TY - JOUR T1 - All-sky search for high-energy neutrinos from gravitational wave event GW170104 with the ANTARES neutrino telescope JF - European Physical Journal C N2 - Advanced LIGO detected a significant gravitational wave signal (GW170104) originating from the coalescence of two black holes during the second observation run on January 4th, 2017. An all-sky high-energy neutrino follow-up search has been made using data from the Antares neutrino telescope, including both upgoing and downgoing events in two separate analyses. No neutrino candidates were found within ±500 s around the GW event time nor any time clustering of events over an extended time window of ±3 months. The non-detection is used to constrain isotropic-equivalent high-energy neutrino emission from GW170104 to less than ∼ 1.2 × \(10^{55}\) erg for a \(E^{−2}\) spectrum. This constraint is valid in the energy range corresponding to the 5–95% quantiles of the neutrino flux [3.2 TeV; 3.6 PeV], if the GW emitter was below the Antares horizon at the alert time. KW - high energy physics KW - high energy neutrinos KW - neutrino telescope KW - neutrino emission KW - neutrino flux Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172174 VL - 77 ER - TY - JOUR A1 - Jannasch, Maren A1 - Gaetzner, Sabine A1 - Weigel, Tobias A1 - Walles, Heike A1 - Schmitz, Tobias A1 - Hansmann, Jan T1 - A comparative multi-parametric in vitro model identifies the power of test conditions to predict the fibrotic tendency of a biomaterial JF - Scientific Reports N2 - Despite growing effort to advance materials towards a low fibrotic progression, all implants elicit adverse tissue responses. Pre-clinical biomaterial assessment relies on animals testing, which can be complemented by in vitro tests to address the Russell and Burch’s 3R aspect of reducing animal burden. However, a poor correlation between in vitro and in vivo biomaterial assessments confirms a need for suitable in vitro biomaterial tests. The aim of the study was to identify a test setting, which is predictive and might be time- and cost-efficient. We demonstrated how sensitive in vitro biomaterial assessment based on human primary macrophages depends on test conditions. Moreover, possible clinical scenarios such as lipopolysaccharide contamination, contact to autologous blood plasma, and presence of IL-4 in an immune niche influence the outcome of a biomaterial ranking. Nevertheless, by using glass, titanium, polytetrafluorethylene, silicone, and polyethylene representing a specific material-induced fibrotic response and by comparison to literature data, we were able to identify a test condition that provides a high correlation to state-of-the-art in vivo studies. Most important, biomaterial ranking obtained under native plasma test conditions showed a high predictive accuracy compared to in vivo assessments, strengthening a biomimetic three-dimensional in vitro test platform. KW - inflammation KW - experimental models of disease KW - biomaterial tests KW - in vitro Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170908 VL - 7 IS - 1689 ER - TY - JOUR A1 - Brodehl, Andreas A1 - Belke, Darrell D. A1 - Garnett, Lauren A1 - Martens, Kristina A1 - Abdelfatah, Nelly A1 - Rodriguez, Marcela A1 - Diao, Catherine A1 - Chen, Yong-Xiang A1 - Gordon, Paul M. K. A1 - Nygren, Anders A1 - Gerull, Brenda T1 - Transgenic mice overexpressing desmocollin-2 (DSC2) develop cardiomyopathy associated with myocardial inflammation and fibrotic remodeling JF - PLoS ONE N2 - Background Arrhythmogenic cardiomyopathy is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure, mainly as a result of mutations in cardiac desmosomal genes. Desmosomes are cell-cell junctions mediating adhesion of cardiomyocytes; however, the molecular and cellular mechanisms underlying the disease remain widely unknown. Desmocollin-2 is a desmosomal cadherin serving as an anchor molecule required to reconstitute homeostatic intercellular adhesion with desmoglein-2. Cardiac specific lack of desmoglein-2 leads to severe cardiomyopathy, whereas overexpression does not. In contrast, the corresponding data for desmocollin-2 are incomplete, in particular from the view of protein overexpression. Therefore, we developed a mouse model overexpressing desmocollin-2 to determine its potential contribution to cardiomyopathy and intercellular adhesion pathology. Methods and results We generated transgenic mice overexpressing DSC2 in cardiac myocytes. Transgenic mice developed a severe cardiac dysfunction over 5 to 13 weeks as indicated by 2D-echocardiography measurements. Corresponding histology and immunohistochemistry demonstrated fibrosis, necrosis and calcification which were mainly localized in patches near the epi- and endocardium of both ventricles. Expressions of endogenous desmosomal proteins were markedly reduced in fibrotic areas but appear to be unchanged in non-fibrotic areas. Furthermore, gene expression data indicate an early up-regulation of inflammatory and fibrotic remodeling pathways between 2 to 3.5 weeks of age. Conclusion Cardiac specific overexpression of desmocollin-2 induces necrosis, acute inflammation and patchy cardiac fibrotic remodeling leading to fulminant biventricular cardiomyopathy. KW - heart KW - mouse models KW - gene expression KW - fibrosis KW - inflammation KW - gene expression KW - genetically modified animals KW - cardiomyopathies KW - hyperexpression techniques Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171084 VL - 12 IS - 3 ER - TY - JOUR A1 - Vangeel, Elise Beau A1 - Pishva, Ehsan A1 - Hompes, Titia A1 - van den Hove, Daniel A1 - Lambrechts, Diether A1 - Allegaert, Karel A1 - Freson, Kathleen A1 - Izzi, Benedetta A1 - Claes, Stephan T1 - Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for \(GABBR1\) JF - Clinical Epigenetics N2 - Background: There is increasing evidence for the role of prenatal stress in shaping offspring DNA methylation and disease susceptibility. In the current study, we aimed to identify genes and pathways associated with pregnancy anxiety using a genome-wide DNA methylation approach. Methods: We selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to the lowest or highest degree of maternal pregnancy anxiety, respectively. Cord blood genome-wide DNA methylation was assayed using the HumanMethylation450 BeadChip (HM450, n = 45) and candidate gene methylation using EpiTYPER (n = 80). Cortisol levels were measured at 2, 4, and 12 months of age to test infant stress system (re)activity. Results: Data showed ten differentially methylated regions (DMR) when comparing newborns exposed to low versus high pregnancy anxiety scores. We validated a top DMR in the GABA-B receptor subunit 1 gene (GABBR1) revealing the association with pregnancy anxiety particularly in male newborns (most significant CpG Pearson R = 0.517, p = 0.002; average methylation Pearson R = 0.332, p = 0.039). Cord blood GABBR1 methylation was associated with infant cortisol levels in response to a routine vaccination at 4 months old. Conclusions: In conclusion, our results show that pregnancy anxiety is associated with differential DNA methylation patterns in newborns and that our candidate gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. Our findings reveal a potential role for GABBR1 methylation in association with stress and provide grounds for further research. KW - DNA methylation KW - GABBR1 KW - gender differences KW - HPA axis KW - pregnancy anxiety KW - prenatal stress Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173825 VL - 9 ER - TY - JOUR A1 - Salker, Madhuri S. A1 - Singh, Yogesh A1 - Zeng, Ni A1 - Chen, Hong A1 - Zhang, Shaqiu A1 - Umbach, Anja T. A1 - Fakhri, Hajar A1 - Kohlhofer, Ursula A1 - Quintanilla-Martinez, Leticia A1 - Durairaj, Ruban R. Peter A1 - Barros, Flavio S. V. A1 - Vrljicak, Pavle A1 - Ott, Sascha A1 - Brucker, Sara Y. A1 - Wallwiener, Diethelm A1 - Madunić, Ivana Vrhovac A1 - Breljak, Davorka A1 - Sabolić, Ivan A1 - Koepsell, Hermann A1 - Brosens, Jan J. A1 - Lang, Florian T1 - Loss of endometrial sodium glucose cotransporter SGLT1 is detrimental to embryo survival and fetal growth in pregnancy JF - Scientific Reports N2 - Embryo implantation requires a hospitable uterine environment. A key metabolic change that occurs during the peri-implantation period, and throughout early pregnancy, is the rise in endometrial glycogen content. Glycogen accumulation requires prior cellular uptake of glucose. Here we show that both human and murine endometrial epithelial cells express the high affinity Na\(^+\)-coupled glucose carrier SGLT1. Ussing chamber experiments revealed electrogenic glucose transport across the endometrium in wild type (\(Slc5a1^{+/+}\)) but not in SGLT1 defcient (\(Slc5a1^{−/−}\)) mice. Endometrial glycogen content, litter size and weight of offspring at birth were signifcantly lower in \(Slc5a1^{−/−}\) mice. In humans, \(SLC5A1\) expression was upregulated upon decidualization of primary endometrial stromal cells. Endometrial \(SLC5A1\) expression during the implantation window was attenuated in patients with recurrent pregnancy loss when compared with control subjects. Our fndings reveal a novel mechanism establishing adequate endometrial glycogen stores for pregnancy. Disruption of this histiotrophic pathway leads to adverse pregnancy outcome. KW - biology KW - embryology KW - intrauterine growth KW - paediatric research Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173814 VL - 7 ER - TY - JOUR A1 - Cerna-Velazco, Nhell A1 - Faber, Thomas A1 - Jones-Pérez, Joel A1 - Porod, Werner T1 - Constraining sleptons at the LHC in a supersymmetric low-scale seesaw scenario JF - European Physical Journal C N2 - We consider a scenario inspired by natural supersymmetry, where neutrino data is explained within a low-scale seesaw scenario. We extend the Minimal Supersymmetric Standard Model by adding light right-handed neutrinos and their superpartners, the R-sneutrinos, and consider the lightest neutralinos to be higgsino-like. We consider the possibilities of having either an R-sneutrino or a higgsino as lightest supersymmetric particle. Assuming that squarks and gauginos are heavy, we systematically evaluate the bounds on slepton masses due to existing LHC data. KW - physics KW - particle physics KW - neutrino KW - R-sneutrino KW - supersymmetry (SUSY) KW - supersymmetric model KW - standard seesaw KW - inverse seesaw KW - minimal supersymmetric standard model (MSSM) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173809 VL - 77 ER - TY - JOUR A1 - Buff, Christine A1 - Brinkmann, Leonie A1 - Bruchmann, Maximilian A1 - Becker, Michael P.I. A1 - Tupak, Sara A1 - Herrmann, Martin J. A1 - Straube, Thomas T1 - Activity alterations in the bed nucleus of the stria terminalis and amygdala during threat anticipation in generalized anxiety disorder JF - Social Cognitive and Affective Neuroscience N2 - Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking. We aimed to explore temporal characteristics of BNST and amygdala activity during threat anticipation in GAD patients. Nineteen GAD patients and nineteen healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during a temporally unpredictable threat anticipation paradigm. We defined phasic and a systematic variation of sustained response models for blood oxygen level-dependent responses during threat anticipation, to disentangle temporally dissociable involvement of the BNST and the amygdala. GAD patients relative to HC responded with increased phasic amygdala activity to onset of threat anticipation and with elevated sustained BNST activity that was delayed relative to the onset of threat anticipation. Both the amygdala and the BNST displayed altered responses during threat anticipation in GAD patients, albeit with different time courses. The results for the BNST activation hint towards its role in sustained threat responding, and contribute to a deeper understanding of pathological sustained anticipatory anxiety in GAD. KW - medicine KW - anticipatory anxiety KW - anxiety KW - fMRI KW - sustained threat responding KW - phasic threat responding Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173298 VL - 12 IS - 11 ER - TY - JOUR A1 - Schamel, Johannes T1 - A demographic perspective on the spatial behaviour of hikers in mountain areas: the example of Berchtesgaden National Park JF - eco.mont - Journal on Protected Mountain Areas Research and Management N2 - In Germany, as in many Western societies, demographic change will lead to a higher number of senior visitors to natural recreational areas and national parks. Given the high physiological requirements of many outdoor recreation activities, especially in mountain areas, it seems likely that demographic change will affect the spatial behaviour of national park visitors, which may pose a challenge to the management of these areas. With the help of GPS tracking and a standardized questionnaire (n=481), this study empirically investigates the spatial behaviour of demographic age brackets in Berchtesgaden National Park (NP) and the potential effects of demographic change on the use of the area. Cluster analysis revealed four activity types in the study area. More than half of the groups with visitors aged 60 and older belong to the activity type of Walker. KW - geography KW - demographic change KW - spatial behaviour KW - GPS tracking KW - outdoor recreation KW - Berchtesgaden NP Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172128 SN - 2073-1558 VL - 9 IS - Special issue ER - TY - JOUR A1 - Zopf, Kathrin A1 - Frey, Kathrin R. A1 - Kienitz, Tina A1 - Ventz, Manfred A1 - Bauer, Britta A1 - Quinkler, Marcus T1 - \(Bcl\)I polymorphism of the glucocorticoid receptor and adrenal crisis in primary adrenal insufficiency JF - Endocrine Connections N2 - Context: Patients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) are at a high risk of adrenal crisis (AC). Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR). Objectives: To determine if a number of intercurrent illnesses and AC are associated with the GR gene polymorphism \(Bcl\)I in patients with PAI and CAH. Design and patients: This prospective, longitudinal study over 37.7 ± 10.1 months included 47 PAI and 25 CAH patients. During the study period, intercurrent illness episodes and AC were documented. Results: The study period covered 223 patient years in which 21 AC occurred (9.4 AC/100 pat years). There were no significant differences between \(Bcl\)I polymorphisms (CC (n=29), CG (n=34) and GG (n=9)) regarding BMI, hydrocortisone equivalent daily dose and blood pressure. We did not find a difference in the number of intercurrent illnesses/patient year among \(Bcl\)I polymorphisms (CC (1.5±1.4/pat year), CG (1.2±1.2/pat year) and GG (1.6±2.2/pat year)). The occurrence of AC was not significantly different among the homozygous (GG) genotype (32.5 AC/100 pat years), the CC genotype (6.7 AC/100 pat years) and the CG genotype (4.9 AC/100 pat years). Concomitant hypothyroidism was the highest in the GG genotype group (5/9), compared to others (CC (11/29) and CG (11/34)). Conclusions: Although sample sizes were relatively small and results should be interpreted with caution, this study suggests that the GR gene polymorphism \(Bcl\)I may not be associated with the frequencies of intercurrent illnesses and AC. KW - medicine KW - adrenal crisis KW - adrenal insufficiency KW - cortisol KW - hydrocortisone KW - polyglandular autoimmune syndrome Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173276 VL - 6 IS - 8 ER - TY - JOUR A1 - Ferero, Andrea A1 - Rivero, Olga A1 - Wäldchen, Sina A1 - Ku, Hsing-Ping A1 - Kiser, Dominik P. A1 - Gärtner, Yvonne A1 - Pennington, Laura S. A1 - Waider, Jonas A1 - Gaspar, Patricia A1 - Jansch, Charline A1 - Edenhofer, Frank A1 - Resink, Thérèse J. A1 - Blum, Robert A1 - Sauer, Markus A1 - Lesch, Klaus-Peter T1 - Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain JF - Frontiers in Cellular Neuroscience N2 - Background: During early prenatal stages of brain development, serotonin (5-HT)-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR), innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13) has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system. Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency. Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs), which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5. Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell density of the developing DR and the posterior innervation of the prefrontal cortex (PFC), and therefore might be involved in the migration, axonal outgrowth and terminal target finding of DR 5-HT neurons. Dysregulation of CDH13 expression may thus contribute to alterations in this system of neurotransmission, impacting cognitive function, which is frequently impaired in neurodevelopmental disorders including attention-deficit/hyperactivity and autism spectrum disorders. KW - serotonin KW - cadherin-13 (CDH13) KW - T-cadherin KW - neurodevelopment KW - psychiatric disorders KW - radial glia KW - dorsal raphe KW - prefrontal cortex Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170313 VL - 11 IS - 307 ER - TY - JOUR A1 - Gilbert, Fabian A1 - Klein, Detlef A1 - Weng, Andreas Max A1 - Köstler, Herbert A1 - Schmitz, Benedikt A1 - Schmalzl, Jonas A1 - Böhm, Dirk T1 - Supraspinatus muscle elasticity measured with real time shear wave ultrasound elastography correlates with MRI spectroscopic measured amount of fatty degeneration JF - BMC Muscoskeletal Disorders N2 - Background: Fatty Degeneration (FD) of the rotator cuff muscles influences functional and anatomical outcome after rotator cuff repair. The MRI based estimation of fatty degeneration is the gold standard. There is some evidence that Ultrasound elastography (EUS) can detect local differences of tissue stiffness in muscles and tendons. Shear-wave elastography (SWE) was evaluated to determine the extent to which shear wave velocity was associated with measures of fatty degeneration. MRI-spectroscopic fat measurement was used as a reference to quantify the amount of fat in the muscle belly. Methods: Forty-two patients underwent SWE of the supraspinatus muscles at its thickest diameter. After ultrasound evaluation an MRI-spectroscopic fat measurement of the supraspinatus muscle was performed using the SPLASH-technique. A gel filled capsule was used to locate the measured area in the MRI. The values of shear wave velocity (SWV) measured with SWE and spectroscopic fat measurement were correlated statistically using Pearson’s correlation test. Results: Correlation of the fat amount measured with MRI-spectroscopy and the SWV measured with SWE was ρ =0.82. Spectroscopic measured fat ratio of the supraspinatus muscle ranged from 0% to 77.41% and SWV from 1.59 m/s to 5.32 m/s. In 4 patients no sufficient SWE could be performed, these individuals showed a larger diameter of the overlying soft tissue. SWV measured with SWE showed a good correlation with MRI spectroscopic fat amount of the supraspinatus muscle. Conclusion: These preliminary data suggest that SWE may be a sufficient tool in detecting and estimating the amount of fatty degeneration in the supraspinatus muscle in real time. Large overlying soft tissue may be a limitation in performing sufficient EUS. KW - shoulder surgery KW - rotator cuff KW - MRI KW - ultrasound KW - fatty degeneration Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159378 VL - 18 IS - 549 ER - TY - JOUR A1 - Jakubietz, Michael G. A1 - Jakubietz, Rafael G. A1 - Meffert, Rainer H. A1 - Schmidt, Karsten A1 - Zahn, Robert K. T1 - Biomechanical properties of first dorsal extensor compartment regarding adequacy as a bone-ligament-bone graft JF - Plastic and Reconstructive Surgery Global Open N2 - Background: Bone-ligament-bone grafts for reconstruction of the scapholunate ligament are a valuable tool to prevent disease progression to carpal collapse. Locally available grafts do not require an additional donor site. The first extensor compartment was evaluated biomechanically regarding its possible use as an autograft. Methods: Twelve native fresh-frozen, human cadaver specimens were tested by applying axial tension in a Zwick Roell machine. Load to failure, transplant elongation, and bony avulsion were recorded. The load to failure was quantitated in newtons (N) and the displacement in length (millimeters). Parameters were set at distinct points as start of tension, 1 mm stretch and 1.5 mm dissociation, failure and complete tear, and were evaluated under magnified visual control. Although actual failure occurred at higher tension, functional failure was defined at a stretch of 1.5 mm. Results: Mean load at 1 mm elongation was 44.1 ± 28 N and at 1.5 mm elongation 57.5 ± 42 N. Failure occurred at 111 ± 83.1 N. No avulsion of the bony insertion was observed. Half the transplants failed in the central part of the ligament, while the rest failed near the insertion but not at the insertion itself. Analysis of tension strength displayed a wide range from 3.8 to 83.7 N/mm at a mean of 33.4 ± 28.4 N/mm. Conclusions: The biomechanical tensile properties of the first dorsal extensor compartment are similar to those of the dorsal part of the scapholunate ligament. A transplant with a larger bone stock and a longer ligament may display an advantage, as insertion is possible in the dorsal, easily accessible part of the carpal bones rather than in the arête-like region adjacent to the insertion of the scapholunate ligament. In this study, 1.5 mm lengthening of the bone–ligament–bone transplant was defined as clinical failure, as such elongation will cause severe gapping and is considered as failure of the transplant. KW - bone ligament graft Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158851 VL - 5 IS - 7 ER - TY - JOUR A1 - Jakubietz, Rafael G. A1 - Nickel, Aljoscha A1 - Neshkova, Iva A1 - Schmidt, Karsten A1 - Gilbert, Fabian A1 - Meffert, Rainer H. A1 - Jakubietz, Michael G. T1 - Long-term patency of twisted vascular pedicles in perforator-based propeller flaps JF - Plastic and Reconstructive Surgery Global Open N2 - Background: Propeller flaps require torsion of the vascular pedicle of up to 180 degrees. Contrary to free flaps, where the relevance of an intact vascular pedicle has been documented, little is known regarding twisted pedicles of propeller flaps. As secondary surgeries requiring undermining of the flap are common in the extremities, knowledge regarding the necessity to protect the pedicle is relevant. The aim of this study was a long-term evaluation of the patency of vascular pedicle of propeller flaps. Methods: In a retrospective clinical study, 22 patients who underwent soft-tissue reconstruction with a propeller flap were evaluated after 43 months. A Doppler probe was used to locate and evaluate the patency of the vascular pedicle of the flap. Results: The flaps were used in the lower extremity in 19 cases, on the trunk in 3 cases. All flaps had healed. In all patients, an intact vascular pedicle could be found. Flap size, source vessel, or infection could therefore not be linked to an increased risk of pedicle loss. Conclusions: The vascular pedicle of propeller flaps remains patent in the long term. This allows reelevation and undermining of the flap. We therefore recommend protecting the pedicle in all secondary cases to prevent later flap loss. KW - long-term patency Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158870 VL - 5 IS - 10 ER - TY - JOUR A1 - Jakubietz, Rafael G. A1 - Jakubietz, Michael G. A1 - Meffert, Rainer H. A1 - Schmidt, Karsten T1 - Multiple-level replantation in elderly patients: risk versus benefit JF - Plastic and Reconstructive Surgery Global Open N2 - Multiple-level amputations of the upper extremity represent a surgical challenge generally only attempted in young patients. This case demonstrates a successful replantation in an elderly woman. The postoperative course was complicated by disseminated intravascular coagulopathy most likely due to inadequate resuscitation. Hand trauma is often underestimated in its general severity. Upper extremity amputations need to be handled similar to polytraumatized patients. KW - multiple-level replantation KW - elderly Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158443 VL - 5 IS - 4 ER - TY - JOUR T1 - Measurements of top-quark pair to \(Z\)-boson cross-section ratios at \(\sqrt{s}\) \(=13 , 8, 7\) TeV with the ATLAS detector JF - Journal of High Energy Physics N2 - Ratios of top-quark pair to \(Z\)-boson cross sections measured from proton-proton collisions at the LHC centre-of-mass energies of \(\sqrt{s}\) = 13 TeV, 8 TeV, and 7 TeV are presented by the ATLAS Collaboration. Single ratios, at a given \(\sqrt{s}\) for the two processes and at different \(\sqrt{s}\) for each process, as well as double ratios of the two processes at different \(\sqrt{s}\), are evaluated. The ratios are constructed using previously published ATLAS measurements of the \({t\overline{t}}\) and \(Z\)-boson production cross sections, corrected to a common phase space where required, and a new analysis of \(Z\) → ℓ\(^+\)ℓ\(^-\) where ℓ = \(e, µ\) at \(\sqrt{s}\) = 13 TeV performed with data collected in 2015 with an integrated luminosity of 3.2 fb\(^−1\). Correlations of systematic uncertainties are taken into account when evaluating the uncertainties in the ratios. The correlation model is also used to evaluate the combined cross section of the \(Z\) → \(e\)\(^+\)\(e\)\(^−\) and the \(Z\) → \(µ\)\(^+\)\(µ\)\(^−\) channels for each \(\sqrt{s}\) value. The results are compared to calculations performed at next-to-next-to-leading-order accuracy using recent sets of parton distribution functions. The data demonstrate significant power to constrain the gluon distribution function for the Bjorken-\(x\) values near 0.1 and the light-quark sea for \(x\) < 0.02. KW - High energy physics KW - Hadron-Hadron scattering (experiments) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173544 VL - 2017 IS - 02 ER - TY - JOUR T1 - Measurement of the \(ZZ\) production cross section in proton-proton collisions at \(\sqrt{s}\) = 8 TeV using the \(ZZ\) → \(ℓ^−ℓ^+ℓ^{′−}ℓ^{′+}\) and \(ZZ\) → \(ℓ^−ℓ^+{ν\overline{ν}}\) decay channels with the ATLAS detector JF - Journal of High Energy Physics N2 - A measurement of the \(ZZ\) production cross section in the \(ℓ^−ℓ^+ℓ^{′−}ℓ^{′+}\) and \(ℓ^−ℓ^+{ν\overline{ν}}\) channels (ℓ = e, µ) in proton-proton collisions at \(\sqrt{s}\) = 8TeV at the Large Hadron Collider at CERN, using data corresponding to an integrated luminosity of 20.3 fb\(^{−1}\) collected by the ATLAS experiment in 2012 is presented. The fiducial cross sections for \(ZZ\) → \(ℓ^−ℓ^+ℓ^{′−}ℓ^{′+}\) and \(ZZ\) → \(ℓ^−ℓ^+{ν\overline{ν}}\) are measured in selected phase-space regions. The total cross section for \(ZZ\) events produced with both \(Z\) bosons in the mass range 66 to 116GeV is measured from the combination of the two channels to be 7.3 ± 0.4(stat) ± 0.3 (syst)\(^{−0.2}_{−0.1}\) (lumi) pb, which is consistent with the Standard Model prediction of 6.6\(^{+0.7}_{−0.6}\) pb. The differential cross sections in bins of various kinematic variables are presented. The differential event yield as a function of the transverse momentum of the leading \(Z\) boson is used to set limits on anomalous neutral triple gauge boson couplings in \(ZZ\) production. KW - high energy physics KW - Hadron-Hadron scattering (experiments) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173616 VL - 2017 IS - 99 ER - TY - JOUR T1 - Measurement of the \({t\overline{t}}Z\) and \({t\overline{t}}W\) production cross sections in multilepton final states using 3.2 fb\(^{-1}\) of \(pp\) collisions at \(\sqrt{s}\) = 13 TeV with the ATLAS detector JF - European Physical Journal C N2 - A measurement of the \({t\overline{t}}Z\) and \({t\overline{t}}W\) production cross sections in final states with either two same-charge muons, or three or four leptons (electrons or muons) is presented. The analysis uses a data sample of proton–proton collisions at \(\sqrt{s}\) = 13 TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015, corresponding to a total integrated luminosity of 3.2 fb\(^{−1}\). The inclusive cross sections are extracted using likelihood fits to signal and control regions, resulting in \(\sigma_{{t\overline{t}}Z}\) = 0.9 ± 0.3 pb and \(\sigma_{{t\overline{t}}W}\) = 1.5 ± 0.8 pb, in agreement with the Standard Model predictions. KW - high energy physics KW - experimental physics KW - Hadron-Hadron scattering (experiments) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173662 VL - 77 IS - 40 ER - TY - JOUR A1 - Haertle, Larissa A1 - Maierhofer, Anna A1 - Böck, Julia A1 - Lehnen, Harald A1 - Böttcher, Yvonne A1 - Blüher, Matthias A1 - Schorsch, Martin A1 - Potabattula, Ramya A1 - El Hajj, Nady A1 - Appenzeller, Silke A1 - Haaf, Thomas T1 - Hypermethylation of the non-imprinted maternal MEG3 and paternal MEST alleles is highly variable among normal individuals JF - PLoS ONE N2 - Imprinted genes show parent-specific activity (functional haploidy), which makes them particularly vulnerable to epigenetic dysregulation. Here we studied the methylation profiles of oppositely imprinted genes at single DNA molecule resolution by two independent parental allele-specific deep bisulfite sequencing (DBS) techniques. Using Roche (GSJunior) next generation sequencing technology, we analyzed the maternally imprinted MEST promoter and the paternally imprinted MEG3 intergenic (IG) differentially methylated region (DMR) in fetal cord blood, adult blood, and visceral adipose tissue. Epimutations were defined as paternal or maternal alleles with >50% aberrantly (de)methylated CpG sites, showing the wrong methylation imprint. The epimutation rates (range 2–66%) of the paternal MEST and the maternal MEG3 IG DMR allele, which should be completely unmethylated, were significantly higher than those (0–15%) of the maternal MEST and paternal MEG3 alleles, which are expected to be fully methylated. This hypermethylation of the non-imprinted allele (HNA) was independent of parental origin. Very low epimutation rates in sperm suggest that HNA occurred after fertilization. DBS with Illumina (MiSeq) technology confirmed HNA for the MEST promoter and the MEG3 IG DMR, and to a lesser extent, for the paternally imprinted secondary MEG3 promoter and the maternally imprinted PEG3 promoter. HNA leads to biallelic methylation of imprinted genes in a considerable proportion of normal body cells (somatic mosaicism) and is highly variable between individuals. We propose that during development and differentiation maintenance of differential methylation at most imprinting control regions may become to some extent redundant. The accumulation of stochastic and environmentally-induced methylation errors on the non-imprinted allele may increase epigenetic diversity between cells and individuals. KW - DNA methylation KW - genomic imprinting KW - polymerase chain reaction KW - blood KW - epigenetics KW - sequence alignment KW - sperm Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170433 VL - 12 IS - 8 ER - TY - JOUR A1 - Balasubramanian, Srikkanth A1 - Othman, Eman M. A1 - Kampik, Daniel A1 - Stopper, Helga A1 - Hentschel, Ute A1 - Ziebuhr, Wilma A1 - Oelschlaeger, Tobias A. A1 - Abdelmohsen, Usama R. T1 - Marine sponge-derived Streptomyces sp SBT343 extract inhibits staphylococcal biofilm formation JF - Frontiers in Microbiology N2 - Staphylococcus epidermidis and Staphylococcus aureus are opportunistic pathogens that cause nosocomial and chronic biofilm-associated infections. Indwelling medical devices and contact lenses are ideal ecological niches for formation of staphylococcal biofilms. Bacteria within biofilms are known to display reduced susceptibilities to antimicrobials and are protected from the host immune system. High rates of acquired antibiotic resistances in staphylococci and other biofilm-forming bacteria further hamper treatment options and highlight the need for new anti-biofilm strategies. Here, we aimed to evaluate the potential of marine sponge-derived actinomycetes in inhibiting biofilm formation of several strains of S. epidermidis, S. aureus, and Pseudomonas aeruginosa. Results from in vitro biofilm-formation assays, as well as scanning electron and confocal microscopy, revealed that an organic extract derived from the marine sponge-associated bacterium Streptomyces sp. SBT343 significantly inhibited staphylococcal biofilm formation on polystyrene, glass and contact lens surfaces, without affecting bacterial growth. The extract also displayed similar antagonistic effects towards the biofilm formation of other S. epidermidis and S. aureus strains tested but had no inhibitory effects towards Pseudomonas biofilms. Interestingly the extract, at lower effective concentrations, did not exhibit cytotoxic effects on mouse fibroblast, macrophage and human corneal epithelial cell lines. Chemical analysis by High Resolution Fourier Transform Mass Spectrometry (HRMS) of the Streptomyces sp. SBT343 extract proportion revealed its chemical richness and complexity. Preliminary physico-chemical characterization of the extract highlighted the heat-stable and non-proteinaceous nature of the active component(s). The combined data suggest that the Streptomyces sp. SBT343 extract selectively inhibits staphylococcal biofilm formation without interfering with bacterial cell viability. Due to absence of cell toxicity, the extract might represent a good starting material to develop a future remedy to block staphylococcal biofilm formation on contact lenses and thereby to prevent intractable contact lens-mediated ocular infections. KW - medicine KW - marine sponges KW - actinomycetes KW - Streptomyces KW - staphilococci KW - biofilms KW - contact lens Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171844 VL - 8 ER - TY - JOUR A1 - Berti, Stefan A1 - Vossel, Gerhard A1 - Gamer, Matthias T1 - The orienting response in healthy aging: Novelty P3 indicates no general decline but reduced efficacy for fast stimulation rates JF - Frontiers in Psychology N2 - Automatic orienting to