@article{ElhfnawyVolkmannSchliesseretal.2019, author = {Elhfnawy, Ahmed Mohamed and Volkmann, Jens and Schliesser, Mira and Fluri, Felix}, title = {Symptomatic vs. asymptomatic 20-40\% internal carotid artery stenosis: Does the plaque size matter?}, series = {Frontiers in Neurology}, volume = {10}, journal = {Frontiers in Neurology}, number = {960}, doi = {10.3389/fneur.2019.00960}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201262}, year = {2019}, abstract = {Background: Around 9-15\% of ischemic strokes are related to internal carotid artery (ICA)-stenosis ≥50\%. However, the extent to which ICA-stenosis <50\% causes ischemic cerebrovascular events is uncertain. We examined the relation between plaque cross-sectional area and length and the risk of ischemic stroke or TIA among patients with ICA-stenosis of 20-40\%. Methods: We retrospectively identified patients admitted to the Department of Neurology, University Hospital of W{\"u}rzburg, from January 2011 until September 2016 with ischemic stroke or TIA and concomitant ICA-stenosis of 20-40\%, either symptomatic or asymptomatic. Plaque length and cross-sectional area were assessed on ultrasound scans. Results: We identified 41 patients with ischemic stroke or TIA and ICA-stenosis of 20-40\%; 14 symptomatic and 27 asymptomatic. The plaque cross-sectional area was significantly larger among symptomatic than asymptomatic ICA-stenosis; median values (IQR) were 0.45 (0.21-0.69) cm2 and 0.27 (0.21-0.38) cm2, p = 0.03, respectively. A plaque cross-sectional area ≥0.36 cm2 had a sensitivity of 71\% and a specificity of 76\% for symptomatic compared with asymptomatic ICA-stenosis. In a sex-adjusted multivariate logistic regression, a plaque cross-sectional area ≥0.36 cm2 and a plaque length ≥1.65 cm were associated with an OR (95\% CI) of 5.54 (1.2-25.6), p = 0.028 and 1.78 (0.36-8.73), p = 0.48, respectively, for symptomatic ICA-stenosis. Conclusion: Large plaques might increase the risk of ischemic stroke or TIA among patients with low-grade ICA-stenosis of 20-40\%. Sufficiently powered prospective longitudinal cohort studies are needed to definitively test the stroke risk stratification value of carotid plaque length and cross-sectional area in the setting of current optimal medical treatment.}, language = {en} } @article{SchleierReuschLummeletal.2019, author = {Schleier, Domenik and Reusch, Engelbert and Lummel, Lisa and Hemberger, Patrick and Fischer, Ingo}, title = {Threshold photoelectron spectroscopy of IO and IOH}, series = {ChemPhysChem}, volume = {20}, journal = {ChemPhysChem}, number = {19}, doi = {10.1002/cphc.201900813}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204751}, pages = {2413-2416}, year = {2019}, abstract = {Iodine oxides appear as reactive intermediates in atmospheric chemistry. Here, we investigate IO and HOI by mass-selective threshold photoelectron spectroscopy (ms-TPES), using synchrotron radiation. IO and HOI are generated by photolyzing iodine in the presence of ozone. For both molecules, accurate ionization energies are determined, 9.71±0.02 eV for IO and 9.79±0.02 eV for HOI. The strong spin-spin interaction in the 3Σ- ground state of IO+ leads to an energy splitting into the Ω=0 and Ω=±1 sublevels. Upon ionization, the I-O bond shortens significantly in both molecules; thus, a vibrational progression, assigned to the I-O stretch, is apparent in both spectra.}, language = {en} } @article{GablonskiPryssProbstetal.2019, author = {Gablonski, Thorsten-Christian and Pryss, R{\"u}diger and Probst, Thomas and Vogel, Carsten and Andreas, Sylke}, title = {Intersession-Online: A smartphone application for systematic recording and controlling of intersession experiences in psychotherapy}, series = {J — Multidisciplinary Scientific Journal}, volume = {2}, journal = {J — Multidisciplinary Scientific Journal}, number = {4}, issn = {2571-8800}, doi = {10.3390/j2040031}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285597}, pages = {480 -- 495}, year = {2019}, abstract = {Mobile health technologies have become more and more important in psychotherapy research and practice. The market is being flooded by several psychotherapeutic online services for different purposes. However, mobile health technologies are particularly suitable for data collection and monitoring, as data can be recorded economically in real time. Currently, there is no appropriate method to assess intersession experiences systematically in psychotherapeutic practice. The aim of our project was the development of a smartphone application framework for systematic recording and controlling of intersession experiences. Intersession-Online, an iOS- and Android-App, offers the possibility to collect data on intersession experiences easily, to provide the results to therapists in an evaluated form and, if necessary, to induce or interrupt intersession experiences with the primary aim to improve outcome of psychotherapy. In general, the smartphone application could be a helpful, evidence-based tool for research and practice. Overall speaking, further research to investigate the efficacy of Intersession-Online is necessary.}, language = {en} } @article{JohnKotzeRibechinietal.2019, author = {John, Vini and Kotze, Leigh A. and Ribechini, Eliana and Walzl, Gerhard and Du Plessis, Nelita and Lutz, Manfred B.}, title = {Caveolin-1 controls vesicular TLR2 expression, p38 signaling and T cell suppression in BCG infected murine monocytic myeloid-derived suppressor cells}, series = {Frontiers in Immunology}, volume = {10}, journal = {Frontiers in Immunology}, number = {2826}, issn = {1664-3224}, doi = {10.3389/fimmu.2019.02826}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195528}, year = {2019}, abstract = {Monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic MDSCs (G-MDSCs) have been found to be massively induced in TB patients as well in murine Mtb infection models. However, the interaction of mycobacteria with MDSCs and its role in TB infection is not well studied. Here, we investigated the role of Cav-1 for MDSCs infected with Mycobacterium bovis Bacille-Calmette-Guer{\´i}n (BCG). MDSCs that were generated from murine bone marrow (MDSCs) of wild-type (WT) or Cav1\(^{-/-}\) mice upregulated Cav-1, TLR4 and TLR2 expression after BCG infection on the cell surface. However, Cav-1 deficiency resulted in a selective defect of intracellular TLR2 levels predominantly in the M-MDSC subset. Further analysis indicated no difference in the phagocytosis of BCG by M-MDSCs from WT and Cav1\(^{-/-}\) mice or caveosome formation, but a reduced capacity to up-regulate surface markers, to secrete various cytokines, to induce iNOS and NO production required for suppression of T cell proliferation, whereas Arg-1 was not affected. Among the signaling pathways affected by Cav-1 deficiency, we found lower phosphorylation of the p38 mitogen-activated protein kinase (MAPK). Together, our findings implicate that (i) Cav-1 is dispensable for the internalization of BCG, (ii) vesicular TLR2 signaling in M-MDSCs is a major signaling pathway induced by BCG, (iii) vesicular TLR2 signals are controlled by Cav-1, (iv) vesicular TLR2/Cav-1 signaling is required for T cell suppressor functions.}, language = {en} } @article{BoetzlKonleKrauss2019, author = {Boetzl, Fabian A. and Konle, Antonia and Krauss, Jochen}, title = {Aphid cards - useful model for assessing predation rates or bias prone nonsense?}, series = {Journal of Applied Entomology}, volume = {144}, journal = {Journal of Applied Entomology}, number = {1-2}, doi = {10.1111/jen.12692}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204798}, pages = {74-80}, year = {2019}, abstract = {Predation on pest organisms is an essential ecosystem function supporting yields in modern agriculture. However, assessing predation rates is intricate, and they can rarely be linked directly to predator densities or functions. We tested whether sentinel prey aphid cards are useful tools to assess predation rates in the field. Therefore, we looked at aphid cards of different sizes on the ground level as well as within the vegetation. Additionally, by trapping ground-dwelling predators, we examined whether obtained predation rates could be linked to predator densities and traits. Predation rates recorded with aphid cards were independent of aphid card size. However, predation rates on the ground level were three times higher than within the vegetation. We found both predatory carabid activity densities as well as community weighted mean body size to be good predictors for predation rates. Predation rates obtained from aphid cards are stable over card type and related to predator assemblages. Aphid cards, therefore, are a useful, efficient method for rapidly assessing the ecosystem function predation. Their use might especially be recommended for assessments on the ground level and when time and resource limitations rule out more elaborate sentinel prey methods using exclosures with living prey animals.}, language = {en} } @article{SacchettoSequeiraBerteroetal.2019, author = {Sacchetto, Claudia and Sequeira, Vasco and Bertero, Edoardo and Dudek, Jan and Maack, Christoph and Calore, Martina}, title = {Metabolic Alterations in Inherited Cardiomyopathies}, series = {Journal of Clinical Medicine}, volume = {8}, journal = {Journal of Clinical Medicine}, number = {12}, issn = {2077-0383}, doi = {10.3390/jcm8122195}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193806}, year = {2019}, abstract = {The normal function of the heart relies on a series of complex metabolic processes orchestrating the proper generation and use of energy. In this context, mitochondria serve a crucial role as a platform for energy transduction by supplying ATP to the varying demand of cardiomyocytes, involving an intricate network of pathways regulating the metabolic flux of substrates. The failure of these processes results in structural and functional deficiencies of the cardiac muscle, including inherited cardiomyopathies. These genetic diseases are characterized by cardiac structural and functional anomalies in the absence of abnormal conditions that can explain the observed myocardial abnormality, and are frequently associated with heart failure. Since their original description, major advances have been achieved in the genetic and phenotype knowledge, highlighting the involvement of metabolic abnormalities in their pathogenesis. This review provides a brief overview of the role of mitochondria in the energy metabolism in the heart and focuses on metabolic abnormalities, mitochondrial dysfunction, and storage diseases associated with inherited cardiomyopathies.}, language = {en} } @article{SauerJuranekMarksetal.2019, author = {Sauer, Markus and Juranek, Stefan A. and Marks, James and De Magis, Alessio and Kazemier, Hinke G and Hilbig, Daniel and Benhalevy, Daniel and Wang, Xiantao and Hafner, Markus and Paeschke, Katrin}, title = {DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, number = {2421}, doi = {10.1038/s41467-019-10432-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227486}, pages = {1-15}, year = {2019}, abstract = {Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress.}, language = {en} } @article{SchneiderHuestegge2019, author = {Schneider, Norbert and Huestegge, Lynn}, title = {Interaction of oculomotor and manual behavior: evidence from simulated driving in an approach-avoidance steering task}, series = {Cognitive Research: Principles and Implications}, volume = {4}, journal = {Cognitive Research: Principles and Implications}, doi = {10.1186/s41235-019-0170-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200419}, pages = {19}, year = {2019}, abstract = {Background While the coordination of oculomotor and manual behavior is essential for driving a car, surprisingly little is known about this interaction, especially in situations requiring a quick steering reaction. In the present study, we analyzed oculomotor gaze and manual steering behavior in approach and avoidance tasks. Three task blocks were implemented within a dynamic simulated driving environment requiring the driver either to steer away from/toward a visual stimulus or to switch between both tasks. Results Task blocks requiring task switches were associated with higher manual response times and increased error rates. Manual response times did not significantly differ depending on whether drivers had to steer away from vs toward a stimulus, whereas oculomotor response times and gaze pattern variability were increased when drivers had to steer away from a stimulus compared to steering toward a stimulus. Conclusion The increased manual response times and error rates in mixed tasks indicate performance costs associated with cognitive flexibility, while the increased oculomotor response times and gaze pattern variability indicate a parsimonious cross-modal action control strategy (avoiding stimulus fixation prior to steering away from it) for the avoidance scenario. Several discrepancies between these results and typical eye-hand interaction patterns in basic laboratory research suggest that the specific goals and complex perceptual affordances associated with driving a vehicle strongly shape cross-modal control of behavior.