, Katja and D{\´e}sir, Julie and Kakar, Naseebullah and Mueller, Thomas D. and Budde, Birgit S. and Gordon, Christopher T. and Horn, Denise and Seemann, Petra and Borck, Guntram}, title = {A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia}, series = {Orphanet Journal of Rare Diseases}, volume = {10}, journal = {Orphanet Journal of Rare Diseases}, number = {84}, doi = {10.1186/s13023-015-0299-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151650}, year = {2015}, abstract = {Background: Grebe dysplasia, Hunter-Thompson dysplasia, and du Pan dysplasia constitute a spectrum of skeletal dysplasias inherited as an autosomal recessive trait characterized by short stature, severe acromesomelic shortening of the limbs, and normal axial skeleton. The majority of patients with these disorders have biallelic loss-of-function mutations of GDF5. In single instances, Grebe dysplasia and a Grebe dysplasia-like phenotype with genital anomalies have been shown to be caused by mutations in BMPR1B, encoding a GDF5 receptor. Methods: We clinically and radiologically characterised an acromesomelic chondrodysplasia in an adult woman born to consanguineous parents. We sequenced GDF5 and BMPR1B on DNA of the proposita. We performed 3D structural analysis and luciferase reporter assays to functionally investigate the identified BMPR1B mutation. Results: We extend the genotype-phenotype correlation in the acromesomelic chondrodysplasias by showing that the milder du Pan dysplasia can be caused by a hypomorphic BMPR1B mutation. We show that the homozygous c.91C>T, p.(Arg31Cys) mutation causing du Pan dysplasia leads to a significant loss of BMPR1B function, but to a lesser extent than the previously reported p.Cys53Arg mutation that results in the more severe Grebe dysplasia. Conclusions: The phenotypic severity gradient of the clinically and radiologically related acromesomelic chondrodysplasia spectrum of skeletal disorders may be due to the extent of functional impairment of the ligand-receptor pair GDF5-BMPR1B.}, language = {en} } @article{Wilhelm1991, author = {Wilhelm, Gernot}, title = {A Hurrian Letter from Tell Brak}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85972}, year = {1991}, abstract = {No abstract available.}, subject = {Tell Brak}, language = {en} } @article{KoenigRammeFaustetal.2022, author = {Koenig, Leopold and Ramme, Anja Patricia and Faust, Daniel and Mayer, Manuela and Fl{\"o}tke, Tobias and Gerhartl, Anna and Brachner, Andreas and Neuhaus, Winfried and Appelt-Menzel, Antje and Metzger, Marco and Marx, Uwe and Dehne, Eva-Maria}, title = {A human stem cell-derived brain-liver chip for assessing blood-brain-barrier permeation of pharmaceutical drugs}, series = {Cells}, volume = {11}, journal = {Cells}, number = {20}, issn = {2073-4409}, doi = {10.3390/cells11203295}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290375}, year = {2022}, abstract = {Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with other relevant organoid systems to integrate the investigation of blood-brain barrier permeation in the larger picture of drug distribution and metabolization is still missing. Here, we report for the first time the combination of a human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier model with a cortical brain and a liver spheroid model from the same donor in a closed microfluidic system (MPS). The two model compounds atenolol and propranolol were used to measure permeation at the blood-brain barrier and to assess metabolization. Both substances showed an in vivo-like permeation behavior and were metabolized in vitro. Therefore, the novel multi-organ system enabled not only the measurement of parent compound concentrations but also of metabolite distribution at the blood-brain barrier.}, language = {en} } @article{GattenloehnerJoerissenHuhnetal.2010, author = {Gattenloehner, Stefan and Joerissen, H. and Huhn, M. and Vincent, A. and Beeson, D. and Tzartos, S. and Mamalaki, A. and Etschmann, B. and Muller-Hermelink, H. K. and Koscielniak, E. and Barth, S. and Marx, A.}, title = {A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model [Research Article]}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68200}, year = {2010}, abstract = {Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA).While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20\% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.}, subject = {Medizin}, language = {en} } @article{WalzMuehlbergerPauli2016, author = {Walz, Nora and M{\"u}hlberger, Andreas and Pauli, Paul}, title = {A human open field test reveals thigmotaxis related to agoraphobic fear}, series = {Biological Psychiatry}, volume = {80}, journal = {Biological Psychiatry}, number = {5}, doi = {10.1016/j.biopsych.2015.12.016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187607}, pages = {390-397}, year = {2016}, abstract = {BACKGROUND: Thigmotaxis refers to a specific behavior of animals (i.e., to stay close to walls when exploring an open space). Such behavior can be assessed with the open field test (OFT), which is a well-established indicator of animal fear. The detection of similar open field behavior in humans may verify the translational validity of this paradigm. Enhanced thigmotaxis related to anxiety may suggest the relevance of such behavior for anxiety disorders, especially agoraphobia. METHODS: A global positioning system was used to analyze the behavior of 16 patients with agoraphobia and 18 healthy individuals with a risk for agoraphobia (i.e., high anxiety sensitivity) during a human OFT and compare it with appropriate control groups (n = 16 and n = 19). We also tracked 17 patients with agoraphobia and 17 control participants during a city walk that involved walking through an open market square. RESULTS: Our human OFT triggered thigmotaxis in participants; patients with agoraphobia and participants with high anxiety sensitivity exhibited enhanced thigmotaxis. This behavior was evident in increased movement lengths along the wall of the natural open field and fewer entries into the center of the field despite normal movement speed and length. Furthermore, participants avoided passing through the market square during the city walk, indicating again that thigmotaxis is related to agoraphobia. CONCLUSIONS: This study is the first to our knowledge to verify the translational validity of the OFT and to reveal that thigmotaxis, an evolutionarily adaptive behavior shown by most species, is related to agoraphobia, a pathologic fear of open spaces, and anxiety sensitivity, a risk factor for agoraphobia.}, language = {en} } @article{ClausHubertBecheretal.2019, author = {Claus, Heike and Hubert, Kerstin and Becher, D{\"o}rte and Otto, Andreas and Pawlik, Marie-Christin and Lappann, Ines and Strobel, Lea and Vogel, Ulrich and Johswich, Kay}, title = {A homopolymeric adenosine tract in the promoter region of nspA influences factor H-mediated serum resistance in Neisseria meningitidis}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-39231-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200956}, pages = {2736}, year = {2019}, abstract = {Although usually asymptomatically colonizing the human nasopharynx, the Gram-negative bacterium Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator factor H (fH). Meningococcal strains belonging to the sequence type (ST-) 41/44 clonal complex (cc41/44) cause a major proportion of serogroup B meningococcal disease worldwide, but they are also common in asymptomatic carriers. Proteome analysis comparing cc41/44 isolates from invasive disease versus carriage revealed differential expression levels of the outer membrane protein NspA, which binds fH. Deletion of nspA reduced serum resistance and NspA expression correlated with fH sequestration. Expression levels of NspA depended on the length of a homopolymeric tract in the nspA promoter: A 5-adenosine tract dictated low NspA expression, whereas a 6-adenosine motif guided high NspA expression. Screening German cc41/44 strain collections revealed the 6-adenosine motif in 39\% of disease isolates, but only in 3.4\% of carriage isolates. Thus, high NspA expression is associated with disease, but not strictly required. The 6-adenosine nspA promoter is most common to the cc41/44, but is also found in other hypervirulent clonal complexes.