unexpected changes in the environment is a pre-requisite for adaptive behavior. One prominent mechanism of automatic attentional control is the Orienting Response (OR). Despite the fundamental significance of the OR in everyday life, only little is known about how the OR is affected by healthy aging. We tested this question in two age groups (19–38 and 55–72 years) and measured skin-conductance responses (SCRs) and event-related brain potentials (ERPs) to novels (i.e., short environmental sounds presented only once in the experiment; 10% of the trials) compared to standard sounds (600 Hz sinusoidal tones with 200 ms duration; 90% of the trials). Novel and standard stimuli were presented in four conditions differing in the inter-stimulus interval (ISI) with a mean ISI of either 10, 3, 1, or 0.5 s (blocked presentation). In both age groups, pronounced SCRs were elicited by novels in the 10 s ISI condition, suggesting the elicitation of stable ORs. These effects were accompanied by pronounced N1 and frontal P3 amplitudes in the ERP, suggesting that automatic novelty processing and orientation of attention are effective in both age groups. Furthermore, the SCR and ERP effects declined with decreasing ISI length. In addition, differences between the two groups were observable with the fastest presentation rates (i.e., 1 and 0.5 s ISI length). The most prominent difference was a shift of the peak of the frontal positivity from around 300 to 200 ms in the 19–38 years group while in the 55–72 years group the amplitude of the frontal P3 decreased linearly with decreasing ISI length. Taken together, this pattern of results does not suggest a general decline in processing efficacy with healthy aging. At least with very rare changes (here, the novels in the 10 s ISI condition) the OR is as effective in healthy older adults as in younger adults. With faster presentation rates, however, the efficacy of the OR decreases. This seems to result in a switch from novelty to deviant processing in younger adults, but less so in the group of older adults. KW - psychology KW - attention KW - change detection KW - auditory system KW - novelty processing KW - event-related potential (ERP) KW - P300 KW - skin conductance response (SCR) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173651 VL - 8 ER - TY - JOUR A1 - Westermann, Alexander J. A1 - Barquist, Lars A1 - Vogel, Jörg T1 - Resolving host-pathogen interactions by dual RNA-seq JF - PLoS Pathogens N2 - The transcriptome is a powerful proxy for the physiological state of a cell, healthy or diseased. As a result, transcriptome analysis has become a key tool in understanding the molecular changes that accompany bacterial infections of eukaryotic cells. Until recently, such transcriptomic studies have been technically limited to analyzing mRNA expression changes in either the bacterial pathogen or the infected eukaryotic host cell. However, the increasing sensitivity of high-throughput RNA sequencing now enables “dual RNA-seq” studies, simultaneously capturing all classes of coding and noncoding transcripts in both the pathogen and the host. In the five years since the concept of dual RNA-seq was introduced, the technique has been applied to a range of infection models. This has not only led to a better understanding of the physiological changes in pathogen and host during the course of an infection but has also revealed hidden molecular phenotypes of virulence-associated small noncoding RNAs that were not visible in standard infection assays. Here, we use the knowledge gained from these recent studies to suggest experimental and computational guidelines for the design of future dual RNA-seq studies. We conclude this review by discussing prospective applications of the technique. KW - Medicine KW - RNA sequencing KW - Salmonellosis KW - Transcriptome analysis KW - Gene expression KW - Bacterial pathogens KW - Salmonella KW - Host cells KW - Lysis (medicine) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171921 VL - 13 IS - 2 ER - TY - JOUR A1 - Krohn-Molt, Ines A1 - Alawi, Malik A1 - Förstner, Konrad U. A1 - Wiegandt, Alena A1 - Burkhardt, Lia A1 - Indenbirken, Daniela A1 - Thieß, Melanie A1 - Grundhoff, Adam A1 - Kehr, Julia A1 - Tholey, Andreas A1 - Streit, Wolfgang R. T1 - Insights into microalga and bacteria interactions of selected phycosphere biofilms using metagenomic, transcriptomic, and proteomic approaches JF - Frontiers in Microbiology N2 - Microalga are of high relevance for the global carbon cycling and it is well-known that they are associated with a microbiota. However, it remains unclear, if the associated microbiota, often found in phycosphere biofilms, is specific for the microalga strains and which role individual bacterial taxa play. Here we provide experimental evidence that \(Chlorella\) \(saccharophila\), \(Scenedesmus\) \(quadricauda\), and \(Micrasterias\) \(crux-melitensis\), maintained in strain collections, are associated with unique and specific microbial populations. Deep metagenome sequencing, binning approaches, secretome analyses in combination with RNA-Seq data implied fundamental differences in the gene expression profiles of the microbiota associated with the different microalga. Our metatranscriptome analyses indicates that the transcriptionally most active bacteria with respect to key genes commonly involved in plant–microbe interactions in the Chlorella (Trebouxiophyceae) and Scenedesmus (Chlorophyceae) strains belong to the phylum of the α-Proteobacteria. In contrast, in the Micrasterias (Zygnematophyceae) phycosphere biofilm bacteria affiliated with the phylum of the Bacteroidetes showed the highest gene expression rates. We furthermore show that effector molecules known from plant-microbe interactions as inducers for the innate immunity are already of relevance at this evolutionary early plant-microbiome level. KW - microbiology KW - microalga-bacteria interaction KW - phycosphere biofilm KW - metagenomics KW - metatranscriptomics KW - metaproteomics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173701 VL - 2017 IS - 8 ER - TY - JOUR A1 - Abu-Halima, Masood A1 - Häusler, Sebastian A1 - Backes, Christina A1 - Fehlmann, Tobias A1 - Staib, Claudia A1 - Nestel, Sigrun A1 - Nazarenko, Irina A1 - Meese, Eckart A1 - Keller, Andreas T1 - Micro-ribonucleic acids and extracellular vesicles repertoire in the spent culture media is altered in women undergoing \(In\) \(Vitro\) Fertilization JF - Scientific Reports N2 - MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71% and a sensitivity of 85%. Among the 621 miRNAs, 102 (16.4%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 10\(^9\)/mL EVs), as compared to a negative outcome (7.35 × 10\(^9\)/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM. KW - Medicine KW - miRNAs KW - Molecular biology KW - Non-coding RNAs Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173632 VL - 7 ER - TY - THES A1 - Löffler, Diana T1 - Color, Metaphor and Culture - Empirical Foundations for User Interface Design T1 - Farbe, Metapher und Kultur - Empirische Grundlagen für die Gestaltung von Benutzeroberflächen N2 - Using color in user interface design is both art and science. Often, designers focus on aesthetic properties of color, but neglect that it also carries meaning and entails profound psychological consequences. Color psychology, filling this gap, is in its infancy, and lacks a theoretical approach that predicts and explains color-meaning associations shared by a large group of people in a large variety of contexts. To amend this situation, this work develops Conceptual Metaphor Theory of Color (CMToC), which predicts and explains cross-cultural and experience-based semantic color associations. The theory is based on the idea from cognitive linguistics that the study of metaphorical language provides valuable insights into our mental models involving color. A discussion of three types of metaphors that cover associations with physical and abstract concepts in light of existing empirical evidence provides the basis for deriving empirical research questions. The first research question addresses the use of color for conveying physical information like weight in user interfaces. The results of four online surveys involving a total of 295 German and Japanese participants show the relative impact of hue, saturation and brightness for associations with 16 physical properties. Two thirds of these color associations were correctly predicted by CMToC. Participants frequently matched physical properties to colors based on sensorimotor correspondences and participants of both cultures did not considerably vary in their performance. The second research question addresses the use of color for conveying abstract information like importance in user interfaces. In one experimental study, a total of 75 German and Japanese participants validated color-to-abstract mappings in form of color population stereotypes like important is dark. The majority of these color associations (86%) were correctly predicted by CMToC. Again, participants of both cultures did not considerably vary in their performance. The third research question addresses whether predicted color associations with physical and abstract information are processed automatically as a precondition for intuitive use. The results of three studies involving a total of 85 German and Japanese participants show on the example of temperature that color automatically influences the identification speed of related physical properties, but not vice versa. Color and abstract information were not automatically associated. As a result of these studies it can be concluded that predictions of CMToC are cross-culturally valid for user interface design. Derived implicit associations with physical properties and explicit associations with abstract concepts can inform design decisions in both hard- and software user interface design. N2 - Der Einsatz von Farbe im User Interface Design ist sowohl Kunst als auch Wissenschaft. Designer legen häufig ästhetische Aspekte der Farbgestaltung in den Fokus, aber vernachlässigen dabei, dass Farbe ein wichtiger Bedeutungsträger ist, der tiefgreifende psychologische Konsequenzen mit sich bringt. Die Farbpsychologie versucht diese Lücke zu füllen, steckt jedoch noch in den Kinderschuhen. Vor allem mangelt es an einem theoretischen Ansatz, der semantische Farbassoziationen vorhersagt und erklärt, die von einer Vielzahl von Menschen in einer Vielzahl von Kontexten geteilt werden. Vor diesem Hintergrund wird in dieser Arbeit die Conceptual Metaphor Theory of Color (CMToC) entwickelt, welche Vorhersagen über kulturübergreifende und erfahrungsbasierte semantische Farbassoziationen trifft und diese unter Berücksichtigung von empirischen Daten erklärt. Die Theorie beruht auf der Idee aus der kognitiven Linguistik, dass die metaphorische Sprache wertvolle Einblicke in unsere mentalen Modelle in Bezug auf Farbe liefert. Aus der Diskussion dreier Arten von konzeptuellen Metaphern, die Farbassoziationen mit physischen und abstrakten Konzepten abdecken, werden schließlich empirische Forschungsfragen abgeleitet. Die erste Forschungsfrage befasst sich mit der Verwendung von Farbe zur Vermittlung von physischen Informationen wie Gewicht im User Interface. Die Ergebnisse von vier Online-Befragungen mit insgesamt 295 deutschen und japanischen Teilnehmern ermitteln den Einfluss von Farbton, Sättigung und Helligkeit auf Assoziationen mit 16 physischen Eigenschaften. Zwei Drittel dieser Farbassoziationen werden von der CMToC korrekt vorhergesagt. Die Teilnehmer aus beiden Kulturen unterschieden sich dabei nicht wesentlich in ihrer Zuordnung von Farben zu physischen Eigenschaften. Die zweite Forschungsfrage befasst sich mit der Verwendung von Farbe zur Vermittlung von abstrakten Informationen wie Wichtigkeit im User Interface. Eine experimentelle Studie mit insgesamt 75 deutschen und japanischen Teilnehmern validiert hierzu Assoziationen zwischen Farben und abstrakten Konzepten in Form von Farb-Populationsstereotypen wie wichtig ist dunkel. Die Mehrheit dieser Farbassoziationen (86%) wird von der CMToC korrekt vorhergesagt. Auch hier unterscheiden sich die Teilnehmer aus beiden Kulturen nicht wesentlich in ihrer Zuordnung von Farben zu abstrakten Konzepten. Die dritte Forschungsfrage befasst sich mit der Automatizität der vorhergesagten Farbassoziationen mit physischen und abstrakten Informationen als eine Voraussetzung für intuitive Benutzung. Die Ergebnisse von drei Studien mit insgesamt 85 deutschen und japanischen Teilnehmern zeigen am Beispiel Temperatur, dass Farbe automatisch die Identifikationsgeschwindigkeit verwandter physischer Eigenschaften beeinflusst, aber nicht umgekehrt. Farbe und abstrakte Informationen werden nicht automatisch assoziiert. Als Ergebnis dieser Studien lässt sich feststellen, dass die Vorhersagen von CMToC kulturübergreifend gültig sind. Abgeleitete implizite Farbassoziationen mit physischen Eigenschaften und explizite Farbassoziationen mit abstrakten Konzepten erlauben es, empirisch fundierte Designentscheidungen zu treffen, die bei der Gestaltung von Hard- und Software nutzbringend eingesetzt werden können. KW - Softwareergonomie KW - Benutzeroberfläche KW - Farbenpsychologie KW - user interface design KW - color psychology KW - human-machine interaction KW - conceptual metaphor theory KW - cross-cultural study KW - Mensch-Maschine Interaktion KW - Schnittstellengestaltung KW - Gestaltungsrichtlinien KW - Kulturvergleich Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153782 ER - TY - THES A1 - Tabisz, Barbara T1 - Site Directed Immobilization of BMP-2: Two Approaches for the Production of Osteoinductive Scaffolds T1 - Gerichtete Immobilisierung von BMP-2: Zwei Ansätze zur Herstellung osteogener Trägerstrukturen N2 - Bone fractures typically heal without surgical intervention. However, pathological situations exist which impede the healing process resulting in so-called non-union fractures. Such fractures are nowadays treated with scaffold material being introduced into the defect area. These scaffolds can be doped with osteogenic factors, such as bone morphogenetic protein (BMP)2. BMP2 belongs to the most osteogenic growth factors known to date. Its medical use, efficiency and safety have been approved by FDA for certain applications. Currently, BMP2 is distributed with a stabilizing scaffold, which is simply soaked with the growth factor. Due to fast release kinetics supraphysiological high doses of BMP2 are required which are causally associated with severe side effects observed in certain applications being most harmful in the area of the cervical spine. These side-effects include inflammation, swelling and breathing problems, leading to disastrous consequences or secondary surgical interventions. Since it could be shown that a retardation of BMP2 release from the scaffold resulted in superior bone forming properties in vivo, it seems obvious to further reduce this release to a minimum. This can be achieved by covalent coupling which in the past was already elaborated using mainly classical EDC/NHS chemistry. Using this technique coupling of the protein occurs non-site-directedly leading mainly to an unpredictable product outcome with variable osteogenic activities. In order to improve the reproducibility of scaffold functionalization by BMP2 we created variants one of which contains a unique unnatural amino acid substitution within the mature polypeptide sequence (BMP2-K3Plk) and another, BMP2-A2C, in which an N-terminal alanine has been substituted by cysteine. These modifications enable site-specific and covalent immobilization of BMP2 e.g. onto polymeric beads. Both proteins were expressed in E. coli, renatured and purified by cation-exchange chromatography. Both variants were extensively analyzed in terms of purity and biological activity which was tested by in vitro interaction analyses as well as in cell based assays. Both proteins could be successfully coupled to polymeric beads. The different BMP2 functionalized beads were shown to interact with the ectodomain of the type I receptor BMPR-IA in vitro indicating that the biological activity of both BMP2 variants retained upon coupling. Both functionalized beads induced osteogenic differentiation C2C12 cells but only of those cells which have been in close contact to the particular beads. This strongly indicates that the BMP2 variant are indeed covalently coupled and not just adsorbed. We claim that we have developed a system for a site-specific and covalent immobilization of BMP-2 onto solid scaffolds, potentially eliminating the necessity of high-dose scaffold loading. Since immobilized proteins are protected from removal by extracellular fluids, their activities now rely mainly on the half-life of the used scaffold and the rate of proteolytic degradation. Assuming that due to prolonged times much lower loading capacities might be required we propose that the immobilization strategy employed in this work may be further refined and optimized to replace the currently used BMP2-containing medical products. N2 - Knochenbrüche heilen typischerweise ohne die Notwendigkeit chirurgischer Eingriffe. Es gibt jedoch pathologische Situationen, in denen keine Heilung erfolgt was zur Ausbildung sogenannter non-union Frakturen führt. Solche Frakturen werden heutzutage mit Trägermaterialen versorgt, welche in die Defektzonen eingebracht werden. Diese Trägermaterialien können mit osteogen wirkenden Faktoren dotiert sein, z.B. mit bone morphogenetic protein (BMP)2. BMP2 gehört zu den am meisten osteogen wirkenden Faktoren, welche derzeit bekannt sind. Die Nutzung dieses Faktors als Medikament, wurde aufgrund seiner Effizienz und der Sicherheit in der Anwendung von der FDA für bestimmte Anwendungsgebiete zugelassen. Derzeit wird BMP2 mit einer stabilisierenden Trägerstruktur vertrieben, wobei diese einfach mit dem Wachstumsfaktor getränkt wird. Aufgrund schneller Freisetzungskinetiken werden unphysiologisch hohe Mengen von BMP2 gebraucht, welche in Beziehung zu extremen Nebeneffekten gebracht werden, die bei verschiedenen Anwendungen, speziell im Wirbelsäulenbereich, beobachtet werden konnten. Die Nebeneffekte umfassen Endzündungen, einhergehend mit Schwellungen und Atemprobleme, welche weitere Operationen nach sich ziehen können. Da bereits gezeigt werden konnte, dass eine Verzögerung der BMP2 Freisetzung aus der Trägerstruktur eine Verbesserung der osteogenen Wirkung mit sich bringt erscheint es offensichtlich, diese Freisetzung auf ein Minimum zu reduzieren. Dies kann durch kovalente Anbindung erreicht werden, was bereits in der Vergangenheit durch die Verwendung klassischer EDC/NHS Kopplungschemie versucht wurde. Bei dieser Art der Anbindung wird das Protein ungerichtet gekoppelt, was zu unvorhersagbaren Produktqualitäten mit variablen osteogenen Aktivitäten führt. Um eine Reproduktion solcher Funktionalisierungen mit BMP2 zu ermöglichen wurden zwei BMP-2 Varianten erzeigt, wobei bei einer der Varianten eine Aminosäure im N-terminalen Teil des reifen Proteinteils gegen eine unnatürliche Aminosäure BMP2-Plk), bei der anderen ein Alanin gegen ein Cystein ausgetauscht wurde BMP2-A2C. Durch diesen Austausch wird es möglich, diese Varianten gerichtet an polymere Strukturen anzubinden. Beide Proteine wurden in E. coli exprimiert, renaturiert und mittels Kationenaustausch-Chromatographie aufgereinigt. Die resultierenden Proteinprodukte wurden intensiv bzgl. ihres Reinheitsgrades sowie ihrer biologischen Aktivität überprüft. Letzteres erfolgte sowohl durch In-vitro Interaktions-Analysen als auch durch zellbasierte Untersuchungen. Beide Proteine konnten erfolgreich an polymere Strukturen ("beads") gekoppelt werden. Es konnte gezeigt werden, dass die verschiedenen BMP2 funktionalisierten beads mit isolierten Ektodomänen des BMP Typ I Rezeptors (BMPR-IA) interagieren. Dies belegt, dass die biologische Aktivität auch nach der Kopplung erhalten bleibt. Die funktionalisierten beads induzieren die osteogene Differenzierung von C2C12 Zellen. Die Differenzierung erfolgt aber nur in jenen Zellen die im direkten Kontakt zu den beads stehen. Dies legt nahe, dass beide BMP2 Varianten wirklich kovalent gekoppelt und nicht nur adsorbiert sind. Es kann behauptet werden, dass im Rahmen dieser Arbeit ein System entwickelt wurde, durch das eine gerichtete Immobilisierung von BMP2 an solide Oberflächen möglich ist. Dadurch können möglicherweise die notwendigen BMP2 Mengen reduziert werden, da bereits Subnanogram Mengen der gekoppelten BMP2 Varianten Osteogenese auslösen können. Da gekoppelte Proteine nicht durch interstitielle Flüssigkeiten entfernt werden können unterliegt die Fortdauer ihrer biologischen Aktivität der Halbwertszeit des verwendeten Trägermaterials, was durch die verlängerten Wirkzeiten eine Verringerung der verwendeten Wachstumsfaktormenge ermöglicht. Es wird beabsichtigt diese Kopplungsstrategie weiterzuentwickeln um die derzeit am Markt befindlichen BMP2 beinhaltenden Medizinprodukte ersetzen zu können. KW - Protein chemistry KW - BMP-2 KW - protein immobilization KW - site-specific immobilization Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153766 ER - TY - THES A1 - Reichert, Thorsten T1 - Classification and Reduction of Equivariant Star Products on Symplectic Manifolds N2 - This doctoral thesis provides a classification of equivariant star products (star products together with quantum momentum maps) in terms of equivariant de Rham cohomology. This classification result is then used to construct an analogon of the Kirwan map from which one can directly obtain the characteristic class of certain reduced star products on Marsden-Weinstein reduced symplectic manifolds from the equivariant characteristic class of their corresponding unreduced equivariant star product. From the surjectivity of this map one can conclude that every star product on Marsden-Weinstein reduced symplectic manifolds can (up to equivalence) be obtained as a reduced equivariant star product. N2 - Diese Doktorarbeit klassifiziert äquivariante Sternprodukte (Sternprodukte zusammen mit Quantenimpulsabbildungen) über die äquivariante de Rham Kohomologie. Diese Klassifizierung wird im Folgenen genutzt um ein Analogon der Kirwan-Abbildung zu konstruieren, welches ermöglicht die charakteristische Klasse von bestimmten reduzierten Sternprodukten auf Marsden-Weinstein reduzierten symplektischen Mannigfaltigkeiten direkt aus der äquivarianten charakteristischen Klasse des zugehörigen unreduzierten äquivarianten Sternprodukts zu erhalten. Die Surjektivität dieser Abbildung zeigt schließlich, dass jedes Sternprodukt auf einer Marsden-Weinstein reduzierten symplektischen Mannigfaltigkeit (bis auf Äquivalenz) als Reduktion eines äquivarianten Sternprodukts verstanden werden kann. T2 - Klassifizierung und Reduktion äquivarianter Sternprodukte auf symplektischen Mannigfaltigkeiten KW - Homologische Algebra KW - Differentialgeometrie KW - Quantenmechanik KW - symplectic geometry KW - deformation quantization KW - equivariant cohomology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153623 ER - TY - JOUR A1 - Musekamp, Gunda A1 - Schuler, Michael A1 - Seekatz, Bettina A1 - Bengel, Jürgen A1 - Faller, Hermann A1 - Meng, Karin T1 - Does improvement in self-management skills predict improvement in quality of life and depressive symptoms? A prospective study in patients with heart failure up to one year after self-management education JF - BMC Cardiovascular Disorders N2 - Background: Heart failure (HF) patient education aims to foster patients’ self-management skills. These are assumed to bring about, in turn, improvements in distal outcomes such as quality of life. The purpose of this study was to test the hypothesis that change in self-reported self-management skills observed after participation in self-management education predicts changes in physical and mental quality of life and depressive symptoms up to one year thereafter. Methods: The sample comprised 342 patients with chronic heart failure, treated in inpatient rehabilitation clinics, who received a heart failure self-management education program. Latent change modelling was used to analyze relationships between both short-term (during inpatient rehabilitation) and intermediate-term (after six months) changes in self-reported self-management skills and both intermediate-term and long-term (after twelve months) changes in physical and mental quality of life and depressive symptoms. Results: Short-term changes in self-reported self-management skills predicted intermediate-term changes in mental quality of life and long-term changes in physical quality of life. Intermediate-term changes in self-reported self-management skills predicted long-term changes in all outcomes. KW - patient education KW - chronic heart failure KW - self-management KW - quality of life KW - latent change KW - cardiac rehabilitation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157501 VL - 17 IS - 51 ER - TY - JOUR A1 - Forkuor, Gerald A1 - Hounkpatin, Ozias K.L. A1 - Welp, Gerhard A1 - Thiel, Michael T1 - High resolution mapping of soil properties using remote sensing variables in south-western Burkina Faso: a comparison of machine learning and multiple linear regression models JF - PLOS One N2 - Accurate and detailed spatial soil information is essential for environmental modelling, risk assessment and decision making. The use of Remote Sensing data as secondary sources of information in digital soil mapping has been found to be cost effective and less time consuming compared to traditional soil mapping approaches. But the potentials of Remote Sensing data in improving knowledge of local scale soil information in West Africa have not been fully explored. This study investigated the use of high spatial resolution satellite data (RapidEye and Landsat), terrain/climatic data and laboratory analysed soil samples to map the spatial distribution of six soil properties–sand, silt, clay, cation exchange capacity (CEC), soil organic carbon (SOC) and nitrogen–in a 580 km2 agricultural watershed in south-western Burkina Faso. Four statistical prediction models–multiple linear regression (MLR), random forest regression (RFR), support vector machine (SVM), stochastic gradient boosting (SGB)–were tested and compared. Internal validation was conducted by cross validation while the predictions were validated against an independent set of soil samples considering the modelling area and an extrapolation area. Model performance statistics revealed that the machine learning techniques performed marginally better than the MLR, with the RFR providing in most cases the highest accuracy. The inability of MLR to handle non-linear relationships between dependent and independent variables was found to be a limitation in accurately predicting soil properties at unsampled locations. Satellite data acquired during ploughing or early crop development stages (e.g. May, June) were found to be the most important spectral predictors while elevation, temperature and precipitation came up as prominent terrain/climatic variables in predicting soil properties. The results further showed that shortwave infrared and near infrared channels of Landsat8 as well as soil specific indices of redness, coloration and saturation were prominent predictors in digital soil mapping. Considering the increased availability of freely available Remote Sensing data (e.g. Landsat, SRTM, Sentinels), soil information at local and regional scales in data poor regions such as West Africa can be improved with relatively little financial and human resources. KW - Agricultural soil science KW - Forecasting KW - Machine learning KW - Support vector machines KW - Paleopedology KW - Trees KW - Clay mineralogy KW - Remote sensing KW - South-western Burkina Faso Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180978 VL - 12 IS - 1 ER - TY - JOUR A1 - Schampel, Andrea A1 - Kuerten, Stefanie T1 - Danger: high voltage - the role of voltage-gated calcium channels in central nervous system pathology JF - Cells N2 - Voltage-gated calcium channels (VGCCs) are widely distributed within the central nervous system (CNS) and presumed to play an important role in the pathophysiology of a broad spectrum of CNS disorders including Alzheimer’s and Parkinson’s disease as well as multiple sclerosis. Several calcium channel blockers have been in clinical practice for many years so that their toxicity and side effects are well studied. However, these drugs are primarily used for the treatment of cardiovascular diseases and most if not all effects on brain functions are secondary to peripheral effects on blood pressure and circulation. While the use of calcium channel antagonists for the treatment of CNS diseases therefore still heavily depends on the development of novel strategies to specifically target different channels and channel subunits, this review is meant to provide an impulse to further emphasize the importance of future research towards this goal. KW - cells KW - calcium KW - calcium channel antagonists KW - CNS KW - EAE KW - neurodegeneration KW - MS KW - regeneration KW - remyelination Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172653 VL - 6 IS - 4 ER - TY - JOUR A1 - Ampattu, Biju Joseph A1 - Hagmann, Laura A1 - Liang, Chunguang A1 - Dittrich, Marcus A1 - Schlüter, Andreas A1 - Blom, Jochen A1 - Krol, Elizaveta A1 - Goesmann, Alexander A1 - Becker, Anke A1 - Dandekar, Thomas A1 - Müller, Tobias A1 - Schoen, Christoph T1 - Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence JF - BMC Genomics N2 - Background: Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence. Results: Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p)ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region. Conclusions: Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis. KW - neisseria meningitidis KW - MITE KW - virulenceregulatory evolution KW - systems biology KW - metabolism KW - cryptic KW - genetic variation KW - stringent response KW - relA Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157534 VL - 18 IS - 282 ER - TY - THES A1 - Hoffmann, Susanne T1 - Demographischer Wandel und innerstädtische Einkaufszentren in Deutschland. Entwicklungen in Erlangen, Koblenz und Zwickau T1 - Demographic change and city-centre shopping locations in Germany. Developments in Erlangen, Koblenz and Zwickau. N2 - Der Anteil älterer und alter Menschen an der Gesamtbevölkerung steigt kontinuierlich an. Diese Entwicklung wird sich auch in den kommenden Jahren fortsetzen. So werden 2050 rund 40 % der deutschen Bevölkerung 60 Jahre oder älter sein. Die Alterung der Bevölkerung wirkt sich auf nahezu alle Lebensbereiche aus und stellt damit Planer und Entscheider auf staatlicher wie auf privater Seite vor neue Herausforderungen. Dies betrifft auch die Frage, wie innerstädtische Einkaufsstandorte, und zwar traditionelle innerstädtische Einkaufsstraßen und innerstädtische Shopping Center, gestaltet werden müssen, um den Anforderungen und Bedürfnissen möglichst aller Altersgruppen und damit auch denjenigen der älteren und alten Konsumenten zu entsprechen. Am Beispiel der Städte Erlangen, Koblenz und Zwickau wird in vorliegender Untersuchung der Frage nachgegangen, wie ältere und alte Menschen die verschiedenen innerstädtischen Einkaufsstandorte wahrnehmen und nutzen, welche Unterschiede diesbezüglich zu jüngeren Kundengruppen bestehen und welche Schlussfolgerungen sich daraus für eine zukunftsgerichtete Gestaltung der traditionellen Einkaufsstraßen und der innerstädtischen Shopping Center ableiten lassen. Für die Untersuchung kam ein breites methodisches Instrumentarium aus Zeitungsrecherchen, Kartierungen, qualitativen Beobachtungen, qualitativen Haushaltsbefragungen sowie quantitativen Passantenbefragungen zur Anwendung. N2 - The portion of the elderly and the aged in Germany’s total population is continuously growing. This development will continue also in the coming years. It is assumed that in 2050 about 40 % of Germany’s population is 60 years of age or older. The ageing of the population has effects on almost all aspects of life und poses new challenges for public and private planners and decision makers. This also goes for the question of designing shopping locations in the city centre including traditional city-centre shopping streets as well as city-centre shopping malls in a way that preferably corresponds to the needs and exigencies of all age groups and hence also to those of the elderly and aged consumers. Using the example of the cities of Erlangen, Koblenz and Zwickau the present investigation explores as to how elderly and aged people conceive and make use of the various shopping locations in the city centre, how this differs from younger groups of customers and which conclusions can be drawn from the results in regard of achieving a forward-looking design of traditional shopping streets and shopping malls in the city centre. A wide methodological spectrum ranging from newspaper research, mapping, qualitative observations and qualitative household surveys to quantitative passers-by surveys were brought to bear within the investigation. T3 - Würzburger Geographische Arbeiten - 119 KW - Demographie KW - Einkaufszentrum KW - Innenstadt KW - demographischer Wandel KW - Erlangen KW - Zwickau KW - Koblenz KW - Shopping Center KW - demographic change KW - elderly and aged consumers KW - city-centre shopping locations KW - city-centre shopping malls Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148218 SN - 978-3-95826-062-7 (print) SN - 978-3-95826-063-4 (online) SN - 0510-9833 SN - 2194-3656 N1 - Parallel erschienen als Druckausgabe in Würzburg University Press, 978-3-95826-062-7, 36,90 EUR. PB - Würzburg University Press CY - Würzburg ER - TY - JOUR A1 - Klughammer, Johanna A1 - Dittrich, Marcus A1 - Blom, Jochen A1 - Mitesser, Vera A1 - Vogel, Ulrich A1 - Frosch, Matthias A1 - Goesmann, Alexander A1 - Müller, Tobias A1 - Schoen, Christoph T1 - Comparative genome sequencing reveals within-host genetic changes in Neisseria meningitidis during invasive disease JF - PLoS ONE N2 - Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo. KW - blood KW - comparative genomics KW - throat KW - genetic loci KW - Neisseria meningitidis KW - genomic libraries KW - genome sequencing KW - sequence assembly tools Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159547 VL - 12 IS - 1 ER - TY - THES A1 - Weis, Michael T1 - Rassismuskritische Fortbildung von Lehrerinnen und Lehrern T1 - Anti-racist teacher training N2 - Rassismus wirkt in der Schule auf individueller, unterrichtlicher und institutioneller Ebene – häufig in subtilen und versteckten Formen. Zwar besitzt das Phänomen einen spezifischen historischen Ausgangspunkt und ist dadurch in seinen Wirkungsweisen (gerade auch in pädagogischen Kontexten) gut zu analysieren und somit folglich auch zu dekonstruieren, allerdings stößt die für eine pädagogische Auseinandersetzung zentrale Voraussetzung einer selbst- und machtreflexiven Herangehensweise bei Pädagoginnen häufig auf Widerstände und Ablehnung. Auch aufgrund der langjährigen Tabuisierung des Begriffs fand eine intensivere Auseinandersetzung mit Rassismus im deutschsprachigen Raum sowohl in der erziehungswissenschaftlichen Theorie wie auch in der pädagogischen Praxis erst ab den 1990er-Jahren statt. Bis heute besteht allerdings ein virulenter Forschungsbedarf für dieses Praxis- und Forschungsfeld in der spezifischen Schnittmenge der Gegenstandsbereiche Lehrerinnenfortbildung und Rassismus. Die hier vorgelegte explorative Studie hatte zum Ziel, dieses Forschungsdefizit aufzuholen und beschäftigte sich deshalb mit der aktuellen Praxis der rassismusrelevanten Lehrerinnen- und Lehrerfortbildung in Deutschland, d.h. mit jenen Konzepten und Angeboten der sogenannten Dritten Phase, in welchen das Thema ‚Rassismus‘ eine explizite wie implizite inhaltliche Relevanz besitzt. Eine empirische Datenbasis konnte auf Grundlage von qualitativen Interviews mit Expertinnen, die für die Konzeption und/oder Durchführung solcher Fortbildungen verantwortlich sind, erhoben und mit Hilfe der Qualitativen Inhaltsanalyse ausgewertet werden. Durch eine Verdichtung des analysierten Materials konnten am Ende des Auswertungsprozesses fünf Kernhypothesen formuliert werden, welche belastbare Aussagen zur aktuellen Praxis der rassismusspezifischen Lehrerinnenfortbildung – also jener Seminare, in denen Rassismus explizit thematisiert wird – darstellen und somit Anknüpfungspunkte für möglichen Folgestudien bieten. N2 - Racism affects schools on an individual, instructional and institutional level – often in a subtle and hidden way. The phenomenon has a specific historical origin and its mechanisms are therefore easy to analyze and, consequently, to deconstruct (especially in an educational context). But since self- and power-reflecting strategies are necessary for an educational confrontation with racism, teachers show often resistant and refusing behavior. Furthermore, it was not until the 1990s that a growing debate on racism in both educational science and practice has begun in German-speaking areas, mostly due to the deep-rooted taboo of the term. Until today there has been a significant need for research, covering both the specific field of action and the specific field of science in the overlapping areas of teacher training and racism. The present thesis wanted to close this gap in research by analyzing the current practice of anti-racist teacher training in Germany in an explorative study. The research included concepts and training offers in which racism is substantially relevant either in an implicit or explicit way. The empirical database was obtained by qualitative interviews with experts who are responsible for either the design or the conduction of this specific kind of teacher trainings. The evaluation was executed with the help of the method of qualitative content analysis. Thanks to the consolidation of the reviewed data it was possible to formulate five major hypotheses at the end of the evaluation process. Those presumptions on the current practice of anti-racist teacher training in Germany provide a reliable foundation for possible follow-up studies. KW - Rassismus KW - Lehrerbildung KW - Lehrerfortbildung KW - Interkulturelle Erziehung KW - Interkulturelle Pädagogik KW - Rassismuskritische Pädagogik Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153527 SN - 978-3-95826-068-9 (Print) SN - 978-3-95826-069-6 (Online) N1 - Parallel erschienen als Druckausgabe in Würzburg University Press, 978-3-95826-068-9, 27,80 EUR. PB - Würzburg University Press CY - Würzburg ET - 1. Auflage ER - TY - THES A1 - Sprengel, Martin T1 - A Theoretical and Numerical Analysis of a Kohn-Sham Equation and Related Control Problems T1 - Eine theoretische und numerische Untersuchung einer Kohn-Sham-Gleichung und verwandter Steuerungsprobleme N2 - In this work, multi-particle quantum optimal control problems are studied in the framework of time-dependent density functional theory (TDDFT). Quantum control problems are of great importance in both fundamental research and application of atomic and molecular systems. Typical applications are laser induced chemical reactions, nuclear magnetic resonance experiments, and quantum computing. Theoretically, the problem of how to describe a non-relativistic system of multiple particles is solved by the Schrödinger equation (SE). However, due to the exponential increase in numerical complexity with the number of particles, it is impossible to directly solve the Schrödinger equation for large systems of interest. An efficient and successful approach to overcome this difficulty is the framework of TDDFT and the use of the time-dependent Kohn-Sham (TDKS) equations therein. This is done by replacing the multi-particle SE with a set of nonlinear single-particle Schrödinger equations that are coupled through an additional potential. Despite the fact that TDDFT is widely used for physical and quantum chemical calculation and software packages for its use are readily available, its mathematical foundation is still under active development and even fundamental issues remain unproven today. The main purpose of this thesis is to provide a consistent and rigorous setting for the TDKS equations and of the related optimal control problems. In the first part of the thesis, the framework of density functional theory (DFT) and TDDFT are introduced. This includes a detailed presentation of the different functional sets forming DFT. Furthermore, the known equivalence of the TDKS system to the original SE problem is further discussed. To implement the TDDFT framework for multi-particle computations, the TDKS equations provide one of the most successful approaches nowadays. However, only few mathematical results concerning these equations are available and these results do not cover all issues that arise in the formulation of optimal control problems governed by the TDKS model. It is the purpose of the second part of this thesis to address these issues such as higher regularity of TDKS solutions and the case of weaker requirements on external (control) potentials that are instrumental for the formulation of well-posed TDKS control problems. For this purpose, in this work, existence and uniqueness of TDKS solutions are investigated in the Galerkin framework and using energy estimates for the nonlinear TDKS equations. In the third part of this thesis, optimal control problems governed by the TDKS model are formulated and investigated. For this purpose, relevant cost functionals that model the purpose of the control are discussed. Henceforth, TDKS control problems result from the requirement of optimising the given cost functionals subject to the differential constraint given by the TDKS equations. The analysis of these problems is novel and represents one of the main contributions of the present thesis. In particular, existence of minimizers is proved and their characterization by TDKS optimality systems is discussed in detail. To this end, Fréchet differentiability of the TDKS model and of the cost functionals is addressed considering \(H^1\) cost of the control. This part is concluded by deriving the reduced gradient in the \(L^2\) and \(H^1\) inner product. While the \(L^2\) optimization is widespread in the literature, the choice of the \(H^1\) gradient is motivated in this work by theoretical consideration and by resulting numerical advantages. The last part of the thesis is devoted to the numerical approximation of the TDKS optimality systems and to their solution by gradient-based optimization techniques. For the former purpose, Strang time-splitting pseudo-spectral schemes are discussed including a review of some recent theoretical estimates for these schemes and a numerical validation of these estimates. For the latter purpose, nonlinear (projected) conjugate gradient methods are implemented and are used to validate the theoretical analysis of this thesis with results of numerical experiments with different cost functional settings. N2 - In dieser Arbeit werden quantenmechanische Vielteilchen-Optimalsteuerungsprobleme im Rahmen der zeitabhängigen Dichtefunktionaltheorie (TDDFT) untersucht. Quantenmechanische Optimalsteuerungsprobleme sind sowohl in der Grundlagenforschung atomarer und molekularer Systeme als auch in entsprechenden Anwendungen von großer Bedeutung. Typische Anwendungen sind laserinduzierte chemische Reaktionen, Kernspinresonanzexperimente und Quantencomputer. Theoretisch ist das Problem einer nicht-relativistischen Beschreibung von Vielteilchensystemen mit der Schrödingergleichung (SG) gelöst. Tatsächlich ist es aber wegen des exponentiellen Anstiegs der numerischen Komplexität mit der Teilchenzahl unmöglich, die Schrödingergleichung für große Systeme von Interesse direkt zu lösen. Ein effizienter und erfolgreicher Ansatz diese Schwierigkeit zu überwinden ist die TDDFT und die Verwendung der zeitabhängigen Kohn-Sham-Gleichungen (TDKS) im Rahmen der TDDFT. Diese ersetzen die Vielteichlchen-SG durch ein System nichtlinearer Einteilchen-SGn, die mittels eines zusätzlichen Potentials gekoppelt sind. Obwohl die TDDFT für physikalische und quantenchemische Rechungen weit verbreitet ist und Softwarepakete zur direkten Verwendung zur Verfügung stehen, sind die mathematischen Grundlagen der TDDFT noch in der Entwicklung und grundlegende Vermutungen sind noch immer unbewiesen. Das Hauptanliegen der vorliegenden Arbeit ist es, einen konsistenten und mathematisch präzisen Rahmen für die TDKS-Gleichungen und verwandte Optimalsteuerungsprobleme zu liefern. Im ersten Teil der Arbeit wird die Dichtefunktionaltheorie (DFT) und die TDDFT eingeführt. Diese Einführung enthält eine detaillierte Darstellung der für die DFT relevanten Funktionenmengen. Außerdem wird die bereits bekannte Äquivalenz zwischen dem ursprünglichen Schrödingerproblem und dem TDKS-System mathematisch weitergehend diskutiert. Der derzeit erfolgreichste Ansatz, Vielteichenrechnungen im Rahmen der TDDFT umzusetzen, sind die TDKS-Gleichungen. Es sind jedoch bisher nur wenige mathematische Resultate über diese Gleichungen verfügbar und diese Ergebnisse behandeln nicht alle Probleme, die bei der Formulierung von Optimalsteuerungsproblemen bei TDKS-Gleichungen auftreten. Es ist das Ziel des zweiten Teils dieser Arbeit, diese für die Wohldefiniertheit der Formulierung der Optimalsteuerungsaufgabe maßgeblichen Probleme, wie die höhere Regularität der Lösungen der TDKS-Gleichungen und schwächere Voraussetzungen an das externe Kontrollpotential, zu behandeln. Dazu wird die Existenz und Eindeutigkeit von Lösungen der nichtlinearen TDKS-Gleichungen mit dem Galerkin-Ansatz und Energieabschätzungen untersucht. Im dritten Teil dieser Arbeit werden Probleme optimaler Steuerung bei TDKS-Gleichungen formuliert und untersucht. Dafür werden relevante Kostenfunktionale, die das Ziel der Steuerung modellieren, diskutiert. Die Optimalsteuerungsprobleme ergeben sich aus der Optimierung dieser Kosten unter der Nebenbedingung der TDKS-Gleichungen. Die Analyse dieser Probleme ist neu und stellt eines der Hauptergebnisse der vorliegenden Arbeit dar. Insbesondere wird die Existenz einer optimalen Steuerung bewiesen und ihre Charakterisierung mittels eines TDKS-Optimalitätssystem im Detail diskutiert. Dazu wird die Fréchet-Differenzierbarkeit des TDKS-Models und des Kostenfunktionals mit \(H^1\)-Steuerungskosten betrachtet. Abschließend wird der reduzierte Gradient im \(L^2\)- und im \(H^1\)-Skalarprodukt hergeleitet. Während die \(L^2\)-Optimierung in der Literatur weit verbreitet ist, wird in dieser Arbeit die Verwendung des \(H^1\)-Gradienten mit theoretischen Argumenten und resultierenden numerischen Vorteilen motiviert. Der letzte Teil dieser Arbeit ist der numerischen Approximation des TDKS-Optimalitätssystems und seiner Lösung mittels gradientenbasierter Optimierungsmethoden gewidmet. Für ersteres wird die Strang Zeitsplitting-Pseudospektralmethode diskutiert, eine Zusammenfassung einiger aktueller theoretischer Abschätzungen für dieses Schema angegeben und diese Abschätzungen numerisch überprüft. Für letzteres wird das (projizierte) nichtlineare Verfahren der konjugierten Gradienten (NCG) implementiert und verwendet um die theoretische Analyse dieser Arbeit mit den Ergebnissen numerischer Rechnungen für verschiedene Kostenfunktionale zu validieren. KW - Optimale Kontrolle KW - Dichtefunktionalformalismus KW - Optimierung KW - TDDFT KW - TD Kohn-Sham equations KW - optimal control Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153545 ER - TY - THES A1 - König, Anna T1 - Die Wirkung von microRNA-132 und microRNA-212 auf Zielgene an der Blut-Hirn-Schranke bei Glucose- und Sauerstoffentzug T1 - The effect of microRNA-132 and microRNA-212 on target genes of the blood-brain-barrier during oxygen-glucose-deprivation N2 - Die Blut-Hirn-Schranke (BHS) bildet eine Barriere, die das ZNS vor dem Einfluss der Substanzen aus der Peripherie schützt. Die Aufrechterhaltung dieser wichtigen Struktur ist für die Homöostase und Vermeidung von Schäden im ZNS von besonderer Bedeutung. Eine häufige Ursache für die Schädigung der BHS ist der ischämische Schlaganfall. In der Hypoxie werden zahlreiche Proteine degradiert oder von den Zellkontakten delokalisiert, die für die Integrität der Zell-Zell-Kontakte eine wichtige Rolle spielen. Als Folge resultiert eine Destabilisierung der BHS mit vermehrtem Durchstrom von ZNS-schädigenden Substanzen. Seit der Entdeckung von miRNAs (Lee et al., 1993) konnte deren Rolle vor allem in der Entstehung von Tumoren und Entzündungen nachgewiesen werden. In der Arbeitsgruppe Förster wurde eine vermehrte Expression von miRNA-132 und miRNA-212 nach OGD festgestellt. Als Zielgene von miRNA-132/212 konnten Cldn1, Tjap1, MMP9 und Jam3 detektiert werden. Die Validierungsversuche wurden an einem etablierten In-vitro-Modell der BHS bestehend aus murinen cerebralen Hirnendothelzellen (cEND-2) durchgeführt. Zu Beginn wurden die Bedingungen zur Kultivierung der Zellen unter Hypoxie und ohne Glucose (eng. oxygen glucose deprivation, OGD) mit und ohne Astrozyten-konditioniertem Medium etabliert. Expression von diversen Genen, die bekannt sind eine Rolle in der OGD zu spielen, wurden mittels qPCR ermittelt. Dabei kam es zu signifikanten Veränderungen der Genexpression von wichtigen Genen in der BHS, die besonders in Kombination mit Astrozyten-konditioniertem Medium noch verstärkt werden konnten. So wurde die Kultivierung der Zellen für die weiteren OGD-Versuche in Astrozyten-konditioniertem Medium gewählt. Des Weiteren wurde die Regulation von miRNA-132/212 auf die Zielgene an der BHS untersucht. Die hemmende Wirkung der miRNAs auf die Genexpression der Zielgene konnte durch Transfektion von pre-miR-132/212 sowohl auf mRNA- als auch auf Proteinebene gezeigt werden. In der OGD konnte durch Hemmung der vermehrt exprimierten miRNA-132/212 ein Anstieg der Zielgene beobachtet werden. Damit konnten sowohl auf mRNA-Ebene als auch auf Proteinebenen Cldn1, Tjap1, Jam3 und MMP9 als Zielgene bestätigt werden. Zusätzlich wurden als funktionelle Tests eine TEER-Messung für den Widerstand und eine Permeabilitätsmessung durchgeführt. Beide Tests bestätigten die Destabilisierung der BHS nach Transfektion von miRNA-132/212. Als therapeutische Implikation könnte durch Inhibition von miRNA-132/212 bei einer Minderperfusion des Gehirns die Barriere stabilisiert werden, was eine neue Möglichkeit in der Therapie des akuten Schlaganfalls bietet. N2 - Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Ischemic stroke leads to hypoperfusion of a brain area that initiates a complex series of events. Excitotoxicity, oxidative stress, microvascular injury, blood-brain barrier dysfunction and postischemic inflammation lead ultimately to cell death of neurons, glia and endothelial cells (Lakhan et al., 2009). However, little is known about the pathomechanism of the dysfunction of the blood-brain barrier after oxygen-glucose-deprivation (OGD) and the microRNA-mediated gene regulation functions via the inhibition of protein translation (Filipowicz et al., 2008). MicroRNAs are 18–22 nucleotides RNAs in length and regulate gene expression at the mRNA level. We used mouse brain microvascular endothelial cells cEND-2 (Forster et al., 2005, Burek et al., 2012). In this study, we looked for microRNAs expressed during OGD and showed that miR-132 and miR-212 expression was upregulated in response to hypoxia after 4 hours OGD and 4 hours OGD followed by 24 hours reoxygenation. Hypoxia and normoxia treatment was performed with astrocyte conditioned media because it is known that astrocytes play a pivotal role during stroke pathogenesis (Neuhaus et al., 2015) as the experiments with and without C6-astrocyte-medium in this study also confirmed. The experimental setup of the normoxia and OGD experiments was already published in the AG Förster (Kleinschnitz et al., 2011). Claudin-1, Tjap-1, Jam-3 and MMP-9 were detected as target genes of miR-132/-212. MicroRNA decreases the mRNA-expression by translational repression and mRNA-degradation (Catalucci et al., 2009). To examine the regulation of miR-132/-212 targets, miR-132/-212 mimics were overexpressed in normoxic cEND-2 or inhibited by transfection of miR-inhibitor in hypoxic cEND-2. The regulation of miR-132/-212 on their target genes Claudin-1, Tjap-1, Jam-3 and MMP-9 could be shown via qPCR and Western Blot. An overexpression of miR-132/-212 decreased the mRNA expression and protein level. Furthermore, inhibition of miR-132/-212 in OGD rescued the mRNA expression and the protein level. To show this regulation also in human cell lines we examined Jam-3 expression in the same way in hDCMEC/D3. Moreover we examined the effect of miR-132/-212 on transendothelial electrical resistance (TEER) and permeability. Both confirm a loss of integrity of the blood-brain-barrier as a result of reduction of resistance and higher permeability after overexpression of miR-132/-212. In summary, the target genes of miR-132 and miR-212 Claudin-1, Tjap-1, Jam-3 and MMP-9 could be identified and evaluated. The regulation of miR-132 and miR-212 on their target genes in the blood-brain-barrier could be confirmed. In future, stabilizing the blood-brain-barrier could be implemented as a therapeutic implication while inhibiting miRNAs by reacting on gene level. KW - Transfektion KW - Schlaganfall KW - microRNA-132 KW - microRNA-212 KW - Hypoxie KW - Blut-Hirn-Schranke KW - Zell-Zell-Kontakte Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153446 ER - TY - JOUR A1 - Hopp, Sarah A1 - Nolte, Marc W. A1 - Stetter, Christian A1 - Kleinschnitz, Christoph A1 - Sirén, Anna-Leena A1 - Albert-Weissenberger, Christiane T1 - Alleviation of secondary brain injury, posttraumatic inflammation, and brain edema formation by inhibition of factor XIIa JF - Journal of Neuroinflammation N2 - Background: Traumatic brain injury (TBI) is a devastating neurological condition and a frequent cause of permanent disability. Posttraumatic inflammation and brain edema formation, two pathological key events contributing to secondary brain injury, are mediated by the contact-kinin system. Activation of this pathway in the plasma is triggered by activated factor XII. Hence, we set out to study in detail the influence of activated factor XII on the abovementioned pathophysiological features of TBI. Methods: Using a cortical cryogenic lesion model in mice, we investigated the impact of genetic deficiency of factor XII and inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused Infestin-4 on the release of bradykinin, the brain lesion size, and contact-kinin system-dependent pathological events. We determined protein levels of bradykinin, intracellular adhesion molecule-1, CC-chemokine ligand 2, and interleukin-1β by enzyme-linked immunosorbent assays and mRNA levels of genes related to inflammation by quantitative real-time PCR. Brain lesion size was determined by tetrazolium chloride staining. Furthermore, protein levels of the tight junction protein occludin, integrity of the blood-brain barrier, and brain water content were assessed by Western blot analysis, extravasated Evans Blue dye, and the wet weight-dry weight method, respectively. Infiltration of neutrophils and microglia/activated macrophages into the injured brain lesions was quantified by immunohistological stainings. Results: We show that both genetic deficiency of factor XII and inhibition of activated factor XII in mice diminish brain injury-induced bradykinin release by the contact-kinin system and minimize brain lesion size, blood-brain barrier leakage, brain edema formation, and inflammation in our brain injury model. Conclusions: Stimulation of bradykinin release by activated factor XII probably plays a prominent role in expanding secondary brain damage by promoting brain edema formation and inflammation. Pharmacological blocking of activated factor XII could be a useful therapeutic principle in the treatment of TBI-associated pathologic processes by alleviating posttraumatic inflammation and brain edema formation. KW - factor XII KW - focal brain lesion KW - brain edema Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157490 VL - 14 IS - 39 ER - TY - JOUR A1 - Koeniger, Tobias A1 - Kuerten, Stefanie T1 - Splitting the "unsplittable": Dissecting resident and infiltrating macrophages in experimental autoimmune encephalomyelitis JF - International Journal of Molecular Sciences N2 - Macrophages predominate the inflammatory landscape within multiple sclerosis (MS) lesions, not only regarding cellularity but also with respect to the diverse functions this cell fraction provides during disease progression and remission. Researchers have been well aware of the fact that the macrophage pool during central nervous system (CNS) autoimmunity consists of a mixture of myeloid cells. Yet, separating these populations to define their unique contribution to disease pathology has long been challenging due to their similar marker expression. Sophisticated lineage tracing approaches as well as comprehensive transcriptome analysis have elevated our insight into macrophage biology to a new level enabling scientists to dissect the roles of resident (microglia and non-parenchymal macrophages) and infiltrating macrophages with unprecedented precision. To do so in an accurate way, researchers have to know their toolbox, which has been filled with diverse, discriminating approaches from decades of studying neuroinflammation in animal models. Every method has its own strengths and weaknesses, which will be addressed in this review. The focus will be on tools to manipulate and/or identify different macrophage subgroups within the injured murine CNS. KW - CNS KW - distinction KW - experimental autoimmune encephalomyelitis KW - inflammation KW - macrophages KW - markers KW - microglia KW - monocytes Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285067 SN - 1422-0067 VL - 18 IS - 10 ER - TY - THES A1 - Jürgens, Stefan T1 - Correlated Topological Materials T1 - Korrelierte Topologische Materialien N2 - The topic of this PhD thesis is the combination of topologically non-trivial phases with correlation effects stemming from Coulomb interaction between the electrons in a condensed matter system. Emphasis is put on both emerging benefits as well as hindrances, e.g. concerning the topological protection in the presence of strong interactions. The physics related to topological effects is established in Sec. 2. Based on the topological band theory, we introduce topological materials including Chern insulators, topological insulators in two and three dimensions as well as Weyl semimetals. Formalisms for a controlled treatment of Coulomb correlations are presented in Sec. 3, starting with the topological field theory. The Random Phase Approximation is introduced as a perturbative approach, while in the strongly interacting limit the theory of quantum Hall ferromagnetism applies. Interactions in one dimension are special, and are treated through the Luttinger liquid description. The section ends with an overview of the expected benefits offered by the combination of topology and interactions, see Sec. 3.3. These ideas are then elaborated in the research part. In Chap. II, we consider weakly interacting 2D topological insulators, described by the Bernevig-Hughes-Zhang model. This is applicable, e.g., to quantum well structures made of HgTe/CdTe or InAs/GaSb. The bulk band structure is here a mixture stemming from linear Dirac and quadratic Schrödinger fermions. We study the low-energy excitations in Random Phase Approximation, where a new interband plasmon emerges due to the combined Dirac and Schrödinger physics, which is absent in the separate limits. Already present in the undoped limit, one finds it also at finite doping, where it competes with the usual intraband plasmon. The broken particle-hole symmetry in HgTe quantum wells allows for an effective separation of the two in the excitation spectrum for experimentally accessible parameters, in the right range for Raman or electron loss spectroscopy. The interacting bulk excitation spectrum shows here clear differences between the topologically trivial and topologically non-trivial regime. An even stronger signal in experiments is expected from the optical conductivity of the system. It thus offers a quantitative way to identify the topological phase of 2D topological insulators from a bulk measurement. In Chap. III, we study a strongly interacting system, forming an ordered, quantum Hall ferromagnetic state. The latter can arise also in weakly interacting materials with an applied strong magnetic field. Here, electrons form flat Landau levels, quenching the kinetic energy such that Coulomb interaction can be dominant. These systems define the class of quantum Hall topological insulators: topologically non-trivial states at finite magnetic field, where the counter-propagating edge states are protected by a symmetry (spatial or spin) other than time-reversal. Possible material realizations are 2D topological insulators like HgTe heterostructures and graphene. In our analysis, we focus on the vicinity of the topological phase transition, where the system is in a strongly interacting quantum Hall ferromagnetic state. The bulk and edge physics can be described by a nonlinear \sigma-model for the collective order parameter of the ordered state. We find that an emerging, continuous U(1) symmetry offers topological protection. If this U(1) symmetry is preserved, the topologically non-trivial phase persists in the presence of interactions, and we find a helical Luttinger liquid at the edge. The latter is highly tunable by the magnetic field, where the effective interaction strength varies from weakly interacting at zero field, K \approx 1, to diverging interaction strength at the phase transition, K -> 0. In the last Chap. IV, we investigate whether a Weyl semimetal and a 3D topological insulator phase can exist together at the same time, with a combined, hybrid surface state at the joint boundaries. An overlap between the two can be realized by Coulomb interaction or a spatial band overlap of the two systems. A tunnel coupling approach allows us to derive the hybrid surface state Hamiltonian analytically, enabling a detailed study of its dispersion relation. For spin-symmetric coupling, new Dirac nodes emerge out of the combination of a single Dirac node and a Fermi arc. Breaking the spin symmetry through the coupling, the dispersion relation is gapped and the former Dirac node gets spin-polarized. We propose experimental realizations of the hybrid physics, including compressively strained HgTe as well as heterostructures of topological insulator and Weyl semimetal materials, connected to each other, e.g., by Coulomb interaction. N2 - Das Thema dieser Doktorarbeit ist die Kombination von topologisch nicht-trivialen (TnT) Phasen mit Coulomb Wechselwirkungseffekten, die zwischen den Elektronen eines Systems der kondensierten Materie auftreten. Ein Schwerpunkt wird sowohl auf die sich ergebenen Vorteile als auch möglichen Nachteile gelegt, z.B. bezogen auf den topologischen Schutz in der Gegenwart von starker Wechselwirkung. Die topologischen Effekte in der Physik werden in Kap. 2 vorgestellt. Basierend auf der topologischen Bandtheorie führen wir die topologischen Materialien ein, inklusive Chern Isolatoren, topologischer Isolatoren (TIs) in zwei und drei Dimensionen und Weyl Halbmetallen (WSMs). Die Formalismen für eine kontrollierte Behandlung der Coulomb Korrelationen werden in Kap. 3 präsentiert, beginnend mit der topologischen Feldtheorie. Die Random Phase Approximation bietet einen störungstheoretischen Ansatz, während im Bereich der starken Wechselwirkung die Theorie des Quanten-Hall-Ferromagnetismus greift. Wechselwirkende Systeme in einer Dimension sind besonders und werden von uns als Luttinger Flüssigkeit beschrieben. Das Kapitel endet mit einem Überblick über die zu erwartenden Vorteile und Möglichkeiten einer Kombination von Topologie und Korrelationen in Kap. 3.3. Diese Ideen werden im Forschungsteil weiter ausgeführt. In Kap. II beschäftigen wir uns mit schwach wechselwirkenden, zweidimensionalen (2D) TIs, beschrieben durch das Bernevig-Hughes-Zhang Modell. Dies ist z.B. anwendbar für Quantentrogstrukturen basierend auf HgTe/CdTe oder InAs/GaSb. Die Bandstruktur im Volumen ist hier gegeben durch eine Mischung aus linearen Dirac and quadratischen Schrödinger Fermionen. Wir untersuchen die Anregungen für kleine Energien mittels Random Phase Approximation und finden ein neues Interbandplasmon, das aus der Kombination von Dirac und Schrödinger Physik entspringt und in den jeweiligen Grenzfällen nicht existiert. Während es bereits im undotierten Fall zu finden ist, konkurriert es bei endlicher Dotierung mit dem gewöhnlichen Intrabandplasmon. Die gebrochene Teilchen-Loch Symmetrie in HgTe Quantentrögen ermöglicht eine Trennung der Beiden im Anregungsspektrum, für experimentell zugängliche Parameter in der richtigen Größenordnung für Raman- oder Elektronenspektroskopie. Das wechselwirkende Anregungsspektrum des Bulk zeigt hier klare Unterschiede zwischen dem topologisch trivialen und nicht-trivialen Regime. Ein noch deutlicheres experimentelles Signal erwarten wir von der optischen Leitfähigkeit des Systems, welche somit eine quantitative Möglichkeit bietet, zwischen den topologischen Phasen eines 2D TIs mittels einer Bulk Messung zu unterscheiden. In Kap. III untersuchen wir stark-wechselwirkende Systeme, die sich in einem geordneten, Quanten-Hall-Ferromagnetischen (QHFM) Zustand befinden. Dieser Zustand kann auch in schwach-wechselwirkenden Systemen in einem starken magnetischen Feld auftreten. In diesem Fall bilden die Elektronen flache Landau-Niveaus mit minimierter kinetischer Energie aus, sodass die Coulomb Wechselwirkung dominiert. Solche Systeme bilden die Klasse der Quanten-Hall topologischen Isolatoren (QHTIs): TnT Zustände bei endlichem Magnetfeld, deren gegenläufige Randzustände nicht durch Zeitumkehr, sondern durch räumliche oder spin Symmetrien geschützt werden. Infrage kommende Materialien sind 2D TIs wie HgTe Heterostrukturen oder Graphen. Unsere Analyse fokussiert sich auf die Umgebung des topologischen Phasenübergangs, in der sich das System in dem stark-wechselwirkenden QHFM Zustand befindet. Hier kann die Physik sowohl des Bulks als auch die der Randzustände mittels des nichtlinearen \sigma-Modells für den Ordnungsparameter beschrieben werden. Wir zeigen, dass eine effektive, kontinuierliche U(1) Symmetrie für den topologischen Schutz sorgt. Ist diese Symmetrie erhalten, bleibt die TnT Phase auch für starke Wechselwirkungen bestehen und die Randzustände bilden eine helikale Luttinger Flüssigkeit. Diese kann durch das magnetische Feld stark beeinflusst werden, sodass die effektive Wechselwirkungsstärke zwischen schwach wechselwirkend für vernachlässigbares Feld, K \approx 1, und stark wechselwirkend am topologischen Phasenübergang, K -> 0, variiert. Im letzten Kap. IV erforschen wir, ob WSM- and drei-dimensionale TI-Phasen zeitgleich und am selben Ort existieren können, mit einem hybriden Oberflächenzustand an der gemeinsamen Grenzfläche. Ein entsprechender Austausch zwischen den Materialien kann durch Coulomb Wechselwirkung oder eine räumliche Bandüberlagerung realisiert werden. Ein Tunnelkopplungsansatz erlaubt es uns, den hybriden Oberflächenhamiltonian analytisch herzuleiten und ermöglicht so eine detaillierte Analyse der Oberflächendispersionsrelation. Im Fall von spin-symmetrischer Kopplung entstehen weitere Diracpunkte aus der Kombination eines einzelnen Diracpunktes und eines Fermibogens. Bricht man die Spinsymmetrie durch die Kopplung entstehen Bandlücken in der Oberflächendispersion und die ursprünglichen Diracpunkte werden spinpolarisiert. Wir schlagen experimentelle Umsetzungen dieser hybriden Physik vor, z.B. kompressiv verspanntes HgTe oder auch Heterostrukturen aus TI and WSM Materialien. KW - Topologie KW - Elektronenkorrelation KW - Mesoskopisches System KW - Topological insulators KW - Weyl semimetals KW - Correlation effects KW - Topologischer Isolator Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152202 ER - TY - THES A1 - Sonnenberg, Christoph T1 - Analyzing