}, language = {en} } @article{RufThomasBrunneretal.2019, author = {Ruf, Katharina and Thomas, Wolfgang and Brunner, Maximilian and Speer, Christian P. and Hebestreit, Helge}, title = {Diverging effects of premature birth and bronchopulmonary dysplasia on exercise capacity and physical activity - a case control study}, series = {Respiratory Research}, volume = {20}, journal = {Respiratory Research}, doi = {10.1186/s12931-019-1238-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202449}, pages = {260}, year = {2019}, abstract = {Background Extreme prematurity has been associated with exercise intolerance and reduced physical activity. We hypothesized that children with bronchopulmonary dysplasia (BPD) would be especially affected based on long-term lung function impairments. Therefore, the objective of this study was to compare exercise capacity and habitual physical activity between children born very and extremely preterm with and without BPD and term-born children. Methods Twenty-two school-aged children (aged 8 to 12 years) born with a gestational age < 32 weeks and a birthweight < 1500 g (9 with moderate or severe BPD (=BPD), 13 without BPD (=No-BPD)) and 15 healthy term-born children (=CONTROL) were included in the study. Physical activity was measured by accelerometry, lung function by spirometry and exercise capacity by an incremental cardiopulmonary exercise test. Results Peak oxygen uptake was reduced in the BPD-group (83 ± 11\%predicted) compared to the No-BPD group (91 ± 8\%predicted) and the CONTROL group (94 ± 9\%predicted). In a general linear model, variance of peak oxygen uptake was significantly explained by BPD status and height but not by prematurity (p < 0.001). Compared to CONTROL, all children born preterm spent significantly more time in sedentary behaviour (BPD 478 ± 50 min, No-BPD 450 ± 52 min, CONTROL 398 ± 56 min, p < 0.05) and less time in moderate-to-vigorous-physical activity (BPD 13 ± 8 min, No-BPD 16 ± 8 min, CONTROL 33 ± 16 min, p < 0.001). Prematurity but not BPD contributed significantly to explained variance in a general linear model of sedentary behaviour and likewise moderate-to-vigorous-physical activity (p < 0.05 and p < 0.001 respectively). Conclusion In our cohort, BPD but not prematurity was associated with a reduced exercise capacity at school-age. However, prematurity regardless of BPD was related to less engagement in physical activity and more time spent in sedentary behaviour. Thus, our findings suggest diverging effects of prematurity and BPD on exercise capacity and physical activity."}, language = {en} } @article{RichterExnerBratengeieretal.2019, author = {Richter, Anne and Exner, Florian and Bratengeier, Klaus and Polat, B{\"u}lent and Flentje, Michael and Weick, Stefan}, title = {Impact of beam configuration on VMAT plan quality for Pinnacle\(^3\)Auto-Planning for head and neck cases}, series = {Radiation Oncology}, volume = {14}, journal = {Radiation Oncology}, doi = {10.1186/s13014-019-1211-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200301}, pages = {12}, year = {2019}, abstract = {Background The purpose of this study was to compare automatically generated VMAT plans to find the superior beam configurations for Pinnacle3 Auto-Planning and share "best practices". Methods VMAT plans for 20 patients with head and neck cancer were generated using Pinnacle3 Auto-Planning Module (Pinnacle3 Version 9.10) with different beam setup parameters. VMAT plans for single (V1) or double arc (V2) and partial or full gantry rotation were optimized. Beam configurations with different collimator positions were defined. Target coverage and sparing of organs at risk were evaluated based on scoring of an evaluation parameter set. Furthermore, dosimetric evaluation was performed based on the composite objective value (COV) and a new cross comparison method was applied using the COVs. Results The evaluation showed a superior plan quality for double arcs compared to one single arc or two single arcs for all cases. Plan quality was superior if a full gantry rotation was allowed during optimization for unilateral target volumes. A double arc technique with collimator setting of 15° was superior to a double arc with collimator 60° and a two single arcs with collimator setting of 15° and 345°. Conclusion The evaluation showed that double and full arcs are superior to single and partial arcs in terms of organs at risk sparing even for unilateral target volumes. The collimator position was found as an additional setup parameter, which can further improve the target coverage and sparing of organs at risk.}, language = {en} } @article{RullmannPreusserPoppitzetal.2019, author = {Rullmann, Michael and Preusser, Sven and Poppitz, Sindy and Heba, Stefanie and Gousias, Konstantinos and Hoyer, Jana and Sch{\"u}tz, Tatjana and Dietrich, Arne and M{\"u}ller, Karsten and Hankir, Mohammed K. and Pleger, Burkhard}, title = {Adiposity Related Brain Plasticity Induced by Bariatric Surgery}, series = {Froniers in Human Neuroscience}, volume = {13}, journal = {Froniers in Human Neuroscience}, doi = {10.3389/fnhum.2019.00290}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227168}, pages = {1-11}, year = {2019}, abstract = {Previous magnetic resonance imaging (MRI) studies revealed structural-functional brain reorganization 12 months after gastric-bypass surgery, encompassing cortical and subcortical regions of all brain lobes as well as the cerebellum. Changes in the mean of cluster-wise gray/white matter density (GMD/WMD) were correlated with the individual loss of body mass index (BMI), rendering the BMI a potential marker of widespread surgery-induced brain plasticity. Here, we investigated voxel-by-voxel associations between surgery-induced changes in adiposity, metabolism and inflammation and markers of functional and structural neural plasticity. We re-visited the data of patients who underwent functional and structural MRI, 6 months (n = 27) and 12 months after surgery (n = 22), and computed voxel-wise regression analyses. Only the surgery-induced weight loss was significantly associated with brain plasticity, and this only for GMD changes. After 6 months, weight loss overlapped with altered GMD in the hypothalamus, the brain's homeostatic control site, the lateral orbitofrontal cortex, assumed to host reward and gustatory processes, as well as abdominal representations in somatosensory cortex. After 12 months, weight loss scaled with GMD changes in right cerebellar lobule VII, involved in language-related/cognitive processes, and, by trend, with the striatum, assumed to underpin (food) reward. These findings suggest time-dependent and weight-loss related gray matter plasticity in brain regions involved in the control of eating, sensory processing and cognitive functioning.}, language = {en} } @article{BratengeierHolubyevWegener2019, author = {Bratengeier, Klaus and Holubyev, Kostyantyn and Wegener, Sonja}, title = {Steeper dose gradients resulting from reduced source to target distance—a planning system independent study}, series = {Journal of Applied Clinical Medical Physics}, volume = {20}, journal = {Journal of Applied Clinical Medical Physics}, number = {1}, doi = {10.1002/acm2.12490}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177424}, pages = {89-100}, year = {2019}, abstract = {Purpose: To quantify the contribution of penumbra in the improvement of healthy tissue sparing at reduced source-to-axis distance (SAD) for simple spherical target and different prescription isodoses (PI). Method: A TPS-independent method was used to estimate three-dimensional (3D) dose distribution for stereotactic treatment of spherical targets of 0.5 cm radius based on single beam two-dimensional (2D) film dosimetry measurements. 1 cm target constitutes the worst case for the conformation with standard Multi-Leaf Collimator (MLC) with 0.5 cm leaf width. The measured 2D transverse dose cross-sections and the profiles in leaf and jaw directions were used to calculate radial dose distribution from isotropic beam arrangement, for both quadratic and circular beam openings, respectively. The results were compared for standard (100 cm) and reduced SAD 70 and 55 cm for different PI. Results: For practical reduction of SAD using quadratic openings, the improvement of healthy tissue sparing (HTS) at distances up to 3 times the PTV radius was at least 6\%-12\%; gradient indices (GI) were reduced by 3-39\% for PI between 40\% and 90\%. Except for PI of 80\% and 90\%, quadratic apertures at SAD 70 cm improved the HTS by up to 20\% compared to circular openings at 100 cm or were at least equivalent; GI were 3\%-33\% lower for reduced SAD in the PI range 40\%-70\%. For PI = 80\% and 90\% the results depend on the circular collimator model. Conclusion: Stereotactic treatments of spherical targets delivered at reduced SAD of 70 or 55 cm using MLC spare healthy tissue around the target at least as good as treatments at SAD 100 cm using circular collimators. The steeper beam penumbra at reduced SAD seems to be as important as perfect target conformity. The authors argue therefore that the beam penumbra width should be addressed in the stereotactic studies.}, language = {en} } @article{MansourSteigerNageletal.2019, author = {Mansour, Ahmed M. and Steiger, Christoph and Nagel, Christoph and Schatzschneider, Ulrich}, title = {Wavelength-dependent control of the CO release kinetics of manganese(I) tricarbonyl PhotoCORMs with benzimidazole coligands}, series = {European Journal of Inorganic Chemistry}, volume = {2019}, journal = {European Journal of Inorganic Chemistry}, number = {42}, doi = {10.1002/ejic.201900894}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218362}, pages = {4572-4581}, year = {2019}, abstract = {A series of photoactivatable CO-releasing molecules (PhotoCORMs) was prepared from manganese pentacarbonyl bromide and 1H-benzimidazol-2-ylmethyl-(N-phenyl)amine ligands (L) bearing different electron-donating and electron-withdrawing groups R = H, 4-CH\(_3\), 4-OCH\(_3\), 4-Cl, 4-NO\(_2\), 2-, 3-, and 4-COOCH\(_3\) on the phenyl substituent to give octahedral manganese(I) complexes of the general formula [MnBr(CO)\(_3\)(L)]. Aerated DMSO solutions of the compounds are stable in the dark for 16 h with no CO release. However, the compounds rapidly release CO upon illumination at 412-525 nm, depending on the substitution pattern. Its influence on the photophysical and photochemical properties was systematically explored using UV/Vis spectroscopy and CO release measurements with a commercial gas sensor system. In the nitro-substituted compound, the electronically excited state switched from benzimidazole- to phenyl-centered, leading to a markedly different photochemical behavior of this visible-light activated PhotoCORM.