}, language = {en} } @article{AmorettiAreanArgurioetal.2017, author = {Amoretti, Andrea and Are{\´a}n, Daniel and Argurio, Riccardo and Musso, Daniele and Zayas, Leopoldo A. Pando}, title = {A holographic perspective on phonons and pseudo-phonons}, series = {Journal of High Energy Physics}, volume = {5}, journal = {Journal of High Energy Physics}, number = {51}, doi = {10.1007/JHEP05(2017)051}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170882}, year = {2017}, abstract = {We analyze the concomitant spontaneous breaking of translation and conformal symmetries by introducing in a CFT a complex scalar operator that acquires a spatially dependent expectation value. The model, inspired by the holographic Q-lattice, provides a privileged setup to study the emergence of phonons from a spontaneous translational symmetry breaking in a conformal field theory and offers valuable hints for the treatment of phonons in QFT at large. We first analyze the Ward identity structure by means of standard QFT techniques, considering both spontaneous and explicit symmetry breaking. Next, by implementing holographic renormalization, we show that the same set of Ward identities holds in the holographic Q-lattice. Eventually, relying on the holographic and QFT results, we study the correlators realizing the symmetry breaking pattern and how they encode information about the low-energy spectrum.}, language = {en} } @article{FarrellGrandeSchmidtetal.2019, author = {Farrell, Jeffrey M. and Grande, Vincenzo and Schmidt, David and W{\"u}rthner, Frank}, title = {A Highly Warped Heptagon-Containing sp\(^2\) Carbon Scaffold via Vinylnaphthyl π-Extension}, series = {Angewandte Chemie International Edition}, volume = {58}, journal = {Angewandte Chemie International Edition}, number = {46}, doi = {10.1002/anie.201909975}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206682}, pages = {16504-16507}, year = {2019}, abstract = {A new strategy is demonstrated for the synthesis of warped, negatively curved, all-sp\(^2\)-carbon π-scaffolds. Multifold C-C coupling reactions are used to transform a polyaromatic borinic acid into a saddle-shaped polyaromatic hydrocarbon (2 ) bearing two heptagonal rings. Notably, this Schwarzite substructure is synthesized in only two steps from an unfunctionalized alkene. A highly warped structure of 2 was revealed by X-ray crystallographic studies and pronounced flexibility of this π-scaffold was ascertained by experimental and computational studies. Compound 2 exhibits excellent solubility, visible range absorption and fluorescence, and readily undergoes two reversible one-electron oxidations at mild potentials.}, language = {en} } @article{WalkerMavrommatisWardelletal.2019, author = {Walker, Brian A. and Mavrommatis, Konstantinos and Wardell, Christopher P. and Ashby, T. Cody and Bauer, Michael and Davies, Faith and Rosenthal, Adam and Wang, Hongwei and Qu, Pingping and Hoering, Antje and Samur, Mehmet and Towfic, Fadi and Ortiz, Maria and Flynt, Erin and Yu, Zhinuan and Yang, Zhihong and Rozelle, Dan and Obenauer, John and Trotter, Matthew and Auclair, Daniel and Keats, Jonathan and Bolli, Niccolo and Fulciniti, Mariateresa and Szalat, Raphael and Moreau, Phillipe and Durie, Brian and Stewart, A. Keith and Goldschmidt, Hartmut and Raab, Marc S. and Einsele, Hermann and Sonneveld, Pieter and San Miguel, Jesus and Lonial, Sagar and Jackson, Graham H. and Anderson, Kenneth C. and Avet-Loiseau, Herve and Munshi, Nikhil and Thakurta, Anjan and Morgan, Gareth}, title = {A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis}, series = {Leukemia}, volume = {33}, journal = {Leukemia}, doi = {10.1038/s41375-018-0196-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233299}, pages = {159-170}, year = {2019}, abstract = {Patients with newly diagnosed multiple myeloma (NDMM) with high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used to identify high-risk patients, each of which has significant weaknesses. Inclusion of molecular features into risk stratification could resolve the current challenges. In a genome-wide analysis of the largest set of molecular and clinical data established to date from NDMM, as part of the Myeloma Genome Project, we have defined DNA drivers of aggressive clinical behavior. Whole-genome and exome data from 1273 NDMM patients identified genetic factors that contribute significantly to progression free survival (PFS) and overall survival (OS) (cumulative R2 = 18.4\% and 25.2\%, respectively). Integrating DNA drivers and clinical data into a Cox model using 784 patients with ISS, age, PFS, OS, and genomic data, the model has a cumlative R2 of 34.3\% for PFS and 46.5\% for OS. A high-risk subgroup was defined by recursive partitioning using either a) bi-allelic TP53 inactivation or b) amplification (≥4 copies) of CKS1B (1q21) on the background of International Staging System III, comprising 6.1\% of the population (median PFS = 15.4 months; OS = 20.7 months) that was validated in an independent dataset. Double-Hit patients have a dire prognosis despite modern therapies and should be considered for novel therapeutic approaches.}, language = {en} } @article{SchmidSchindelinCardonaetal.2010, author = {Schmid, Benjamin and Schindelin, Johannes and Cardona, Albert and Longair, Martin and Heisenberg, Martin}, title = {A high-level 3D visualization API for Java and ImageJ}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67851}, year = {2010}, abstract = {Background: Current imaging methods such as Magnetic Resonance Imaging (MRI), Confocal microscopy, Electron Microscopy (EM) or Selective Plane Illumination Microscopy (SPIM) yield three-dimensional (3D) data sets in need of appropriate computational methods for their analysis. The reconstruction, segmentation and registration are best approached from the 3D representation of the data set. Results: Here we present a platform-independent framework based on Java and Java 3D for accelerated rendering of biological images. Our framework is seamlessly integrated into ImageJ, a free image processing package with a vast collection of community-developed biological image analysis tools. Our framework enriches the ImageJ software libraries with methods that greatly reduce the complexity of developing image analysis tools in an interactive 3D visualization environment. In particular, we provide high-level access to volume rendering, volume editing, surface extraction, and image annotation. The ability to rely on a library that removes the low-level details enables concentrating software development efforts on the algorithm implementation parts. Conclusions: Our framework enables biomedical image software development to be built with 3D visualization capabilities with very little effort. We offer the source code and convenient binary packages along with extensive documentation at http://3dviewer.neurofly.de.