Technology-Enhanced Learning Processes: What Can Process Mining Techniques Contribute to the Evaluation of Instructional Support? T1 - Eine Analyse technologieunterstützter Lernprozesse: Welchen Beitrag kann Process Mining für die Bewertung instruktionaler Hilfe leisten? N2 - The current dissertation addresses the analysis of technology-enhanced learning processes by using Process Mining techniques. For this purpose, students’ coded think-aloud data served as the measurement of the learning process, in order to assess the potential of this analysis method for evaluating the impact of instructional support. The increasing use of digital media in higher education and further educational sectors enables new potentials. However, it also poses new challenges to students, especially regarding the self-regulation of their learning process. To help students with optimally making progress towards their learning goals, instructional support is provided during learning. Besides the use of questionnaires and tests for the assessment of learning, researchers make use increasingly of process data to evaluate the effects of provided support. The analysis of observed behavioral traces while learning (e.g., log files, eye movements, verbal reports) allows detailed insights into the student’s activities as well as the impact of interventions on the learning process. However, new analytical challenges emerge, especially when going beyond the analysis of pure frequencies of observed events. For example, the question how to deal with temporal dynamics and sequences of learning activities arises. Against this background, the current dissertation concentrates on the application of Process Mining techniques for the detailed analysis of learning processes. In particular, the focus is on the additional value of this approach in comparison to a frequency-based analysis, and therefore on the potential of Process Mining for the evaluation of instructional support. An extensive laboratory study with 70 university students, which was conducted to investigate the impact of a support measure, served as the basis for pursuing the research agenda of this dissertation. Metacognitive prompts supported students in the experimental group (n = 35) during a 40-minute hypermedia learning session; whereas the control group (n = 35) received no support. Approximately three weeks later, all students participated in another learning session; however, this time all students learned without any help. The participants were instructed to verbalize their learning activities concurrently while learning. In the three analyses of this dissertation, the coded think aloud data were examined in detail by using frequency-based methods as well as Process Mining techniques. The first analysis addressed the comparison of the learning activities between the experimental and control groups during the first learning session. This study concentrated on the research questions whether metacognitive prompting increases the number of metacognitive learning activities, whether a higher number of these learning activities corresponds with learning outcome (mediation), and which differences regarding the sequential structure of learning activities can be revealed. The second analysis investigated the impact of the individual prompts as well as the conditions of their effectiveness on the micro level. In addition to Process Mining, we used a data mining approach to compare the findings of both analysis methods. More specifically, we classified the prompts by their effectiveness, and we examined the learning activities preceding and following the presentation of instructional support. Finally, the third analysis considered the long-term effects of metacognitive prompting on the learning process during another learning session without support. It was the key objective of this study to examine which fostered learning activities and process patterns remained stable during the second learning session. Overall, all three analyses indicated the additional value of Process Mining in comparison to a frequency-based analysis. Especially when conceptualizing the learning process as a dynamic sequence of multiple activities, Process Mining allows identifying regulatory loops and crucial routing points of the process. These findings might contribute to optimizing intervention strategies. However, before drawing conclusions for the design of instructional support based on the revealed process patterns, additional analyses need to investigate the generalizability of results. Moreover, the application of Process Mining remains challenging because guidelines for analytical decisions and parameter settings in technology-enhanced learning context are currently missing. Therefore, future studies need to examine further the potential of Process Mining as well as related analysis methods to provide researchers with concrete recommendations for use. Nevertheless, the application of Process Mining techniques can already contribute to advance the understanding of the impact of instructional support through the use of fine-grained process data. N2 - Die vorliegende Dissertation beschäftigt sich mit der Analyse technologieunterstützter Lernprozesse unter Verwendung von Process Mining Methoden. Dabei werden kodierte Protokolle des lauten Denkens als Prozessmaß genutzt, um eine Bewertung des Potentials dieses Analyseansatzes für die Evaluation der Effekte instruktionaler Hilfe vornehmen zu können. Die zunehmende Verbreitung digitaler Medien in der Hochschulbildung und weiteren Ausbildungssektoren schafft neue Potentiale, allerdings auch neue Anforderungen an den Lerner, insbesondere an die Regulation seines Lernprozesses. Um ihn dabei zu unterstützen seinen Lernfortschritt optimal zu gestalten, wird ihm während des Lernens instruktionale Hilfe angeboten. Neben der Evaluation mittels Fragebögen und Testverfahren wird die Wirksamkeit der angebotenen Unterstützung zunehmend durch Prozessdaten bewertet. Die Analyse von beobachteten Verhaltensspuren während des Lernens (z.B. Logfiles, Blickbewegungen, Verbalprotokolle) ermöglicht einen detaillierten Einblick in die Lernhandlungen und die Folgen von Unterstützungsmaßnahmen. Allerdings stellen sich auch eine Reihe von neuen analytischen Herausforderungen, wie der Umgang mit zeitlichen Dynamiken und Sequenzen von Lernhandlungen, insbesondere wenn man über Häufigkeitsanalysen der beobachteten Ereignisse hinausgehen möchte. Vor diesem Hintergrund beschäftigt sich die vorliegende Arbeit mit der Anwendung von Process Mining Methoden zur detaillierten Betrachtung von Lernprozessen. Insbesondere der Mehrwert dieses Ansatzes gegenüber einer reinen Häufigkeitsanalyse und somit die Potentiale von Process Mining für die Evaluation von Fördermaßen sollen herausgestellt werden. Als Grundlage für die Bearbeitung der Fragestellung diente eine umfangreiche Laborstudie mit 70 Universitätsstudierenden, die durchgeführt wurde um die Effekte einer instruktionalen Fördermaßnahme zu prüfen. Die Probanden der Experimentalgruppe (n = 35) erhielten in einer 40-minütigen Hypermedia-Lernsitzung eine Förderung durch metakognitive Prompts, während die Kontrollgruppe (n = 35) ohne Hilfe lernte. In einer weiteren Lernsitzung drei Wochen später bearbeiteten alle Teilnehmer eine weitere Lerneinheit, diesmal ohne Unterstützung für alle Probanden. Während des Lernens wurden alle Teilnehmer instruiert, ihre Lernhandlungen kontinuierlich zu verbalisieren. Die kodierten Verbalprotokolle wurden in den drei Analysen dieser Dissertation detailliert mit Häufigkeits- und Process Mining Analysen untersucht. Die erste Analyse konzentrierte sich auf den Vergleich der Lernhandlungen der Experimental- und Kontrollgruppe während der ersten Sitzung. Es wurde den Fragen nachgegangen, ob metakognitive Prompts die Lerner dazu anregen mehr metakognitive Lernhandlungen auszuführen, ob eine höhere Anzahl dieser Lernhandlungen mit dem Lernerfolg zusammenhängt (Mediation) und welche Unterschiede sich in den Abfolgen der Lernhandlungen finden lassen. In der zweiten Analyse wurden die Effekte der einzelnen Prompts sowie die Bedingungen für ihre Wirksamkeit auf einer sehr detaillierten Ebene betrachtet. Zusätzlich zu Process Mining wurde auch eine Data Mining Methode eingesetzt, um deren Befunde zu vergleichen. Im Detail fanden eine Klassifikation der Prompts anhand ihrer Effektivität und eine Untersuchung der kodierten Lernaktivitäten vor und nach der Präsentation instruktionaler Hilfe statt. Schließlich untersuchte die dritte Analyse die langfristigen Effekte metakognitiver Prompts auf den Lernprozess in einer weiteren Lernsitzung ohne Unterstützung. Hier stand die Frage im Mittelpunkt, welche geförderten Lernaktivitäten und Prozessmuster während der zweiten Lernsitzung stabil blieben. Insgesamt belegen die Ergebnisse aller drei durchgeführten Analysen den Mehrwert von Process Mining im Vergleich zu reinen häufigkeitsbasierten Analysemethoden. Insbesondere unter Betrachtung des Lernprozesses als dynamische Abfolge von mehreren Lernhandlungen, ermöglicht Process Mining die Identifikation von Regulationsschleifen und zentralen Verzweigungen des Prozesses. Diese Befunde könnten zur Optimierung von Interventionen verwendet werden. Bevor aus den aufgedeckten Prozessmustern Schlussfolgerungen für die Gestaltung instruktionaler Hilfe gezogen werden können, müssen allerdings weitere Analysen erst noch die Generalisierbarkeit der Befunde belegen. Darüber hinaus bleibt die Anwendung von Process Mining herausfordernd, da derzeit keine Richtlinien für analytische Entscheidungen und Parametereinstellungen für technologieunterstützte Lernkontexte vorhanden sind. Darum müssen in Zukunft weitere Studien das Potential von Process Mining und verwandten Analysemethoden betrachten, um Forschern konkrete Anwendungsempfehlungen zur Verfügung stellen zu können. Generell kann Process Mining aber bereits jetzt dazu beitragen, das Verständnis der Auswirkungen instruktionaler Hilfe auf der Prozessebene voran zu treiben. KW - Selbstgesteuertes Lernen KW - Prozessanalyse KW - Process Mining KW - Metacognitive Prompting KW - Instructional Support KW - Technology-Enhanced Learning KW - Self-Regulated Learning KW - Metakognition KW - Lautes Denken Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152354 ER - TY - THES A1 - Slaby, Beate Magdalena T1 - Exploring the microbiome of the Mediterranean sponge \(Aplysina\) \(aerophoba\) by single-cell and metagenomics T1 - Untersuchungen am Mikrobiom des Mittelmeerschwamms \(Aplysina\) \(aerophoba\) mittels Einzelzell- und Metagenomik N2 - Sponges (phylum Porifera) are evolutionary ancient, sessile filter-feeders that harbor a largely diverse microbial community within their internal mesohyl matrix. Throughout this thesis project, I aimed at exploring the adaptations of these symbionts to life within their sponge host by sequencing and analyzing the genomes of a variety of bacteria from the microbiome of the Mediterranean sponge Aplysina aerophoba. Employed methods were fluorescence-activated cell sorting with subsequent multiple displacement amplification and single-cell / ‘mini-metagenome’ sequencing, and metagenomic sequencing followed by differential coverage binning. These two main approaches both aimed at obtaining genome sequences of bacterial symbionts of A. aerophoba, that were then compared to each other and to references from other environments, to gain information on adaptations to the host sponge environment and on possible interactions with the host and within the microbial community. Cyanobacteria are frequent members of the sponge microbial community. My ‘mini-metagenome’ sequencing project delivered three draft genomes of “Candidatus Synechococcus spongiarum,” the cyanobacterial symbiont of A. aerophoba and many more sponges inhabiting the photic zone. The most complete of these genomes was compared to other clades of this symbiont and to closely related free-living cyanobacterial references in a collaborative project published in Burgsdorf I*, Slaby BM* et al. (2015; *shared first authorship). Although the four clades of “Ca. Synechococcus spongiarum” from the four sponge species A. aerophoba, Ircinia variabilis, Theonella swinhoei, and Carteriospongia foliascens were approximately 99% identical on the level of 16S rRNA gene sequences, they greatly differed on the genomic level. Not only the genome sizes were different from clade to clade, but also the gene content and a number of features including proteins containing the eukaryotic-type domains leucine-rich repeats or tetratricopeptide repeats. On the other hand, the four clades shared a number of features such as ankyrin repeat domain-containing proteins that seemed to be conserved also among other microbial phyla in different sponge hosts and from different geographic locations. A possible novel mechanism for host phagocytosis evasion and phage resistance by means of an altered O antigen of the lipopolysaccharide was identified. To test previous hypotheses on adaptations of sponge-associated bacteria on a broader spectrum of the microbiome of A. aerophoba while also taking a step forward in methodology, I developed a bioinformatic pipeline to combine metagenomic Illumina short-read sequencing data with PacBio long-read data. At the beginning of this project, no pipelines to combine short-read and long-read data for metagenomics were published, and at time of writing, there are still no projects published with a comparable aim of un-targeted assembly, binning and analysis of a metagenome. I tried a variety of assembly programs and settings on a simulated test dataset reflecting the properties of the real metagenomic data. The developed assembly pipeline improved not only the overall assembly statistics, but also the quality of the binned genomes, which was evaluated by comparison to the originally published genome assemblies. The microbiome of A. aerophoba was studied from various angles in the recent years, but only genomes of the candidate phylum Poribacteria and the cyanobacterial sequences from my above-described project have been published to date. By applying my newly developed assembly pipeline to a metagenomic dataset of A. aerophoba consisting of a PacBio long-read dataset and six Illumina short-read datasets optimized for subsequent differential coverage binning, I aimed at sequencing a larger number and greater diversity of symbionts. The results of this project are currently in review by The ISME Journal. The complementation of Illumina short-read with PacBio long-read sequencing data for binning of this highly complex metagenome greatly improved the overall assembly statistics and improved the quality of the binned genomes. Thirty-seven genomes from 13 bacterial phyla and candidate phyla were binned representing the most prominent members of the microbiome of A. aerophoba. A statistical comparison revealed an enrichment of genes involved in restriction modification and toxin-antitoxin systems in most symbiont genomes over selected reference genomes. Both are defense features against incoming foreign DNA, which may be important for sponge symbionts due to the sponge’s filtration and phagocytosis activity that exposes the symbionts to high levels of free DNA. Also host colonization and matrix utilization features were significantly enriched. Due to the diversity of the binned symbiont genomes, a within-symbionts genome comparison was possible, that revealed three guilds of symbionts characterized by i) nutritional specialization on the metabolization of carnitine, ii) specialization on sulfated polysaccharides, and iii) apparent nutritional generalism. Both carnitine and sulfated polysaccharides are abundant in the sponge extracellular matrix and therefore available to the sponge symbionts as substrates. In summary, the genomes of the diverse community of symbionts in A. aerophoba were united in their defense features, but specialized regarding their nutritional preferences. N2 - Schwämme (Phylum Porifera) sind evolutionär alte, sessile Filtrierer, die eine äußerst vielfältige mikrobielle Gemeinschaft in ihrer internen Mesohylmatrix beherbergen. Das Ziel meiner Doktorarbeit war es, die Anpassungen dieser Symbionten an das Leben in ihrem Schwammwirt zu erforschen. Dazu habe ich die Genome einer Vielzahl von Bakterien aus dem Mikrobiom des Mittelmeer-Schwammes Aplysina aerophoba sequenziert und analysiert. Meine angewandten Methoden waren die fluoreszenzaktivierte Zellsortierung mit anschließender so genannter „multiple displacement amplification“ und Einzelzell- / „Mini-Metagenom“-Sequenzierung und metagenomischer Sequenzierung gefolgt von „differential coverage binning“. Diese beiden Ansätze zielten darauf ab, Genomsequenzen von bakteriellen Symbionten von A. aerophoba zu erhalten, die dann sowohl miteinander, als auch mit Referenzen aus anderen Habitaten verglichen wurden. So sollten Informationen gewonnen werden über Anpassungen an ein Leben im Wirtsschwamm und über mögliche Interaktionen mit dem Wirt und innerhalb der mikrobiellen Gemeinschaft. Cyanobakterien sind häufig Mitglieder der bakteriellen Gemeinschaft in Schwämmen. Mein "Mini-Metagenom"-Sequenzierprojekt lieferte drei Genom-Entwürfe von „Candidatus Synechococcus spongiarum,“ dem cyanobakteriellen Symbionten von A. aerophoba und vieler weiterer Schwämme, die die photische Zone bewohnen. Das vollständigste dieser Genome wurden mit anderen Kladen dieses Symbionten verglichen und mit nah verwandten, freien lebenden Cyanobakterien-Referenzen in Burgsdorf I *, Slaby BM * et al. (2015; * geteilte Erstautorenschaft). Obwohl die vier Kladen von „Ca. Synechococcus spongiarum“ aus den vier Schwammarten A. aerophoba, Ircinia variabilis, Theonella swinhoei und Carteriospongia foliascens auf der Ebene der 16S-rRNA-Gensequenzen zu etwa 99% identisch waren, unterschieden sie sich deutlich auf Genom-Ebene. Nicht nur die Genomgrößen waren von Klade zu Klade verschieden, sondern auch der Gengehalt und eine Reihe von Merkmalen, einschließlich Proteinen mit genannten „eukaryotic-like domains,“ leucinreiche „repeats“ oder Tetratricopeptid-„repeats“. Auf der anderen Seite teilten die vier Kladen eine Reihe von Merkmalen wie Ankyrin-„repeat“-Domänen-haltige Proteine, die auch in anderen Phyla von Schwammsymbionten in verschiedenen Wirtsschwämmen und aus verschiedenen geografischen Orten konserviert zu sein schienen. Ein möglicher neuartiger Mechanismus zur Phagozytose-Vermeidung und zur Phagenresistenz mittels eines veränderten O-Antigens des Lipopolysaccharids wurde identifiziert. Um vorherige Hypothesen über die Anpassung von Schwamm-assoziierten Bakterien auf ein breiteres Spektrum des Mikrobioms von A. aerophoba zu testen und gleichzeitig in der Methodik voran zu schreiten, entwickelte ich einen bioinformatischen Arbeitsablauf, um metagenomische Illumina-„short-read“-Sequenzdaten mit PacBio-„long-reads“ zu kombinieren. Zu Beginn dieses Projektes gab es keine veröffentlichte Methodik zur Verknüpfung von „short-reads“ und „long-reads“ für die Metagenomik, und auch jetzt gibt es keine veröffentlichten Projekte mit einem vergleichbaren Ziel von nicht-gezieltem „Assembly“, „Binning“ und Analyse eines Metagenoms. Ich habe eine Auswahl von „Assembly“-Programmen und Einstellungen auf einem simulierten Testdatensatz getestet, der die Eigenschaften der realen metagenomischen Daten widerspiegelt. Die entwickelte „Assembly“-Methode verbesserte nicht nur die Gesamtstatistik, sondern auch die Qualität der einzelnen, „gebinnten“ Genome, die durch Vergleich zu den ursprünglich veröffentlichten Genom-Sequenzen evaluiert wurde. Das Mikrobiom von A. aerophoba wurde in den letzten Jahren aus verschiedenen Blickwinkeln untersucht, aber nur Genome des Candidatus-Phylum Poribakterien und die Cyanobakteriensequenzen aus meinem oben beschriebenen Projekt wurden bisher veröffentlicht. Durch die Anwendung meiner neu entwickelten „Assembly“-Methodik auf einen metagenomischen Datensatz von A. aerophoba bestehend aus einem PacBio-„long-read“-Datensatz und sechs Illumina-„short-read“-Datensätzen, die für das anschließende „differential coverage binning“ optimiert waren, zielte ich darauf ab, eine größere Anzahl und Vielfalt von Symbionten zu sequenzieren. Die Ergebnisse dieses Projektes sind derzeit bei The ISME Journal in Review. Die Komplementierung von Illumina „short-read“ mit PacBio „long-read“-Sequenzdaten für das „binning“ dieses hochkomplexen Metagenoms hat die Gesamt-„assembly“-Statistik sowie die Qualität der „gebinnten“ Genome deutlich verbessert. Siebenunddreißig Genome aus 13 Bakterienphyla und Candidatus-Phyla wurden „gebinnt“, die die prominentesten Mitglieder des Mikrobioms von A. aerophoba darstellten. Ein statistischer Vergleich zeigte eine Anreicherung von Genen, die mit Restriktionsmodifikationen und Toxin-Antitoxin-Systemen zusammenhängen, in den meisten Symbionten-Genomen im Vergleich zu ausgewählten Referenzgenomen. Beides sind Mechanismen zur Verteidigung gegen eindringende Fremd-DNA, die für Schwamm-Symbionten aufgrund der Schwamm-Filtration und Phagozytose-Aktivität wichtig sein können, die die Symbionten hohen Konzentrationen von freier DNA aussetzen. Auch mögliche Wirtskolonisations- und Matrixnutzungsmechanismen waren signifikant angereichert. Wegen der Vielfalt der „gebinnten“ Symbionten-Genome war ein Genom-Vergleich innerhalb der Symbionten möglich, der drei Gilden von Symbionten zum Vorschein brachte, die gekennzeichnet waren durch i) Ernährungsspezialisierung auf die Metabolisierung von Carnitin, ii) Spezialisierung auf sulfatierte Polysaccharide und iii) scheinbaren Nahrungs-Generalismus. Sowohl Carnitin als auch sulfatierte Polysaccharide sind in der extrazellulären Schwammmatrix reichlich vorhanden und stehen so den Schwammsymbionten als Substrat zur Verfügung. Die Genome der diversen Symbionten-Gemeinschaft in A. aerophoba waren in ihren Verteidigungsmechanismen vereint, aber spezialisiert hinsichtlich ihrer Ernährung. KW - Metagenom KW - metagenomics KW - single-cell genomics KW - sponge microbiome KW - differential coverage binning KW - PacBio sequencing KW - Illumina HiSeq KW - hybrid assembly KW - Aplysina aerophoba KW - Mikroorganismus Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151869 ER - TY - JOUR A1 - Shityakov, Sergey A1 - Roewer, Norbert A1 - Förster, Carola A1 - Broscheit, Jens-Albert T1 - In silico modeling of indigo and Tyrian purple single-electron nano-transistors using density functional theory approach JF - Nanoscale Research Letters N2 - The purpose of this study was to develop and implement an in silico model of indigoid-based single-electron transistor (SET) nanodevices, which consist of indigoid molecules from natural dye weakly coupled to gold electrodes that function in a Coulomb blockade regime. The electronic properties of the indigoid molecules were investigated using the optimized density-functional theory (DFT) with a continuum model. Higher electron transport characteristics were determined for Tyrian purple, consistent with experimentally derived data. Overall, these results can be used to correctly predict and emphasize the electron transport functions of organic SETs, demonstrating their potential for sustainable nanoelectronics comprising the biodegradable and biocompatible materials. KW - density functional theory KW - indigo KW - Tyrian purple KW - single-electron transistor Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158332 VL - 12 IS - 439 ER - TY - THES A1 - Lang, Jean-Nicolas Olivier T1 - Automation of electroweak NLO corrections in general models T1 - Automatisierung von elektroschwachen NLO Korrekturen in allgemeinen Modellen N2 - The thesis deals with the automated generation and efficient evaluation of scattering amplitudes in general relativistic quantum field theories at one-loop order in perturbation theory. At the present time we lack signals beyond the Standard Model which, in the past, have guided the high-energy physics community, and ultimately led to the discovery of new physics phenomena. In the future, precision tests could acquire this guiding role by systematically probing the Standard Model and constraining Beyond the Standard Model theories. As current experimental constraints strongly favour Standard Model-like theories, only small deviations with respect to the Standard Model are expected which need to be studied in detail. The required precision demands one-loop corrections in all future analyses, ideally in a fully automated way, allowing to test a variety of observables in different models and in an effective field theory approach. In the process of achieving this goal we have developed an enhanced version of the tool Recola and on this basis the generalization Recola2. These tools represent fully automated tree- and one-loop-amplitude providers for the Standard Model, or in the case of Recola2 for general models. Concerning the algorithm, we use a purely numerical and fully recursive approach allowing for extreme calculations of yet unmatched complexity. Recola has led to the first computation involving 9-point functions. Beyond the Standard Model theories and Effective Field theories are integrated into the Recola2 framework as model files. Renormalized model files are produced with the newly developed tool Rept1l, which can perform the renormalization in a fully automated way, starting from nothing but Feynman rules. In view of validation, we have extended Recola2 to new gauges such as the Background-Field Method and the class of Rxi gauges. In particular, the Background-Field Method formulation for new theories serves as an automated validation, and is very useful in practical calculations and the formulation of renormalization conditions. We have applied the system to produce the first results for Higgs-boson production in Higgs strahlung and vector-boson fusion in the Two-Higgs-Doublet Model and the Higgs-Singlet Extension of the Standard Model. All in all, we have laid the foundation for an automated generation and computation of one-loop amplitudes within a large class of phenomenologically interesting theories. Furthermore, we enable the use of our system via a very flexible and dynamic control which does not require any intermediate intervention. N2 - In dieser Arbeit behandeln wir die automatisierte Generierung und effiziente Auswertung von Streuamplituden in allgemeinen relativistischen Quantenfeldtheorien auf Einschleifen-Niveau. Gegenwärtig gibt es keine konkreten Hinweise auf Physik jenseits des Standard Models und daher auch keine Möglichkeit, gezielt nach neuer Physik in Teilchenbeschleuniger-Experimenten zu suchen. In der Zukunft könnten Präzisionstests eine richtungsweisende Rolle übernehmen und Aufschluss über Abweichungen zum Standard Model geben, und dabei möglicherweise erlauben, indirekt auf neue Physik zu schließen. Nach dem derzeitigen experimentellen Stand werden Standard-Model-artige Theorien deutlich bevorzugt. Infolgedessen werden nur kleine Abweichungen zum Standard Model erwartet, die mit hoher Präzision untersucht werden müssen. Auf der theoretischen Seite erfordert die nötige Präzision die Berechnung von Einschleifen-Korrekturen in allen zukünftigen Analysen, die, idealerweise, vollautomatisiert durchgeführt werden, um alle grundsätzlich zugänglichen Observablen in verschiedensten Theorien testen zu können. Um dieses Ziel schrittweise zu erreichen, haben wir das Programm Recola weiterentwickelt, und auf dieser Basis die Verallgemeinerung Recola2 entwickelt. Die Programme erlauben eine vollautomatisierte Erzeugung und Auswertung von Baumgraphen- und Einschleifen-Amplituden für das Standard Model, beziehungsweise, im Falle von Recola2, für allgemeine Theorien. Der zugrundeliegende numerische Algorithmus arbeitet vollständig rekursiv und erlaubt die Berechnung von Prozessen mit bislang unerreichter Komplexität. Beispielsweise hat Recola zur ersten Berechnung mit 9-Punkt Funktionen geführt. In Recola2 werden neue Theorien durch spezifische Recola2 Modelfiles in das System integriert. Die Renormierung wird mit dem neu entwickelten Programm Reptil vollautomatisch durchgeführt, wobei lediglich die Feynman Regeln als externe Abhängigkeit benötigt werden. Zur Validierung des Systems wurden zum einen Vergleiche mit unabhängigen Rechnungen durchgeführt, und zum anderen Recola2 soweit verallgemeinert, dass dessen Konsistenz in verschiedenen Eichungen getestet werden kann. Besonders die Background-Field Formulierung erlaubt es neue Theorien automatisch zu validieren und ist darüberhinaus sehr nützlich für praktische Rechnungen, sowie für die Formulierung von Renormierungsbedingungen. Mit diesem System haben wir die ersten Berechnungen zur Higgs-Boson-Produktion in Higgs-Strahlung und Vektor-Boson-Fusion im Zwei-Higgs-Doublet Model und der Higgs-Singlet Erweiterung des Standard Models durchgeführt. Alles in allem wurden die Voraussetzungen geschaffen, Einschleifen-Amplituden in einer großen Klasse von phänomenologisch interessanten Theorien automatisiert erzeugen zu können. Darüberhinaus ermöglichen wir die Nutzung für andere durch eine sehr flexible und dynamische Bedienung, die keinerlei Zwischenschritte benötigt. KW - Standardmodell KW - Feynman diagrams KW - One-loop corrections KW - Beyond the Standard Model KW - Atomphysik KW - Molekularphysik KW - Kernphysik KW - Elementarteilchen Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154426 ER - TY - THES A1 - Faist, Hanna T1 - Bedeutung und Charakterisierung der bakteriellen Flora in Vitis vinifera mit und ohne Wurzelhalsgallen T1 - Significance and characterization of the bacterial community in Vitis vinifera with and without crown galls N2 - Am Rebstock werden in der Natur von Agrobacterium vitis, dem Auslöser Wurzelhalsgallenerkrankung, charakteristische Wurzelhalsgallentumore induziert. Virulente Vertreter der Gattung der Agrobacteria schleusen bakterielle DNA in das pflanzliche Genom ein, wodurch die Pflanze Tumore produziert. Die Wurzelhalsgallenerkrankung wird seit einem Jahrhundert als ein Beispiel der Pflanzen-Pathogen-Interaktion untersucht. Die Rolle der bakteriellen Flora im Zusammenhang mit der Wurzelhalsgallenerkrankung beim Rebstock wurde bisher kaum betrachtet. Um dieser Frage nachzugehen, habe ich die endophytische mikrobielle Zusammensetzung von Rebstöcken mit und ohne Wurzelhalsgalle analysiert. Es werden Proben von drei Zeitpunkten einer Wachstumsperiode (Frühling, Sommer und Herbst) und von den Organen der Rebstöcke (Wurzeln, Pfropfstelle und einjährige Triebe) sowie dem Boden in einer Weinanlage bei Himmelstadt in Unterfranken genommen. Die Bakterienflora dieser Umweltproben wird mit kultivierungsabhängigen (Isolierung von Bakterien) und kultivierungsunabhängigen (Hochdurchsatzsequenzierungen) Methoden untersucht. Zudem werden i) die Virulenz der verschiedenen Agrobacterium-Isolate in Tumorassays bestimmt, ii) synthetische Bakteriengemeinschaften von in vitro kultivierten Weinpflänzchen mit Wurzelhalsgallen analysiert, iii) die Genome von einem virulenten und einem nicht-virulenten Agrobacteria-Isolat aus der Wurzelhalsgalle verglichen, iv) erste Interaktionsstudien auf festen Nährmedien durchgeführt und v) virulente Agrobacteria mittels bildgebender Fluoreszenz-Lebenszeit-Mikroskopie (FLIM) in Wurzelhalsgallen lokalisiert. Die Rebstöcke dieser Studie haben eine organspezifische Bakterienflora, die innerhalb einer Wachstumsperiode variiert. Nur die Bakterienflora der Pfropfstelle (mit oder ohne Wurzelhalsgalle) aber nicht die des Bodens, der Wurzeln, und der einjährigen Triebe unterscheidet sich strukturell zwischen gesunden und erkrankten Rebstöcken. Mikroskopisch konnten virulente Agrobacteria punktuell in Interzellularen, sklerenchymatischen Geweben und assoziiert mit Leitgefäßen nachgewiesen werden. Dadurch ist ausreichend Lebensraum vorhanden, der zusätzlich von tumorspezifischen Bakterien besiedelt werden kann. Im Gegensatz zur gesunden Pfropfstelle ist in der Wurzelhalsgalle eine saisonal stabile Kernmikroflora, bestehend aus Vertreter von A. vitis, Pseudomonas, Enterobacteriaceae, Agrobacterium tumefaciens, Gammaproteobacteria und Burkholderiales, vorhanden. Diese Bakterien werden überwiegend aus dem Boden rekrutiert und profitieren von der Nährstoffsituation in der Wurzelhalsgalle. Wurzelhalsgallen enthalten Opine, die nur von der transformierten Pflanzenzelle produziert werden. Interessanterweise hat in dieser Arbeit ein Agrobacterium-Isolat Gene, die zum Opinkatabolismus beitragen und ein Pseudomonas-Isolat kann Opine als einzige Kohlenstoffquelle nutzen. Trotzdem sind beide Isolate weder virulent noch verdrängen sie die virulenten A. vitis, die ebenso Opine nutzen, aus der Wurzelhalsgalle. In synthetischen Bakteriengemeinschaften an in vitro kultivierten Weinpflänzchen konnte gezeigt werden, dass diese und weitere tumorspezifischen Bakterien, neben A. vitis, nicht essentiell zur Entstehung der Wurzelhalsgalle nötig sind aber unterschiedliche Funktionen in der Wurzelhalsgalle übernehmen. Ein Serratia-Isolat hemmt das Wachstum von A. vitis auf festen Nährmedium, andere fördern oder hemmen das Wachstum der Wurzelhalsgalle. Nach Studien in der Literatur erhöhen weitere Bakterien die Resistenz des Rebstocks gegenüber biotischem und abiotischem Stress. Zusammengefasst identifizierten und isolierte ich in dieser Studie unter 150 unterschiedlichen Bakterien in der Wurzelhalsgalle jene Bakterien, die neben A. vitis von der neuen ökologischen Nische profitieren und somit wahrscheinlich Opportunisten mit unterschiedlichen Funktionen sind. In Folge von multiplen Interaktionen in der Wurzelhalsgalle entsteht ein ökologisches Gleichgewicht zwischen den opportunistischen Bakterien, der Wurzelhalsgalle und dem Rebstock, das den Fortbestand des Rebstocks mit Wurzelhalsgalle ermöglicht. N2 - In nature, Agrobacterium vitis is known for the ability to introduce bacterial DNA into the grapevine genome, thereby causing crown gall disease. This plant disease has been studied for a century as a model for plant-pathogen interaction, while the role of the plant microbiota in disease development is not well understood. My study contributes to the understanding of the