}, language = {en} } @article{LenczykRoyNitschetal.2019, author = {Lenczyk, Carsten and Roy, Dipak Kumar and Nitsch, J{\"o}rn and Radacki, Krzysztof and Rauch, Florian and Dewhurst, Rian D. and Bickelhaupt, F. Matthias and Marder, Todd B. and Braunschweig, Holger}, title = {Steric Effects Dictate the Formation of Terminal Arylborylene Complexes of Ruthenium from Dihydroboranes}, series = {Chemistry - A European Journal}, volume = {25}, journal = {Chemistry - A European Journal}, number = {59}, issn = {1521-3765}, doi = {10.1002/chem.201902890}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219537}, pages = {13566-13571}, year = {2019}, abstract = {The steric and electronic properties of aryl substituents in monoaryl borohydrides (Li[ArBH\(_3\)]) and dihydroboranes were systematically varied and their reactions with [Ru(PCy\(_3\))\(_2\)HCl(H\(_2\))] (Cy: cyclohexyl) were studied, resulting in bis(σ)-borane or terminal borylene complexes of ruthenium. These variations allowed for the investigation of the factors involved in the activation of dihydroboranes in the synthesis of terminal borylene complexes. The complexes were studied by multinuclear NMR spectroscopy, mass spectrometry, X-ray diffraction analysis, and density functional theory (DFT) calculations. The experimental and computational results suggest that the ortho-substitution of the aryl groups is necessary for the formation of terminal borylene complexes.}, language = {en} } @article{Belanger‐ChabotBraunschweig2019, author = {B{\´e}langer-Chabot, Guillaume and Braunschweig, Holger}, title = {Hexahalodiborate Dianions: A New Family of Binary Boron Halides}, series = {Angewandte Chemie International Edition}, volume = {58}, journal = {Angewandte Chemie International Edition}, number = {40}, doi = {10.1002/anie.201906666}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219688}, pages = {14270-14274}, year = {2019}, abstract = {The electron-precise binary boron subhalide species [B\(_2\)X\(_6\)]\(^{2-}\) X=F, Br, I) were synthesized and their structures confirmed by X-ray crystallography. The existence of the previously claimed [B\(_2\)Cl\(_6\)]\(^{2-}\), which had been questioned, was also confirmed by X-ray crystallography. The dianions are isoelectronic to hexahaloethanes, are subhalide analogues of the well-known tetrahaloborate anions (BX\(_4\)\(^-\)), and are rare examples of molecular electron-precise binary boron species beyond B\(_2\)X\(_4\), BX\(_3\), and [BX\(_4\)]\(^-\).}, language = {en} } @article{SteinmetzgerBessiLenzetal.2019, author = {Steinmetzger, Christian and Bessi, Irene and Lenz, Ann-Kathrin and H{\"o}bartner, Claudia}, title = {Structure-fluorescence activation relationships of a large Stokes shift fluorogenic RNA aptamer}, series = {Nucleic Acids Research}, journal = {Nucleic Acids Research}, doi = {10.1093/nar/gkz1084/5628921}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192340}, pages = {gkz1084}, year = {2019}, abstract = {The Chili RNA aptamer is a 52 nt long fluorogen-activating RNA aptamer (FLAP) that confers fluorescence to structurally diverse derivatives of fluorescent protein chromophores. A key feature of Chili is the formation of highly stable complexes with different ligands, which exhibit bright, highly Stokes-shifted fluorescence emission. In this work, we have analyzed the interactions between the Chili RNA and a family of conditionally fluorescent ligands using a variety of spectroscopic, calorimetric and biochemical techniques to reveal key structure - fluorescence activation relationships (SFARs). The ligands under investigation form two categories with emission maxima of ~540 nm or ~590 nm, respectively, and bind with affinities in the nanomolar to low-micromolar range. Isothermal titration calorimetry was used to elucidate the enthalpic and entropic contributions to binding affinity for a cationic ligand that is unique to the Chili aptamer. In addition to fluorescence activation, ligand binding was also observed by NMR spectroscopy, revealing characteristic signals for the formation of a G-quadruplex only upon ligand binding. These data shed light on the molecular features required and responsible for the large Stokes shift and the strong fluorescence enhancement of red and green emitting RNA-chromophore complexes.}, language = {en} } @article{PoepplerLuebtowSchlauersbachetal.2019, author = {P{\"o}ppler, Ann-Christin and L{\"u}btow, Michael M. and Schlauersbach, Jonas and Wiest, Johannes and Meinel, Lorenz and Luxenhofer, Robert}, title = {Loading dependent Structural Model of Polymeric Micelles Encapsulating Curcumin by Solid-State NMR Spectroscopy}, series = {Angewandte Chemie International Edition}, volume = {58}, journal = {Angewandte Chemie International Edition}, number = {51}, doi = {10.1002/anie.201908914}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206705}, pages = {18540-18546}, year = {2019}, abstract = {Detailed insight into the internal structure of drug-loaded polymeric micelles is scarce, but important for developing optimized delivery systems. We observed that an increase in the curcumin loading of triblock copolymers based on poly(2-oxazolines) and poly(2-oxazines) results in poorer dissolution properties. Using solid-state NMR spectroscopy and complementary tools we propose a loading-dependent structural model on the molecular level that provides an explanation for these pronounced differences. Changes in the chemical shifts and cross-peaks in 2D NMR experiments give evidence for the involvement of the hydrophobic polymer block in the curcumin coordination at low loadings, while at higher loadings an increase in the interaction with the hydrophilic polymer blocks is observed. The involvement of the hydrophilic compartment may be critical for ultrahigh-loaded polymer micelles and can help to rationalize specific polymer modifications to improve the performance of similar drug delivery systems.}, language = {en} } @article{ZhangMichailSaaletal.2019, author = {Zhang, Fangyuan and Michail, Evripidis and Saal, Fridolin and Krause, Ana-Maria and Ravat, Prince}, title = {Stereospecific Synthesis and Photophysical Properties of Propeller-Shaped C\(_{90}\)H\(_{48}\) PAH}, series = {Chemistry - A European Journal}, volume = {25}, journal = {Chemistry - A European Journal}, number = {71}, doi = {10.1002/chem.201904962}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208682}, pages = {16241-16245}, year = {2019}, abstract = {Herein, we have synthesized an enantiomerically pure propeller-shaped PAH, C\(_{90}\)H\(_{48}\), possessing three [7]helicene and three [5]helicene subunits. This compound can be obtained in gram quantities in a straightforward manner. The photophysical and chiroptical properties were investigated using UV/Vis absorption and emission, optical rotation and circular dichroism spectroscopy, supported by DFT calculations. The nonlinear optical properties were investigated by two-photon absorption measurements using linearly and circularly polarized light. The extremely twisted structure and packing of the homochiral compound were investigated by single-crystal X-ray diffraction analysis.}, language = {en} } @article{BekesLoebHolzheuetal.2019, author = {Bekes, Inga and L{\"o}b, Sanja and Holzheu, Iris and Janni, Wolfgang and Baumann, Lisa and W{\"o}ckel, Achim and Wulff, Christine}, title = {Nectin-2 in ovarian cancer: how is it expressed and what might be its functional role?}, series = {Cancer Science}, volume = {110}, journal = {Cancer Science}, number = {6}, doi = {10.1111/cas.13992}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202748}, pages = {1872- 1882}, year = {2019}, abstract = {Nectin-2 is an adhesion molecule that has been reported to play a role in tumor growth, metastasis and tumor angiogenesis. Herein, we investigated Nectin-2 in ovarian cancer patients and in cell culture. Tumor as well as peritoneal biopsies of 60 ovarian cancer patients and 22 controls were dual stained for Nectin-2 and CD31 using immunohistochemistry. Gene expression of Nectin-2 was quantified by real-time PCR and differences analyzed in relation to various tumor characteristics. In the serum of patients, vascular endothelial growth factor (VEGF) was quantified by ELISA. Effect of VEGF on Nectin-2 expression as well as permeability was investigated in HUVEC. In tumor biopsies, Nectin-2 protein was mainly localized in tumor cells, whereas in peritoneal biopsies, clear colocalization was found in the vasculature. T3 patients had a significantly higher percentage of positive lymph nodes and this correlated with survival. Nectin-2 was significantly upregulated in tumor biopsies in patients with lymph node metastasis and with residual tumor >1 cm after surgery. Nectin-2 expression was significantly suppressed in the peritoneal endothelium of patients associated with significantly increased VEGF serum levels. In cell culture, VEGF stimulation led to a significant downregulation of Nectin-2 which was reversed by VEGF-inhibition. In addition, Nectin-2 knockdown in endothelial cells was associated with significantly increased endothelial permeability. Nectin-2 expression in ovarian cancer may support tumor cell adhesion, leading to growth and lymph node metastasis. In addition, VEGF-induced Nectin-2 suppression in peritoneal endothelium may support an increase in vascular permeability leading to ascites production.}, language = {en} } @article{GehrkeScherzadHagenetal.2019, author = {Gehrke, Thomas and Scherzad, Agmal and Hagen, Rudolf and Hackenberg, Stephan}, title = {Risk factors for children requiring adenotonsillectomy and their impact on postoperative complications: a retrospective analysis of 2000 patients}, series = {Anaesthesia}, volume = {74}, journal = {Anaesthesia}, number = {12}, doi = {10.1111/anae.14844}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204787}, pages = {1572-1579}, year = {2019}, abstract = {Adenotonsillectomies are commonly performed procedures and sleep-disordered breathing is becoming increasingly important as an indication for surgery. Because of the higher risks in patients with obstructive sleep apnoea, the required level of postoperative care for these patients is currently under discussion, and better identification of patients at risk may reduce unnecessary postoperative monitoring. To evaluate the influence of obstructive sleep apnoea, and other risk factors, on peri-operative complications in children requiring adenotonsillectomy, we performed a retrospective case-control study that included 1995 patients treated between January 2009 and June 2017. In our analysis, young age (OR 3.8, 95\%CI 2.1-7.1), low body weight (OR 2.6, 95\%CI 1.5-4.4), obstructive sleep apnoea (OR 2.4, 95\%CI 1.5-3.8), pre-existing craniofacial or syndromal disorders (OR 2.3, 95\%CI 1.4-3.8) and adenotonsillectomy, compared with adenoidectomy alone, (OR 7.9, 95\%CI 4.7-13.1) were identified as risk factors for complications during or after surgery, p < 0.001. All 13 patients suffering from complications more than 3 h postoperatively had obstructive sleep apnoea plus at least one more of these risk factors. Patients at risk of postoperative complications can therefore be identified by several criteria pre-operatively, and should be monitored postoperatively using pulse oximetry overnight. For all other patients, postoperative observation on a surgical ward without extra monitoring is sufficient. Admission to paediatric intensive care should be reserved for patients suffering serious intra-operative complications.}, language = {en} } @article{PereiraTrivanovićHerrmann2019, author = {Pereira, A. R. and Trivanović, D. and Herrmann, M.}, title = {Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro}, series = {European Cells and Materials}, volume = {37}, journal = {European Cells and Materials}, issn = {1473-2262}, doi = {10.22203/eCM.v037a07}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268823}, pages = {88-112}, year = {2019}, abstract = {Mesenchymal stem/stromal cells (MSCs) are an essential element of most modern tissue engineering and regenerative medicine approaches due to their multipotency and immunoregulatory functions. Despite the prospective value of MSCs for the clinics, the stem cells community is questioning their developmental origin, in vivo localization, identification, and regenerative potential after several years of far-reaching research in the field. Although several major progresses have been made in mimicking the complexity of the MSC niche in vitro, there is need for comprehensive studies of fundamental mechanisms triggered by microenvironmental cues before moving to regenerative medicine cell therapy applications. The present comprehensive review extensively discusses the microenvironmental cues that influence MSC phenotype and function in health and disease - including cellular, chemical and physical interactions. The most recent and relevant illustrative examples of novel bioengineering approaches to mimic biological, chemical, and mechanical microenvironmental signals present in the native MSC niche are summarized, with special emphasis on the forefront techniques to achieve bio-chemical complexity and dynamic cultures. In particular, the skeletal MSC niche and applications focusing on the bone regenerative potential of MSC are addressed. The aim of the review was to recognize the limitations of the current MSC niche in vitro models and to identify potential opportunities to fill the bridge between fundamental science and clinical application of MSCs.