}, subject = {Visualisierung}, language = {en} } @article{GerovaWickeChiharaetal.2021, author = {Gerova, Milan and Wicke, Laura and Chihara, Kotaro and Schneider, Cornelius and Lavigne, Rob and Vogel, J{\"o}rg}, title = {A grad-seq view of RNA and protein complexes in Pseudomonas aeruginosa under standard and bacteriophage predation conditions}, series = {mbio}, volume = {12}, journal = {mbio}, number = {1}, doi = {10.1128/mBio.03454-20}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259054}, pages = {e03454-20}, year = {2021}, abstract = {The Gram-negative rod-shaped bacterium Pseudomonas aeruginosa is not only a major cause of nosocomial infections but also serves as a model species of bacterial RNA biology. While its transcriptome architecture and posttranscriptional regulation through the RNA-binding proteins Hfq, RsmA, and RsmN have been studied in detail, global information about stable RNA-protein complexes in this human pathogen is currently lacking. Here, we implement gradient profiling by sequencing (Grad-seq) in exponentially growing P. aeruginosa cells to comprehensively predict RNA and protein complexes, based on glycerol gradient sedimentation profiles of >73\% of all transcripts and ∼40\% of all proteins. As to benchmarking, our global profiles readily reported complexes of stable RNAs of P. aeruginosa, including 6S RNA with RNA polymerase and associated product RNAs (pRNAs). We observe specific clusters of noncoding RNAs, which correlate with Hfq and RsmA/N, and provide a first hint that P. aeruginosa expresses a ProQ-like FinO domain-containing RNA-binding protein. To understand how biological stress may perturb cellular RNA/protein complexes, we performed Grad-seq after infection by the bacteriophage ΦKZ. This model phage, which has a well-defined transcription profile during host takeover, displayed efficient translational utilization of phage mRNAs and tRNAs, as evident from their increased cosedimentation with ribosomal subunits. Additionally, Grad-seq experimentally determines previously overlooked phage-encoded noncoding RNAs. Taken together, the Pseudomonas protein and RNA complex data provided here will pave the way to a better understanding of RNA-protein interactions during viral predation of the bacterial cell. IMPORTANCE Stable complexes by cellular proteins and RNA molecules lie at the heart of gene regulation and physiology in any bacterium of interest. It is therefore crucial to globally determine these complexes in order to identify and characterize new molecular players and regulation mechanisms. Pseudomonads harbor some of the largest genomes known in bacteria, encoding ∼5,500 different proteins. Here, we provide a first glimpse on which proteins and cellular transcripts form stable complexes in the human pathogen Pseudomonas aeruginosa. We additionally performed this analysis with bacteria subjected to the important and frequently encountered biological stress of a bacteriophage infection. We identified several molecules with established roles in a variety of cellular pathways, which were affected by the phage and can now be explored for their role during phage infection. Most importantly, we observed strong colocalization of phage transcripts and host ribosomes, indicating the existence of specialized translation mechanisms during phage infection. All data are publicly available in an interactive and easy to use browser.}, language = {en} } @article{AdeyemoShapiraTombaccinietal.1991, author = {Adeyemo, O. M. and Shapira, S. and Tombaccini, D. and Pollard, H. and Feuerstein, G. and Sir{\´e}n, Anna-Leena}, title = {A goldfish model for evaluation of the neurotoxicit of \(\omega\)-conotoxin GVIA and screening of monoclonal antibodies}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63087}, year = {1991}, abstract = {A Goldfish Model for Evaluation of the Neurotaxicity of \(\omega\)-Conotoxin GVI A and Screening of Monoclonal Antibodies. ADEYEMO, 0. M .. SHAPIRA, S., TOMBACCINI, D., POLLARD, H. 8 .• FEUERSTEIN, G .. AND SIREN, A-L. ( 1991 ). Toxicol. App/. Pharmaco/. 108, 489-496. The neurotoxicity of \(\omega\)-conotoxin (\(\omega\)-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. \(\omega\)-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. \(\omega\)CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antiborlies was investigated in vivo by either ( l) preincubation of the antibody with w-CgTx at 4°C overnight, or (2) pretreatment with antibody, 30 min before \(\omega\)CgTx injection in a 10:1 antibody/\(\omega\)-CgTx molar ratio. The LD50 dose of \(\omega\)-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with \(\omega\)-CgTx (5 nmol/kg ip) significantly (p < 0.05) reduced mortality. ASB, and toxicity time. The antitoxin activity of the monoclonal antiborlies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by \(\omega\)-CgTx (0.03 nmol/rat icv) were significantly (p < 0.02 and p < 0.0 l, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple. accurate, and inexpensive in vivo model for the study of the toxicity of \(\omega\)CgTx}, subject = {Neurobiologie}, language = {en} } @article{Zillober1993, author = {Zillober, Christian}, title = {A globally convergent version of the method of moving asymptotes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31984}, year = {1993}, abstract = {No abstract available}, language = {en} } @article{CarradecPelletierDaSilvaetal.2018, author = {Carradec, Quentin and Pelletier, Eric and Da Silva, Corinne and Alberti, Adriana and Seeleuthner, Yoann and Blanc-Mathieu, Romain and Lima-Mendez, Gipsi and Rocha, Fabio and Tirichine, Leila and Labadie, Karine and Kirilovsky, Amos and Bertrand, Alexis and Engelen, Stefan and Madoui, Mohammed-Amin and M{\´e}heust, Rapha{\"e}l and Poulain, Julie and Romac, Sarah and Richter, Daniel J. and Yoshikawa, Genki and Dimier, C{\´e}line and Kandels-Lewis, Stefanie and Picheral, Marc and Searson, Sarah and Jaillon, Olivier and Aury, Jean-Marc and Karsenti, Eric and Sullivan, Matthew B. and Sunagawa, Shinichi and Bork, Peer and Not, Fabrice and Hingamp, Pascal and Raes, Jeroen and Guidi, Lionel and Ogata, Hiroyuki and de Vargas, Colomban and Iudicone, Daniele and Bowler, Chris and Wincker, Patrick}, title = {A global ocean atlas of eukaryotic gene}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, organization = {Tara Oceans Coordinators}, doi = {10.1038/s41467-017-02342-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222250}, year = {2018}, abstract = {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.}, language = {en} } @article{BarYosefGildorRamirezZavalaetal.2018, author = {Bar-Yosef, Hagit and Gildor, Tsvia and Ram{\´i}rez-Zavala, Bernardo and Schmauch, Christian and Weissman, Ziva and Pinsky, Mariel and Naddaf, Rawi and Morschh{\"a}user, Joachim and Arkowitz, Robert A. and Kornitzer, Daniel}, title = {A global analysis of kinase function in Candida albicans hyphal morphogenesis reveals a role for the endocytosis regulator Akl1}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {8}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2018.00017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197204}, year = {2018}, abstract = {The human pathogenic fungus Candida albicans can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of C. albicans protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter. Proportionately more phosphatases than kinases were identified that inhibited hyphal morphogenesis, consistent with the known role of protein phosphorylation in hyphal induction. Among the kinases, we identified AKL1 as a gene that significantly suppressed hyphal morphogenesis in serum. Akl1 specifically affected hyphal elongation rather than initiation: overexpression of AKL1 repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the absence of Akl1, the Pan1 patches were delocalized from the sub-apical region, and fluid-phase endocytosis was intensified. These results underscore the requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore, these results suggest that under standard conditions, endocytosis is rate-limiting for hyphal elongation.