microbial ecology in crown galls of grapevine, combining culture-dependent with culture-independent high-throughput sequencing techniques. I analysed the structure of the endophytic microbiota by collecting different samples (soil, roots, graft unions and canes) of diseased and non-diseased grapevines from one vine-yard in Franconia, Bavaria, Germany during one growing season (spring, summer, autumn). The characterization of the grapevine-associated bacterial microbiota was completed by (i) detecting the virulence of diverse agrobacterial isolates using a tumour growth assay with in vitro cultivated grapevine plantlets, (ii) microbial analysis of synthetic communities of in vitro cultivated grapevine plantlets with crown galls, (iii) genome sequencing of a virulent and a non-virulent agrobacterial isolate, (iv) in vitro interaction studies on solid medium with bacterial isolates and (v) localisation of virulent A. vitis using Fluorescence Lifetime Imaging Microscopy (FLIM) in tumour tissues. Grapevine plants of this study have an organ-specific bacterial community that varies during one growing season. Healthy and diseased grapevine plants differed in the struc-ture of the bacterial community only in the graft union (with or without a crown gall), but not in the soil, root and one-year old cane. Microscopy revealed that virulent Agrobacteria mainly accumulate in defined spots of sclerenchymatous tissue, intercellular space and tissues associated with vessels. Therefore, there is unoccupied living space in a crown gall, which can be additionally colonized by tumour-specific bacteria. A season-independent stable core bacteria exists in grapevine crown galls in contrast to healthy graft unions, consisting of OTUs assigned to A. vitis, Pseudomonas, Enterobacteriaceae, Agrobacterium tumefaciens, Gammaproteobacteria and Burkholderiales. These bacteria are predominantly recruited from the soil and most likely profit from special nutrients in the crown gall. The crown gall contains opines, exclusively produced by transformed plant cells. Curiously individual isolates of Agrobacteria and Pseudo-monas of this study that are non-virulent do not outcompete virulent A. vitis in the crown gall but harbour, like A. vitis, genes involved in octopin-catabolism or use opines in liquid cultures as a sole nutrient source. Although synthetic bacterial communities revealed that the tumour-specific bacteria are not required for crown gall induction us-ing in vitro grown grapevine plantlets, they may have different functions in crown gall persistence. A Serratia-isolate inhibits the growth of A. vitis on solid medium, others reduce or support crown gall development, while some, according to literature, increase resistance of the grapevine plant against biotic and abiotic stresses. Taken together, among the 150 bacteria found in the crown galls, I identified and isolated bacteria in addition to A. vitis that profit from the new ecological niche suggesting an opportunistic lifestyle with different ecological functions. An ecological equilibrium in a bacterial community that balances crown gall growth will support the existence of grapevine plants with a crown gall in vineyards. KW - Wurzelhalsgalle KW - DNA Barcoding KW - Agrobacterium vitis KW - Weinrebe KW - Angewandte Mikrobiologie KW - bakterielle Flora KW - Holobiont KW - Mikrobiota Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154359 ER - TY - JOUR A1 - Krstic, Jelena A1 - Herrmann, Marietta A1 - Gadjanski, Ivana A1 - Mojsilovic, Slavko T1 - Editorial: Microenvironment-derived stem cell plasticity JF - Frontiers in Cell and Developmental Biology N2 - No abstract available. KW - plasticity KW - stem cells KW - microenvironment KW - imaging KW - extracellular vesicles (EVs) KW - oxygen tension KW - tissue regeneration KW - immunomodulation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197424 SN - 2296-634X VL - 5 ER - TY - JOUR T1 - Studies of \(Zγ\) production in association with a high-mass dijet system in \(pp\) collisions at \(\sqrt{s}\) = 8 TeV with the ATLAS detector JF - Journal of High Energy Physics N2 - The production of a \(Z\) boson and a photon in association with a high-mass dijet system is studied using 20.2 fb\(^{−1}\) of proton-proton collision data at a centre-of-mass energy of \(\sqrt{s}\) = 8 TeV recorded with the ATLAS detector in 2012 at the Large Hadron Collider. Final states with a photon and a Z boson decaying into a pair of either electrons, muons, or neutrinos are analysed. Electroweak and total \(pp\) → \(Zγjj\) cross-sections are extracted in two fiducial regions with different sensitivities to electroweak production processes. Quartic couplings of vector bosons are studied in regions of phase space with an enhanced contribution from pure electroweak production, sensitive to vector-boson scattering processes \(V V → Zγ\). No deviations from Standard Model predictions are observed and constraints are placed on anomalous couplings parameterized by higher-dimensional operators using effective field theory. KW - High energy physics KW - Electroweak interaction KW - Hadron-Hadron scattering (experiments) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173229 VL - 2017 IS - 07 ER - TY - JOUR A1 - Rodrigues, Johannes A1 - Ulrich, Natalie A1 - Mussel, Patrick A1 - Carlo, Gustavo A1 - Hewig, Johannes T1 - Measuring prosocial tendencies in Germany: sources of validity and reliablity of the revised prosocial tendency measure JF - Frontiers in Psychology N2 - The prosocial tendencies measure (PTM; Carlo and Randall, 2002) is a widely used measurement for prosocial tendencies in English speaking participants. This instrument distinguishes between six different types of prosocial tendencies that partly share some common basis, but also can be opposed to each other. To examine these constructs in Germany, a study with 1067 participants was conducted. The study investigated the structure of this German version of the PTM-R via exploratory factor analysis, confirmatory factor analysis, correlations with similar constructs in subsamples as well as via measurement invariance test concerning the original English version. The German translation showed a similar factor structure to the English version in exploratory factor analysis and in confirmatory factor analysis. Measurement invariance was found between the English and German language versions of the PTM and support for the proposed six-factor structure (altruistic, anonymous, compliant, dire, emotional and public prosocial behavior) was also found in confirmatory factor analysis. Furthermore, the expected interrelations of these factors of prosocial behavior tendencies were obtained. Finally, correlations of the prosocial behavior tendencies with validating constructs and behaviors were found. Thus, the findings stress the importance of seeing prosocial behavior not as a single dimension construct, but as a factored construct which now can also be assessed in German speaking participants. KW - measurement invariance KW - prosocial tendency measure KW - prosocial behavior KW - altruism KW - validation KW - German translation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159351 VL - 8 ER - TY - JOUR A1 - Radu, Laura A1 - Schoenwetter, Elisabeth A1 - Braun, Cathy A1 - Marcoux, Julien A1 - Koelmel, Wolfgang A1 - Schmitt, Dominik R. A1 - Kuper, Jochen A1 - Cianférani, Sarah A1 - Egly, Jean M. A1 - Poterszman, Arnaud A1 - Kisker, Caroline T1 - The intricate network between the p34 and p44 subunits is central to the activity of the transcription/DNA repair factor TFIIH JF - Nucleic Acids Research N2 - The general transcription factor IIH (TFIIH) is a multi-protein complex and its 10 subunits are engaged in an intricate protein–protein interaction network critical for the regulation of its transcription and DNA repair activities that are so far little understood on a molecular level. In this study, we focused on the p44 and the p34 subunits, which are central for the structural integrity of core-TFIIH. We solved crystal structures of a complex formed by the p34 N-terminal vWA and p44 C-terminal zinc binding domains from Chaetomium thermophilum and from Homo sapiens. Intriguingly, our functional analyses clearly revealed the presence of a second interface located in the C-terminal zinc binding region of p34, which can rescue a disrupted interaction between the p34 vWA and the p44 RING domain. In addition, we demonstrate that the C-terminal zinc binding domain of p34 assumes a central role with respect to the stability and function of TFIIH. Our data reveal a redundant interaction network within core-TFIIH, which may serve to minimize the susceptibility to mutational impairment. This provides first insights why so far no mutations in the p34 or p44 TFIIH-core subunits have been identified that would lead to the hallmark nucleotide excision repair syndromes xeroderma pigmentosum or trichothiodystrophy. KW - general transcription factor IIH (TFIIH) KW - DNA repair KW - protein–protein interaction KW - p44 KW - p34 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170173 VL - 45 IS - 18 ER - TY - JOUR A1 - Mitjans, M. A1 - Begemann, M. A1 - Ju, A. A1 - Dere, E. A1 - Wüstefeld, L. A1 - Hofer, S. A1 - Hassouna, I. A1 - Balkenhol, J. A1 - Oliveira, B. A1 - Van der Auwera, S. A1 - Tammer, R. A1 - Hammerschmidt, K. A1 - Völzke, H. A1 - Homuth, G. A1 - Cecconi, F. A1 - Chowdhury, K. A1 - Grabe, H. A1 - Frahm, J. A1 - Boretius, S. A1 - Dandekar, T. A1 - Ehrenreich, H. T1 - Sexual dimorphism of \(AMBRA1\)-related autistic features in human and mouse JF - Translational Psychiatry N2 - \(Ambra1\) is linked to autophagy and neurodevelopment. Heterozygous \(Ambra1\) deficiency induces autism-like behavior in a sexually dimorphic manner. Extraordinarily, autistic features are seen in female mice only, combined with stronger Ambra1 protein reduction in brain compared to males. However, significance of \(AMBRA1\) for autistic phenotypes in humans and, apart from behavior, for other autism-typical features, namely early brain enlargement or increased seizure propensity, has remained unexplored. Here we show in two independent human samples that a single normal \(AMBRA1\) genotype, the intronic SNP rs3802890-AA, is associated with autistic features in women, who also display lower \(AMBRA1\) mRNA expression in peripheral blood mononuclear cells relative to female GG carriers. Located within a non-coding RNA, likely relevant for mRNA and protein interaction, rs3802890 (A versus G allele) may affect its stability through modification of folding, as predicted by \(in\) \(silico\) analysis. Searching for further autism-relevant characteristics in \(Ambra1^{+/−}\) mice, we observe reduced interest of female but not male mutants regarding pheromone signals of the respective other gender in the social intellicage set-up. Moreover, altered pentylentetrazol-induced seizure propensity, an \(in\) \(vivo\) readout of neuronal excitation–inhibition dysbalance, becomes obvious exclusively in female mutants. Magnetic resonance imaging reveals mild prepubertal brain enlargement in both genders, uncoupling enhanced brain dimensions from the primarily female expression of all other autistic phenotypes investigated here. These data support a role of \(AMBRA1/Ambra1\) partial loss-of-function genotypes for female autistic traits. Moreover, they suggest \(Ambra1\) heterozygous mice as a novel multifaceted and construct-valid genetic mouse model for female autism. KW - biology KW - clinical genetics KW - molecular neuroscience Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173782 VL - 2017 IS - 7 ER - TY - JOUR A1 - Haunert, Jan-Henrik A1 - Wolff, Alexander T1 - Beyond maximum independent set: an extended integer programming formulation for point labeling JF - ISPRS International Journal of Geo-Information N2 - Map labeling is a classical problem of cartography that has frequently been approached by combinatorial optimization. Given a set of features in a map and for each feature a set of label candidates, a common problem is to select an independent set of labels (that is, a labeling without label–label intersections) that contains as many labels as possible and at most one label for each feature. To obtain solutions of high cartographic quality, the labels can be weighted and one can maximize the total weight (rather than the number) of the selected labels. We argue, however, that when maximizing the weight of the labeling, the influences of labels on other labels are insufficiently addressed. Furthermore, in a maximum-weight labeling, the labels tend to be densely packed and thus the map background can be occluded too much. We propose extensions of an existing model to overcome these limitations. Since even without our extensions the problem is NP-hard, we cannot hope for an efficient exact algorithm for the problem. Therefore, we present a formalization of our model as an integer linear program (ILP). This allows us to compute optimal solutions in reasonable time, which we demonstrate both for randomly generated point sets and an existing data set of cities. Moreover, a relaxation of our ILP allows for a simple and efficient heuristic, which yielded near-optimal solutions for our instances. KW - integer linear programming KW - cartographic requirements KW - map labeling KW - point-feature label placement KW - NP-hard Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158960 VL - 6 IS - 11 ER - TY - THES A1 - Fischbach, Martin Walter T1 - Enhancing Software Quality of Multimodal Interactive Systems T1 - Verbesserung der Softwarequalität multimodaler interaktiver Systeme N2 - Multimodal interfaces (MMIs) are a promising human-computer interaction paradigm. They are feasible for a wide rang of environments, yet they are especially suited if interactions are spatially and temporally grounded with an environment in which the user is (physically) situated. Real-time interactive systems (RISs) are technical realizations for situated interaction environments, originating from application areas like virtual reality, mixed reality, human-robot interaction, and computer games. RISs include various dedicated processing-, simulation-, and rendering subsystems which collectively maintain a real-time simulation of a coherent application state. They thus fulfil the complex functional requirements of their application areas. Two contradicting principles determine the architecture of RISs: coupling and cohesion. On the one hand, RIS subsystems commonly use specific data structures for multiple purposes to guarantee performance and rely on close semantic and temporal coupling between each other to maintain consistency. This coupling is exacerbated if the integration of artificial intelligence (AI) methods is necessary, such as for realizing MMIs. On the other hand, software qualities like reusability and modifiability call for a decoupling of subsystems and architectural elements with single well-defined purposes, i.e., high cohesion. Systems predominantly favour performance and consistency over reusability and modifiability to handle this contradiction. They thus accept low maintainability in general and hindered scientific progress in the long-term. This thesis presents six semantics-based techniques that extend the established entity-component system (ECS) pattern and pose a solution to this contradiction without sacrificing maintainability: semantic grounding, a semantic entity-component state, grounded actions, semantic queries, code from semantics, and decoupling by semantics. The extension solves the ECS pattern's runtime type deficit, improves component granularity, facilitates access to entity properties outside a subsystem's component association, incorporates a concept to semantically describe behavior as complement to the state representation, and enables compatibility even between RISs. The presented reference implementation Simulator X validates the feasibility of the six techniques and may be (re)used by other researchers due to its availability under an open-source licence. It includes a repertoire of common multimodal input processing steps that showcase the particular adequacy of the six techniques for such processing. The repertoire adds up to the integrated multimodal processing framework miPro, making Simulator X a RIS platform with explicit MMI support. The six semantics-based techniques as well as the reference implementation are validated by four expert reviews, multiple proof of concept prototypes, and two explorative studies. Informal insights gathered throughout the design and development supplement this assessment in the form of lessons learned meant to aid future development in the area. N2 - Multimodale Schnittstellen sind ein vielversprechendes Paradigma der Mensch-Computer-Interaktion. Sie sind in einer Vielzahl von Umgebungen einsetzbar und eignen sich besonders wenn Interaktionen zeitlich und räumlich mit einer Umgebung verankert sind in welcher der Benutzer (physikalisch) situiert ist. Interaktive Echtzeitsysteme (engl. Real-time Interactive Systems, RIS) sind technische Umsetzungen situierter Interaktionsumgebungen, die vor allem in Anwendungsgebieten wie der virtuellen Realität, der gemischten Realität, der Mensch-Roboter-Interaktion und im Bereich der Computerspiele eingesetzt werden. Interaktive Echtzeitsysteme bestehen aus vielfältigen dedizierten Subsystemen, die zusammen die Echtzeitsimulation eines kohärenten Anwendungszustands aufrecht erhalten und die komplexen funktionalen Anforderungen des Anwendungsgebiets erfüllen. Zwei gegensätzliche Prinzipien bestimmen die Softwarearchitekturen interaktiver Echtzeitsysteme: Kopplung und Kohäsion. Einerseits verwenden Subsysteme typischerweise spezialisierte Datenstrukturen um Performanzanforderungen gerecht zu werden. Um Konsistenz aufrecht zu erhalten sind sie zudem auf enge zeitliche- und semantische Abhängigkeiten untereinander angewiesen. Diese enge Kopplung wird verstärkt, falls Methoden der künstlichen Intelligenz in das RIS integriert werden müssen, wie es für die Umsetzung multimodaler Schnittstellen der Fall ist. Andererseits bedingen Softwarequalitätsmerkmale wie Wiederverwendbarkeit und Modifizierbarkeit die Entkopplung von Subsystemen und Architekturelementen und fordern hohe Kohäsion. Bestehende Systeme lösen diesen Konflikt überwiegend zu Gunsten von Performanz und Konsistenz und zu Lasten von Wiederverwendbarkeit und Modifizierbarkeit. Insgesamt wird auf diese Weise geringe Wartbarkeit akzeptiert und auf lange Sicht der wissenschaftliche Fortschritt eingeschränkt. Diese Arbeit stellt sechs Softwaretechniken auf Basis von Methoden der Wissensrepräsentation vor, welche das etablierte Entity-Component System (ECS) Entwurfsmuster erweitern und eine Lösung des Konflikts darstellen, die die Wartbarkeit nicht missachtet: semantic grounding, semantic entity-component state, grounded actions, semantic queries, code from semantics und decoupling by semantics. Diese Erweiterung löst das Introspektionsdefizit des ECS-Musters, verbessert die Granularität von ECS-Komponenten, erleichtert den Zugriff auf Entity-Eigenschaften außerhalb der Subsystem-Komponentenzuordnung, beinhaltet ein Konzept zur einheitlichen Beschreibung von Verhalten als Komplement zur Zustandsrepräsentation und ermöglicht sogar Kompatibilität zwischen interaktiven Echtzeitsystemen. Die vorgestellte Referenzimplementierung Simulator X weist die technische Machbarkeit der sechs Softwaretechniken nach. Sie kann von anderen Forschern auf Basis einer Open-Source Lizenz (wieder)verwendet werden und beinhaltet ein Repertoire an üblichen Verarbeitungsschritten für multimodalen Eingaben, welche die besondere Eignung der sechs Softwaretechniken für eine solche Eingabeverarbeitung veranschaulichen. Dieses Repertoire bildet zusammen das integrierte multimodale Eingabeverarbeitungs-Framework miPro und macht damit Simulator X zu einem RIS, welches explizit die Umsetzung von multimodalen Schnittstellen unterstützt. Die sechs Softwaretechniken sowie die Referenzimplementierung sind durch vier Expertengutachten, eine Vielzahl an technischen Demonstrationen sowie durch zwei explorative Studien validiert. Informelle Erkenntnisse, die während Design und Entwicklung gesammelt wurden, ergänzen diese Beurteilung in Form von lessons learned, welche bei künftigen Entwicklungsarbeiten in diesem Gebiet helfen sollen. KW - Echtzeitsystem KW - Framework KW - Ontologie KW - Multimodales System KW - Intelligent Real-time Interactive System KW - Virtual Reality KW - Mixed Reality KW - Multimodal System KW - Software Quality KW - Software Architecture KW - Multimodal Processing KW - Virtuelle Realität KW - Software Engineering Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152723 ER - TY - THES A1 - Spinner, Simon T1 - Self-Aware Resource Management in Virtualized Data Centers T1 - Selbstwahrnehmende Ressourcenverwaltung in virtualisierten Rechenzentren N2 - Enterprise applications in virtualized data centers are often subject to time-varying workloads, i.e., the load intensity and request mix change over time, due to seasonal patterns and trends, or unpredictable bursts in user requests. Varying workloads result in frequently changing resource demands to the underlying hardware infrastructure. Virtualization technologies enable sharing and on-demand allocation of hardware resources between multiple applications. In this context, the resource allocations to virtualized applications should be continuously adapted in an elastic fashion, so that "at each point in time the available resources match the current demand as closely as possible" (Herbst el al., 2013). Autonomic approaches to resource management promise significant increases in resource efficiency while avoiding violations of performance and availability requirements during peak workloads. Traditional approaches for autonomic resource management use threshold-based rules (e.g., Amazon EC2) that execute pre-defined reconfiguration actions when a metric reaches a certain threshold (e.g., high resource utilization or load imbalance). However, many business-critical applications are subject to Service-Level-Objectives defined on an application performance metric (e.g., response time or throughput). To determine thresholds so that the end-to-end application SLO is fulfilled poses a major challenge due to the complex relationship between the resource allocation to an application and the application performance. Furthermore, threshold-based approaches are inherently prone to an oscillating behavior resulting in unnecessary reconfigurations. In order to overcome the deficiencies of threshold-based approaches and enable a fully automated approach to dynamically control the resource allocations of virtualized applications, model-based approaches are required that can predict the impact of a reconfiguration on the application performance in advance. However, existing model-based approaches are severely limited in their learning capabilities. They either require complete performance models of the application as input, or use a pre-identified model structure and only learn certain model parameters from empirical data at run-time. The former requires high manual efforts and deep system knowledge to create the performance models. The latter does not provide the flexibility to capture the specifics of complex and heterogeneous system architectures. This thesis presents a self-aware approach to the resource management in virtualized data centers. In this context, self-aware means that it automatically learns performance models of the application and the virtualized infrastructure and reasons based on these models to autonomically adapt the resource allocations in accordance with given application SLOs. Learning a performance model requires the extraction of the model structure representing the system architecture as well as the estimation of model parameters, such as resource demands. The estimation of resource demands is a key challenge as they cannot be observed directly in most systems. The major scientific contributions of this thesis are: - A reference architecture for online model learning in virtualized systems. Our reference architecture is based on a set of model extraction agents. Each agent focuses on specific tasks to automatically create and update model skeletons capturing its local knowledge of the system and collaborates with other agents to extract the structural parts of a global performance model of the system. We define different agent roles in the reference architecture and propose a model-based collaboration mechanism for the agents. The agents may be bundled within virtual appliances and may be tailored to include knowledge about the software stack deployed in a specific virtual appliance. - An online method for the statistical estimation of resource demands. For a given request processed by an application, the resource time consumed for a specified resource within the system (e.g., CPU or I/O device), referred to as resource demand, is the total average time the resource is busy processing the request. A request could be any unit of work (e.g., web page request, database transaction, batch job) processed by the system. We provide a systematization of existing statistical approaches to resource demand estimation and conduct an extensive experimental comparison to evaluate the accuracy of these approaches. We propose a novel method to automatically select estimation approaches and demonstrate that it increases the robustness and accuracy of the estimated resource demands significantly. - Model-based controllers for autonomic vertical scaling of virtualized applications. We design two controllers based on online model-based reasoning techniques in order to vertically scale applications at run-time in accordance with application SLOs. The controllers exploit the knowledge from the automatically extracted performance models when determining necessary reconfigurations. The first controller adds and removes virtual CPUs to an application depending on the current demand. It uses a layered performance model to also consider the physical resource contention when determining the required resources. The second controller adapts the resource allocations proactively to ensure the availability of the application during workload peaks and avoid reconfiguration during phases of high workload. We demonstrate the applicability of our approach in current virtualized environments and show its effectiveness leading to significant increases in resource efficiency and improvements of the application performance and availability under time-varying workloads. The evaluation of our approach is based on two case studies representative of widely used enterprise applications in virtualized data centers. In our case studies, we were able to reduce the amount of required CPU resources by up to 23% and the number of reconfigurations by up to 95% compared to a rule-based approach while ensuring full compliance with application SLO. Furthermore, using workload forecasting techniques we were able to schedule expensive reconfigurations (e.g., changes to the memory size) during phases of load load and thus were able to reduce their impact on application availability by over 80% while significantly improving application performance compared to a reactive controller. The methods and techniques for resource demand estimation and vertical application scaling were developed and evaluated in close collaboration with VMware and Google. N2 - Unternehmensanwendungen in virtualisierten Rechenzentren unterliegen häufig zeitabhängigen Arbeitslasten, d.h. die Lastintensität und der Anfragemix ändern sich mit der Zeit wegen saisonalen Mustern und Trends, sowie unvorhergesehenen Lastspitzen bei den Nutzeranfragen. Variierende Arbeitslasten führen dazu, dass sich die Ressourcenanforderungen an die darunterliegende Hardware-Infrastruktur häufig ändern. Virtualisierungstechniken erlauben die gemeinsame Nutzung und bedarfsgesteuerte Zuteilung von Hardware-Ressourcen zwischen mehreren Anwendungen. In diesem Zusammenhang sollte die Zuteilung von Ressourcen an virtualisierte Anwendungen fortwährend in einer elastischen Art und Weise angepasst werden, um sicherzustellen, dass "zu jedem Zeitpunkt die verfügbaren Ressourcen dem derzeitigen Bedarf möglichst genau entsprechen" (Herbst et al., 2013). Autonome Ansätze zur Ressourcenverwaltung versprechen eine deutliche Steigerung der Ressourceneffizienz wobei Verletzungen der Anforderungen hinsichtlich Performanz und Verfügbarkeit bei Lastspitzen vermieden werden. Herkömmliche Ansätze zur autonomen Ressourcenverwaltung nutzen feste Regeln (z.B., Amazon EC2), die vordefinierte Rekonfigurationen durchführen sobald eine Metrik einen bestimmten Schwellwert erreicht (z.B., hohe Ressourcenauslastung oder ungleichmäßige Lastverteilung). Viele geschäftskritische Anwendungen unterliegen jedoch Zielvorgaben hinsichtlich der Dienstgüte (SLO, engl. Service Level Objectives), die auf Performanzmetriken der Anwendung definiert sind (z.B., Antwortzeit oder Durchsatz). Die Bestimmung von Schwellwerten, sodass die Ende-zu-Ende Anwendungs-SLOs erfüllt werden, stellt aufgrund des komplexen Zusammenspiels zwischen der Ressourcenzuteilung und der Performanz einer Anwendung eine bedeutende Herausforderung dar. Des Weiteren sind Ansätze basierend auf Schwellwerten inhärent anfällig für Oszillationen, die zu überflüssigen Rekonfigurationen führen können. Um die Schwächen schwellwertbasierter Ansätze zu lösen und einen vollständig automatisierten Ansatz zur dynamischen Steuerung von Ressourcenzuteilungen virtualisierter Anwendungen zu ermöglichen, bedarf es modellbasierter Ansätze, die den Einfluss einer Rekonfiguration auf die Performanz einer Anwendung im Voraus vorhersagen können. Bestehende modellbasierte Ansätze sind jedoch stark eingeschränkt hinsichtlich ihrer Lernfähigkeiten. Sie erfordern entweder vollständige Performanzmodelle der Anwendung als Eingabe oder nutzen vorbestimmte Modellstrukturen und lernen nur bestimmte Modellparameter auf Basis von empirischen Daten zur Laufzeit. Erstere erfordern hohe manuelle Aufwände und eine tiefe Systemkenntnis um die Performanzmodelle zu erstellen. Letztere bieten nur eingeschränkte Möglichkeiten um die Besonderheiten von komplexen und heterogenen Systemarchitekturen zu erfassen. Diese Arbeit stellt einen selbstwahrnehmenden (engl. self-aware) Ansatz zur Ressourcenverwaltung in virtualisierten Rechenzentren vor. In diesem Zusammenhang bedeutet Selbstwahrnehmung, dass der Ansatz automatisch Performanzmodelle der Anwendung und der virtualisierten Infrastruktur lernt Basierend auf diesen Modellen entscheidet er autonom wie die Ressourcenzuteilungen angepasst werden, um die Anwendungs-SLOs zu erfüllen. Das Lernen von Performanzmodellen erfordert sowohl die Extraktion der Modellstruktur, die die Systemarchitektur abbildet, als auch die Schätzung von Modellparametern, wie zum Beispiel der Ressourcenverbräuche einzelner Funktionen. Die Schätzung der Ressourcenverbräuche stellt hier eine zentrale Herausforderung dar, da diese in den meisten Systemen nicht direkt gemessen werden können. Die wissenschaftlichen Hauptbeiträge dieser Arbeit sind wie folgt: - Eine Referenzarchitektur, die das Lernen von Modellen in virtualisierten Systemen während des Betriebs ermöglicht. Unsere Referenzarchitektur basiert auf einer Menge von Modellextraktionsagenten. Jeder Agent fokussiert sich auf bestimmte Aufgaben um automatisch ein Modellskeleton, das sein lokales Wissen über das System erfasst, zu erstellen und zu aktualisieren. Jeder Agent arbeitet mit anderen Agenten zusammen um die strukturellen Teile eines globalen Performanzmodells des Systems zu extrahieren. Die Rereferenzarchitektur definiert unterschiedliche Agentenrollen und beinhaltet einen modellbasierten Mechanismus, der die Kooperation unterschiedlicher Agenten ermöglicht. Die Agenten können als Teil virtuellen Appliances gebündelt werden und können dabei maßgeschneidertes Wissen über die Software-Strukturen in dieser virtuellen Appliance beinhalten. - Eine Methode zur fortwährenden statistischen Schätzung von Ressourcenverbräuchen. Der Ressourcenverbrauch (engl. resource demand) einer Anfrage, die von einer Anwendung verarbeitet wird, entspricht der Zeit, die an einer spezifischen Ressource im System (z.B., CPU oder I/O-Gerät) verbraucht wird. Eine Anfrage kann dabei eine beliebige Arbeitseinheit, die von einem System verarbeitet wird, darstellen (z.B. eine Webseitenanfrage, eine Datenbanktransaktion, oder ein Stapelverarbeitungsauftrag). Die vorliegende Arbeit bietet eine Systematisierung existierender Ansätze zur statistischen Schätzung von Ressourcenverbräuchen und führt einen umfangreichen, auf Experimenten aufbauenden Vergleich zur Bewertung der Genauigkeit dieser Ansätze durch. Es wird eine neuartige Methode zur automatischen Auswahl eines Schätzverfahrens vorgeschlagen und gezeigt, dass diese die Robustheit und Genauigkeit der geschätzten Ressourcenverbräuche maßgeblich verbessert. - Modellbasierte Regler für das autonome, vertikale Skalieren von virtualisierten Anwendungen. Es werden zwei Regler entworfen, die auf modellbasierten Entscheidungstechniken basieren, um Anwendungen zur Laufzeit vertikal in Übereinstimmung mit Anwendungs-SLOs zu skalieren. Die Regler nutzen das Wissen aus automatisch extrahierten Performanzmodellen bei der Bestimmung notwendiger Rekonfigurationen. Der erste Regler fügt virtuelle CPUs zu Anwendungen hinzu und entfernt sie wieder in Abhängigkeit vom aktuellen Bedarf. Er nutzt ein geschichtetes Performanzmodell, um bei der Bestimmung der benötigten Ressourcen die Konkurrenzsituation der physikalischen Ressourcen zu beachten. Der zweite Regler passt Ressourcenzuteilungen proaktiv an, um die Verfügbarkeit einer Anwendung während Lastspitzen sicherzustellen und Rekonfigurationen unter großer Last zu vermeiden. Die Arbeit demonstriert die Anwendbarkeit unseres Ansatzes in aktuellen virtualisierten Umgebungen und zeigt seine Effektivität bei der Erhöhung der Ressourceneffizienz und der Verbesserung der Anwendungsperformanz und -verfügbarkeit