}, language = {en} } @article{RichterKruppaMunzetal.2019, author = {Richter, Gesa M. and Kruppa, Jochen and Munz, Matthias and Wiehe, Ricarda and H{\"a}sler, Robert and Franke, Andre and Martins, Orlando and Jockel-Schneider, Yvonne and Bruckmann, Corinna and Dommisch, Henrik and Schaefer, Arne S.}, title = {A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers}, series = {Clinical Epigenetics}, volume = {11}, journal = {Clinical Epigenetics}, doi = {10.1186/s13148-019-0697-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226175}, pages = {1-18}, year = {2019}, abstract = {Background The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking. Results Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1;best p=5.5x10(-8)) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p=5.9x10(-9)). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p=4.0x10(-10). RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p=2.2x10(-14)), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1. Conclusion This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa.}, subject = {AHRR}, language = {en} } @article{WagnerKunzChowdhuryetal.2019, author = {Wagner, Fabienne and Kunz, Tobias C. and Chowdhury, Suvagata R. and Thiede, Bernd and Fraunholz, Martin and Eger, Debora and Kozjak-Pavlovic, Vera}, title = {Armadillo repeat-containing protein 1 is a dual localization protein associated with mitochondrial intermembrane space bridging complex}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0218303}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202670}, pages = {e0218303}, year = {2019}, abstract = {Cristae architecture is important for the function of mitochondria, the organelles that play the central role in many cellular processes. The mitochondrial contact site and cristae organizing system (MICOS) together with the sorting and assembly machinery (SAM) forms the mitochondrial intermembrane space bridging complex (MIB), a large protein complex present in mammalian mitochondria that partakes in the formation and maintenance of cristae. We report here a new subunit of the mammalian MICOS/MIB complex, an armadillo repeat-containing protein 1 (ArmC1). ArmC1 localizes both to cytosol and mitochondria, where it associates with the outer mitochondrial membrane through its carboxy-terminus. ArmC1 interacts with other constituents of the MICOS/MIB complex and its amounts are reduced upon MICOS/MIB complex depletion. Mitochondria lacking ArmC1 do not show defects in cristae structure, respiration or protein content, but appear fragmented and with reduced motility. ArmC1 represents therefore a peripheral MICOS/MIB component that appears to play a role in mitochondrial distribution in the cell.}, language = {en} } @article{BelkaNickelKurth2019, author = {Belka, Janina and Nickel, Joachim and Kurth, Dirk G.}, title = {Growth on metallo-supramolecular coordination polyelectrolyte (MEPE) stimulates osteogenic differentiation of human osteosarcoma cells (MG63) and human bone marrow derived mesenchymal stem cells}, series = {Polymers}, volume = {11}, journal = {Polymers}, number = {7}, issn = {2073-4360}, doi = {10.3390/polym11071090}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197264}, pages = {1090}, year = {2019}, abstract = {Background: Culturing of cells is typically performed on standard tissue culture plates generating growth conditions, which in general do not reflect the native three-dimensional cellular environment. Recent investigations provide insights in parameters, which strongly affect the general cellular behavior triggering essential processes such as cell differentiation. The physical properties of the used material, such as stiffness, roughness, or topology, as well as the chemical composition of the cell-surface interface are shown to play a key role in the initiation of particular cellular responses. Methods: We extended our previous research, which identified thin films of metallo-supramolecular coordination polyelectrolytes (MEPEs) as substrate to trigger the differentiation of muscular precursor cells. Results: Here, we show that the same MEPEs similarly stimulate the osteogenic differentiation of pre-osteoblasts. Remarkably, MEPE modified surfaces also trigger the differentiation of primary bone derived mesenchymal stem cells (BMSCs) towards the osteogenic lineage. Conclusion: This result leads to the conclusion that these surfaces individually support the specification of cell differentiation toward lineages that correspond to the natural commitment of the particular cell types. We, therefore, propose that Fe-MEPEs may be used as scaffold for the treatment of defects at least in muscular or bone tissue.}, language = {en} } @article{ReuschHolzmeierGerlachetal.2019, author = {Reusch, Engelbert and Holzmeier, Fabian and Gerlach, Marius and Fischer, Ingo and Hemberger, Patrick}, title = {Decomposition of Picolyl Radicals at High Temperature: A Mass Selective Threshold Photoelectron Spectroscopy Study}, series = {Chemistry - A European Journal}, volume = {25}, journal = {Chemistry - A European Journal}, number = {72}, doi = {10.1002/chem.201903937}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208132}, pages = {16652-16659}, year = {2019}, abstract = {The reaction products of the picolyl radicals at high temperature were characterized by mass-selective threshold photoelectron spectroscopy in the gas phase. Aminomethylpyridines were pyrolyzed to initially produce picolyl radicals (m /z =92). At higher temperatures further thermal reaction products are generated in the pyrolysis reactor. All compounds were identified by mass-selected threshold photoelectron spectroscopy and several hitherto unexplored reactive molecules were characterized. The mechanism for several dissociation pathways was outlined in computations. The spectrum of m /z =91, resulting from hydrogen loss of picolyl, shows four isomers, two ethynyl pyrroles with adiabatic ionization energies (IE\(_{ad}\)) of 7.99 eV (2-ethynyl-1H -pyrrole) and 8.12 eV (3-ethynyl-1H -pyrrole), and two cyclopentadiene carbonitriles with IE′s of 9.14 eV (cyclopenta-1,3-diene-1-carbonitrile) and 9.25 eV (cyclopenta-1,4-diene-1-carbonitrile). A second consecutive hydrogen loss forms the cyanocyclopentadienyl radical with IE′s of 9.07 eV (T\(_0\)) and 9.21 eV (S\(_1\)). This compound dissociates further to acetylene and the cyanopropynyl radical (IE=9.35 eV). Furthermore, the cyclopentadienyl radical, penta-1,3-diyne, cyclopentadiene and propargyl were identified in the spectra. Computations indicate that dissociation of picolyl proceeds initially via a resonance-stabilized seven-membered ring.}, language = {en} } @article{RuizDiefenbacherNelsonetal.2019, author = {Ruiz, E. Josue and Diefenbacher, Markus E. and Nelson, Jessica K. and Sancho, Rocio and Pucci, Fabio and Chakraborty, Atanu and Moreno, Paula and Annibaldi, Alessandro and Liccardi, Gianmaria and Encheva, Vesela and Mitter, Richard and Rosenfeldt, Mathias and Snijders, Ambrosius P. and Meier, Pascal and Calzado, Marco A. and Behrens, Axel}, title = {LUBAC determines chemotherapy resistance in squamous cell lung cancer}, series = {Journal of Experimental Medicine}, volume = {216}, journal = {Journal of Experimental Medicine}, number = {2}, doi = {10.1084/jem.20180742}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227146}, pages = {450-465}, year = {2019}, abstract = {Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10(+), but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-kappa B signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-kappa B activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.}, language = {en} } @article{WoersdoerferDaldaKernetal.2019, author = {W{\"o}rsd{\"o}rfer, Philipp and Dalda, Nahide and Kern, Anna and Kr{\"u}ger, Sarah and Wagner, Nicole and Kwok, Chee Keong and Henke, Erik and Erg{\"u}n, S{\"u}leyman}, title = {Generation of complex human organoid models including vascular networks by incorporation of mesodermal progenitor cells}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-52204-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202681}, pages = {15663}, year = {2019}, abstract = {Organoids derived from human pluripotent stem cells are interesting models to study mechanisms of morphogenesis and promising platforms for disease modeling and drug screening. However, they mostly remain incomplete as they lack stroma, tissue resident immune cells and in particular vasculature, which create important niches during development and disease. We propose, that the directed incorporation of mesodermal progenitor cells (MPCs) into organoids will overcome the aforementioned limitations. In order to demonstrate the feasibility of the method, we generated complex human tumor as well as neural organoids. We show that the formed blood vessels display a hierarchic organization and mural cells are assembled into the vessel wall. Moreover, we demonstrate a typical blood vessel ultrastructure including endothelial cell-cell junctions, a basement membrane as well as luminal caveolae and microvesicles. We observe a high plasticity in the endothelial network, which expands, while the organoids grow and is responsive to anti-angiogenic compounds and pro-angiogenic conditions such as hypoxia. We show that vessels within tumor organoids connect to host vessels following transplantation. Remarkably, MPCs also deliver Iba1\(^+\) cells that infiltrate the neural tissue in a microglia-like manner.}, language = {en} } @article{DietrichMeisterDietrichetal.2019, author = {Dietrich, Laura and Meister, Julia and Dietrich, Oliver and Notroff, Jens and Kiep, Janika and Heeb, Julia and Beuger, Andr{\´e} and Sch{\"u}tt, Brigitta}, title = {Cereal processing at Early Neolithic G{\"o}bekli Tepe, southeastern Turkey}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0215214}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201504}, pages = {e0215214}, year = {2019}, abstract = {We analyze the processing of cereals and its role at Early Neolithic G{\"o}bekli Tepe, southeastern Anatolia (10th / 9th millennium BC), a site that has aroused much debate in archaeological discourse. To date, only zooarchaeological evidence has been discussed in regard to the subsistence of its builders. G{\"o}bekli Tepe consists of monumental round to oval buildings, erected in an earlier phase, and smaller rectangular buildings, built around them in a partially contemporaneous and later phase. The monumental buildings are best known as they were in the focus of research. They are around 20 m in diameter and have stone pillars that are up to 5.5 m high and often richly decorated. The rectangular buildings are smaller and-in some cases-have up to 2 m high, mostly undecorated, pillars. Especially striking is the number of tools related to food processing, including grinding slabs/bowls, handstones, pestles, and mortars, which have not been studied before. We analyzed more than 7000 artifacts for the present contribution. The high frequency of artifacts is unusual for contemporary sites in the region. Using an integrated approach of formal, experimental, and macro- / microscopical use-wear analyses we show that Neolithic people at G{\"o}bekli Tepe have produced standardized and efficient grinding tools, most of which have been used for the processing of cereals. Additional phytolith analysis confirms the massive presence of cereals at the site, filling the gap left by the weakly preserved charred macro-rests. The organization of work and food supply has always been a central question of research into G{\"o}bekli Tepe, as the construction and maintenance of the monumental architecture would have necessitated a considerable work force. Contextual analyses of the distribution of the elements of the grinding kit on site highlight a clear link between plant food preparation and the rectangular buildings and indicate clear delimitations of working areas for food production on the terraces the structures lie on, surrounding the circular buildings. There is evidence for extensive plant food processing and archaeozoological data hint at large-scale hunting of gazelle between midsummer and autumn. As no large storage facilities have been identified, we argue for a production of food for immediate use and interpret these seasonal peaks in activity at the site as evidence for the organization of large work feasts.