}, language = {en} } @article{HerrmannKarunakaranFichtner2020, author = {Herrmann, Thomas and Karunakaran, Mohindar Murugesh and Fichtner, Alina Suzann}, title = {A glance over the fence: Using phylogeny and species comparison for a better understanding of antigen recognition by human γδ T-cells}, series = {Immunological Reviews}, volume = {298}, journal = {Immunological Reviews}, number = {1}, doi = {10.1111/imr.12919}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218373}, pages = {218 -- 236}, year = {2020}, abstract = {Both, jawless and jawed vertebrates possess three lymphocyte lineages defined by highly diverse antigen receptors: Two T-cell- and one B-cell-like lineage. In both phylogenetic groups, the theoretically possible number of individual antigen receptor specificities can even outnumber that of lymphocytes of a whole organism. Despite fundamental differences in structure and genetics of these antigen receptors, convergent evolution led to functional similarities between the lineages. Jawed vertebrates possess αβ and γδ T-cells defined by eponymous αβ and γδ T-cell antigen receptors (TCRs). "Conventional" αβ T-cells recognize complexes of Major Histocompatibility Complex (MHC) class I and II molecules and peptides. Non-conventional T-cells, which can be αβ or γδ T-cells, recognize a large variety of ligands and differ strongly in phenotype and function between species and within an organism. This review describes similarities and differences of non-conventional T-cells of various species and discusses ligands and functions of their TCRs. A special focus is laid on Vγ9Vδ2 T-cells whose TCRs act as sensors for phosphorylated isoprenoid metabolites, so-called phosphoantigens (PAg), associated with microbial infections or altered host metabolism in cancer or after drug treatment. We discuss the role of butyrophilin (BTN)3A and BTN2A1 in PAg-sensing and how species comparison can help in a better understanding of this human Vγ9Vδ2 T-cell subset.}, language = {en} } @article{HuesteggePieczykolanKoch2023, author = {Huestegge, Lynn and Pieczykolan, Aleks and Koch, Iring}, title = {A Gestalt account of human behavior is supported by evidence from switching between single and dual actions}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-023-47788-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357862}, year = {2023}, abstract = {The question of how behavior is represented in the mind lies at the core of psychology as the science of mind and behavior. While a long-standing research tradition has established two opposing fundamental views of perceptual representation, Structuralism and Gestalt psychology, we test both accounts with respect to action representation: Are multiple actions (characterizing human behavior in general) represented as the sum of their component actions (Structuralist view) or holistically (Gestalt view)? Using a single-/dual-response switch paradigm, we analyzed switches between dual ([A + B]) and single ([A], [B]) responses across different effector systems and revealed comparable performance in partial repetitions and full switches of behavioral requirements (e.g., in [A + B] → [A] vs. [B] → [A], or [A] → [A + B] vs. [B] → [A + B]), but only when the presence of dimensional overlap between responses allows for Gestalt formation. This evidence for a Gestalt view of behavior in our paradigm challenges some fundamental assumptions in current (tacitly Structuralist) action control theories (in particular the idea that all actions are represented compositionally with reference to their components), provides a novel explanatory angle for understanding complex, highly synchronized human behavior (e.g., dance), and delimitates the degree to which complex behavior can be analyzed in terms of its basic components.}, language = {en} } @article{RaynerColemanPurvesetal.2019, author = {Rayner, Christopher and Coleman, Jonathan R. I. and Purves, Kirstin L. and Hodsoll, John and Goldsmith, Kimberley and Alpers, Georg W. and Andersson, Evelyn and Arolt, Volker and Boberg, Julia and B{\"o}gels, Susan and Creswell, Cathy and Cooper, Peter and Curtis, Charles and Deckert, J{\"u}rgen and Domschke, Katharina and El Alaoui, Samir and Fehm, Lydia and Fydrich, Thomas and Gerlach, Alexander L. and Grocholewski, Anja and Hahlweg, Kurt and Hamm, Alfons and Hedman, Erik and Heiervang, Einar R. and Hudson, Jennifer L. and J{\"o}hren, Peter and Keers, Robert and Kircher, Tilo and Lang, Thomas and Lavebratt, Catharina and Lee, Sang-hyuck and Lester, Kathryn J. and Lindefors, Nils and Margraf, J{\"u}rgen and Nauta, Maaike and Pan{\´e}-Farr{\´e}, Christiane A. and Pauli, Paul and Rapee, Ronald M. and Reif, Andreas and Rief, Winfried and Roberts, Susanna and Schalling, Martin and Schneider, Silvia and Silverman, Wendy K. and Str{\"o}hle, Andreas and Teismann, Tobias and Thastum, Mikael and Wannem{\"u}ller, Andre and Weber, Heike and Wittchen, Hans-Ulrich and Wolf, Christiane and R{\"u}ck, Christian and Breen, Gerome and Eley, Thalia C.}, title = {A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders}, series = {Translational Psychiatry}, volume = {9}, journal = {Translational Psychiatry}, number = {150}, doi = {10.1038/s41398-019-0481-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225048}, pages = {1-13}, year = {2019}, abstract = {Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.}, language = {en} } @article{LuisHorrerPhilippetal.2021, author = {Luis, Werner and Horrer, G{\"u}nther and Philipp, Michael and Lubitz, Katharina and Kuntze-Fechner, Maximilian W. and Radius, Udo}, title = {A General Synthetic Route to NHC-Phosphinidenes: NHC-mediated Dehydrogenation of Primary Phosphines}, series = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie}, volume = {647}, journal = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie}, number = {8}, doi = {10.1002/zaac.202000405}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258016}, pages = {881-895}, year = {2021}, abstract = {The dehydrocoupling of primary phosphines with N-heterocyclic carbenes (NHCs) to yield NHC-phosphinidenes is reported. The reaction of two equivalents of the NHCs Me\(_2\)Im (1,3-dimethylimidazolin-2-ylidene), Me\(_4\)Im (1,3,4,5-tetramethylimidazolin-2-ylidene), iPr\(_2\)Im (1,3-di-iso-propylimidazolin-2-ylidene) and Mes\(_2\)Im (2,4,6-trimethylphenylimidazolin-2-ylidene) with PhPH\(_2\) and MesPH\(_2\) led to the NHC stabilized phosphinidenes (NHC)PAr: (iPr\(_2\)Im)PPh (1), (Mes\(_2\)Im)PPh (2), (Me\(_4\)Im)PPh (3), (Mes\(_2\)Im)PMes (4), (Me\(_2\)Im)PMes (5), (Me\(_4\)Im)PMes (6) and (iPr\(_2\)Im)PMes (7). The reaction of tBuPH\(_2\) with two equivalents of the NHCs afforded the corresponding NHC stabilized parent phosphinidenes (NHC)PH: (iPr\(_2\)Im)PH (8), (Mes\(_2\)Im)PH (9) and (Me\(_4\)Im)PH (10). Reaction of 1 with oxygen and sulfur led to isolation of iPr\(_2\)Im-P(O)\(_2\)Ph (11) and iPr\(_2\)Im-P(S)\(_2\)Ph (12), whereas the reaction with elemental selenium and tellurium gave (NHC)PPh cleavage with formation of (iPr\(_2\)Im)Se (13), iPr\(_2\)ImTe (14) and different cyclo-oligophosphines. Furthermore, the complexes [{(iPr\(_2\)Im)PPh}W(CO)\(_5\)] (15), [Co(CO)\(_2\)(NO){(iPr\(_2\)Im)PPh}] (16) and [(η\(^5\)-C\(_5\)Me\(_2\))Co(η\(^2\)-C\(_2\)H\(_4\)){(iPr\(_2\)Im)PPh}] (17) have been prepared starting from 1 and a suitable transition metal complex precursor. The complexes 16 and 17 decompose in solution upon heating to ca. 80 °C to yield the NHC complexes [Co(iPr\(_2\)Im)(CO)\(_2\)(NO)] and [(η\(^5\)-C\(_5\)Me\(_5\))Co(iPr\(_2\)Im)(η\(^2\)-C\(_2\)H\(_4\))] with formation of cyclo-oligophosphines. The reaction of 1 with [Ni(COD)\(_2\)] afforded the diphosphene complex [Ni(iPr\(_2\)Im)\(_2\)(trans-PhP=PPh)] 18.