unter zeitabhängigen Arbeitslasten. Die Evaluation des Ansatzes basiert auf zwei Fallstudien, die repräsentativ für gängige Unternehmensanwendungen in virtualisierten Rechenzentren sind. In den Fallstudien wurde eine Reduzierung der benötigten CPU-Ressourcen von bis zu 23% und der Anzahl der Rekonfigurationen von bis zu 95% im Vergleich zu regel-basierten Ansätzen erreicht, bei gleichzeitiger Erfüllung der Anwendungs-SLOs. Mit Hilfe von Vorhersagetechniken für die Arbeitslast konnten außerdem aufwändige Rekonfigurationen (z.B., Änderungen bei der Menge an zugewiesenem Arbeitsspeicher) so geplant werden, dass sie in Phasen geringer Last durchgeführt werden. Dadurch konnten deren Auswirkungen auf die Verfügbarkeit der Anwendung um mehr als 80% verringert werden bei gleichzeitiger Verbesserung der Anwendungsperformanz verglichen mit einem reaktiven Regler. Die Methoden und Techniken zur Schätzung von Ressourcenverbräuchen und zur vertikalen Skalierung von Anwendungen wurden in enger Zusammenarbeit mit VMware und Google entwickelt und evaluiert. KW - Cloud Computing KW - Virtualisierung KW - Leistungsbewertung KW - Autonomic Computing KW - Self-Aware Computing KW - Model extraction Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153754 ER - TY - JOUR A1 - Strohmeier, Michael A1 - Montenegro, Sergio T1 - Coupled GPS/MEMS IMU Attitude Determination of Small UAVs with COTS JF - Electronics N2 - This paper proposes an attitude determination system for small Unmanned Aerial Vehicles (UAV) with a weight limit of 5 kg and a small footprint of 0.5m x 0.5 m. The system is realized by coupling single-frequency Global Positioning System (GPS) code and carrier-phase measurements with the data acquired from a Micro-Electro-Mechanical System (MEMS) Inertial Measurement Unit (IMU) using consumer-grade Components-Off-The-Shelf (COTS) only. The sensor fusion is accomplished using two Extended Kalman Filters (EKF) that are coupled by exchanging information about the currently estimated baseline. With a baseline of 48 cm, the static heading accuracy of the proposed system is comparable to the one of a commercial single-frequency GPS heading system with an accuracy of approximately 0.25°/m. Flight testing shows that the proposed system is able to obtain a reliable and stable GPS heading estimation without an aiding magnetometer. KW - Attitude Heading Reference System (AHRS) KW - magnetometer KW - MEMS IMU KW - Real-time Kinematics (RTK) KW - GPS KW - UAV KW - attitude determination Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171179 VL - 6 IS - 1 ER - TY - THES A1 - Bach, Tobias T1 - Electromechanical interactions in lithium-ion batteries: Aging effects and analytical use T1 - Elektromechanische Wechselwirkungen in Lithium-Ionen Batterien: Alterungseffekte und analytische Anwendungsmöglichkeiten N2 - In the first part of his work, the causes for the sudden degradation of useable capacity of lithium-ion cells have been studied by means of complementary methods such as computed tomography, Post-Mortem studies and electrochemical analyses. The results obtained point unanimously to heterogeneous aging as a key-factor for the sudden degradation of cell capacity, which in turn is triggered by differences in local compression. At high states of health, the capacity fade rate is moderate but some areas of the graphite electrode degrade faster than others. Still, the localized changes are hardly noticeable on cell level due to averaging effects. Lithium plating occurs first in unevenly compressed areas, creating patterns visible to the human eye. As lithium plating leads to rapid consumption of active lithium, a sudden drop in capacity is observed on cell level. Lithium plating appears to spread out from the initial areas over the whole graphite electrode, quickly consuming the remaining useful lithium and active graphite. It can be hypothesized that a self-amplifying circle of reciprocal acceleration of local lithium loss and material loss causes rapid local degradation. Battery cell designers can improve cycle life by homogeneous pressure distribution in the cell and using negative active materials that are resilient to elevated discharge potentials such as improved carbons or lithium titanate. Also, a sufficiently oversized negative electrode and suitable electrolyte additives can help to avoid lithium plating. When packs are designed, care must be taken not to exert local pressure on parts of cells and to avoid both very high and low states of charge. In the second part of this dissertation the resilience of cylindrical and pouchbag cells to shocks and different vibrations was investigated. Stresses inflicted by vibration and shock tests according to the widely recognized UN38.3 transport test were compared to a long-time test that exposed cells to a 186 days long ordeal of sine sweep vibrations with a profile based on real-world applications. All cells passed visual and electric inspection performed by TU München after the vibration tests. Only cylindrical cells subjected to long-term vibrations in axial direction showed an increase in impedance and a loss of capacity that could be recuperated in part. The detailed analyses presented in this thesis gave more details on the damages inflicted by vibrations and shocks and revealed drastic damages in some cases. In cylindrical cells, only movement in axial direction caused damage. Long term vibrations were found to be especially detrimental. No damage whatsoever could be detected for pouch cells, regardless of the test protocol and the direction of movement. The extreme resilience of pouchbag cells shows that the electrode stack of lithium-ion cells is resistant to vibrations, and that damages are caused by design imperfections that can be improved at low cost. The findings of this work, and the general state of research show that it is most crucial to control the lithiation and thus potential of the graphite electrode. In the last part of this work, a new, direct method for charge estimation based on changing transmission is presented. A correlation between transmission of short ultrasonic pulses and state of charge is found. This new technology allows direct measurement of the state of charge. The method is demonstrated for batteries with different positive active materials, showing its versatility. As the observed changes can be traced to the lithiation of graphite, it can be determined without a reference electrode. Already at this early stage of development, the found correlations allow estimation of state of charge. The present hysteresis in the signal height of the slow wave, which is unneglectable especially during discharging at higher currents, will be subject to further investigation. The observed effects can be explained by effects on different length scales. Biot’s theory explains the second wave’s slowness based on the active material particles size in the range of 0.01 mm and electrolyte-filled pores. Lithiation of graphite changes the porosity of the electrode and thereby the velocity and wavelength of the impulse. When the wavelength approaches the length scale of the layers, 0.1 mm, scattering effects dampen the transmitted signal. Finally, the wavelength of the pulse should be shorter than the transducers diameter to obtain a homogeneous wave front. To conclude, the new method allows the control of each individual cell in a pack independent from the electrical connections of the cells. As the method shows great promise, further studies regarding factors such as long-term behavior, temperature and current rates should be conducted. In this thesis hysteresis was observed and a deeper understanding of the reasons behind it may allow further improvements of measurement precision. N2 - Im ersten Teil dieser Doktorarbeit wurden die Ursachen des plötzlichen Kapazitätseinbruchs von Lithium-Ionen Zellen untersucht. Die mittels sich ergänzender Methoden wie Röntgentomographie, Post-Mortem Untersuchungen und elektrochemischer Analysen gewonnenen Ergebnisse weisen darauf hin, dass heterogene Alterungseffekte eine Schlüsselrolle für den beschleunigten Kapazitätsverlust spielen. Die beobachteten Ungleichmäßigkeiten auf gealterten Elektroden konnten wiederum auf Kompressionsunterschiede zurückgeführt werden. Im frühen Alterungsstadium war zwar nur ein moderater Kapazitätsverlust zu verzeichnen, einige Bereiche der Graphitelektrode altern jedoch schneller als andere. Diese lokalen Alterungseffekte sind auf Zellebene aufgrund von Mittelungseffekten zunächst schwer nachweisbar, sobald jedoch in Bereichen abweichender Kompression Lithiumplating auftritt, entstehen Muster welche nach Öffnen der Zelle gut zu erkennen sind. Inaktives Lithium, dicke Passivschichten sowie erhöhte Mengen an abgelagertem Mangan und anderen Metallen die aus dem positiven Aktivmaterial herausgewaschen wurden, konnten in geschädigten Bereichen der Zellen B und C, welche direkt beim Einsetzen beziehungsweise 150 Zyklen später geöffnet wurden, nachgewiesen werden. Da Lithiumplating zu raschem Verbrauch von aktivem Lithium führt, kann ein plötzlicher Einbruch der Zellkapazität beobachtet werden. Das Lithiumplating scheint sich von den geschädigten Bereichen über die gesamte Elektrode auszubreiten, wobei rasch das verbleibende aktive Lithium und teilweise auch das negative Aktivmaterial verbraucht wird. Daher wird die Hypothese aufgestellt, dass durch lokales Lithiumplating ein sich selbst verstärkender Kreislauf in Gang gesetzt wird, wobei sich lokaler Lithium- und Aktivmaterialverlust gegenseitig beschleunigen. Im zweiten Teil der Arbeit wurde die Widerstandsfähigkeit von zylindrischen und Pouchbagzellen gegenüber Schocks und Vibrationen untersucht. Belastungen durch Vibrationen und Schocks gemäß des weitläufig anerkannten Transporttests UN38.3 wurden mit 186 Tage dauernden Langzeittests verglichen. Alle Zellen bestanden die visuellen und elektrischen Überprüfungen die an der TU München nach Durchführung der Vibrationstests durchgeführt wurden. Nur die zylindrischen Zellen zeigten einen Anstieg des Innenwiderstands sowie einen weitgehend reversiblen Kapazitätsverlust. Die in dieser Arbeit vorgestellte tiefergehenden Analysen gaben ein detaillierteres Bild der beobachteten Effekte auf und zeigten teilweise schwere versteckte Schäden auf, wobei ausschließlich in axialer Richtung belastete Rundzellen Schäden aufwiesen. Langzeitvibrationen führten zu besonders schweren Schadensbildern. An den untersuchten Pouchzellen konnte keinerlei Schädigung durch die Vibration festgestellt werden. Die Widerstandsfähigkeit der Pouchzellen zeigt, dass der Elektrodenstapel, der die Grundlage jeder Lithium-Ionen Zelle bildet, äußerst vibrationsstabil ist und auftretende Schäden auf ungenügendes Zelldesign zurückzuführen sind. Die hier vorgestellten Ergebnisse und der Stand der Wissenschaft zeigen die Bedeutung des Lithiierungsgrad der Graphitelektrode für die Alterung auf. Im letzten Teil der Arbeit wurde daher eine neue Methode zur Ladezustandsbestimmung mittels Ultraschall vorgestellt. Die beobachteten Amplituden- und Laufzeitänderungen erlauben die direkte Bestimmung des Ladezustands von Lithium-Ionen Zellen und die Anwendbarkeit konnte an Zellen mit verschiedenen positiven Aktivmaterialien gezeigt werden. Die beobachteten Effekte können auf Vorgänge auf verschiedenen Längenskalen zurückgeführt werden. Biots Theorie bietet eine Erklärung der geringen Geschwindigkeit der zweiten Welle aufgrund der Ausbreitungsmodi der Schallwellen im porösen, elektrolytgefüllten Aktivmaterial. Die im Vergleich zur Wellenlänge kleine Längenskala der Aktivpartikel und der elektrolytgefüllten Poren von 0,01 mm führt hierbei dazu, dass sich das Material als Effektivmedium verhält. Durch die Lithiierung der Graphitpartikel ändern sich Eigenschaften und Porosität der Elektrode. Insbesondere die Porositätsänderung kann laut Biots Theorie die Geschwindigkeit und somit die Wellenlänge der zweiten Welle wesentlich verändern. Wenn die Wellenlänge auf die Größenordnung der Schichtdicken der Zelle, 0,1 mm, reduziert wird, treten Streuungseffekte auf, die die transmittierte Welle abschwächen. Schlussendlich muss der Durchmesser der eingesetzten Schallwandler größer als die Wellenlänge der Pulse sein um ein homogenes Schallfeld zu erzeugen. Da der Einsatz von Ultraschallpulsen vielversprechend erscheint, sollten in weiteren Studien Faktoren wie Langzeitverhalten, Temperatur- und Rateneinflüsse untersucht werden. In dieser Arbeit wurde weiterhin Hysterese beobachtet deren tieferes Verständnis nicht nur die Ladezustandsbestimmung, sondern auch das Verständnis der dynamischen Prozesse in Lithium-Ionen Zellen verbessern könnte. KW - Lithium-Ionen-Akkumulator KW - Lithium-Plating KW - Alterung KW - Ultraschall KW - Ultraschallsensor KW - vibration testing KW - mechanical shock KW - heterogeneous compression Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153325 ER - TY - JOUR A1 - Uri, Anna A1 - Werner, Sandra A1 - Lühder, Fred A1 - Hünig, Thomas A1 - Kerkau, Thomas A1 - Beyersdorf, Niklas T1 - Protection of mice from acute graft-versus-host disease requires CD28 co-stimulation on donor CD4\(^{+}\) Foxp3\(^{+}\) regulatory T Cells JF - Frontiers in Immunology N2 - Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4\(^{+}\) conventional (CD4\(^{+}\)CD25\(^{-}\)Foxp3\(^{-}\), Tconv) and regulatory (CD4\(^{+}\)CD25\(^{+}\)Foxp3\(^{+}\), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4\(^{+}\) Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4\(^{+}\) Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice. Selective depletion of CD28 on donor Treg did not abrogate protection of recipient mice from aGvHD until about day 20 after allo-HSCT. Later, however, the pool of CD28-depleted Treg drastically declined as compared to wt Treg. Consequently, only wt, but not CD28-deficient, Treg were able to continuously suppress aGvHD and induce long-term survival of the recipient mice. To our knowledge, this is the first study that specifically evaluates the impact of CD28 expression on donor Treg in aGvHD. Moreover, the delayed kinetics of aGvHD lethality after transplantation of iCD28KO Treg provides a novel animal model for similar disease courses found in patients after allo-HSCT. KW - co-stimulation, KW - inducible deletion KW - regulatory T cells KW - acute graft-versus-host disease KW - CD28 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158469 VL - 8 IS - 721 ER - TY - THES A1 - Künzel, Elena Carolin T1 - Zeitliche Untersuchung von Adipositas-Prävalenz und assoziierten Risikofaktoren während der Schwangerschaft T1 - Prevalence and Associated Risk Factors for Obesity During Pregnancy Over Time N2 - Einleitung: Die steigende Prävalenz adipöser Menschen führt weltweit zu einer relevanten Morbidität, die auch junge Frauen im geschlechtsreifen Alter betrifft. Damit gerät der Themenkomplex Adipositas und assoziierte Komplikationen auch im Hinblick auf die Versorgung Schwangerer in den Fokus. Das Ziel dieser Arbeit war es deshalb, die Adipositasprävalenz und hiermit assoziierte maternale und fetale Risikofaktoren zwischen 2006 und 2011 in einem lokalen Kollektiv zu untersuchen. Material und Methoden: Die retrospektive Analyse umfasste alle maternalen und fetalen Daten von Patientinnen, die 2006 und 2011 an der Universitätsfrauenklinik Würzburg von einem Einling entbunden wurden. Die deskriptive Statistik umfasste die Prävalenz von Adipositas und Gewichtszunahme, maternale Risikofaktoren, Schwangerschaftskomplikationen und fetales Outcome. Ergebnisse: Unsere Analyse umfasste 2838 Patientinnen mit Einlingsgraviditäten, die in den Jahren 2006 (n=1292) und 2011 (n=1545) an der Uniklinik Würzburg entbunden haben. Es zeigte sich, dass weder der initiale BMI noch die Gewichtszunahme während der Schwangerschaft zwischen 2006 und 2011 signifikant anstiegen. Die Mehrheit der übergewichtigen (71%) oder adipösen (60,4%) Patientinnen überstieg die empfohlene Gewichtszunahme. Die Prävalenz von adipositasassoziierten Erkrankungen wie Gestationsdiabetes und Präeklampsie stiegen signifikant an und waren mit einem hohen initialen BMI assoziiert. Während Übergewichtigkeit nicht mit einer Terminüberschreitung assoziiert war, wurden adipöse Patientinnen signifikant häufiger per Sectio caesarea entbunden. Das Geburtsgewicht war 2011 signifikant höher als 2006, wobei keine signifikanten Änderungen im fetalen Outcome dargestellt werden konnten. Schlussfolgerung: Es gibt einen Trend zu vermehrter Gewichtszunahme während der Schwangerschaft. Assoziierte Risikofaktoren wie Gestationsdiabetes und Präeklampsie sind erhöht. N2 - Objective: To compare prevalence and associated risk factors of obesity during pregnancy in 2006 and 2011 Study Design: Maternal and fetal records of women who delivered at the University of Wuerzburg after a 5-year-period (2006 and 2011) were retrospectively analyzed concerning the prevalence of obesity and associated maternal and fetal complications Results: Our analyses included 2838 mothers with singleton pregnancies who delivered in 2006 (n=1293) or 2011 (n=1545) in our department. We observed that neither pre-pregnancy BMI nor weight gain increased significantly over time. But especially the majority of all included overweight (71%) or obese (60.4%) mothers gained more weight than recommended by the Institute of Medicine (IOM). Obesity-associated illnesses such as gestational diabetes and pre-existing hypertension increased significantly over time and were shown to be associated with high pre-pregnancy BMI as well as preeclampsia and gestational hypertension. Obesity was not associated with prolonged pregnancy but was significantly associated with cesarean section. Fetal birth weight was significantly increased in 2011 when compared to 2006, while fetal outcome for term infants did not seem to be impaired by maternal overweight or obesity. Conclusion: There is a trend to increasing weight gain during pregnancy and a majority of mothers especially those with a high pre-pregnancy BMI exceed weight gain recommendations. Associated risk factors such as gestational diabetes, hypertension and delivery by cesarean section are increased. KW - Fettsucht KW - Gestationsdiabetes KW - Eklampsie KW - Gestationsdiabetes KW - IOM-Kriterien KW - Adipositas KW - Kaiserschnitt KW - Makrosomie KW - gestational diabetes KW - obesity KW - Weight Gain During Pregnancy KW - macrosomia KW - cesarean section Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-155544 ER - TY - JOUR A1 - Müller, Bettina A1 - Richter, Tobias A1 - Karageorgos, Panagiotis A1 - Krawietz, Sabine A1 - Ennemoser, Marco T1 - Effects of a syllable-based reading intervention in poor-reading fourth graders JF - Frontiers in Psychology N2 - In transparent orthographies, persistent reading fluency difficulties are a major cause of poor reading skills in primary school. The purpose of the present study was to investigate effects of a syllable-based reading intervention on word reading fluency and reading comprehension among German-speaking poor readers in Grade 4. The 16-session intervention was based on analyzing the syllabic structure of words to strengthen the mental representations of syllables and words that consist of these syllables. The training materials were designed using the 500 most frequent syllables typically read by fourth graders. The 75 poor readers were randomly allocated to the treatment or the control group. Results indicate a significant and strong effect on the fluency of recognizing single words, whereas text-level reading comprehension was not significantly improved by the training. The specific treatment effect provides evidence that a short syllable-based approach works even in older poor readers at the end of primary school. KW - word reading fluency KW - syllable-based intervention KW - older poor readers KW - primary school KW - reading comprehension Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158841 VL - 8 IS - 1635 ER - TY - JOUR A1 - Flechsenhar, Aleya Felicia A1 - Gamer, Matthias T1 - Top-down influence on gaze patterns in the presence of social features JF - PLoS ONE N2 - Visual saliency maps reflecting locations that stand out from the background in terms of their low-level physical features have proven to be very useful for empirical research on attentional exploration and reliably predict gaze behavior. In the present study we tested these predictions for socially relevant stimuli occurring in naturalistic scenes using eye tracking. We hypothesized that social features (i.e. human faces or bodies) would be processed preferentially over non-social features (i.e. objects, animals) regardless of their low-level saliency. To challenge this notion, we included three tasks that deliberately addressed non-social attributes. In agreement with our hypothesis, social information, especially heads, was preferentially attended compared to highly salient image regions across all tasks. Social information was never required to solve a task but was regarded nevertheless. More so, after completing the task requirements, viewing behavior reverted back to that of free-viewing with heavy prioritization of social features. Additionally, initial eye movements reflecting potentially automatic shifts of attention, were predominantly directed towards heads irrespective of top-down task demands. On these grounds, we suggest that social stimuli may provide exclusive access to the priority map, enabling social attention to override reflexive and controlled attentional processes. Furthermore, our results challenge the generalizability of saliency-based attention models. KW - eye movements KW - social features KW - visual saliency KW - gaze KW - face KW - attention Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170468 VL - 12 IS - 8 ER - TY - JOUR A1 - Ritzer, J. A1 - Lühmann, T. A1 - Rode, C. A1 - Pein-Hackelbusch, M. A1 - Immohr, I. A1 - Schedler, U. A1 - Thiele, T. A1 - Stübinger, S. A1 - Rechenberg, B.v. A1 - Waser-Althaus, J. A1 - Schlottig, F. A1 - Merli, M. A1 - Dawe, H. A1 - Karpíšek, M. A1 - Wyrwa, R. A1 - Schnabelrauch, M. A1 - Meinel, L. T1 - Diagnosing peri-implant disease using the tongue as a 24/7 detector JF - Nature Communications N2 - Our ability of screening broad communities for clinically asymptomatic diseases critically drives population health. Sensory chewing gums are presented targeting the tongue as 24/7 detector allowing diagnosis by “anyone, anywhere, anytime”. The chewing gum contains peptide sensors consisting of a protease cleavable linker in between a bitter substance and a microparticle. Matrix metalloproteinases in the oral cavity, as upregulated in peri-implant disease, specifically target the protease cleavable linker while chewing the gum, thereby generating bitterness for detection by the tongue. The peptide sensors prove significant success in discriminating saliva collected from patients with peri-implant disease versus clinically asymptomatic volunteers. Superior outcome is demonstrated over commercially available protease-based tests in saliva. “Anyone, anywhere, anytime” diagnostics are within reach for oral inflammation. Expanding this platform technology to other diseases in the future features this diagnostic as a massive screening tool potentially maximizing impact on population health. KW - peri-implant disease KW - sensory chewing gums KW - tongue KW - detector KW - peptide sensors Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170471 VL - 8 IS - 264 ER - TY - JOUR A1 - Kraft, Peter A1 - Schuhmann, Michael K. A1 - Garz, Cornelia A1 - Jandke, Solveig A1 - Urlaub, Daniela A1 - Mencl, Stine A1 - Zernecke, Alma A1 - Heinze, Hans-Jochen A1 - Carare, Roxana O. A1 - Kleinschnitz, Christoph A1 - Schreiber, Stefanie T1 - Hypercholesterolemia induced cerebral small vessel disease JF - PLoS ONE N2 - Background While hypercholesterolemia plays a causative role for the development of ischemic stroke in large vessels, its significance for cerebral small vessel disease (CSVD) remains unclear. We thus aimed to understand the detailed relationship between hypercholesterolemia and CSVD using the well described Ldlr\(^{−/-}\) mouse model. Methods We used Ldlr\(^{−/-}\) mice (n = 16) and wild-type (WT) mice (n = 15) at the age of 6 and 12 months. Ldlr\(^{−/-}\) mice develop high plasma cholesterol levels following a high fat diet. We analyzed cerebral capillaries and arterioles for intravascular erythrocyte accumulations, thrombotic vessel occlusions, blood-brain barrier (BBB) dysfunction and microbleeds. Results We found a significant increase in the number of erythrocyte stases in 6 months old Ldlr\(^{−/-}\) mice compared to all other groups (P < 0.05). Ldlr\(^{−/-}\) animals aged 12 months showed the highest number of thrombotic occlusions while in WT animals hardly any occlusions could be observed (P < 0.001). Compared to WT mice, Ldlr\(^{−/-}\) mice did not display significant gray matter BBB breakdown. Microhemorrhages were observed in one Ldlr\(^{−/-}\) mouse that was 6 months old. Results did not differ when considering subcortical and cortical regions. Conclusions In Ldlr\(^{−/-}\) mice, hypercholesterolemia is related to a thrombotic CSVD phenotype, which is different from hypertension-related CSVD that associates with a hemorrhagic CSVD phenotype. Our data demonstrate a relationship between hypercholesterolemia and the development of CSVD. Ldlr\(^{−/-}\) mice appear to be an adequate animal model for research into CSVD. KW - hypercholesterolemia KW - cerebral small vessel disease KW - mouse model KW - histology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170493 VL - 12 IS - 8 ER - TY - JOUR A1 - Kredel, Markus A1 - Kunzmann, Steffen A1 - Schlegel, Paul-Gerhardt A1 - Wölfl, Matthias A1 - Nordbeck, Peter A1 - Bühler, Christoph A1 - Lotz, Christopher A1 - Lepper, Philipp M. A1 - Wirbelauer, Johannes A1 - Roewer, Norbert A1 - Muellenbach, Ralf M. T1 - Double Peripheral Venous and Arterial Cannulation for Extracorporeal Membrane Oxygenation in Combined Septic and Cardiogenic Shock JF - American Journal of Case Reports N2 - Background: The use of venoarterial extracorporeal membrane oxygenation (va-ECMO) via peripheral cannulation for septic shock is limited by blood flow and increased afterload for the left ventricle. Case Report: A 15-year-old girl with acute myelogenous leukemia, suffering from severe septic and cardiogenic shock, was treated by venoarterial extracorporeal membrane oxygenation (va-ECMO). Sufficient extracorporeal blood flow matching the required oxygen demand could only be achieved by peripheral cannulation of both femoral arteries. Venous drainage was performed with a bicaval cannula inserted via the left V. femoralis. To accomplish left ventricular unloading, an additional drainage cannula was placed in the left atrium via percutaneous atrioseptostomy (va-va-ECMO). Cardiac function recovered and the girl was weaned from the ECMO on day 6. Successful allogenic stem cell transplantation took place 2 months later. Conclusions: In patients with vasoplegic septic shock and impaired cardiac contractility, double peripheral venoarterial extracorporeal membrane oxygenation (va-va-ECMO) with transseptal left atrial venting can by a lifesaving option. KW - extracorporeal membrane oxygenation KW - myeloid KW - leukemia KW - acute KW - shock KW - cardiogenic KW - septic Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158193 VL - 18 ER - TY - JOUR A1 - Hellmann, Anna-Maria A1 - Lother, Jasmin A1 - Wurster, Sebastian A1 - Lutz, Manfred B. A1 - Schmitt, Anna Lena A1 - Morton, Charles Oliver A1 - Eyrich, Matthias A1 - Czakai, Kristin A1 - Einsele, Hermann A1 - Loeffler, Juergen T1 - Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus JF - Frontiers in Immunology N2 - Aspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus. However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed a comparative functional analysis of human and murine dendritic cells (DCs), macrophages, and polymorphonuclear cells (PMNs) using standardized and reproducible working conditions, laboratory protocols, and readout assays. A. fumigatus did not provoke identical responses in murine and human immune cells but rather initiated relatively specific responses. While human DCs showed a significantly stronger upregulation of their maturation markers and major histocompatibility complex molecules and phagocytosed A. fumigatus more efficiently compared to their murine counterparts, murine PMNs and macrophages exhibited a significantly stronger release of reactive oxygen species after exposure to A. fumigatus. For all studied cell types, human and murine samples differed in their cytokine response to conidia or germ tubes of A. fumigatus. Furthermore, Dectin-1 showed inverse expression patterns on human and murine DCs after fungal stimulation. These specific differences should be carefully considered and highlight potential limitations in the transferability of murine host–pathogen interaction studies. KW - murine model KW - humans KW - Aspergillus fumigatus KW - innate immune response KW - fungal infection Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169926 VL - 8 IS - 1716 ER - TY - JOUR A1 - Moremi, Nyambura A1 - Claus, Heike A1 - Vogel, Ulrich A1 - Mshana, Stephen E. T1 - Surveillance of surgical site infections by Pseudomonas aeruginosa and strain characterization in Tanzanian hospitals does not provide proof for a role of hospital water plumbing systems in transmission JF - Antimicrobial Resistance and Infection Control N2 - Background The role of hospital water systems in the development of Pseudomonas aeruginosa (P. aeruginosa) surgical site infections (SSIs) in low-income countries is barely studied. This study characterized P. aeruginosa isolates from patients and water in order to establish possible epidemiological links. Methods: Between December 2014 and September 2015, rectal and wound swabs, and water samples were collected in the frame of active surveillance for SSIs in the two Tanzanian hospitals. Typing of P. aeruginosa was done by multi-locus sequence typing. Results: Of 930 enrolled patients, 536 were followed up, of whom 78 (14.6%, 95% CI; 11.6–17.5) developed SSIs. P. aeruginosa was found in eight (14%) of 57 investigated wounds. Of the 43 water sampling points, 29 were positive for P. aeruginosa. However, epidemiological links to wound infections were not confirmed. The P. aeruginosa carriage rate on admission was 0.9% (8/930). Of the 363 patients re-screened upon discharge, four (1.1%) possibly acquired P. aeruginosa during hospitalization. Wound infections of the three of the eight P. aeruginosa SSIs were caused by a strain of the same sequence type (ST) as the one from intestinal carriage. Isolates from patients were more resistant to antibiotics than water isolates. Conclusions: The P. aeruginosa SSI rate was low. There was no evidence for transmission from tap water. Not all P. aeruginosa SSI were proven to be endogenous, pointing to other routes of transmission. KW - Tanzania KW - P. aeruginosa KW - surgical site infection KW - water microbiology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158168 VL - 6 IS - 56 ER - TY - JOUR A1 - Biedermann, Benedikt A1 - Bräuer, Stephan A1 - Denner, Ansgar A1 - Pellen, Mathieu A1 - Schumann, Steffen A1 - Thompson, Jennifer M. T1 - Automation of NLO QCD and EW corrections with SHERPA and RECOLA JF - European Physical Journal C N2 - This publication presents the combination of the one-loop matrix-element generator Recola with the multipurpose Monte Carlo program Sherpa. Since both programs are highly automated, the resulting Sherpa +Recola framework allows for the computation of – in principle – any Standard Model process at both NLO QCD and EW accuracy. To illustrate this, three representative LHC processes have been computed at NLO QCD and EW: vector-boson production in association with jets, off-shell Z-boson pair production, and the production of a top-quark pair in association with a Higgs boson. In addition to fixed-order computations, when considering QCD corrections, all functionalities of Sherpa, i.e. particle decays, QCD parton showers, hadronisation, underlying events, etc. can be used in combination with Recola. This is demonstrated by the merging and matching of one-loop QCD matrix elements for Drell–Yan production in association with jets to the parton shower. The implementation is fully automatised, thus making it a perfect tool for both experimentalists and theorists who want to use state-of-the-art predictions at NLO accuracy. KW - RECOLA KW - SHERPA KW - NLO QCD KW - EW KW - Higgs boson KW - Large Hadron Collider Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170615 VL - 77 IS - 492 ER - TY - JOUR A1 - Fehrholz, Markus A1 - Seidenspinner, Silvia A1 - Kunzmann, Steffen T1 - Expression of surfactant protein B is dependent on cell density in H441 lung epithelial cells JF - PLoS ONE N2 - Background Expression of surfactant protein (SP)-B, which assures the structural stability of the pulmonary surfactant film, is influenced by various stimuli, including glucocorticoids; however, the role that cell-cell contact plays in SP-B transcription remains unknown. The aim of the current study was to investigate the impact of cell-cell contact on SP-B mRNA and mature SP-B expression in the lung epithelial cell line H441. Methods Different quantities of H441 cells per growth area were either left untreated or incubated with dexamethasone. The expression of SP-B, SP-B transcription factors, and tight junction proteins were determined by qPCR and immunoblotting. The influence of cell density on SP-B mRNA stability was investigated using the transcription inhibitor actinomycin D. Results SP-B mRNA and mature SP-B expression levels were significantly elevated in untreated and dexamethasone-treated H441 cells with increasing cell density. High cell density as a sole stimulus was found to barely have an impact on SP-B transcription factor and tight junction mRNA levels, while its stimulatory ability on SP-B mRNA expression could be mimicked using SP-B-negative cells. SP-B mRNA stability was significantly increased in high-density cells, but