}, language = {en} } @article{WegenerSauer2019, author = {Wegener, Sonja and Sauer, Otto A.}, title = {The effective point of measurement for depth-dose measurements in small MV photon beams with different detectors}, series = {Medical Physics}, volume = {46}, journal = {Medical Physics}, number = {11}, doi = {10.1002/mp.13788}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206148}, pages = {5209-5215}, year = {2019}, abstract = {Purpose: The effective point of measurement (EPOM) of cylindrical ionization chambers differs from their geometric center. The exact shift depends on chamber construction details, above all the chamber size, and to some degree on the field-size and beam quality. It generally decreases as the chamber dimensions get smaller. In this work, effective points of measurement in small photon fields of a range of cylindrical chambers of different sizes are investigated, including small chambers that have not been studied previously. Methods: In this investigation, effective points of measurement for different ionization chambers (Farmer type, scanning chambers, micro-ionization chambers) and solid state detectors were determined by measuring depth-ionization curves in a 6 MV beam in field sizes between 2 9 2 cm2 and 10 9 10 cm2 and comparing those curves with curves measured with plane-parallel chambers. Results: It was possible to average the results to one shift per detector, as the results were sufficiently independent of the studied field sizes. For cylindrical ion chambers, shifts of the EPOM were determined to be between 0.49 and 0.30 times the inner chamber radius from the reference point. Conclusions: We experimentally confirmed the previously reported decrease of the EPOM shift with decreasing detector size. Highly accurate data for a large range of detectors, including new very small ones, were determined. Thus, small chambers noticeably differ from the 0.5-times to 0.6-times the inner chamber radius recommendations in current dosimetry protocols. The detector-individual EPOMs need to be considered for measurements of depth-dose curves.}, language = {en} } @article{KammererHoppenstedtPryssetal.2019, author = {Kammerer, Klaus and Hoppenstedt, Burkhard and Pryss, R{\"u}diger and St{\"o}kler, Steffen and Allgaier, Johannes and Reichert, Manfred}, title = {Anomaly Detections for Manufacturing Systems Based on Sensor Data—Insights into Two Challenging Real-World Production Settings}, series = {Sensors}, volume = {19}, journal = {Sensors}, number = {24}, issn = {1424-8220}, doi = {10.3390/s19245370}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193885}, pages = {5370}, year = {2019}, abstract = {o build, run, and maintain reliable manufacturing machines, the condition of their components has to be continuously monitored. When following a fine-grained monitoring of these machines, challenges emerge pertaining to the (1) feeding procedure of large amounts of sensor data to downstream processing components and the (2) meaningful analysis of the produced data. Regarding the latter aspect, manifold purposes are addressed by practitioners and researchers. Two analyses of real-world datasets that were generated in production settings are discussed in this paper. More specifically, the analyses had the goals (1) to detect sensor data anomalies for further analyses of a pharma packaging scenario and (2) to predict unfavorable temperature values of a 3D printing machine environment. Based on the results of the analyses, it will be shown that a proper management of machines and their components in industrial manufacturing environments can be efficiently supported by the detection of anomalies. The latter shall help to support the technical evangelists of the production companies more properly.}, language = {en} } @article{KittelSchneiderWolffQueiseretal.2019, author = {Kittel-Schneider, Sarah and Wolff, Sarah and Queiser, Kristin and Wessendorf, Leonie and Meier, Anna Maria and Verdenhalven, Moritz and Brunkhorst-Kanaan, Nathalie and Grimm, Oliver and McNeill, Rhiannon and Grabow, Sascha and Reimertz, Christoph and Nau, Christoph and Klos, Michelle and Reif, Andreas}, title = {Prevalence of ADHD in accident victims: results of the PRADA study}, series = {Journal of Clinical Medicine}, volume = {8}, journal = {Journal of Clinical Medicine}, number = {10}, issn = {2077-0383}, doi = {10.3390/jcm8101643}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193293}, pages = {1643}, year = {2019}, abstract = {Background: Recent research has shown an increased risk of accidents and injuries in ADHD patients, which could potentially be reduced by stimulant treatment. Therefore, the first aim of our study was to evaluate the prevalence of adult ADHD in a trauma surgery population. The second aim was to investigate accident mechanisms and circumstances which could be specific to ADHD patients, in comparison to the general population. Methods: We screened 905 accident victims for ADHD using the ASRS 18-item self-report questionnaire. The basic demographic data and circumstances of the accidents were also assessed. Results: Prevalence of adult ADHD was found to be 6.18\% in our trauma surgery patient sample. ADHD accident victims reported significantly higher rates of distraction, stress and overconfidence in comparison to non-ADHD accident victims. Overconfidence and being in thoughts as causal mechanisms for the accidents remained significantly higher in ADHD patients after correction for multiple comparison. ADHD patients additionally reported a history of multiple accidents. Conclusion: The majority of ADHD patients in our sample had not previously been diagnosed and were therefore not receiving treatment. The results subsequently suggest that general ADHD screening in trauma surgery patients may be useful in preventing further accidents in ADHD patients. Furthermore, psychoeducation regarding specific causal accident mechanisms could be implemented in ADHD therapy to decrease accident incidence rate}, language = {en} } @article{DrayssClausHubertetal.2019, author = {Drayß, Maria and Claus, Heike and Hubert, Kerstin and Thiel, Katrin and Berger, Anja and Sing, Andreas and van der Linden, Mark and Vogel, Ulrich and L{\^a}m, Thi{\^e}n-Tr{\´i}}, title = {Asymptomatic carriage of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Group A Streptococcus and Staphylococcus aureus among adults aged 65 years and older}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0212052}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201042}, pages = {e0212052}, year = {2019}, abstract = {Objective The aim of this study was to determine the prevalence of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, group A Streptococcus (GAS), and Staphylococcus aureus in asymptomatic elderly people and to unravel risk factors leading to colonization. Methods A multi-centre cross-sectional study was conducted including 677 asymptomatic adults aged 65 years or more, living at home or in nursing homes. Study areas were Greater Aachen (North-Rhine-Westphalia) and Wuerzburg (Bavaria), both regions with medium to high population density. Nasal and oropharyngeal swabs as well as questionnaires were collected from October 2012 to May 2013. Statistical analysis included multiple logistic regression models. Results The carriage rate was 1.9\% ([95\%CI: 1.0-3.3\%]; 13/677) for H. influenzae, 0.3\% ([95\%CI: 0-1.1\%]; 2/677) for N. meningitidis and 0\% ([95\% CI: 0-0.5\%]; 0/677) for S. pneumoniae and GAS. Staphylococcus aureus was harboured by 28.5\% of the individuals ([95\% CI: 25.1-32.1\%]; 193/677) and 0.7\% ([95\% CI: 0.2-1.7\%]; 5/677) were positive for methicillin-resistant S. aureus. Among elderly community-dwellers colonization with S. aureus was significantly associated with higher educational level (adjusted OR: 1.905 [95\% CI: 1.248-2.908]; p = 0.003). Among nursing home residents colonization was associated with being married (adjusted OR: 3.367 [1.502-7.546]; p = 0.003). Conclusion The prevalence of N. meningitidis, H. influenzae, S. pneumoniae and GAS was low among older people in Germany. The S. aureus rate was expectedly high, while MRSA was found in less than 1\% of the individuals.}, language = {en} } @article{PasosSteigerwaldReichetal.2019, author = {Pasos, Uri E. Ramirez and Steigerwald, Frank and Reich, Martin M. and Matthies, Cordula and Volkmann, Jens and Reese, Ren{\´e}}, title = {Levodopa modulates functional connectivity in the upper beta band between bubthalamic nucleus and muscle activity in tonic and phasic motor activity patterns in Parkinson's disease}, series = {Frontiers in Human Neuroscience}, volume = {13}, journal = {Frontiers in Human Neuroscience}, number = {223}, doi = {10.3389/fnhum.2019.00223}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201540}, year = {2019}, abstract = {Introduction: Striatal dopamine depletion disrupts basal ganglia function and causes Parkinson's disease (PD). The pathophysiology of the dopamine-dependent relationship between basal ganglia signaling and motor control, however, is not fully understood. We obtained simultaneous recordings of local field potentials (LFPs) from the subthalamic nucleus (STN) and electromyograms (EMGs) in patients with PD to investigate the impact of dopaminergic state and movement on long-range beta functional connectivity between basal ganglia and lower motor neurons. Methods: Eight PD patients were investigated 3 months after implantation of a deep brain stimulation (DBS)-system capable of recording LFPs via chronically-implanted leads (Medtronic, ACTIVA PC+S®). We analyzed STN spectral power and its coherence with EMG in the context of two different movement paradigms (tonic wrist extension vs. alternating wrist extension and flexion) and the effect of levodopa (L-Dopa) intake using an unbiased data-driven approach to determine regions of interest (ROI). Results: Two ROIs capturing prominent coherence within a grand average coherogram were identified. A trend of a dopamine effect was observed for the first ROI (50-150 ms after movement start) with higher STN-EMG coherence in medicated patients. Concerning the second ROI (300-500 ms after movement start), an interaction effect of L-Dopa medication and movement task was observed with higher coherence in the isometric contraction task compared to alternating movements in the medication ON state, a pattern which was reversed in L-Dopa OFF. Discussion: L-Dopa medication may normalize functional connectivity between remote structures of the motor system with increased upper beta coherence reflecting a physiological restriction of the amount of information conveyed between remote structures. This may be necessary to maintain simple movements like isometric contraction. Our study adds dynamic properties to the complex interplay between STN spectral beta power and the nucleus' functional connectivity to remote structures of the motor system as a function of movement and dopaminergic state. This may help to identify markers of neuronal activity relevant for more individualized programming of DBS therapy.}, language = {en} } @article{DjuzenovaFiedlerMemmeletal.2019, author = {Djuzenova, Cholpon S. and Fiedler, Vanessa and Memmel, Simon and Katzer, Astrid and Sisario, Dmitri and Brosch, Philippa K. and G{\"o}hrung, Alexander and Frister, Svenja and Zimmermann, Heiko and Flentje, Michael and Sukhorukov, Vladimir L.