}, language = {en} } @article{BrehmHaasGoebeletal.1992, author = {Brehm, Klaus and Haas, Albert and Goebel, Werner and Kreft, J{\"u}rgen}, title = {A gene encoding a superoxide dismutase of the facultative intracellular bacterium Listeria monocytogenes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60515}, year = {1992}, abstract = {A gene (Imsod) encoding superoxide dismutase (SOD; EC 1.15.1.1) of the facultative intracellular pathogen, Listeria monocytogenes, was cloned by functional complementation of an SOD-deficient Escherichia coli mutant. The nucleotide sequence was determined and the deduced amino acid (aa) sequence (202 aa) showed close similarity to manganese-containing SOD's from other organisms. Subunits of the recombinant L. monocytogenes SOD (re-SOD) and of both E. coli SODs formed enzymatically active hybrid enzymes in vivo. DNA/DNA-hybridization experiments showed that this type of recombinant re-sod gene is conserved within the genus Listeria.}, subject = {Biologie}, language = {en} } @article{DegenkolbeKoenigZimmeretal.2013, author = {Degenkolbe, Elisa and K{\"o}nig, Jana and Zimmer, Julia and Walther, Maria and Reißner, Carsten and Nickel, Joachim and Pl{\"o}ger, Frank and Raspopovic, Jelena and Sharpe, James and Dathe, Katharina and Hecht, Jacqueline T. and Mundlos, Stefan and Doelken, Sandra C. and Seemann, Petra}, title = {A GDF5 Point Mutation Strikes Twice - Causing BDA1 and SYNS2}, series = {PLOS Genetics}, volume = {9}, journal = {PLOS Genetics}, number = {10}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003846}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127556}, pages = {e1003846}, year = {2013}, abstract = {Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role during limb development. GDF5 is a susceptibility gene for osteoarthritis (OA) and mutations in GDF5 are associated with a wide variety of skeletal malformations ranging from complex syndromes such as acromesomelic chondrodysplasias to isolated forms of brachydactylies or multiple synostoses syndrome 2 (SYNS2). Here, we report on a family with an autosomal dominant inherited combination of SYNS2 and additional brachydactyly type A1 (BDA1) caused by a single point mutation in GDF5 (p.W414R). Functional studies, including chondrogenesis assays with primary mesenchymal cells, luciferase reporter gene assays and Surface Plasmon Resonance analysis, of the GDF5 W-414R variant in comparison to other GDF5 mutations associated with isolated BDA1 (p.R399C) or SYNS2 (p.E491K) revealed a dual pathomechanism characterized by a gain-and loss-of-function at the same time. On the one hand insensitivity to the main GDF5 antagonist NOGGIN (NOG) leads to a GDF5 gain of function and subsequent SYNS2 phenotype. Whereas on the other hand, a reduced signaling activity, specifically via the BMP receptor type IA (BMPR1A), is likely responsible for the BDA1 phenotype. These results demonstrate that one mutation in the overlapping interface of antagonist and receptor binding site in GDF5 can lead to a GDF5 variant with pathophysiological relevance for both, BDA1 and SYNS2 development. Consequently, our study assembles another part of the molecular puzzle of how loss and gain of function mutations in GDF5 affect bone development in hands and feet resulting in specific types of brachydactyly and SYNS2. These novel insights into the biology of GDF5 might also provide further clues on the pathophysiology of OA.}, language = {en} } @article{SteuerCostaVanderAuweraGlocketal.2019, author = {Steuer Costa, Wagner and Van der Auwera, Petrus and Glock, Caspar and Liewald, Jana F. and Bach, Maximilian and Sch{\"u}ler, Christina and Wabnig, Sebastian and Oranth, Alexandra and Masurat, Florentin and Bringmann, Henrik and Schoofs, Liliane and Stelzer, Ernst H. K. and Fischer, Sabine C. and Gottschalk, Alexander}, title = {A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, doi = {10.1038/s41467-019-12098-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223273}, year = {2019}, abstract = {Animals must slow or halt locomotion to integrate sensory inputs or to change direction. In Caenorhabditis elegans, the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show RIS functions additionally as a locomotion stop neuron. RIS optogenetic stimulation caused acute and persistent inhibition of locomotion and pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides and GABA. RIS photoactivation allows the animal to maintain its body posture by sustaining muscle tone, yet inactivating motor neuron oscillatory activity. During locomotion, RIS axonal Ca2+ signals revealed functional compartmentalization: Activity in the nerve ring process correlated with locomotion stop, while activity in a branch correlated with induced reversals. GABA was required to induce, and FLP-11 neuropeptides were required to sustain locomotion stop. RIS attenuates neuronal activity and inhibits movement, possibly enabling sensory integration and decision making, and exemplifies dual use of one cell across development in a compact nervous system.}, language = {en} } @article{HommersRichterYangetal.2018, author = {Hommers, L. G. and Richter, J. and Yang, Y. and Raab, A. and Baumann, C. and Lang, K. and Schiele, M. A. and Weber, H. and Wittmann, A. and Wolf, C. and Alpers, G. W. and Arolt, V. and Domschke, K. and Fehm, L. and Fydrich, T. and Gerlach, A. and Gloster, A. T. and Hamm, A. O. and Helbig-Lang, S. and Kircher, T. and Lang, T. and Pan{\´e}-Farr{\´e}, C. A. and Pauli, P. and Pfleiderer, B. and Reif, A. and Romanos, M. and Straube, B. and Str{\"o}hle, A. and Wittchen, H.-U. and Frantz, S. and Ertl, G. and Lohse, M. J. and Lueken, U. and Deckert, J.}, title = {A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety}, series = {Translational Psychiatry}, volume = {8}, journal = {Translational Psychiatry}, doi = {10.1038/s41398-018-0278-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322497}, year = {2018}, abstract = {Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.}, language = {en} } @article{PalmisanoKullmannHanafietal.2022, author = {Palmisano, Chiara and Kullmann, Peter and Hanafi, Ibrahem and Verrecchia, Marta and Latoschik, Marc Erich and Canessa, Andrea and Fischbach, Martin and Isaias, Ioannis Ugo}, title = {A fully-immersive virtual reality setup to study gait modulation}, series = {Frontiers in Human Neuroscience}, volume = {16}, journal = {Frontiers in Human Neuroscience}, issn = {1662-5161}, doi = {10.3389/fnhum.2022.783452}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267099}, year = {2022}, abstract = {Objective: Gait adaptation to environmental challenges is fundamental for independent and safe community ambulation. The possibility of precisely studying gait modulation using standardized protocols of gait analysis closely resembling everyday life scenarios is still an unmet need. Methods: We have developed a fully-immersive virtual reality (VR) environment where subjects have to adjust their walking pattern to avoid collision with a virtual agent (VA) crossing their gait trajectory. We collected kinematic data of 12 healthy young subjects walking in real world (RW) and in the VR environment, both with (VR/A+) and without (VR/A-) the VA perturbation. The VR environment closely resembled the RW scenario of the gait laboratory. To ensure standardization of the obstacle presentation the starting time speed and trajectory of the VA were defined using the kinematics of the participant as detected online during each walking trial. Results: We did not observe kinematic differences between walking in RW and VR/A-, suggesting that our VR environment per se might not induce significant changes in the locomotor pattern. When facing the VA all subjects consistently reduced stride length and velocity while increasing stride duration. Trunk inclination and mediolateral trajectory deviation also facilitated avoidance of the obstacle. Conclusions: This proof-of-concept study shows that our VR/A+ paradigm effectively induced a timely gait modulation in a standardized immersive and realistic scenario. This protocol could be a powerful research tool to study gait modulation and its derangements in relation to aging and clinical conditions.