not by dexamethasone alone. Conclusion SP-B expression in H441 cells is dependent on cell-cell contact, which increases mRNA stability and thereby potentiates the glucocorticoid-mediated induction of transcription. Loss of cell integrity might contribute to reduced SP-B secretion in damaged lung cells via downregulation of SP-B transcription. Cell density-mediated effects should thus receive greater attention in future cell culture-based research. KW - messenger RNA KW - surfactants KW - epithelial cells KW - transcription factors KW - gene expression KW - tight junctions KW - adenocarcinoma of the lung KW - immunoblotting Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158291 VL - 12 IS - 9 ER - TY - JOUR A1 - Böhm, Lena A1 - Torsin, Sanda A1 - Tint, Su Hlaing A1 - Eckstein, Marie Therese A1 - Ludwig, Tobias A1 - Pérez, J. Christian T1 - The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice JF - PLoS Pathogens N2 - Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice. In contrast to the heterogeneous morphologies found in the latter, we establish that in germ free animals the fungus almost uniformly adopts the yeast cell form, a proxy of its commensal state. By screening a collection of C. albicans transcription regulator deletion mutants in gnotobiotic mice, we identify several genes previously unknown to contribute to in vivo fitness. We investigate three of these regulators—ZCF8, ZFU2 and TRY4—and show that indeed they favor the yeast form over other morphologies. Consistent with this finding, we demonstrate that genetically inducing non-yeast cell morphologies is detrimental to the fitness of C. albicans in the gut. Furthermore, the identified regulators promote adherence of the fungus to a surface covered with mucin and to mucus-producing intestinal epithelial cells. In agreement with this result, histology sections indicate that C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus, our findings reveal a set of regulators that endows C. albicans with the ability to endure in the intestine through multiple mechanisms. KW - Candida albicans KW - deletion mutagenesis KW - gastrointestinal tract KW - fungi KW - regulator genes KW - gene regulation KW - mouse models KW - fungal genetics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159120 VL - 13 IS - 10 ER - TY - JOUR T1 - Search for pair production of heavy vector-like quarks decaying to high-\(p_T\) \(W\) bosons and \(b\) quarks in the lepton-plus-jets final state in \(pp\) collisions at \(\sqrt{s}=13\) TeV with the ATLAS detector JF - Journal of High Energy Physics N2 - A search is presented for the pair production of heavy vector-like \(T\) quarks, primarily targeting the \(T\) quark decays to a \(W\) boson and a \(b\)-quark. The search is based on 36.1 fb\(^{−1}\) of \(pp\) collisions at \(\sqrt{s}=13\) TeV recorded in 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. Data are analysed in the lepton-plus-jets final state, including at least one \(b\)-tagged jet and a large-radius jet identified as originating from the hadronic decay of a high-momentum \(W\) boson. No significant deviation from the Standard Model expectation is observed in the reconstructed \(T\) mass distribution. The observed 95% confidence level lower limit on the \(T\) mass are 1350 GeV assuming 100% branching ratio to \(Wb\). In the SU(2) singlet scenario, the lower mass limit is 1170 GeV. This search is also sensitive to a heavy vector-like \(B\) quark decaying to \(Wt\) and other final states. The results are thus reinterpreted to provide a 95% confidence level lower limit on the \(B\) quark mass at 1250 GeV assuming 100% branching ratio to \(Wt\); in the SU(2) singlet scenario, the limit is 1080 GeV. Mass limits on both \(T\) and \(B\) production are also set as a function of the decay branching ratios. The 100% branching ratio limits are found to be applicable to heavy vector-like \(Y\) and \(X\) production that decay to \(Wb\) and \(Wt\), respectively. KW - High energy physics KW - Exotics KW - Hadron-Hadron scattering (experiments) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172472 VL - 2017 IS - 141 ER - TY - JOUR T1 - Measurements of top quark spin observables in \(t\overline{t}\) events using dilepton final states in \(\sqrt{s}\) = 8 TeV \(pp\) collisions with the ATLAS detector JF - Journal of High Energy Physics N2 - Measurements of top quark spin observables in \(t\overline{t}\) events are presented based on 20.2 fb\(^{−1}\) of \(\sqrt{s}\) = 8 TeV proton-proton collisions recorded with the ATLAS detector at the LHC. The analysis is performed in the dilepton final state, characterised by the presence of two isolated leptons (electrons or muons). There are 15 observables, each sensitive to a different coefficient of the spin density matrix of \(t\overline{t}\) production, which are measured independently. Ten of these observables are measured for the first time. All of them are corrected for detector resolution and acceptance effects back to the parton and stable-particle levels. The measured values of the observables at parton level are compared to Standard Model predictions at next-to-leading order in QCD. The corrected distributions at stable-particle level are presented and the means of the distributions are compared to Monte Carlo predictions. No significant deviation from the Standard Model is observed for any observable. KW - High energy physics KW - Hadron-Hadron scattering (experiments) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173505 VL - 2017 IS - 03 ER - TY - JOUR A1 - Jannasch, Maren A1 - Weigel, Tobias A1 - Engelhardt, Lisa A1 - Wiezoreck, Judith A1 - Gaetzner, Sabine A1 - Walles, Heike A1 - Schmitz, Tobias A1 - Hansmann, Jan T1 - \({In}\) \({vitro}\) chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction JF - ALTEX - Alternatives to Animal Experimentation N2 - Surgical implantation of a biomaterial triggers foreign-body-induced fibrous encapsulation. Two major mechanisms of this complex physiological process are (I) chemotaxis of fibroblasts from surrounding tissue to the implant region, followed by (II) tissue remodeling. As an alternative to animal studies, we here propose a process-aligned \({in}\) \({vitro}\) test platform to investigate the material dependency of fibroblast chemotaxis and tissue remodeling mediated by material-resident macrophages. Embedded in a biomimetic three-dimensional collagen hydrogel, chemotaxis of fibroblasts in the direction of macrophage-material-conditioned cell culture supernatant was analyzed by live cell imaging. A combination of statistical analysis with a complementary parameterized random walk model allowed quantitative and qualitative characterization of the cellular walk process. We thereby identified an increasing macrophage-mediated chemotactic potential ranking of biomaterials from glass over polytetrafluorethylene to titanium. To address long-term effects of biomaterial-resident macrophages on fibroblasts in a three-dimensional microenvironment, we further studied tissue remodeling by applying macrophage-material-conditioned medium on fibrous \({in}\) \({vitro}\) tissue models. A high correlation of the \({in}\) \({vitro}\) tissue model to state of the art \({in}\) \({vivo}\) study data was found. Titanium exhibited a significantly lower tissue remodeling capacity compared to polytetrafluorethylene. With this approach, we identified a material dependency of both chemotaxis and tissue remodeling processes, strengthening knowledge on their specific contribution to the foreign body reaction. KW - medicine KW - foreign body reaction KW - fibroblast chemotaxis KW - tissue remodeling KW - in vitro KW - quanititative characterization Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172080 VL - 34 IS - 2 ER - TY - JOUR A1 - Beer, Katharina A1 - Joschinski, Jens A1 - Sastre, Alazne Arrazola A1 - Krauss, Jochen A1 - Helfrich-Förster, Charlotte T1 - A damping circadian clock drives weak oscillations in metabolism and locomotor activity of aphids (Acyrthosiphon pisum) JF - Scientific Reports N2 - Timing seasonal events, like reproduction or diapause, is crucial for the survival of many species. Global change causes phenologies worldwide to shift, which requires a mechanistic explanation of seasonal time measurement. Day length (photoperiod) is a reliable indicator of winter arrival, but it remains unclear how exactly species measure day length. A reference for time of day could be provided by a circadian clock, by an hourglass clock, or, as some newer models suggest, by a damped circadian clock. However, damping of clock outputs has so far been rarely observed. To study putative clock outputs of Acyrthosiphon pisum aphids, we raised individual nymphs on coloured artificial diet, and measured rhythms in metabolic activity in light-dark illumination cycles of 16:08 hours (LD) and constant conditions (DD). In addition, we kept individuals in a novel monitoring setup and measured locomotor activity. We found that A. pisum is day-active in LD, potentially with a bimodal distribution. In constant darkness rhythmicity of locomotor behaviour persisted in some individuals, but patterns were mostly complex with several predominant periods. Metabolic activity, on the other hand, damped quickly. A damped circadian clock, potentially driven by multiple oscillator populations, is the most likely explanation of our results. KW - circadian mechanisms KW - behavioural ecology KW - damped circadian clock KW - Acyrthosiphon pisum Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170020 VL - 7 IS - 14906 ER - TY - JOUR A1 - Arenas, Andrés A1 - Roces, Flavio T1 - Avoidance of plants unsuitable for the symbiotic fungus in leaf-cutting ants: Learning can take place entirely at the colony dump JF - PLoS ONE N2 - Plants initially accepted by foraging leaf-cutting ants are later avoided if they prove unsuitable for their symbiotic fungus. Plant avoidance is mediated by the waste produced in the fungus garden soon after the incorporation of the unsuitable leaves, as foragers can learn plant odors and cues from the damaged fungus that are both present in the recently produced waste particles. We asked whether avoidance learning of plants unsuitable for the symbiotic fungus can take place entirely at the colony dump. In order to investigate whether cues available in the waste chamber induce plant avoidance in naïve subcolonies, we exchanged the waste produced by subcolonies fed either fungicide-treated privet leaves or untreated leaves and measured the acceptance of untreated privet leaves before and after the exchange of waste. Second, we evaluated whether foragers could perceive the avoidance cues directly at the dump by quantifying the visits of labeled foragers to the waste chamber. Finally, we asked whether foragers learn to specifically avoid untreated leaves of a plant after a confinement over 3 hours in the dump of subcolonies that were previously fed fungicide-treated leaves of that species. After the exchange of the waste chambers, workers from subcolonies that had access to waste from fungicide-treated privet leaves learned to avoid that plant. One-third of the labeled foragers visited the dump. Furthermore, naïve foragers learned to avoid a specific, previously unsuitable plant if exposed solely to cues of the dump during confinement. We suggest that cues at the dump enable foragers to predict the unsuitable effects of plants even if they had never been experienced in the fungus garden. KW - leaves KW - ants KW - fungi KW - foraging KW - animal sociality KW - social systems KW - learning KW - symbiosis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157559 VL - 12 IS - 3 ER - TY - JOUR T1 - Top-quark mass measurement in the all-hadronic \(t\overline{t}\) decay channel at \(\sqrt{s}=8\) TeV with the ATLAS detector JF - Journal of High Energy Physics N2 - The top-quark mass is measured in the all-hadronic top-antitop quark decay channel using proton-proton collisions at a centre-of-mass energy of \(\sqrt{s}=8\) TeV with the ATLAS detector at the CERN Large Hadron Collider. The data set used in the analysis corresponds to an integrated luminosity of 20.2 fb\(^{−1}\). The large multi-jet background is modelled using a data-driven method. The top-quark mass is obtained from template fits to the ratio of the three-jet to the dijet mass. The three-jet mass is obtained from the three jets assigned to the top quark decay. From these three jets the dijet mass is obtained using the two jets assigned to the W boson decay. The top-quark mass is measured to be 173.72 ± 0.55 (stat.) ± 1.01 (syst.) GeV. KW - High energy physics KW - Hadron-Hadron scattering (experiments) KW - Top physics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172762 VL - 2017 IS - 09 ER - TY - JOUR A1 - Banks, Sarah A1 - Millard, Koreen A1 - Behnamian, Amir A1 - White, Lori A1 - Ullmann, Tobias A1 - Charbonneau, Francois A1 - Chen, Zhaohua A1 - Wang, Huili A1 - Pasher, Jon A1 - Duffe, Jason T1 - Contributions of actual and simulated satellite SAR data for substrate type differentiation and shoreline mapping in the Canadian Arctic JF - Remote Sensing N2 - Detailed information on the land cover types present and the horizontal position of the land–water interface is needed for sensitive coastal ecosystems throughout the Arctic, both to establish baselines against which the impacts of climate change can be assessed and to inform response operations in the event of environmental emergencies such as oil spills. Previous work has demonstrated potential for accurate classification via fusion of optical and SAR data, though what contribution either makes to model accuracy is not well established, nor is it clear what shorelines can be classified using optical or SAR data alone. In this research, we evaluate the relative value of quad pol RADARSAT-2 and Landsat 5 data for shoreline mapping by individually excluding both datasets from Random Forest models used to classify images acquired over Nunavut, Canada. In anticipation of the RADARSAT Constellation Mission (RCM), we also simulate and evaluate dual and compact polarimetric imagery for shoreline mapping. Results show that SAR data is needed for accurate discrimination of substrates as user’s and producer’s accuracies were 5–24% higher for models constructed with quad pol RADARSAT-2 and DEM data than models constructed with Landsat 5 and DEM data. Models based on simulated RCM and DEM data achieved significantly lower overall accuracies (71–77%) than models based on quad pol RADARSAT-2 and DEM data (80%), with Wetland and Tundra being most adversely affected. When classified together with Landsat 5 and DEM data, however, model accuracy was less affected by the SAR data type, with multiple polarizations and modes achieving independent overall accuracies within a range acceptable for operational mapping, at 89–91%. RCM is expected to contribute positively to ongoing efforts to monitor change and improve emergency preparedness throughout the Arctic. KW - geography KW - RADARSAT-2 KW - RADARSAT Constellation Mission KW - Random Forests KW - Arctic KW - shorelines Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172630 VL - 9 IS - 12 ER - TY - JOUR T1 - Search for new high-mass phenomena in the dilepton final state using 36 fb\(^{−1}\) of proton-proton collision data at \(\sqrt{s}=13\) TeV with the ATLAS detector JF - Journal of High Energy Physics N2 - A search is conducted for new resonant and non-resonant high-mass phenomena in dielectron and dimuon final states. The search uses 36.1 fb\(^{−1}\) of proton-proton collision data, collected at \(\sqrt{s}=13\) TeV by the ATLAS experiment at the LHC in 2015 and 2016. No significant deviation from the Standard Model prediction is observed. Upper limits at 95% credibility level are set on the cross-section times branching ratio for resonances decaying into dileptons, which are converted to lower limits on the resonance mass, up to 4.1 TeV for the E\(_6\)-motivated \(Z^′_χ\). Lower limits on the \({qqℓℓ}\) contact interaction scale are set between 2.4 TeV and 40 TeV, depending on the model. KW - High energy physics KW - Beyond Standard Model KW - Hadron-Hadron scattering (experiments) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172462 VL - 2017 IS - 182 ER - TY - JOUR T1 - Measurement of the inclusive jet cross-sections in proton-proton collisions at \(\sqrt{s}=8\) TeV with the ATLAS detector JF - Journal of High Energy Physics N2 - Inclusive jet production cross-sections are measured in proton-proton collisions at a centre-of-mass energy of \(\sqrt{s} = 8\) TeV recorded by the ATLAS experiment at the Large Hadron Collider at CERN. The total integrated luminosity of the analysed data set amounts to 20.2 fb\(^{−1}\). Double-differential cross-sections are measured for jets defined by the anti-\(k_t\) jet clustering algorithm with radius parameters of \(R\) = 0.4 and \(R\) = 0.6 and are presented as a function of the jet transverse momentum, in the range between 70 GeV and 2.5 TeV and in six bins of the absolute jet rapidity, between 0 and 3.0. The measured cross-sections are compared to predictions of quantum chromodynamics, calculated at next-to-leading order in perturbation theory, and corrected for non-perturbative and electroweak effects. The level of agreement with predictions, using a selection of different parton distribution functions for the proton, is quantified. Tensions between the data and the theory predictions are observed. KW - High energy physics KW - Hadron-Hadron scattering (experiments) KW - Jet physics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173123 VL - 2017 IS - 09 ER - TY - JOUR T1 - Search for direct top squark pair production in events with a Higgs or \(Z\) boson, and missing transverse momentum in \(\sqrt{s}\) = 13 TeV \(pp\) collisions with the ATLAS detector JF - Journal of High Energy Physics N2 - A search for direct top squark pair production resulting in events with either a same-flavour opposite-sign dilepton pair with invariant mass compatible with a \(Z\) boson or a pair of jets compatible with a Standard Model (SM) Higgs boson (\(h\)) is presented. Requirements on the missing transverse momentum, together with additional selections on leptons, jets, jets identified as originating from \(b\)-quarks are imposed to target the other decay products of the top squark pair. The analysis is performed using proton-proton collision data at \(\sqrt{s}\) = 13 TeV collected with the ATLAS detector at the LHC in 2015–2016, corresponding to an integrated luminosity of 36.1 fb\(^{-1}\). No excess is observed in the data with respect to the SM predictions. The results are interpreted in two sets of models. In the first set, direct production of pairs of lighter top squarks (\(\tilde{t}_1\)) with long decay chains involving \(Z\) or Higgs bosons is considered. The second set includes direct pair production of the heavier top squark pairs (\(\tilde{t}_2\)) decaying via \(\tilde{t}_2\) → \(Z\tilde{t}_1\) or \(\tilde{t}_2\) → \(h\tilde{t}_1\). The results exclude at 95% confidence level \(\tilde{t}_2\) and \(\tilde{t}_1\) masses up to about 800 GeV, extending the exclusion region of supersymmetric parameter space covered by previous LHC searches. KW - High energy physics KW - Beyond Standard Model KW - Hadron-Hadron scattering (experiments) KW - Higgs physics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173210 VL - 2017 IS - 08 ER - TY - JOUR A1 - Baur, Johannes A1 - Büntemeyer, Tjark-Ole A1 - Megerle, Felix A1 - Deutschbein, Timo A1 - Spitzweg, Christine A1 - Quinkler, Marcus A1 - Nawroth, Peter A1 - Kroiss, Matthias A1 - Germer, Christoph-Thomas A1 - Fassnacht, Martin A1 - Steger, Ulrich T1 - Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study JF - BMC Cancer N2 - Background: Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC. Methods: A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included. Results: Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival. Conclusions: Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome. KW - Adrenocortical Carcinoma KW - liver resection KW - retrospective study KW - prognosis KW - survival analysis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159409 VL - 17 IS - 522 ER - TY - JOUR A1 - Appelt-Menzel, Antje A1 - Cubukova, Alevtina A1 - Günther, Katharina A1 - Edenhofer, Frank A1 - Piontek, Jörg A1 - Krause, Gerd A1 - Stüber, Tanja A1 - Walles, Heike A1 - Neuhaus, Winfried A1 - Metzger, Marco T1 - Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells JF - Stem Cell Reports N2 - In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm\(^{2}\) and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies. KW - blood-brain barrier (BBB) model KW - human induced pluripotent stem cells (hiPSCs)human induced pluripotent stem cells (hiPSCs) KW - multipotent fetal neural stem cells (fNSCs) KW - neurovascular unit in vitro Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170982 VL - 8 IS - 4 ER - TY - JOUR A1 - Wagner, Martin A1 - Wanner, Christoph A1 - Schich, Martin A1 - Kotseva, Kornelia A1 - Wood, David A1 - Hartmann, Katrin A1 - Fette, Georg A1 - Rücker, Viktoria A1 - Oezkur, Mehmet A1 - Störk, Stefan A1 - Heuschmann, Peter U. T1 - Patient’s and physician’s awareness of kidney disease in coronary heart disease patients – a cross-sectional analysis of the German subset of the EUROASPIRE IV survey JF - BMC Nephrology N2 - Background Chronic kidney disease (CKD) is a common comorbid condition in coronary heart disease (CHD). CKD predisposes the patient to acute kidney injury (AKI) during hospitalization. Data on awareness of kidney dysfunction among CHD patients and their treating physicians are lacking. In the current cross-sectional analysis of the German EUROASPIRE IV sample we aimed to investigate the physician’s awareness of kidney disease of patients hospitalized for CHD and also the patient’s awareness of CKD in a study visit following hospital discharge. Methods All serum creatinine (SCr) values measured during the hospital stay were used to describe impaired kidney function (eGFR\(_{CKD-EPI}\) < 60 ml/min/1.73m2) at admission, discharge and episodes of AKI (KDIGO definition). Information extracted from hospital discharge letters and correct ICD coding for kidney disease was studied as a surrogate of physician’s awareness of kidney disease. All patients were interrogated 0.5 to 3 years after hospital discharge, whether they had ever been told about kidney disease by a physician. Results Of the 536 patients, 32% had evidence for acute or chronic kidney disease during the index hospital stay. Either condition was mentioned in the discharge letter in 22%, and 72% were correctly coded according to ICD-10. At the study visit in the outpatient setting 35% had impaired kidney function. Of 158 patients with kidney disease, 54 (34%) were aware of CKD. Determinants of patient’s awareness were severity of CKD (OR\(_{eGFR}\) 0.94; 95%CI 0.92–0.96), obesity (OR 1.97; 1.07–3.64), history of heart failure (OR 1.99; 1.00–3.97), and mentioning of kidney disease in the index event’s hospital discharge letter (OR 5.51; 2.35–12.9). Conclusions Although CKD is frequent in CHD, only one third of patients is aware of this condition. Patient’s awareness was associated with kidney disease being mentioned in the hospital discharge letter. Future studies should examine how raising physician’s awareness for kidney dysfunction may improve patient’s awareness of CKD. KW - coronary heart disease KW - ICD-coding of CKD KW - chronic kidney disease KW - patients’ awareness KW - physicians’ awareness KW - EUROASPIRE survey Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158387 VL - 18 IS - 321 ER - TY - JOUR A1 - Deacon, R. S. A1 - Wiedenmann, J. A1 - Bocquillon, E. A1 - Domínguez, F. A1 - Klapwijk, T. M. A1 - Leubner, P. A1 - Brüne, C. A1 - Hankiewicz, E. M. A1 - Tarucha, S. A1 - Ishibashi, K. A1 - Buhmann, H. A1 - Molenkamp, L. W. T1 - Josephson Radiation from Gapless Andreev Bound States in HgTe-Based Topological Junctions JF - Physical Review X N2 - Frequency analysis of the rf emission of oscillating Josephson supercurrent is a powerful passive way of probing properties of topological Josephson junctions. In particular, measurements of the Josephson emission enable the detection of topological gapless Andreev bound states that give rise to emission at half the Josephson frequency f\(_{J}\) rather than conventional emission at f\(_{J}\). Here, we report direct measurement of rf emission spectra on Josephson junctions made of HgTe-based gate-tunable topological weak links. The emission spectra exhibit a clear signal at half the Josephson frequency f\(_{J}\)/2. The linewidths of emission lines indicate a coherence time of 0.3–4 ns for the f\(_{J}\)/2 line, much shorter than for the f\(_{J}\) line (3–4 ns). These observations strongly point towards the presence of topological gapless Andreev bound states and pave the way for a future HgTe-based platform for topological quantum computation. KW - condensed matter physics KW - Josephson junctions KW - topological materials KW - gapless Andreev bound states Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170969 VL - 7 IS - 021011 ER - TY - JOUR A1 - Arnholdt, Jörg A1 - Gilbert, Fabian A1 - Blank, Marc A1 - Papazoglou, Jannis A1 - Rudert, Maximilian A1 - Nöth, Ulrich A1 - Steinert, Andre F. T1 - The Mayo conservative hip: complication analysis and management of the first 41 cases performed at a University level 1 department JF - BMC Muskoskeletal Disorders N2 - Background: To prevent bone loss in hip arthroplasty, several short stem systems have been developed, including the Mayo conservative hip system. While there is a plethora of data confirming inherent advantages of these systems, only little is known about potential complications, especially when surgeons start to use these systems. Methods: In this study, we present a retrospective analysis of the patients’ outcome, complications and the complication management of the first 41 Mayo conservative hips performed in 37 patients. For this reason, functional scores, radiographic analyses, peri- and postoperative complications were assessed at an average follow-up of 35 months. Results: The overall HHS improved from 61.2 pre-operatively to 85.6 post-operatively. The German Extra Short Musculoskeletal Function Assessment Questionnaire (XSFMA-D) improved from 30.3 pre-operatively to 12.2 post-operatively. The most common complication was an intraoperative non-displaced fracture of the proximal femur observed in 5 cases (12.1%). Diabetes, higher BMI and older ages were shown to be risk factors for these intra-operative periprosthetic fractures (p < 0.01). Radiographic analysis revealed a good offset reconstruction in all cases. Conclusion: In our series, a high complication rate with 12.1% of non-displaced proximal femoral fractures was observed using the Mayo conservative hip. This may be attributed to the flat learning curve of the system or the inherent patient characteristics of the presented cohort." KW - total hip arthroplasty KW - short hip stem KW - mayo stem KW - minimal invasive surgery Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157812 VL - 18 IS - 250 ER - TY - JOUR A1 - Jakubietz, Michael G. A1 - Meffert, Rainer H. A1 - Schmidt, Karsten A1 - Gruenert, Joerg G. A1 - Jakubietz, Rafael G. T1 - Acute A4 Pulley Reconstruction with a First Extensor Compartment Onlay Graft JF - Plastic and Reconstructive Surgery Global Open N2 - Background: The integrity of the flexor tendon pulley apparatus is crucial for unimpaired function of the digits. Although secondary reconstruction is an established procedure in multi-pulley injuries, acute reconstruction of isolated, closed pulley ruptures is a rare occurrence. There are 3 factors influencing the functional outcome of a reconstruction: gapping distance between tendon and bone (E-space), bulkiness of the reconstruction, and stability. As direct repair is rarely done, grafts are used to reinforce the pulley. An advantage of the first extensor retinaculum graft is the synovial coating providing the possibility to be used both as a direct graft with synovial coating or as an onlay graft after removal of the synovia when the native synovial layer is present. Methods: A graft from the first dorsal extensor compartment is used as an onlay graft to reinforce the sutured A4 pulley. This technique allows reconstruction of the original dimensions of the pulley system while stability is ensured by anchoring the onlay graft to the bony insertions of the pulley. Results: Anatomical reconstruction can be achieved with this method. The measured E-space remained 0 mm throughout the recovery, while the graft incorporated as a slim reinforcement of the pulley, displaying no bulkiness. Conclusions: The ideal reconstruction should provide synovial coating and sufficient strength with minimal bulk. Early reconstruction using an onlay graft offers these options. The native synovial lining is preserved and the graft is used to reinforce the pulley. KW - surgery KW - pulley rupture Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158057 VL - 5 IS - 6 ER - TY - JOUR A1 - Jordan, Martin C. A1 - Bittrich, Leonie A. A1 - Fehske, Kai A1 - Meffert, Rainer H. A1 - Jansen, Hendrik T1 - A rare case of Hoffa fracture combined with lateral patellar dislocation JF - Trauma Case Reports N2 - The coronal unicondylar fracture of the distal femur (AO 33-B3) is a rare intraarticular injury within the weight bearing area of the knee, initially described by Albert Hoffa in 1904. We report an unusual combination of a Hoffa fracture with lateral patellar dislocation in a young adult. Our patient sustained the injury by a sudden twist of his leg during sports. He presented clinically with knee swelling, dislocation of the patella, and localized tenderness; unable to bare weight. After plane radiograph confirmed the injury, manual reduction of the patella was done by hyperextension of the knee and medialward pressure. Afterwards, a CT scan and MRI were conducted. The injury was surgically treated with lag-screws, locking-plate and MPFL-reconstruction. KW - dislocation KW - femur KW - fracture KW - Hoffa KW - MPFL KW - patella Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158315 VL - 9 ER - TY - THES A1 - Höhn, Stefan T1 - Geologischer Rahmen und Genese der Kupferberger Cu-Zn-Lagerstätte T1 - Geology, geochemistry and genesis of the Cu-Zn deposit at Kupferberg N2 - Bei der Cu-Zn-Lagerstätte bei Kupferberg, 10 km nordöstlich von Kulmbach, handelt es sich um Bayerns größten, historischen Buntmetallabbau. Der etwa 4 km lange Zug einzelner, stratiformer Erzlinsen befindet sich im Nordwesten in der parautochthonen Randschiefer Formation und im Südosten in der Prasinit-Phyllit Formation, die ein Teil der allochthonen Münchberger Gneismasse ist. Bisherige Versuche, die Genese der Lagerstätte zu erklären, scheiterten daran, den versatzlosen Übertritt einer stratiformen Lagerstätte über eine regional bedeutende Störungszone zu erklären. U-Pb Zirkondatierungen an mafischen und felsischen Vulkaniten im Umfeld der Lagerstätte bestätigten das Bild eines kambrisch-ordovizischen Extensionsvulkanismus. Das Fehlen von N-MORB-ähnlichen geochemischen Signaturen in den untersuchten Proben der gesamten südwestlichen, saxothuringischen Vogtland Synklinale deutet auf eine gescheiterte Riftbildung am Nordrand Gondwanas hin und setzt somit den geotektonischen Rahmen für die Ablagerung der Wirtsformation(en). Die Cu-Zn-Vererzung selbst liegt hier im Wesentlichen als Vergesellschaftung von Pyrit, Chalkopyrit, Sphalerit, Quarz und Kalzit in kohlenstoffreichem Tonschiefer vor. Die verschiedenen Untersuchungen an den beiden Erzlinsen zeigten, dass in der „St. Veits“ Erzlinse eine syngenetische Pyrit-Anreicherung mit charakteristisch niedrigen Co/Ni-Verhältnissen (ø = 3,7) vorliegt. Darüber hinaus konnte dort noch mindestens eine hydrothermale Pyrit-Generation (Co/Ni-Verhältnis ca. 35) nachgewiesen werden, die nur dort auftritt, wo auch Chalkopyrit angereichert ist und deutlich höhere Co/Ni-Verhältnisse aufweist (ø = 35). Die Ermittlung der Cu-Isotopenverhältnisse des Chalkopyrits zeigte ein δ65Cu-Spektrum von -0,26 bis 0,36 ‰, was stark für eine hydrothermale Anreicherung unter hohen (>250 °C) Temperaturbedingungen spricht. Während sich die Erzlinsen in der Randschiefer und Prasinit-Phyllit Formation hinsichtlich ihrer Sulfid-Mineralogie so ähnlich sind, dass sie bisher immer als eine Lagerstätte angesprochen wurden, erbrachte ein statistischer Vergleich der beiden δ34S-Datensätze, dass es sich hier nur mit einer Wahrscheinlichkeit von ca. 2 % um Stichproben der gleichen Grundgesamtheit handelt. Entsprechend liegen innerhalb der Kupferberger Lagerstätte zwei unterschiedliche Schichten, reich an syngenetischem Pyrit, vor. Die Tatsache, dass das δ34S-Spektrum potentieller Schwefelquellen für die hydrothermale Chalkopyrit-Mineralisation theoretisch sehr groß, de facto aber mit dem δ34S-Spektrum der syngenetischen Sulfidanreicherung fast identisch ist (δ34S = 3,2 ± 0,6 ‰ bzw. δ34S = 3,1 ± 0,9 ‰), spricht für eine schichtinterne Sulfidmobilisierung. Aus den hier erbrachten Ergebnissen wird ein genetisches Modell für die Kupferberger Lagerstätte geschlussfolgert, in dem jeweils eine der zahlreichen sedimentären, Pyrit-reichen Schichten aus der Randschiefer und der Prasinit-Phyllit Formation bei der Überschiebung der Münchberger Gneismasse tektonisch in Kontakt gebracht wurden. Im Zuge eben dieser Raumnahme der allochthonen Masse wurden Teile der Randschiefer Formation unter Grünschiefer-fazielle Bedingungen gebracht. Dabei kam es sowohl zur Freisetzung von Buntmetallen, die vorher zum Großteil in Pyrit gebunden waren, als auch zur Entwässerung der umliegenden Tonschiefer. Durch die überlagernden, impermeablen metamorphen Decken wurde das entstandene metallreiche Fluid an der Überschiebungsbahn kanalisiert. Durch den Druckabfall in der Spröde-Duktil-Übergangszone kam es zum Sieden des aufsteigenden Fluids, was zur Ausfällung der Sulfide führte. Die Bildung bedeutender Erzlinsen erfolgte vor allem dort, wo das übersättigte