}, title = {Differential effects of the Akt inhibitor MK-2206 on migration and radiation sensitivity of glioblastoma cells}, series = {BMC Cancer}, volume = {19}, journal = {BMC Cancer}, doi = {10.1186/s12885-019-5517-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200290}, pages = {299}, year = {2019}, abstract = {Background Most tumor cells show aberrantly activated Akt which leads to increased cell survival and resistance to cancer radiotherapy. Therefore, targeting Akt can be a promising strategy for radiosensitization. Here, we explore the impact of the Akt inhibitor MK-2206 alone and in combination with the dual PI3K and mTOR inhibitor PI-103 on the radiation sensitivity of glioblastoma cells. In addition, we examine migration of drug-treated cells. Methods Using single-cell tracking and wound healing migration tests, colony-forming assay, Western blotting, flow cytometry and electrorotation we examined the effects of MK-2206 and PI-103 and/or irradiation on the migration, radiation sensitivity, expression of several marker proteins, DNA damage, cell cycle progression and the plasma membrane properties in two glioblastoma (DK-MG and SNB19) cell lines, previously shown to differ markedly in their migratory behavior and response to PI3K/mTOR inhibition. Results We found that MK-2206 strongly reduces the migration of DK-MG but only moderately reduces the migration of SNB19 cells. Surprisingly, MK-2206 did not cause radiosensitization, but even increased colony-forming ability after irradiation. Moreover, MK-2206 did not enhance the radiosensitizing effect of PI-103. The results appear to contradict the strong depletion of p-Akt in MK-2206-treated cells. Possible reasons for the radioresistance of MK-2206-treated cells could be unaltered or in case of SNB19 cells even increased levels of p-mTOR and p-S6, as compared to the reduced expression of these proteins in PI-103-treated samples. We also found that MK-2206 did not enhance IR-induced DNA damage, neither did it cause cell cycle distortion, nor apoptosis nor excessive autophagy. Conclusions Our study provides proof that MK-2206 can effectively inhibit the expression of Akt in two glioblastoma cell lines. However, due to an aberrant activation of mTOR in response to Akt inhibition in PTEN mutated cells, the therapeutic window needs to be carefully defined, or a combination of Akt and mTOR inhibitors should be considered.}, language = {en} } @article{StrahlGerlichAlpersetal.2019, author = {Strahl, Andr{\´e} and Gerlich, Christian and Alpers, Georg W. and Gehrke, J{\"o}rg and M{\"u}ller-Garnn, Annette and Vogel, Heiner}, title = {An instrument for quality assurance in work capacity evaluation: development, evaluation, and inter-rater reliability}, series = {BMC Health Services Research}, volume = {19}, journal = {BMC Health Services Research}, doi = {10.1186/s12913-019-4387-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200289}, pages = {556}, year = {2019}, abstract = {Background: Employees insured in pension insurance, who are incapable of working due to ill health, are entitled to a disability pension. To assess whether an individual meets the medical requirements to be considered as disabled, a work capacity evaluation is conducted. However, there are no official guidelines on how to perform an external quality assurance for this evaluation process. Furthermore, the quality of medical reports in the field of insurance medicine can vary substantially, and systematic evaluations are scarce. Reliability studies using peer review have repeatedly shown insufficient ability to distinguish between high, moderate and low quality. Considering literature recommendations, we developed an instrument to examine the quality of medical experts'reports. Methods: The peer review manual developed contains six quality domains (formal structure, clarity, transparency, completeness, medical-scientific principles, and efficiency) comprising 22 items. In addition, a superordinate criterion (survey confirmability) rank the overall quality and usefulness of a report. This criterion evaluates problems of innerlogic and reasoning. Development of the manual was assisted by experienced physicians in a pre-test. We examined the observable variance in peer judgements and reliability as the most important outcome criteria. To evaluate inter-rater reliability, 20 anonymous experts' reports detailing the work capacity evaluation were reviewed by 19 trained raters (peers). Percentage agreement and Kendall's W, a reliability measure of concordance between two or more peers, were calculated. A total of 325 reviews were conducted. Results: Agreement of peer judgements with respect to the superordinate criterion ranged from 29.2 to 87.5\%. Kendall's W for the quality domain items varied greatly, ranging from 0.09 to 0.88. With respect to the superordinate criterion, Kendall's W was 0.39, which indicates fair agreement. The results of the percentage agreement revealed systemic peer preferences for certain deficit scale categories. Conclusion: The superordinate criterion was not sufficiently reliable. However, in comparison to other reliability studies, this criterion showed an equivalent reliability value. This report aims to encourage further efforts to improve evaluation instruments. To reduce disagreement between peer judgments, we propose the revision of the peer review instrumentand the development and implementation of a standardized rater training to improve reliability.}, language = {en} } @article{NoHolzmeisterLuetal.2019, author = {No, Young Jung and Holzmeister, Ib and Lu, Zufu and Prajapati, Shubham and Shi, Jeffrey and Gbureck, Uwe and Zreiqat, Hala}, title = {Effect of Baghdadite Substitution on the Physicochemical Properties of Brushite Cements}, series = {Materials}, volume = {12}, journal = {Materials}, number = {10}, issn = {1996-1944}, doi = {10.3390/ma12101719}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196980}, year = {2019}, abstract = {Brushite cements have been clinically used for irregular bone defect filling applications, and various strategies have been previously reported to modify and improve their physicochemical properties such as strength and injectability. However, strategies to address other limitations of brushite cements such as low radiopacity or acidity without negatively impacting mechanical strength have not yet been reported. In this study, we report the effect of substituting the beta-tricalcium phosphate reactant in brushite cement with baghdadite (Ca\(_3\)ZrSi\(_2\)O\(_9\)), a bioactive zirconium-doped calcium silicate ceramic, at various concentrations (0, 5, 10, 20, 30, 50, and 100 wt\%) on the properties of the final brushite cement product. X-ray diffraction profiles indicate the dissolution of baghdadite during the cement reaction, without affecting the crystal structure of the precipitated brushite. EDX analysis shows that calcium is homogeneously distributed within the cement matrix, while zirconium and silicon form cluster-like aggregates with sizes ranging from few microns to more than 50 µm. X-ray images and µ-CT analysis indicate enhanced radiopacity with increased incorporation of baghdadite into brushite cement, with nearly a doubling of the aluminium equivalent thickness at 50 wt\% baghdadite substitution. At the same time, compressive strength of brushite cement increased from 12.9 ± 3.1 MPa to 21.1 ± 4.1 MPa with 10 wt\% baghdadite substitution. Culture medium conditioned with powdered brushite cement approached closer to physiological pH values when the cement is incorporated with increasing amounts of baghdadite (pH = 6.47 for pure brushite, pH = 7.02 for brushite with 20 wt\% baghdadite substitution). Baghdadite substitution also influenced the ionic content in the culture medium, and subsequently affected the proliferative activity of primary human osteoblasts in vitro. This study indicates that baghdadite is a beneficial additive to enhance the radiopacity, mechanical performance and cytocompatibility of brushite cement}, language = {en} } @article{BruecknerMeiningerGrolletal.2019, author = {Br{\"u}ckner, Theresa and Meininger, Markus and Groll, J{\"u}rgen and K{\"u}bler, Alexander C. and Gbureck, Uwe}, title = {Magnesium Phosphate Cement as Mineral Bone Adhesive}, series = {Materials}, volume = {12}, journal = {Materials}, number = {23}, issn = {1996-1944}, doi = {10.3390/ma12233819}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193052}, year = {2019}, abstract = {Mineral bone cements were actually not developed for their application as bone-bonding agents, but as bone void fillers. In particular, calcium phosphate cements (CPC) are considered to be unsuitable for that application, particularly under moist conditions. Here, we showed the ex vivo ability of different magnesium phosphate cements (MPC) to adhere on bovine cortical bone substrates. The cements were obtained from a mixture of farringtonite (Mg\(_3\)(PO\(_4\))\(_2\)) with different amounts of phytic acid (C\(_6\)H\(_{18}\)O\(_{24}\)P\(_6\), inositol hexaphosphate, IP6), whereas cement setting occurred by a chelation reaction between Mg\(^{2+}\) ions and IP6. We were able to show that cements with 25\% IP6 and a powder-to-liquid ratio (PLR) of 2.0 g/mL resulted in shear strengths of 0.81 ± 0.12 MPa on bone even after 7 d storage in aqueous conditions. The samples showed a mixed adhesive-cohesive failure with cement residues on the bone surface as indicated by scanning electron microscopy and energy-dispersive X-ray analysis. The presented material demonstrated appropriate bonding characteristics, which could enable a broadening of the mineral bone cements' application field to bone adhesives}, language = {en} } @article{MottolaMorschhaeuser2019, author = {Mottola, Austin and Morschh{\"a}user, Joachim}, title = {An intragenic recombination event generates a Snf4-independent form of the essential protein kinase SNF1 in Candida albicans}, series = {mSphere}, volume = {4}, journal = {mSphere}, number = {3}, doi = {10.1128/mSphere.00352-19}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202170}, pages = {e00352-19}, year = {2019}, abstract = {The heterotrimeric protein kinase SNF1 plays a key role in the metabolic adaptation of the pathogenic yeast Candida albicans. It consists of the essential catalytic α-subunit Snf1, the γ-subunit Snf4, and one of the two β-subunits Kis1 and Kis2. Snf4 is required to release the N-terminal catalytic domain of Snf1 from autoinhibition by the C-terminal regulatory domain, and snf4Δ mutants cannot grow on carbon sources other than glucose. In a screen for suppressor mutations that restore growth of a snf4Δ mutant on alternative carbon sources, we isolated a mutant in which six amino acids between the N-terminal kinase domain and the C-terminal regulatory domain of Snf1 were deleted. The deletion was caused by an intragenic recombination event between two 8-bp direct repeats flanking six intervening codons. In contrast to truncated forms of Snf1 that contain only the kinase domain, the Snf4-independent Snf1\(^{Δ311 - 316}\) was fully functional and could replace wild-type Snf1 for normal growth, because it retained the ability to interact with the Kis1 and Kis2 β-subunits via its C-terminal domain. Indeed, the Snf4-independent Snf1\(^{Δ311 - 316}\) still required the β-subunits of the SNF1 complex to perform its functions and did not rescue the growth defects of kis1Δ mutants. Our results demonstrate that a preprogrammed in-frame deletion event within the SNF1 coding region can generate a mutated form of this essential kinase which abolishes autoinhibition and thereby overcomes growth deficiencies caused by a defect in the γ-subunit Snf4.}, language = {en} } @article{LuberLutzAbeleHornetal.2019, author = {Luber, Verena and Lutz, Mathias and Abele-Horn, Marianne and Einsele, Hermann and Grigoleit, G{\"o}tz Ulrich and Mielke, Stephan}, title = {Excretion of Ascaris lumbricoides following reduced-intensity allogeneic hematopoietic stem cell transplantation and consecutive treatment with mebendazole}, series = {Transplant Infectious Disease}, volume = {22}, journal = {Transplant Infectious Disease}, number = {1}, issn = {1399-3062}, doi = {10.1111/tid.13224}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219608}, pages = {1-4}, year = {2019}, abstract = {Here, we present the unique case of a 51-year-old German patient with multiple myeloma excreting Ascaris lumbricoides in his stool five weeks after allogeneic hematopoietic stem cell transplantation. Stool analysis remained negative for the presence of eggs, and there was no eosinophilia in the peripheral blood at any time around stem cell transplantation. The patient was commenced on a three-day treatment with mebendazole, which was well tolerated. No serious interactions with the concomitant post-transplant medication or negative effects on the hematopoiesis were observed, and the myeloma still is in complete remission. To our knowledge, this is the first report on excretion of A lumbricoides in the context of allogeneic stem cell transplantation. The case is remarkable with view to the fact that the parasite has supposedly survived all courses of myeloma treatment including autologous and allogeneic conditioning. Parasitosis with A lumbricoides has a worldwide prevalence of about a billion and is extremely rare in northern Europe. Possibly the patient got infected during a trip to Egypt years before multiple myeloma was diagnosed.