}, language = {en} } @article{UereyenBachoferKuenzer2022, author = {Uereyen, Soner and Bachofer, Felix and Kuenzer, Claudia}, title = {A framework for multivariate analysis of land surface dynamics and driving variables — a case study for Indo-Gangetic river basins}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {1}, issn = {2072-4292}, doi = {10.3390/rs14010197}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255295}, year = {2022}, abstract = {The analysis of the Earth system and interactions among its spheres is increasingly important to improve the understanding of global environmental change. In this regard, Earth observation (EO) is a valuable tool for monitoring of long term changes over the land surface and its features. Although investigations commonly study environmental change by means of a single EO-based land surface variable, a joint exploitation of multivariate land surface variables covering several spheres is still rarely performed. In this regard, we present a novel methodological framework for both, the automated processing of multisource time series to generate a unified multivariate feature space, as well as the application of statistical time series analysis techniques to quantify land surface change and driving variables. In particular, we unify multivariate time series over the last two decades including vegetation greenness, surface water area, snow cover area, and climatic, as well as hydrological variables. Furthermore, the statistical time series analyses include quantification of trends, changes in seasonality, and evaluation of drivers using the recently proposed causal discovery algorithm Peter and Clark Momentary Conditional Independence (PCMCI). We demonstrate the functionality of our methodological framework using Indo-Gangetic river basins in South Asia as a case study. The time series analyses reveal increasing trends in vegetation greenness being largely dependent on water availability, decreasing trends in snow cover area being mostly negatively coupled to temperature, and trends of surface water area to be spatially heterogeneous and linked to various driving variables. Overall, the obtained results highlight the value and suitability of this methodological framework with respect to global climate change research, enabling multivariate time series preparation, derivation of detailed information on significant trends and seasonality, as well as detection of causal links with minimal user intervention. This study is the first to use multivariate time series including several EO-based variables to analyze land surface dynamics over the last two decades using the causal discovery algorithm PCMCI.}, language = {en} } @article{HermJanieschHelmetal.2023, author = {Herm, Lukas-Valentin and Janiesch, Christian and Helm, Alexander and Imgrund, Florian and Hofmann, Adrian and Winkelmann, Axel}, title = {A framework for implementing robotic process automation projects}, series = {Information Systems and e-Business Management}, volume = {21}, journal = {Information Systems and e-Business Management}, number = {1}, issn = {1617-9846}, doi = {10.1007/s10257-022-00553-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323798}, pages = {1-35}, year = {2023}, abstract = {Robotic process automation is a disruptive technology to automate already digital yet manual tasks and subprocesses as well as whole business processes rapidly. In contrast to other process automation technologies, robotic process automation is lightweight and only accesses the presentation layer of IT systems to mimic human behavior. Due to the novelty of robotic process automation and the varying approaches when implementing the technology, there are reports that up to 50\% of robotic process automation projects fail. To tackle this issue, we use a design science research approach to develop a framework for the implementation of robotic process automation projects. We analyzed 35 reports on real-life projects to derive a preliminary sequential model. Then, we performed multiple expert interviews and workshops to validate and refine our model. The result is a framework with variable stages that offers guidelines with enough flexibility to be applicable in complex and heterogeneous corporate environments as well as for small and medium-sized companies. It is structured by the three phases of initialization, implementation, and scaling. They comprise eleven stages relevant during a project and as a continuous cycle spanning individual projects. Together they structure how to manage knowledge and support processes for the execution of robotic process automation implementation projects.}, language = {en} } @article{GroeberEngelhardtLangeetal.2016, author = {Groeber, Florian and Engelhardt, Lisa and Lange, Julia and Kurdyn, Szymon and Schmid, Freia F. and R{\"u}cker, Christoph and Mielke, Stephan and Walles, Heike and Hansmann, Jan}, title = {A First Vascularized Skin Equivalent as an Alternative to Animal Experimentation}, series = {ALTEX - Alternatives to Animal Experimentation}, volume = {33}, journal = {ALTEX - Alternatives to Animal Experimentation}, number = {4}, doi = {10.14573/altex.1604041}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164438}, pages = {415-422}, year = {2016}, abstract = {Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin \& eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.}, language = {en} } @article{ThonfeldGessnerHolzwarthetal.2022, author = {Thonfeld, Frank and Gessner, Ursula and Holzwarth, Stefanie and Kriese, Jennifer and da Ponte, Emmanuel and Huth, Juliane and Kuenzer, Claudia}, title = {A first assessment of canopy cover loss in Germany's forests after the 2018-2020 drought years}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {3}, issn = {2072-4292}, doi = {10.3390/rs14030562}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255306}, year = {2022}, abstract = {Central Europe was hit by several unusually strong periods of drought and heat between 2018 and 2020. These droughts affected forest ecosystems. Cascading effects with bark beetle infestations in spruce stands were fatal to vast forest areas in Germany. We present the first assessment of canopy cover loss in Germany for the period of January 2018-April 2021. Our approach makes use of dense Sentinel-2 and Landsat-8 time-series data. We computed the disturbance index (DI) from the tasseled cap components brightness, greenness, and wetness. Using quantiles, we generated monthly DI composites and calculated anomalies in a reference period (2017). From the resulting map, we calculated the canopy cover loss statistics for administrative entities. Our results show a canopy cover loss of 501,000 ha for Germany, with large regional differences. The losses were largest in central Germany and reached up to two-thirds of coniferous forest loss in some districts. Our map has high spatial (10 m) and temporal (monthly) resolution and can be updated at any time.