Fluid auf Pyrit-reiche Schwarzschiefer bzw. Phyllite traf. Da die Abbauwürdigkeit dieser Erzlinsen im Wesentlichen auf die epigenetische Überprägung im Zuge der Deckenüberschiebung zurückzuführen ist, handelt es sich bei der Kupferberger Cu-Zn-Vererzung um eines der seltenen Beispiele für eine tatsächliche metamorphogene bzw. syntektonische Buntmetalllagerstätte. N2 - Kupferberg is located c. 10 km in the east of Kulmbach in Upper Franconia (northeastern Bavaria). The stratiform Cu-Zn deposit represents Bavaria´s largest base metal deposit, for which up to now no decent genetic model existed. In the northeast, the c. 4 km long string of separate, stratiform ore lenses is part of the parautochthonous Randschiefer Formation and in the southeast, it is hosted by the high-grade, allochthonous Münchberg metamorphic complex. None of the previous investigations were able to explain, why this stratiform ore deposit cross-cuts on of the region´s major fault zones without any offset. The ore itself has a remarkably simple mineralogy, it consists mainly of pyrite with variable amounts of chalcopyrite and sphalerite, accompanied by quartz and calcite. Various investigations (among others U-Pb zircon dating, Cu- and S-isotopic analyses) revealed a two-stage genetic model for the Kupferberg Cu-Zn deposit: A syngenetic pyrite-enrichment and a hydrothermal sulfide-enrichment. The latter was the product of a syn-orogenic fluid-expulsion from beneath the Münchberg metamorphic complex, which makes Kupferberg a syntectonic, metamorphogenic base metal deposit. KW - Lagerstätte KW - Saxothuringikum KW - Kupferberg KW - Kupfer KW - Variszische Gebirgsbildung KW - Variszische Orogenese KW - Metamorphogen Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-155759 ER - TY - BOOK A1 - Brix, Kerstin T1 - Die deutsche Suetonübersetzung Jakob Vielfelds (1536). Transkript nach dem Digitalisat der Bayerischen Staatsbibliothek München (Res/2 A.lat.b. 705; VD16 S 10107) N2 - Der vorliegende Text ist das Transkript der ersten deutschen Gesamtübersetzung von Suetons Kaiserviten, die 1536 bei dem Straßburger Drucker Jakob Cammerlander erschien und die in der Dissertation „Sueton in Straßburg. Die Übersetzung der Kaiserviten durch Jakob Vielfeld (1536)“ (Spolia Berolinensia; Verlag Olms, Hildesheim 2017) umfassend untersucht worden ist. Das Transkript präsentiert diese Übersetzung, obwohl Digitalisate des Cammerlanderdruckes existieren. Dem liegt zugrunde, dass das Transkript im Zuge der erwähnten Dissertation entstand, deren Zentrum der direkte und detaillierte Textvergleich bildet; der Nachvollzug dieses Textvergleichs sollte mithilfe des entsprechend aufbereiteten Transkripts erleichtert werden. Außerdem war es das Ziel, neben den Detailuntersuchungen auch den bisher wenig beachteten deutschen Sueton als ganzen stärker zur Geltung zu bringen. Aber auch ohne die Konsultation der Studie kann das Transkript Grundlage für den bequemen Vergleich der Übersetzung mit dem lateinischen Text in der Referenzausgabe von Maximilian Ihm (editio maior, 1907) sein. Gegenüber dem digitalisierten Druck sind die deutschen Kaiserviten besonders durch zwei Eingriffe für moderne Leser aufbereitet worden: Zum einen enthält der frühneuzeitliche Druck keine Abschnittszählung, sodass es umständlicher ist, frühneuhochdeutsche Textstellen den entsprechenden Passagen in der Ausgabe Ihms zuzuordnen, und so ist das Transkript durchgängig mit Abschnittsziffern ausgestattet, die sich an der lateinischen Edition orientieren. Zum anderen kommen bei der Wiedergabe der deutschen Übersetzung – auch dies in Analogie zu Ihms Ausgabe – konsequent moderne Interpunktionsregeln zum Einsatz, wodurch sich die gedanklichen Strukturen des Textes leichter überblicken lassen und dieser insgesamt flüssiger zu lesen ist. KW - Vielfeld KW - Sueton KW - Suetonübersetzung KW - Kaiserviten KW - Cammerlander KW - Kaiserbiographien KW - De vita Caesarum KW - Übersetzung KW - 1536 KW - Straßburg Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152831 N1 - Transkript einer frühneuhochdeutschen Übersetzung als Begleitmaterial zu der im Buchhandel erschienenen Dissertation: "Brix, Kerstin: Sueton in Straßburg. - Hildesheim : Weidmann, 2017. - ISBN: 978-3-615-00427-4" ER - TY - JOUR A1 - Born, Dennis‐Peter A1 - Kunz, Philipp A1 - Sperlich, Billy T1 - Reliability and validity of an agility‐like incremental exercise test with multidirectional change‐of‐direction movements in response to a visual stimulus JF - Physiological Reports N2 - The aim of the study was to evaluate the reliability and validity of cardiorespiratory and metabolic variables, that is, peak oxygen uptake (V'O\(_{2peak}\)) and heart rate (HR\(_{peak}\)), obtained from an agility‐like incremental exercise test for team sport athletes. To investigate the test–retest reliability, 25 team sport athletes (age: 22 ± 3 years, body mass: 75 ± 7 kg, height: 182 ± 6 cm) performed an agility‐like incremental exercise test on the SpeedCourt (SC) system incorporating multidirectional change‐of‐direction (COD) movements twice. For each step of the incremental SC test, the athletes covered a 40‐m distance interspersed with a 10‐sec rest period. Each 40 m distance was split into short sprints (2.25–6.36 m) separated by multidirectional COD movements (0°–180°), which were performed in response to an external visual stimulus. All performance and physiological data were validated with variables obtained from a ramp‐like treadmill and Yo‐Yo intermittent recovery level 2 test (Yo‐Yo IR2). The incremental SC test revealed high test–retest reliability for the time to exhaustion (ICC = 0.85, typical error [TE] = 0.44, and CV% = 3.88), V'O\(_{2peak}\), HR\(_{peak}\), ventilation, and breathing frequency (ICC = 0.84, 0.72, 0.89, 0.77, respectively). The time to exhaustion (r = 0.50, 0.74) of the incremental SC test as well as the peak values for V'O\(_{2}\) (r = 0.59, 0.52), HR (r = 0.75, 0.78), ventilation (r = 0.57, 0.57), and breathing frequency (r = 0.68, 0.68) were significantly correlated (P ≤ 0.01) with the ramp‐like treadmill test and the Yo‐Yo IR2, respectively. The incremental SC test represents a reliable and valid method to assess peak values for V'O\(_{2}\) and HR with respect to the specific demand of team sport match play by incorporating multidirectional COD movements, decision making, and cognitive components. KW - speed KW - Yo‐Yo intermittent recovery KW - change‐of‐direction movement KW - repeated sprint ability KW - team sport Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158265 VL - 5 IS - 9 ER - TY - JOUR A1 - Kaiser, Sebastian A1 - Sauer, Florian A1 - Kisker, Caroline T1 - The structural and functional characterization of human RecQ4 reveals insights into its helicase mechanism JF - Nature Communications N2 - RecQ4 is a member of the RecQ helicase family, an evolutionarily conserved class of enzymes, dedicated to preserving genomic integrity by operating in telomere maintenance, DNA repair and replication. While reduced RecQ4 activity is associated with cancer predisposition and premature aging, RecQ4 upregulation is related to carcinogenesis and metastasis. Within the RecQ family, RecQ4 assumes an exceptional position, lacking several characteristic RecQ domains. Here we present the crystal structure of human RecQ4, encompassing the conserved ATPase core and a novel C-terminal domain that lacks resemblance to the RQC domain observed in other RecQ helicases. The new domain features a zinc-binding site and two distinct types of winged-helix domains, which are not involved in canonical DNA binding or helicase activity. Based on our structural and functional analysis, we propose that RecQ4 exerts a helicase mechanism, which may be more closely related to bacterial RecQ helicases than to its human family members. KW - x-ray crystallography KW - enzymes KW - RecQ4 KW - humans Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170769 VL - 8 IS - 15907 ER - TY - JOUR A1 - Ruf, Franziska A1 - Fraunholz, Martin A1 - Öchsner, Konrad A1 - Kaderschabeck, Johann A1 - Wegener, Christian T1 - WEclMon - A simple and robust camera-based system to monitor Drosophila eclosion under optogenetic manipulation and natural conditions JF - PLoS ONE N2 - Eclosion in flies and other insects is a circadian-gated behaviour under control of a central and a peripheral clock. It is not influenced by the motivational state of an animal, and thus presents an ideal paradigm to study the relation and signalling pathways between central and peripheral clocks, and downstream peptidergic regulatory systems. Little is known, however, about eclosion rhythmicity under natural conditions, and research into this direction is hampered by the physically closed design of current eclosion monitoring systems. We describe a novel open eclosion monitoring system (WEclMon) that allows the puparia to come into direct contact with light, temperature and humidity. We demonstrate that the system can be used both in the laboratory and outdoors, and shows a performance similar to commercial closed funnel-type monitors. Data analysis is semi-automated based on a macro toolset for the open imaging software Fiji. Due to its open design, the WEclMon is also well suited for optogenetic experiments. A small screen to identify putative neuroendocrine signals mediating time from the central clock to initiate eclosion showed that optogenetic activation of ETH-, EH and myosuppressin neurons can induce precocious eclosion. Genetic ablation of myosuppressin-expressing neurons did, however, not affect eclosion rhythmicity. KW - chronobiology KW - infrared radiation KW - light pulses KW - molting KW - Drosophila melanogaster KW - optogenetics KW - eclosion Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170755 VL - 12 IS - 6 ER - TY - JOUR A1 - Hillmann, Steffi A1 - Wiedmann, Silke A1 - Rücker, Viktoria A1 - Berger, Klaus A1 - Nabavi, Darius A1 - Bruder, Ingo A1 - Koennecke, Hans-Christian A1 - Seidel, Günter A1 - Misselwitz, Björn A1 - Janssen, Alfred A1 - Burmeister, Christoph A1 - Matthis, Christine A1 - Busse, Otto A1 - Hermanek, Peter A1 - Heuschmann, Peter Ulrich T1 - Stroke unit care in Germany: the German stroke registers study group (ADSR) JF - BMC Neurology N2 - Background: Factors influencing access to stroke unit (SU) care and data on quality of SU care in Germany are scarce. We investigated characteristics of patients directly admitted to a SU as well as patient-related and structural factors influencing adherence to predefined indicators of quality of acute stroke care across hospitals providing SU care. Methods: Data were derived from the German Stroke Registers Study Group (ADSR), a voluntary network of 9 regional registers for monitoring quality of acute stroke care in Germany. Multivariable logistic regression analyses were performed to investigate characteristics influencing direct admission to SU. Generalized Linear Mixed Models (GLMM) were used to estimate the influence of structural hospital characteristics (percentage of patients admitted to SU, year of SU-certification, and number of stroke and TIA patients treated per year) on adherence to predefined quality indicators. Results: In 2012 180,887 patients were treated in 255 hospitals providing certified SU care participating within the ADSR were included in the analysis; of those 82.4% were directly admitted to a SU. Ischemic stroke patients without disturbances of consciousness (p < .0001), an interval onset to admission time ≤3 h (p < .0001), and weekend admission (p < .0001) were more likely to be directly admitted to a SU. A higher proportion of quality indicators within predefined target ranges were achieved in hospitals with a higher proportion of SU admission (p = 0.0002). Quality of stroke care could be maintained even if certification was several years ago. Conclusions: Differences in demographical and clinical characteristics regarding the probability of SU admission were observed. The influence of structural characteristics on adherence to evidence-based quality indicators was low. KW - stroke register KW - stroke unit care KW - quality of health care KW - quality indicators Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159447 VL - 17 IS - 49 ER - TY - JOUR A1 - Bening, Constanze A1 - Hamouda, Khaled A1 - Oezkur, Mehmet A1 - Schimmer, Christoph A1 - Schade, Ina A1 - Gorski, Armin A1 - Aleksic, Ivan A1 - Leyh, Rainer T1 - Rapid deployment valve system shortens operative times for aortic valve replacement through right anterior minithoracotomy JF - Journal of Cardiothoracic Surgery N2 - Background: There is growing evidence from the literature that right anterior minithoracotomy aortic valve replacement (RAT-AVR) improves clinical outcome. However, increased cross clamp time is the strongest argument for surgeons not performing RAT-AVR. Rapid deployment aortic valve systems have the potential to decrease cross-clamp time and ease this procedure. We assessed clinical outcome of rapid deployment and conventional valves through RAT. Methods: Sixty-eight patients (mean age 76 ± 6 years, 32% females) underwent RAT-AVR between 9/2013 and 7/2015. According to the valve type implanted the patients were divided into two groups. In 43 patients (R-group; mean age 74.1 ± 6.6 years) a rapid deployment valve system (Edwards Intuity, Edwards Lifesciences Corp; Irvine, Calif) and in 25 patients (C-group; mean age 74.2 ± 6.6 years) a conventional stented biological aortic valve was implanted. Results: Aortic cross-clamp (42.1 ± 12 min vs. 68.3 ± 20.3 min; p < 0.001) and bypass time (80.4 ± 39.3 min vs. 106.6 ± 23.2 min; p = 0.001) were shorter in the rapid deployment group (R-group). We observed no differences in clinical outcome. Postoperative gradients (R-group: max gradient, 14.3 ± 8 mmHg vs. 15.5 ± 5 mmHg (C-group), mean gradient, 9.2 ± 1.7 mmHg (R-group) vs. 9.1 ± 2.3 mmHg (C-group) revealed no differences. However, larger prostheses were implanted in C-group (25 mm; IQR 23–27 mm vs. 23 mm; IQR 21–25; p = 0.009). Conclusions: Our data suggest that the rapid deployment aortic valve system reduced cross clamp and bypass time in patients undergoing RAT-AVR with similar hemodynamics as with larger size stented prosthesis. However, larger studies and long-term follow-up are mandatory to confirm our findings. KW - aortic valve replacement KW - minimally invasive surgery KW - heart valve prosthesis KW - biological rapid deployment aortic valve Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159439 VL - 12 IS - 27 ER - TY - JOUR A1 - Düking, Peter A1 - Holmberg, Hans-Christer A1 - Sperlich, Billy T1 - Instant Biofeedback Provided by Wearable Sensor Technology Can Help to Optimize Exercise and Prevent Injury and Overuse JF - Frontiers in Physiology KW - sports KW - training optimization KW - performance monitoring KW - health monitoring KW - technology KW - coaching Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158044 VL - 8 IS - 167 ER - TY - JOUR A1 - Helmprobst, Frederik A1 - Lillesaar, Christina A1 - Stigloher, Christian T1 - Expression of sept3, sept5a and sept5b in the Developing and Adult Nervous System of the Zebrafish (Danio rerio) JF - Frontiers in Neuroanatomy N2 - Septins are a highly conserved family of small GTPases that form cytoskeletal filaments. Their cellular functions, especially in the nervous system, still remain largely enigmatic, but there are accumulating lines of evidence that septins play important roles in neuronal physiology and pathology. In order to further dissect septin function in the nervous system a detailed temporal resolved analysis in the genetically well tractable model vertebrate zebrafish (Danio rerio) is crucially necessary. To close this knowledge gap we here provide a reference dataset describing the expression of selected septins (sept3, sept5a and sept5b) in the zebrafish central nervous system. Strikingly, proliferation zones are devoid of expression of all three septins investigated, suggesting that they have a role in post-mitotic neural cells. Our finding that three septins are mainly expressed in non-proliferative regions was further confirmed by double-stainings with a proliferative marker. Our RNA in situ hybridization (ISH) study, detecting sept3, sept5a and sept5b mRNAs, shows that all three septins are expressed in largely overlapping regions of the developing brain. However, the expression of sept5a is much more confined compared to sept3 and sept5b. In contrast, the expression of all the three analyzed septins is largely similar in the adult brain. KW - retinal development KW - sept5b KW - septin KW - RNA in situ hybridization KW - neuronal development KW - sept3 KW - sept5a Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157625 VL - 11 IS - 6 ER - TY - JOUR A1 - Lilla, Nadine A1 - Füllgraf, Hannah A1 - Stetter, Christian A1 - Köhler, Stefan A1 - Ernestus, Ralf-Ingo A1 - Westermaier, Thomas T1 - First Description of Reduced Pyruvate Dehydrogenase Enzyme Activity Following Subarachnoid Hemorrhage (SAH) JF - Frontiers in Neuroscience N2 - Object: Several previous studies reported metabolic derangements and an accumulation of metabolic products in the early phase of experimental subarachnoid hemorrhage (SAH), which may contribute to secondary brain damage. This may be a result of deranged oxygen utilization due to enzymatic dysfunction in aerobic glucose metabolism. This study was performed to investigate, if pyruvate dehydrogenase enzyme (PDH) is affected in its activity giving further hints for a derangement of oxidative metabolism. Methods: Eighteen male Sprague-Dawley rats were randomly assigned to one of two experimental groups (n = 9): (1) SAH induced by the endovascular filament model and (2) sham-operated controls. Mean arterial blood pressure (MABP), intracranial pressure (ICP), and local cerebral blood flow (LCBF; laser-Doppler flowmetry) were continuously monitored from 30 min before until 3 h after SAH. Thereafter, the animals were sacrificed and PDH activity was measured by ELISA. Results: PDH activity was significantly reduced in animals subjected to SAH compared to controls. Conclusion: The results of this study demonstrate for the first time a reduction of PDH activity following SAH, independent of supply of substrates and may be an independent factor contributing to a derangement of oxidative metabolism, failure of oxygen utilization, and secondary brain damage. KW - secondary brain damage KW - aerobic glycolysis KW - CBF KW - metabolism KW - PDH KW - SAH Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157636 VL - 11 IS - 37 ER - TY - JOUR A1 - Erdmenger, Johanna A1 - Hoyos, Carlos A1 - O'Bannon, Andy A1 - Papadimitriou, Ioannis A1 - Probst, Jonas A1 - Wu, Jackson M.S. T1 - Two-point functions in a holographic Kondo model JF - Journal of High Energy Physics N2 - We develop the formalism of holographic renormalization to compute two-point functions in a holographic Kondo model. The model describes a (0 + 1)-dimensional impurity spin of a gauged SU(N ) interacting with a (1 + 1)-dimensional, large-N , strongly-coupled Conformal Field Theory (CFT). We describe the impurity using Abrikosov pseudo-fermions, and define an SU(N )-invariant scalar operator O built from a pseudo-fermion and a CFT fermion. At large N the Kondo interaction is of the form O\(^{†}\)O, which is marginally relevant, and generates a Renormalization Group (RG) flow at the impurity. A second-order mean-field phase transition occurs in which O condenses below a critical temperature, leading to the Kondo effect, including screening of the impurity. Via holography, the phase transition is dual to holographic superconductivity in (1 + 1)-dimensional Anti-de Sitter space. At all temperatures, spectral functions of O exhibit a Fano resonance, characteristic of a continuum of states interacting with an isolated resonance. In contrast to Fano resonances observed for example in quantum dots, our continuum and resonance arise from a (0 + 1)-dimensional UV fixed point and RG flow, respectively. In the low-temperature phase, the resonance comes from a pole in the Green’s function of the form −i〈O〉\(^{2}\), which is characteristic of a Kondo resonance. KW - holography and condensed matter physics (AdS/CMT) KW - AdS-CFT Correspondence KW - gauge-gravity correspondence Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171139 VL - 3 IS - 39 ER - TY - JOUR A1 - Grabarczyk, Daniel B. A1 - Berks, Ben C. T1 - Intermediates in the Sox sulfur oxidation pathway are bound to a sulfane conjugate of the carrier protein SoxYZ JF - PLoS ONE N2 - The Sox pathway found in many sulfur bacteria oxidizes thiosulfate to sulfate. Pathway intermediates are covalently bound to a cysteine residue in the carrier protein SoxYZ. We have used biochemical complementation by SoxYZ-conjugates to probe the identity of the intermediates in the Sox pathway. We find that unconjugated SoxYZ and SoxYZ-S-sulfonate are unlikely to be intermediates during normal turnover in disagreement with current models. By contrast, conjugates with multiple sulfane atoms are readily metabolised by the Sox pathway. The most parsimonious interpretation of these data is that the true carrier species in the Sox pathway is a SoxYZ-S-sulfane adduct. KW - thiosulfates KW - oxidation KW - sulfur KW - cysteine KW - sulfides KW - thermodynamics KW - sulfates KW - sulfites Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171147 VL - 12 IS - 3 ER - TY - JOUR A1 - Pfister, Roland A1 - Schwarz, Katharina A. A1 - Wirth, Robert A1 - Lindner, Isabel T1 - My Command, My Act: Observation Inflation in Face-To-Face Interactions JF - Advances in Cognitive Psychology N2 - When observing another agent performing simple actions, these actions are systematically remembered as one’s own after a brief period of time. Such observation inflation has been documented as a robust phenomenon in studies in which participants passively observed videotaped actions. Whether observation inflation also holds for direct, face-to-face interactions is an open question that we addressed in two experiments. In Experiment 1, participants commanded the experimenter to carry out certain actions, and they indeed reported false memories of self-performance in a later memory test. The effect size of this inflation effect was similar to passive observation as confirmed by Experiment 2. These findings suggest that observation inflation might affect action memory in a broad range of real-world interactions. KW - observation inflation KW - memory bias KW - action observation KW - motor simulation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170739 VL - 13 IS - 2 ER - TY - JOUR A1 - Hofmann, Lukas A1 - Karl, Franziska A1 - Sommer, Claudia A1 - Üçeyler, Nurcan T1 - Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease JF - PLoS ONE N2 - Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A (α-Gal A) deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO) and compared results with those of age-matched male wildtype (WT) littermates. Young (3 months) and old (≥ 18 months) mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA) as an inflammatory pain model. We used the elevated plus maze (EPM), the light-dark box (LDB) and the open field test (OF) to investigate anxiety-like behavior. The forced swim test (FST) and Morris water maze (MWM) were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05). After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05) and naïve young Fabry KO mice (p<0.05) in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05). Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors. KW - cognitive impairment KW - mouse models KW - depression KW - swimming KW - learning KW - Fabry disease KW - genetics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170745 VL - 12 IS - 6 ER - TY - JOUR A1 - Dombert, Benjamin A1 - Balk, Stefanie A1 - Lüningschrör, Patrick A1 - Moradi, Mehri A1 - Sivadasan, Rajeeve A1 - Saal-Bauernschubert, Lena A1 - Jablonka, Sibylle T1 - BDNF/trkB induction of calcium transients through Ca\(_{v}\)2.2 calcium channels in motoneurons corresponds to F-actin assembly and growth cone formation on β2-chain laminin (221) JF - Frontiers in Molecular Neuroscience N2 - Spontaneous Ca\(^{2+}\) transients and actin dynamics in primary motoneurons correspond to cellular differentiation such as axon elongation and growth cone formation. Brain-derived neurotrophic factor (BDNF) and its receptor trkB support both motoneuron survival and synaptic differentiation. However, in motoneurons effects of BDNF/trkB signaling on spontaneous Ca\(^{2+}\) influx and actin dynamics at axonal growth cones are not fully unraveled. In our study we addressed the question how neurotrophic factor signaling corresponds to cell autonomous excitability and growth cone formation. Primary motoneurons from mouse embryos were cultured on the synapse specific, β2-chain containing laminin isoform (221) regulating axon elongation through spontaneous Ca\(^{2+}\) transients that are in turn induced by enhanced clustering of N-type specific voltage-gated Ca\(^{2+}\) channels (Ca\(_{v}\)2.2) in axonal growth cones. TrkB-deficient (trkBTK\(^{-/-}\)) mouse motoneurons which express no full-length trkB receptor and wildtype motoneurons cultured without BDNF exhibited reduced spontaneous Ca\(^{2+}\) transients that corresponded to altered axon elongation and defects in growth cone morphology which was accompanied by changes in the local actin cytoskeleton. Vice versa, the acute application of BDNF resulted in the induction of spontaneous Ca\(^{2+}\) transients and Ca\(_{v}\)2.2 clustering in motor growth cones, as well as the activation of trkB downstream signaling cascades which promoted the stabilization of β-actin via the LIM kinase pathway and phosphorylation of profilin at Tyr129. Finally, we identified a mutual regulation of neuronal excitability and actin dynamics in axonal growth cones of embryonic motoneurons cultured on laminin-221/211. Impaired excitability resulted in dysregulated axon extension and local actin cytoskeleton, whereas upon β-actin knockdown Ca\(_{v}\)2.2 clustering was affected. We conclude from our data that in embryonic motoneurons BDNF/trkB signaling contributes to axon elongation and growth cone formation through changes in the local actin cytoskeleton accompanied by increased Ca\(_{v}\)2.2 clustering and local calcium transients. These findings may help to explore cellular mechanisms which might be dysregulated during maturation of embryonic motoneurons leading to motoneuron disease. KW - growth cone KW - BDNF KW - trkB KW - Ca\(_{v}\)2.2 KW - F-actin KW - motor axon Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159094 VL - 10 IS - 346 ER - TY - JOUR A1 - Geiger, Julia A1 - Hirtler, Daniel A1 - Gottfried, Kristina A1 - Rahman, Ozair A1 - Bollache, Emilie A1 - Barker, Alex J. A1 - Markl, Michael A1 - Stiller, Brigitte T1 - Longitudinal Evaluation of Aortic Hemodynamics in Marfan Syndrome: New Insights from a 4D Flow Cardiovascular Magnetic Resonance Multi-Year Follow-Up Study JF - Journal of Cardiovascular Magnetic Resonance N2 - Background The aim of this 4D flow cardiovascular magnetic resonance (CMR) follow-up study was to investigate longitudinal changes in aortic hemodynamics in adolescent patients with Marfan syndrome (MFS). Methods 4D flow CMR for the assessment of in-vivo 3D blood flow with full coverage of the thoracic aorta was performed twice (baseline scan t1/follow-up scan t2) in 19 adolescent MFS patients (age at t1: 12.7 ± 3.6 years, t2: 16.2 ± 4.3 years) with a mean follow-up duration of 3.5 ± 1.2 years. Ten healthy volunteers (24 ± 3.8 years) served as a control group. Data analysis included aortic blood flow visualization by color-coded 3D pathlines, and grading of flow patterns (helices/vortices) on a 3-point scale (none, moderate, severe; blinded reading, 2 observers). Regional aortic peak systolic velocities and systolic 3D wall shear stress (WSS) along the entire aortic wall were quantified. Z-Scores of the aortic root and proximal descending aorta (DAo) were assessed. Results Regional systolic WSS was stable over the follow-up duration, except for a significant decrease in the proximal inner DAo segment (p = 0.02) between t1 and t2. MFS patients revealed significant lower mean systolic WSS in the proximal inner DAo compared with volunteers (0.78 ± 0.15 N/m\(^{2}\)) at baseline t1 (0.60 ± 0.18 N/m\(^{2}\); p = 0.01) and follow-up t2 (0.55 ± 0.16 N/m\(^{2}\); p = 0.001). There were significant relationships (p < 0.01) between the segmental WSS in the proximal inner DAo, DAo Z-scores (r = −0.64) and helix/vortex pattern grading (r = −0.55) at both t1 and t2. The interobserver agreement for secondary flow patterns assessment was excellent (Cohen’s k = 0.71). Conclusions MFS patients have lower segmental WSS in the inner proximal DAo segment which correlates with increased localized aberrant vortex/helix flow patterns and an enlarged diameter at one of the most critical sites for aortic dissection. General aortic hemodynamics are stable but these subtle localized DAo changes are already present at young age and tend to be more pronounced in the course of time. KW - Marfan syndrome KW - wall shear stress KW - hemodynamics KW - 4D flow cardiovascular magnetic resonance KW - follow-up KW - aorta Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171119 VL - 19 IS - 33 ER - TY - JOUR A1 - Fehrholz, Markus A1 - Glaser, Kirsten A1 - Speer, Christian P. A1 - Seidenspinner, Silvia A1 - Ottensmeier, Barbara A1 - Kunzmann, Steffen T1 - Caffeine modulates glucocorticoid-induced expression of CTGF in lung epithelial cells and fibroblasts JF - Respiratory Research N2 - Background: Although caffeine and glucocorticoids are frequently used to treat chronic lung disease in preterm neonates, potential interactions are largely unknown. While anti-inflammatory effects of glucocorticoids are well defined, their impact on airway remodeling is less characterized. Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling. Connective tissue growth factor (CTGF, CCN2) plays a key role in airway remodeling and has been implicated in the pathogenesis of chronic lung diseases such as bronchopulmonary dysplasia (BPD) in preterm infants. The current study addressed the impact of glucocorticoids on the regulation of CTGF in the presence of caffeine using human lung epithelial and fibroblast cells. Methods: The human airway epithelial cell line H441 and the fetal lung fibroblast strain IMR-90 were exposed to different glucocorticoids (dexamethasone, budesonide, betamethasone, prednisolone, hydrocortisone) and caffeine. mRNA and protein expression of CTGF, TGF-β1-3, and TNF-α were determined by means of quantitative real-time PCR and immunoblotting. H441 cells were additionally treated with cAMP, the adenylyl cyclase activator forskolin, and the selective phosphodiesterase (PDE)-4 inhibitor cilomilast to mimic caffeine-mediated PDE inhibition. Results: Treatment with different glucocorticoids (1 μM) significantly increased CTGF mRNA levels in H441 (p < 0.0001) and IMR-90 cells (p < 0.01). Upon simultaneous exposure to caffeine (10 mM), both glucocorticoid-induced mRNA and protein expression were significantly reduced in IMR-90 cells (p < 0.0001). Of note, 24 h exposure to caffeine alone significantly suppressed basal expression of CTGF mRNA and protein in IMR-90 cells. Caffeine-induced reduction of CTGF mRNA expression seemed to be independent of cAMP levels, adenylyl cyclase activation, or PDE-4 inhibition. While dexamethasone or caffeine treatment did not affect TGF-β1 mRNA in H441 cells, increased expression of TGF-β2 and TGF-β3 mRNA was detected upon exposure to dexamethasone or dexamethasone and caffeine, respectively. Moreover, caffeine increased TNF-α mRNA in H441 cells (6.5 ± 2.2-fold, p < 0.05) which has been described as potent inhibitor of CTGF expression. Conclusions: In addition to well-known anti-inflammatory features, glucocorticoids may have adverse effects on long-term remodeling by TGF-β1-independent induction of CTGF in lung cells. Simultaneous treatment with caffeine may attenuate glucocorticoid-induced expression of CTGF, thereby promoting restoration of lung homeostasis. KW - airway remodeling KW - fibrosis KW - bronchopulmonary dysplasia KW - caffeine KW - CCN2 KW - CTGF KW - glucocorticoids KW - H441 KW - IMR-90 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157672 VL - 18 IS - 51 ER - TY - JOUR A1 - Schindler, Julia A1 - Richter, Tobias A1 - Eyßer, Carolin T1 - Mood moderates the effect of self-generation during learning JF - Frontline Learning Research N2 - Generating information, compared to reading, improves learning and enhances long-term retention of the learned content. This so-called generation effect has been demonstrated repeatedly for recall and recognition of single words. However, before adopting generating as a learning strategy in educational contexts, conditions moderating the effect need to be identified. This study investigated the impact of positive and negative mood states on the generation effect with short expository texts. According to the dual-force framework (Fiedler, Nickel, Asbeck, & Pagel, 2003), positive mood should facilitate generation by enhancing creative knowledge-based top-down processing (assimilation). Negative mood, however, should facilitate learning in the read-condition by enhancing critical stimulus-driven bottom-up processing (accommodation). In contrast to our expectations, we found no general generation effect but an overall learning advantage of read compared to generated texts. However, a significant interaction of learning condition and mood indicates that learners in a better mood recall generated texts better than learners in a more negative mood, whereas no mood effect was found when the texts were read. The results of the present study partially support the predictions of the dual-force framework and are discussed in the context of recent theoretical approaches to the generation effect. KW - mood states KW - generation effect KW - learning with expository texts Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159282 VL - 5 IS - 4 ER -