}, language = {en} } @article{LangePauli2019, author = {Lange, Bastian and Pauli, Paul}, title = {Social anxiety changes the way we move—A social approach-avoidance task in a virtual reality CAVE system}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0226805}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200528}, pages = {e0226805}, year = {2019}, abstract = {Investigating approach-avoidance behavior regarding affective stimuli is important in broadening the understanding of one of the most common psychiatric disorders, social anxiety disorder. Many studies in this field rely on approach-avoidance tasks, which mainly assess hand movements, or interpersonal distance measures, which return inconsistent results and lack ecological validity. Therefore, the present study introduces a virtual reality task, looking at avoidance parameters (movement time and speed, distance to social stimulus, gaze behavior) during whole-body movements. These complex movements represent the most ecologically valid form of approach and avoidance behavior. These are at the core of complex and natural social behavior. With this newly developed task, the present study examined whether high socially anxious individuals differ in avoidance behavior when bypassing another person, here virtual humans with neutral and angry facial expressions. Results showed that virtual bystanders displaying angry facial expressions were generally avoided by all participants. In addition, high socially anxious participants generally displayed enhanced avoidance behavior towards virtual people, but no specifically exaggerated avoidance behavior towards virtual people with a negative facial expression. The newly developed virtual reality task proved to be an ecological valid tool for research on complex approach-avoidance behavior in social situations. The first results revealed that whole body approach-avoidance behavior relative to passive bystanders is modulated by their emotional facial expressions and that social anxiety generally amplifies such avoidance.}, language = {en} } @article{ElhfnawyVolkmannSchliesseretal.2019, author = {Elhfnawy, Ahmed Mohamed and Volkmann, Jens and Schliesser, Mira and Fluri, Felix}, title = {Are cerebral white matter lesions related to the presence of bilateral internal carotid artery stenosis or to the length of stenosis among patients with ischemic cerebrovascular events?}, series = {Frontiers in Neurology}, volume = {10}, journal = {Frontiers in Neurology}, number = {919}, doi = {10.3389/fneur.2019.00919}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201241}, year = {2019}, abstract = {Background and purpose: Previous studies delivered contradicting results regarding the relation between the presence of an internal carotid artery stenosis (ICAS) and the occurence of white matter lesions (WMLs). We hypothesize that special characteristics related to the ICAS might be related to the WMLs. We examined the relation between the presence of bilateral ICAS, the degree and length of stenosis and ipsi-, contralateral as well as mean white matter lesion load (MWMLL). Methods: In a retrospective cohort, patients with ischemic stroke or transient ischemic attack (TIA) as well as ipsi- and/or contralateral ICAS were identified. The length and degree of ICAS, as well as plaque morphology (hypoechoic, mixed or echogenic), were assessed on ultrasound scans and, if available, the length was also measured on magnetic resonance angiography (MRA) scans, and/or digital subtraction angiography (DSA). The WMLs were assessed in 4 areas separately, (periventricular and deep WMLs on each hemispherer), using the Fazekas scale. The MWMLL was calculated as the mean of these four values. Results: 136 patients with 177 ICAS were identified. A significant correlation between age and MWMLL was observed (Spearman correlation coefficient, ρ = 0.41, p < 0.001). Before adjusting for other risk factors, a significantly positive relation was found between the presence of bilateral ICAS and MWMLL (p = 0.039). The length but not the degree of ICAS showed a very slight trend toward association with ipsilateral WMLs and with MWMLL. In an age-adjusted multivariate logistic regression with MWMLL ≥2 as the outcome measure, atrial fibrillation (OR 3.54, 95\% CI 1.12-11.18, p = 0.03), female sex (OR 3.11, 95\% CI 1.19-8.11, p = 0.02) and diabetes mellitus (OR 2.76, 95\% CI 1.16-6.53, p = 0.02) were significantly related to WMLs, whereas the presence of bilateral stenosis showed a trend toward significance (OR 2.25, 95\% CI 0.93-5.45, p = 0.074). No relation was found between plaque morphology and MWMLL, periventricular, or deep WMLs. Conclusion: We have shown a slight correlation between the length of stenosis and the presence of WMLs which might be due to microembolisation originating from the carotid plaque. However, the presence of bilateral ICAS seems also to be related to WMLs which may point to common underlying vascular risk factors contributing to the occurrence of WML.}, language = {en} } @article{SaraceniLabopinBrechtetal.2019, author = {Saraceni, Francesco and Labopin, Myriam and Brecht, Arne and Kr{\"o}ger, Nicolaus and Eder, Matthias and Tischer, Johanna and Labussiere-Wallet, Helene and Einsele, Hermann and Beelen, Dietrich and Bunjes, Donald and Niederwieser, Dietger and Bochtler, Tilman and Savani, Bipin N. and Mohty, Mohamad and Nagler, Arnon}, title = {Fludarabine-treosulfan compared to thiotepa-busulfan-fludarabine or FLAMSA as conditioning regimen for patients with primary refractory or relapsed acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)}, series = {Journal of Hematology \& Oncology}, volume = {12}, journal = {Journal of Hematology \& Oncology}, number = {44}, doi = {10.1186/s13045-019-0727-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227345}, pages = {1-10}, year = {2019}, abstract = {Background Limited data is available to guide the choice of the conditioning regimen for patients with acute myeloid leukemia (AML) undergoing transplant with persistent disease. Methods We retrospectively compared outcome of fludarabine-treosulfan (FT), thiotepa-busulfan-fludarabine (TBF), and sequential fludarabine, intermediate dose Ara-C, amsacrine, total body irradiation/busulfan, cyclophosphamide (FLAMSA) conditioning in patients with refractory or relapsed AML. Results Complete remission rates at day 100 were 92\%, 80\%, and 88\% for FT, TBF, and FLAMSA, respectively (p=0.13). Non-relapse mortality, incidence of relapse, acute (a) and chronic (c) graft-versus-host disease (GVHD) rates did not differ between the three groups. Overall survival at 2years was 37\% for FT, 24\% for TBF, and 34\% for FLAMSA (p=0.10). Independent prognostic factors for survival were Karnofsky performance score and patient CMV serology (p=0.01; p=0.02), while survival was not affected by age at transplant. The use of anti-thymocyte globulin (ATG) was associated with reduced risk of grade III-IV aGVHD (p=0.02) and cGVHD (p=0.006), with no influence on relapse. Conclusions In conclusion, FT, TBF, and FLAMSA regimens provided similar outcome in patients undergoing transplant with active AML. Survival was determined by patient characteristics as Karnofsky performance score and CMV serology, however was not affected by age at transplant. ATG appears able to reduce the incidence of acute and chronic GVHD without influencing relapse risk.}, language = {en} } @article{PetschkeHelmStaab2019, author = {Petschke, Danny and Helm, Ricardo and Staab, Torsten E.M.}, title = {Data on pure tin by Positron Annihilation Lifetime Spectroscopy (PALS) acquired with a semi-analog/digital setup using DDRS4PALS}, series = {Data in Brief}, volume = {22}, journal = {Data in Brief}, doi = {10.1016/j.dib.2018.11.121}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177698}, pages = {16-29}, year = {2019}, abstract = {Positron annihilation lifetime spectroscopy (PALS) provides a powerful technique for non-destructive microstructure investigations in a broad field of material classes such as metals, semiconductors, polymers or porous glasses. Even though this method is well established for more than five decades, no proper standardization for the used setup configuration and subsequent data processing exists. Eventually, this could lead to an insufficiency of data reproducibility and avoidable deviations. Here we present experimentally obtained and simulated data of positron lifetime spectra at various statistics measured on pure tin (4N-Sn) by using a semi-analog/digital setup, where the digital section consists of the DRS4 evaluation board, "Design and performance of the 6 GHz waveform digitizing chip DRS4" [1]. The analog section consists of nuclear instrument modules (NIM), which externally trigger the DRS4 evaluation board to reduce the digitization and, thus, increase the acquisition efficiency. For the experimentally obtained lifetime spectra, 22Na sealed in Kapton foil served as a positron source, whereas 60Co was used for the acquisition of the prompt spectrum, i.e. the quasi instrument response function. Both types of measurements were carried out under the same conditions. All necessary data and information regarding the data acquisition and data reduction are provided to allow reproducibility by other research groups.}, language = {en} } @article{KehrbergerHolzschuh2019, author = {Kehrberger, Sandra and Holzschuh, Andrea}, title = {Warmer temperatures advance flowering in a spring plant more strongly than emergence of two solitary spring bee species}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0218824}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201165}, pages = {e0218824}, year = {2019}, abstract = {Climate warming has the potential to disrupt plant-pollinator interactions or to increase competition of co-flowering plants for pollinators, due to species-specific phenological responses to temperature. However, studies focusing on the effect of temperature on solitary bee emergence and the flowering onset of their food plants under natural conditions are still rare. We studied the effect of temperature on the phenology of the two spring bees Osmia cornuta and Osmia bicornis, by placing bee cocoons on eleven grasslands differing in mean site temperature. On seven grasslands, we additionally studied the effect of temperature on the phenology of the red-list plant Pulsatilla vulgaris, which was the first flowering plant, and of co-flowering plants with later flowering. With a warming of 0.1°C, the abundance-weighted mean emergence of O. cornuta males advanced by 0.4 days. Females of both species did not shift their emergence. Warmer temperatures advanced the abundance-weighted mean flowering of P. vulgaris by 1.3 days per 0.1°C increase, but did not shift flowering onset of co-flowering plants. Competition for pollinators between P. vulgaris and co-flowering plants does not increase within the studied temperature range. We demonstrate that temperature advances plant flowering more strongly than bee emergence suggesting an increased risk of pollinator limitation for the first flowers of P. vulgaris.