}, language = {en} } @article{AdolfiDuKneitzetal.2021, author = {Adolfi, Mateus C. and Du, Kang and Kneitz, Susanne and Cabau, C{\´e}dric and Zahm, Margot and Klopp, Christophe and Feron, Romain and Paix{\~a}o, R{\^o}mulo V. and Varela, Eduardo S. and de Almeida, Fernanda L. and de Oliveira, Marcos A. and N{\´o}brega, Rafael H. and Lopez-Roques, C{\´e}line and Iampietro, Carole and Lluch, J{\´e}r{\^o}me and Kloas, Werner and Wuertz, Sven and Schaefer, Fabian and St{\"o}ck, Matthias and Guiguen, Yann and Schartl, Manfred}, title = {A duplicated copy of id2b is an unusual sex-determining candidate gene on the Y chromosome of arapaima (Arapaima gigas)}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-01066-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265672}, year = {2021}, abstract = {Arapaima gigas is one of the largest freshwater fish species of high ecological and economic importance. Overfishing and habitat destruction are severe threats to the remaining wild populations. By incorporating a chromosomal Hi-C contact map, we improved the arapaima genome assembly to chromosome-level, revealing an unexpected high degree of chromosome rearrangements during evolution of the bonytongues (Osteoglossiformes). Combining this new assembly with pool-sequencing of male and female genomes, we identified id2bbY, a duplicated copy of the inhibitor of DNA binding 2b (id2b) gene on the Y chromosome as candidate male sex-determining gene. A PCR-test for id2bbY was developed, demonstrating that this gene is a reliable male-specific marker for genotyping. Expression analyses showed that this gene is expressed in juvenile male gonads. Its paralog, id2ba, exhibits a male-biased expression in immature gonads. Transcriptome analyses and protein structure predictions confirm id2bbY as a prime candidate for the master sex-determiner. Acting through the TGF beta signaling pathway, id2bbY from arapaima would provide the first evidence for a link of this family of transcriptional regulators to sex determination. Our study broadens our current understanding about the evolution of sex determination genetic networks and provide a tool for improving arapaima aquaculture for commercial and conservation purposes.}, language = {en} } @article{EisenhuthVellmerRauhetal.2021, author = {Eisenhuth, Nicole and Vellmer, Tim and Rauh, Elisa T. and Butter, Falk and Janzen, Christian J.}, title = {A DOT1B/Ribonuclease H2 Protein Complex Is Involved in R-Loop Processing, Genomic Integrity, and Antigenic Variation in Trypanosoma brucei}, series = {mbio}, volume = {12}, journal = {mbio}, number = {6}, doi = {10.1128/mBio.01352-21}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260698}, pages = {e01352-21}, year = {2021}, abstract = {The parasite Trypanosoma brucei periodically changes the expression of protective variant surface glycoproteins (VSGs) to evade its host's immune sys-tem in a process known as antigenic variation. One route to change VSG expres-sion is the transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing the VSG genes. Homologous recombination of a different VSG from a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machin-ery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We iden-tified several novel DOT1B interactors. One of these was the RNase H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage, and ES switch-ing events. Surprisingly, a similar pattern of VSG deregulation was observed in RNase H2 mutants. We propose that both proteins act together in resolving R-loops to ensure genome integrity and contribute to the tightly regulated process of anti-genic variation.}, language = {en} } @article{ColvillBoothNilletal.2016, author = {Colvill, Emma and Booth, Jeremy and Nill, Simeon and Fast, Martin and Bedford, James and Oelfke, Uwe and Nakamura, Mitsuhiro and Poulsen, Per and Worm, Esben and Hansen, Rune and Ravkilde, Thomas and Rydh{\"o}g, Jonas Scherman and Pommer, Tobias and af Rosenschold, Per Munck and Lang, Stephanie and Guckenberger, Matthias and Groh, Christian and Herrmann, Christian and Verellen, Dirk and Poels, Kenneth and Wang, Lei and Hadsell, Michael and Sothmann, Thilo and Blanck, Oliver and Keall, Paul}, title = {A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: a multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking}, series = {Radiotherapy and Oncology}, volume = {119}, journal = {Radiotherapy and Oncology}, number = {1}, doi = {10.1016/j.radonc.2016.03.006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189605}, pages = {159-165}, year = {2016}, abstract = {Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for gamma-tests recorded. Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2\%/2 mm gamma-fail rate of 1.6\% with adaptation and 15.2\% without adaptation (p < 0.001). For all prostate the mean 2\%/2 mm gamma-fail rate was 1.4\% with adaptation and 17.3\% without adaptation (p < 0.001). The difference between the four systems was small with an average 2\%/2 mm gamma-fail rate of <3\% for all systems with adaptation for lung and prostate. Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.}, language = {en} } @article{HollerFischerWeberetal.1987, author = {Holler, E. and Fischer, H. and Weber, C. and Stopper, Helga and Steger, H. and Simek, H.}, title = {A DNA polymerase with unusual properties from the slime mold Physarum polycephalum}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63501}, year = {1987}, abstract = {Two forms of a DNA polymerase have been purified from microplasmodia of Physarum polycephalum by poly(ethyleneimine) precipitation and chromatography on DEAE-Sephacel, phosphocellulose, heparin Sepharose, hydroxyapatite, DNA-agarose, blue-Sepharose. They were separated from DNA polymerase cx on phosphocellulose and from each other on heparin-Sepharose. Form HS1 enzymewas 30-40\% pure and form HS2 enzyme 60\% with regard toprotein contents of the preparations. Form HS2 enzymewas generated from form HS1 enzyme on prolonged standing of enzyme preparations. The DNA polymerases were obtained as complexes of a 60-kDa protein associated with either a 135-kDa (HS1) or a 110-kDa (HS2) DNA-polymerizing polypeptidein a 1:1 molar stoichiometry. The biochemical function of the 60-kDa protein remained unknown. The complexes tended to dissociate during gradient centrifugation and during partition chromatography as weil as during polyacrylamide gradient gel electrophoresis under nondenaturing conditions at high dilutions of samples. Both forms existed in plasmodia extracts, their proportions depending on several factors including those which promoted proteolysis. The DNA polymerases resembled eucaryotic DNA polymerase ß by several criteria and were functionally indistinguishable from each other. It is suggested that lower eucaryotes contain repair DNA polymerases, which are similar to those of eubacteria on a molecular mass basis.}, subject = {Toxikologie}, language = {en} } @article{KistlerSiwyFranketal.2011, author = {Kistler, Andreas D. and Siwy, Justyna and Frank, Breunig and Jeevaratnam, Praveen and Scherl, Alexander and Mullen, William and Warnock, David G. and Wanner, Christoph and Hughes, Derralynn A. and Mischak, Harald and W{\"u}thrich, Rudolf P. and Serra, Andreas L.}, title = {A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0020534}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133526}, pages = {e20534}, year = {2011}, abstract = {Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naive female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2\% sensitivity and 97.8\% specificity when tested in an independent validation cohort consisting of 17 treatment-naive Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy.}, language = {en} } @article{KarunakaranSubramanianJinetal.2023, author = {Karunakaran, Mohindar M. and Subramanian, Hariharan and Jin, Yiming and Mohammed, Fiyaz and Kimmel, Brigitte and Juraske, Claudia and Starick, Lisa and N{\"o}hren, Anna and L{\"a}nder, Nora and Willcox, Carrie R. and Singh, Rohit and Schamel, Wolfgang W. and Nikolaev, Viacheslav O. and Kunzmann, Volker and Wiemer, Andrew J. and Willcox, Benjamin E. and Herrmann, Thomas}, title = {A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-41938-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358179}, year = {2023}, abstract = {Butyrophilin (BTN)-3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members.}, language = {en} } @article{LanghauserCasasDaoetal.2018, author = {Langhauser, Friederike and Casas, Ana I. and Dao, Vu-Thao-Vi and Guney, Emre and Menche, J{\"o}rg and Geuss, Eva and Kleikers, Pamela W. M. and L{\´o}pez, Manuela G. and Barab{\´a}si, Albert-L. and Kleinschnitz, Christoph and Schmidt, Harald H. H. W.