}, language = {en} } @article{LuebtowMarciniakSchmiedeletal.2019, author = {L{\"u}btow, Michael M. and Marciniak, Henning and Schmiedel, Alexander and Roos, Markus and Lambert, Christoph and Luxenhofer, Robert}, title = {Ultra-high to ultra-low drug loaded micelles: Probing host-guest interactions by fluorescence spectroscopy}, series = {Chemistry - A European Journal}, volume = {25}, journal = {Chemistry - A European Journal}, number = {54}, doi = {10.1002/chem.201902619}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206128}, pages = {12601-12610}, year = {2019}, abstract = {Polymer micelles are an attractive means to solubilize water insoluble compounds such as drugs. Drug loading, formulations stability and control over drug release are crucial factors for drug-loaded polymer micelles. The interactions between the polymeric host and the guest molecules are considered critical to control these factors but typically barely understood. Here, we compare two isomeric polymer micelles, one of which enables ultra-high curcumin loading exceeding 50 wt.\%, while the other allows a drug loading of only 25 wt.\%. In the low capacity micelles, steady-state fluorescence revealed a very unusual feature of curcumin fluorescence, a high energy emission at 510 nm. Time-resolved fluorescence upconversion showed that the fluorescence life time of the corresponding species is too short in the high-capacity micelles, preventing an observable emission in steady-state. Therefore, contrary to common perception, stronger interactions between host and guest can be detrimental to the drug loading in polymer micelles.}, subject = {Polymer-drug interaction}, language = {en} } @article{WinterAndelovicKampfetal.2019, author = {Winter, Patrick and Andelovic, Kristina and Kampf, Thomas and Gutjahr, Fabian Tobias and Heidenreich, Julius and Zernecke, Alma and Bauer, Wolfgang Rudolf and Jakob, Peter Michael and Herold, Volker}, title = {Fast self-navigated wall shear stress measurements in the murine aortic archusing radial 4D-phase contrast cardiovascular magnetic resonance at 17.6 T}, series = {Journal of Cardiovascular Magnetic Resonance}, volume = {21}, journal = {Journal of Cardiovascular Magnetic Resonance}, doi = {10.1186/s12968-019-0566-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201120}, pages = {64}, year = {2019}, abstract = {Purpose 4D flow cardiovascular magnetic resonance (CMR) and the assessment of wall shear stress (WSS) are non-invasive tools to study cardiovascular risks in vivo. Major limitations of conventional triggered methods are the long measurement times needed for high-resolution data sets and the necessity of stable electrocardiographic (ECG) triggering. In this work an ECG-free retrospectively synchronized method is presented that enables accelerated high-resolution measurements of 4D flow and WSS in the aortic arch of mice. Methods 4D flow and WSS were measured in the aortic arch of 12-week-old wildtype C57BL/6 J mice (n = 7) with a radial 4D-phase-contrast (PC)-CMR sequence, which was validated in a flow phantom. Cardiac and respiratory motion signals were extracted from the radial CMR signal and were used for the reconstruction of 4D-flow data. Rigid motion correction and a first order B0 correction was used to improve the robustness of magnitude and velocity data. The aortic lumen was segmented semi-automatically. Temporally averaged and time-resolved WSS and oscillatory shear index (OSI) were calculated from the spatial velocity gradients at the lumen surface at 14 locations along the aortic arch. Reproducibility was tested in 3 animals and the influence of subsampling was investigated. Results Volume flow, cross-sectional areas, WSS and the OSI were determined in a measurement time of only 32 min. Longitudinal and circumferential WSS and radial stress were assessed at 14 analysis planes along the aortic arch. The average longitudinal, circumferential and radial stress values were 1.52 ± 0.29 N/m2, 0.28 ± 0.24 N/m2 and - 0.21 ± 0.19 N/m2, respectively. Good reproducibility of WSS values was observed. Conclusion This work presents a robust measurement of 4D flow and WSS in mice without the need of ECG trigger signals. The retrospective approach provides fast flow quantification within 35 min and a flexible reconstruction framework.}, language = {en} } @article{HeroldKampfJakob2019, author = {Herold, Volker and Kampf, Thomas and Jakob, Peter Michael}, title = {Dynamic magnetic resonance scattering}, series = {Communications Physics}, volume = {2}, journal = {Communications Physics}, doi = {10.1038/s42005-019-0136-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201091}, pages = {46}, year = {2019}, abstract = {Dynamic light scattering is a popular technique to determine the size distribution of small particles in the sub micrometer region. It operates in reciprocal space, by analyzing the signal fluctuations with the photon auto correlation function. Equally, pulsed field gradient magnetic resonance is a technique generating data in the reciprocal space of the density distribution of an object. Here we show the feasibility of employing a magnetic resonance imaging system as a dynamic scattering device similar to dynamic light scattering appliances. By acquiring a time series of single data points from reciprocal space, analogue to dynamic light scattering, we demonstrate the examination of motion patterns of microscopic particles. This method allows the examination of particle dynamics significantly below the spatial resolution of magnetic resonance imaging. It is not limited by relaxation times and covers a wide field of applications for particle or cell motion in opaque media.}, language = {en} } @article{DaViaSolimandoGaritanoTrojaolaetal.2019, author = {Da Vi{\`a}, Matteo Claudio and Solimando, Antonio Giovanni and Garitano-Trojaola, Andoni and Barrio, Santiago and Munawar, Umair and Strifler, Susanne and Haertle, Larissa and Rhodes, Nadine and Vogt, Cornelia and Lapa, Constantin and Beilhack, Andreas and Rasche, Leo and Einsele, Hermann and Kort{\"u}m, K. Martin}, title = {CIC Mutation as a Molecular Mechanism of Acquired Resistance to Combined BRAF-MEK Inhibition in Extramedullary Multiple Myeloma with Central Nervous System Involvement}, series = {The Oncologist}, volume = {25}, journal = {The Oncologist}, number = {2}, doi = {10.1634/theoncologist.2019-0356}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219549}, pages = {112-118}, year = {2019}, abstract = {Combined MEK-BRAF inhibition is a well-established treatment strategy in BRAF-mutated cancer, most prominently in malignant melanoma with durable responses being achieved through this targeted therapy. However, a subset of patients face primary unresponsiveness despite presence of the activating mutation at position V600E, and others acquire resistance under treatment. Underlying resistance mechanisms are largely unknown, and diagnostic tests to predict tumor response to BRAF-MEK inhibitor treatment are unavailable. Multiple myeloma represents the second most common hematologic malignancy, and point mutations in BRAF are detectable in about 10\% of patients. Targeted inhibition has been successfully applied, with mixed responses observed in a substantial subset of patients mirroring the widespread spatial heterogeneity in this genomically complex disease. Central nervous system (CNS) involvement is an extremely rare, extramedullary form of multiple myeloma that can be diagnosed in less than 1\% of patients. It is considered an ultimate high-risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases. Here we not only describe the first patient with an extramedullary CNS relapse responding to targeted dabrafenib and trametinib treatment, we furthermore provide evidence that a point mutation within the capicua transcriptional repressor (CIC) gene mediated the acquired resistance in this patient.}, language = {en} } @article{SailerWiedemannStraussetal.2019, author = {Sailer, Clara Odilia and Wiedemann, Sophia Julia and Strauss, Konrad and Schnyder, Ingeborg and Fenske, Wiebke Kristin and Christ-Crain, Mirjam}, title = {Markers of systemic inflammation in response to osmotic stimulus in healthy volunteers}, series = {Endocrine Connections}, volume = {8}, journal = {Endocrine Connections}, number = {9}, doi = {10.1530/EC-19-0280}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227204}, pages = {1282-1287}, year = {2019}, abstract = {Osmotic stimulus or stress results in vasopressin release. Animal and human in vitro studies have shown that inflammatory parameters, such as interle ukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), increase in parallel in the central nervous system and bronchial, corneal or intestinal epithelial cell lines in response to osmotic stimulus. Whether osmotic stimulus directly causes a systemic inflammatory response in humans is unknown. We therefore investigated the influence of osmotic stimulus on circulatory markers of systemic inflammation in healthy volunteers. In this prospective cohort study, 44 healthy volunteers underwent a standardized test protocol with an osmotic stimulus leading into the hyperosmotic/hypernatremic range (serum sodium >= 150 mmol/L) by hypertonic saline infusion. Copeptin - a marker indicating vasopressin activity - serum sodium and osmolality, plasma IL-8 and TNF-alpha were measured at baseline and directly after osmotic stimulus. Median (range) serum sodium increased from 141 mmol/L (136, 147) to 151 mmol/L (145, 154) (P < 0.01), serum osmolality increased from 295 mmol/L (281, 306) to 315 mmol/L (304, 325) (P < 0.01). Median (range) copeptin increased from 4.3 pg/L (1.1, 21.4) to 28.8 pg/L (19.9, 43.4) (P < 0.01). Median (range) IL-8 levels showed a trend to decrease from 0.79 pg/mL (0.37, 1.6) to 0.7 pg/mL (0.4, 1.9) (P < 0.09) and TNF-alpha levels decreased from 0.53 pg/mL (0.11, 1.1) to 0.45 pg/mL (0.1 2, 0.97) (P < 0.036). Contrary to data obtained in vitro, circulating proinflammatory cytokines tend to or decrease in human plasma after osmotic stimulus. In this study, osmotic stimulus does not increase circulating markers of systemic inflammation.}, subject = {Hyperosmotic Stress}, language = {en} } @article{HermSchurigMartineketal.2019, author = {Herm, Juliane and Schurig, Johannes and Martinek, Martin R. and H{\"o}ltgen, Reinhard and Schirdewan, Alexander and Kirchhof, Paulus and Wieczorek, Marcus and P{\"u}rerfellner, Helmut and Heuschmann, Peter U. and Fiebach, Jochen B. and Haeusler, Karl Georg}, title = {MRI-detected brain lesions in AF patients without further stroke risk factors undergoing ablation - a retrospective analysis of prospective studies}, series = {BMC Cardiovascular Disorders}, volume = {19}, journal = {BMC Cardiovascular Disorders}, doi = {10.1186/s12872-019-1035-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201226}, pages = {58}, year = {2019}, abstract = {Background Atrial fibrillation (AF) without other stroke risk factors is assumed to have a low annual stroke risk comparable to patients without AF. Therefore, current clinical guidelines do not recommend oral anticoagulation for stroke prevention of AF in patients without stroke risk factors. We analyzed brain magnetic resonance imaging (MRI) imaging to estimate the rate of clinically inapparent ("silent") ischemic brain lesions in these patients. Methods We pooled individual patient-level data from three prospective studies comprising stroke-free patients with symptomatic AF. All study patients underwent brain MRI within 24-48 h before planned left atrial catheter ablation. MRIs were analyzed by a neuroradiologist blinded to clinical data. Results In total, 175 patients (median age 60 (IQR 54-67) years, 32\% female, median CHA\(_2\)DS\(_2\)-VASc = 1 (IQR 0-2), 33\% persistent AF) were included. In AF patients without or with at least one stroke risk factor, at least one silent ischemic brain lesion was observed in 4 (8\%) out of 48 and 10 (8\%) out of 127 patients, respectively (p > 0.99). Presence of silent ischemic brain lesions was related to age (p = 0.03) but not to AF pattern (p = 0.77). At least one cerebral microbleed was detected in 5 (13\%) out of 30 AF patients without stroke risk factors and 25 (25\%) out of 108 AF patients with stroke risk factors (p = 0.2). Presence of cerebral microbleeds was related to male sex (p = 0.04) or peripheral artery occlusive disease (p = 0.03). Conclusion In patients with symptomatic AF scheduled for ablation, brain MRI detected silent ischemic brain lesions in approximately one in 12 patients, and microbleeds in one in 5 patients. The prevalence of silent ischemic brain lesions did not differ in AF patients with or without further stroke risk factors.}, language = {en} }