}, title = {A diseasome cluster-based drug repurposing of soluble guanylate cyclase activators from smooth muscle relaxation to direct neuroprotection}, series = {npj Systems Biology and Applications}, volume = {4}, journal = {npj Systems Biology and Applications}, doi = {10.1038/s41540-017-0039-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236381}, year = {2018}, abstract = {Network medicine utilizes common genetic origins, markers and co-morbidities to uncover mechanistic links between diseases. These links can be summarized in the diseasome, a comprehensive network of disease-disease relationships and clusters. The diseasome has been influential during the past decade, although most of its links are not followed up experimentally. Here, we investigate a high prevalence unmet medical need cluster of disease phenotypes linked to cyclic GMP. Hitherto, the central cGMP-forming enzyme, soluble guanylate cyclase (sGC), has been targeted pharmacologically exclusively for smooth muscle modulation in cardiology and pulmonology. Here, we examine the disease associations of sGC in a non-hypothesis based manner in order to identify possibly previously unrecognized clinical indications. Surprisingly, we find that sGC, is closest linked to neurological disorders, an application that has so far not been explored clinically. Indeed, when investigating the neurological indication of this cluster with the highest unmet medical need, ischemic stroke, pre-clinically we find that sGC activity is virtually absent post-stroke. Conversely, a heme-free form of sGC, apo-sGC, was now the predominant isoform suggesting it may be a mechanism-based target in stroke. Indeed, this repurposing hypothesis could be validated experimentally in vivo as specific activators of apo-sGC were directly neuroprotective, reduced infarct size and increased survival. Thus, common mechanism clusters of the diseasome allow direct drug repurposing across previously unrelated disease phenotypes redefining them in a mechanism-based manner. Specifically, our example of repurposing apo-sGC activators for ischemic stroke should be urgently validated clinically as a possible first-in-class neuroprotective therapy.}, language = {en} } @article{WongPittig2022, author = {Wong, Alex H. K. and Pittig, Andre}, title = {A dimensional measure of safety behavior: A non-dichotomous assessment of costly avoidance in human fear conditioning}, series = {Psychological Research}, volume = {86}, journal = {Psychological Research}, number = {1}, issn = {1430-2772}, doi = {10.1007/s00426-021-01490-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267688}, pages = {312-330}, year = {2022}, abstract = {Safety behavior prevents the occurrence of threat, thus it is typically considered adaptive. However, safety behavior in anxiety-related disorders is often costly, and persists even the situation does not entail realistic threat. Individuals can engage in safety behavior to varying extents, however, these behaviors are typically measured dichotomously (i.e., to execute or not). To better understand the nuances of safety behavior, this study developed a dimensional measure of safety behavior that had a negative linear relationship with the admission of an aversive outcome. In two experiments, a Reward group receiving fixed or individually calibrated incentives competing with safety behavior showed reduced safety behavior than a Control group receiving no incentives. This allowed extinction learning to a previously learnt warning signal in the Reward group (i.e., updating the belief that this stimulus no longer signals threat). Despite the Reward group exhibited extinction learning, both groups showed a similar increase in fear to the warning signal once safety behavior was no longer available. This null group difference was due to some participants in the Reward group not incentivized enough to disengage from safety behavior. Dimensional assessment revealed a dissociation between low fear but substantial safety behavior to a safety signal in the Control group. This suggests that low-cost safety behavior does not accurately reflect the fear-driven processes, but also other non-fear-driven processes, such as cost (i.e., engage in safety behavior merely because it bears little to no cost). Pinpointing both processes is important for furthering the understanding of safety behavior.}, language = {en} } @article{BayerPruckner2023, author = {Bayer, Daniel and Pruckner, Marco}, title = {A digital twin of a local energy system based on real smart meter data}, series = {Energy Informatics}, volume = {6}, journal = {Energy Informatics}, doi = {10.1186/s42162-023-00263-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357456}, year = {2023}, abstract = {The steadily increasing usage of smart meters generates a valuable amount of high-resolution data about the individual energy consumption and production of local energy systems. Private households install more and more photovoltaic systems, battery storage and big consumers like heat pumps. Thus, our vision is to augment these collected smart meter time series of a complete system (e.g., a city, town or complex institutions like airports) with simulatively added previously named components. We, therefore, propose a novel digital twin of such an energy system based solely on a complete set of smart meter data including additional building data. Based on the additional geospatial data, the twin is intended to represent the addition of the abovementioned components as realistically as possible. Outputs of the twin can be used as a decision support for either system operators where to strengthen the system or for individual households where and how to install photovoltaic systems and batteries. Meanwhile, the first local energy system operators had such smart meter data of almost all residential consumers for several years. We acquire those of an exemplary operator and discuss a case study presenting some features of our digital twin and highlighting the value of the combination of smart meter and geospatial data.}, language = {en} } @article{MuellerChandraFuraijatetal.2020, author = {M{\"u}ller, Frank and Chandra, Shivani and Furaijat, Ghefar and Kruse, Stefan and Waligorski, Alexandra and Simmenroth, Anne and Kleinert, Evelyn}, title = {A digital communication assistance tool (DCAT) to obtain medical history from foreign-language patients: development and pilot testing in a primary health care center for refugees}, series = {International Journal of Environmental Research and Public Health}, volume = {17}, journal = {International Journal of Environmental Research and Public Health}, number = {4}, issn = {1660-4601}, doi = {10.3390/ijerph17041368}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200640}, year = {2020}, abstract = {Background: Language barriers play a critical role in the treatment of migrant and refugee patients. In Germany, primary care interpreters are often not available especially in rural areas or if patients demand spontaneous or urgent consultations. Methods: In order to enable patients and their physicians to communicate effectively about the current illness history, we developed a digital communication assistance tool (DCAT) for 19 different languages and dialects. This paper reports the multidisciplinary process of the conceptual design and the iterative development of this cross-cultural user-centered application in an action-oriented approach. Results: We piloted our app with 36 refugee patients prior to a clinical study and used the results for further development. The acceptance and usability of the app by patients was high. Conclusion: Using digital tools for overcoming language barriers can be a feasible approach when providing health care to foreign-language patients.}, language = {en} }