@article{Scheer2018, author = {Scheer, Ulrich}, title = {Boveri's research at the Zoological Station Naples: Rediscovery of his original microscope slides at the University of W{\"u}rzburg}, series = {Marine Genomics}, volume = {40}, journal = {Marine Genomics}, doi = {10.1016/j.margen.2018.01.003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228453}, pages = {1-8}, year = {2018}, abstract = {Eric Davidson once wrote about Theodor Boveri: "From his own researches, and perhaps most important, his generalized interpretations, derive the paradigms that underlie modern inquiries into the genomic basis of embryogenesis" (Davidson, 1985). As luck would have it, the "primary data" of Boveri's experimental work, namely the microscope slides prepared by him and his wife Marcella during several stays at the Zoological Station in Naples (1901/02, 1911/12 and 1914), have survived at the University of Wurzburg. More than 600 slides exist and despite their age they are in a surprisingly good condition. The slides are labelled and dated in Boveri's handwriting and thus can be assigned to his published experimental work on sea urchin development. The results allowed Boveri to unravel the role of the cell nucleus and its chromosomes in development and inheritance. Here, I present an overview of the slides in the context of Boveri's work along with photographic images of selected specimens taken from the original slides. It is planned to examine the slides in more detail, take high-resolution focal image series of significant specimens and make them online available.}, language = {en} } @article{GrimmHufnagelWobseretal.2018, author = {Grimm, Johannes and Hufnagel, Anita and Wobser, Marion and Borst, Andreas and Haferkamp, Sebastian and Houben, Roland and Meierjohann, Svenja}, title = {BRAF inhibition causes resilience of melanoma cell lines by inducing the secretion of FGF1}, series = {Oncogenesis}, volume = {7}, journal = {Oncogenesis}, number = {71}, doi = {10.1038/s41389-018-0082-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177261}, year = {2018}, abstract = {Approximately half of all melanoma patients harbour activating mutations in the serine/threonine kinase BRAF. This is the basis for one of the main treatment strategies for this tumor type, the targeted therapy with BRAF and MEK inhibitors. While the initial responsiveness to these drugs is high, resistance develops after several months, frequently at sites of the previously responding tumor. This indicates that tumor response is incomplete and that a certain tumor fraction survives even in drug-sensitive patients, e.g., in a therapy-induced senescence-like state. Here, we show in several melanoma cell lines that BRAF inhibition induces a secretome with stimulating effect on fibroblasts and naive melanoma cells. Several senescence-associated factors were found to be transcribed and secreted in response to BRAF or MEK inhibition, among them members of the fibroblast growth factor family. We identified the growth factor FGF1 as mediator of resilience towards BRAF inhibition, which limits the pro-apoptotic effects of the drug and activates fibroblasts to secrete HGF. FGF1 regulation was mediated by the PI3K pathway and by FRA1, a direct target gene of the MAPK pathway. When FGFR inhibitors were applied in parallel to BRAF inhibitors, resilience was broken, thus providing a rationale for combined therapeutical application.}, language = {en} } @phdthesis{Weidner2018, author = {Weidner, Magdalena Theodora}, title = {Brain serotonin throughout development - for better and for worse}, publisher = {Magdalena T. Weidner}, address = {Maastricht, the Netherlands}, isbn = {978-94-6233-940-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163345}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {The work presented in this thesis covers the effects of early-life adversity in the context of altered serotonin (5-HT; 5-hydroxytryptamine) system functioning in mice. The main body is focussing on a screening approach identifying molecular processes, potentially involved in distinct behavioural manifestations that emerge from or are concomitant with early adversity and, with regard to some behavioural manifestations, dependent on the functioning of the 5-HT system.}, subject = {Gehirn}, language = {en} } @phdthesis{Botrel2018, author = {Botrel, Loic}, title = {Brain-computer interfaces (BCIs) based on sensorimotor rhythms - Evaluating practical interventions to improve their performance and reduce BCI inefficiency}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168110}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Brain computer interfaces based on sensorimotor rhythms modulation (SMR-BCIs) allow people to emit commands to an interface by imagining right hand, left hand or feet movements. The neurophysiological activation associated with those specific mental imageries can be measured by electroencephalography and detected by machine learning algorithms. Improvements for SMR-BCI accuracy in the last 30 years seem to have reached a limit. The currrent main issue with SMR-BCIs is that between 15\% to 30\% cannot use the BCI, called the "BCI inefficiency" issue. Alternatively to hardware and software improvements, investigating the individual characteristics of the BCI users has became an interesting approach to overcome BCI inefficiency. In this dissertation, I reviewed existing literature concerning the individual sources of variation in SMR-BCI accuracy and identified generic individual characteristics. In the empirical investigation, attention and motor dexterity predictors for SMR-BCI performance were implemented into a trainings that would manipulate those predictors and lead to higher SMR-BCI accuracy. Those predictors were identified by Hammer et al. (2012) as the ability to concentrate (associated with relaxation levels) and "mean error duration" in a two-hand visuo-motor coordination task (VMC). Prior to a SMR-BCI session, a total of n=154 participants in two locations took part of 23 min sessions of either Jacobson's Progressive Muscle Relaxation session (PMR), a VMC session, or a control group (CG). No effect of PMR or VMC manipulation was found, but the manipulation checks did not consistently confirm whether PMR had an effect of relaxation levels and VMC on "mean error duration". In this first study, correlations between relaxation levels or "mean error duration" and accuracy were found but not in both locations. A second study, involving n=39 participants intensified the training in four sessions on four consecutive days or either PMR, VMC or CG. The effect or manipulation was assessed for in terms of a causal relationship by using a PRE-POST study design. The manipulation checks of this second study validated the positive effect of training on both relaxation and "mean error duration". But the manipulation did not yield a specific effect on BCI accuracy. The predictors were not found again, displaying the instability of relaxation levels and "mean error duration" in being associated with BCI performance. An effect of time on BCI accuracy was found, and a correlation between State Mindfulness Scale and accuracy were reported. Results indicated that a short training of PMR or VMC were insufficient in increasing SMR-BCI accuracy. This study contrasted with studies succeeding in increasing SMR-BCI accuracy Tan et al. (2009, 2014), by the shortness of its training and the relaxation training that did not include mindfulness. It also contrasted by its manipulation checks and its comprehensive experimental approach that attempted to replicate existing predictors or correlates for SMR-BCI accuracy. The prediction of BCI accuracy by individual characteristics is receiving increased attention, but requires replication studies and a comprehensive approach, to contribute to the growing base of evidence of predictors for SMR-BCI accuracy. While short PMR and VMC trainings could not yield an effect on BCI performance, mindfulness meditation training might be beneficial for SMR-BCI accuracy. Moreover, it could be implemented for people in the locked-in-syndrome, allowing to reach the end-users that are the most in need for improvements in BCI performance.}, subject = {Gehirn-Computer-Schnittstelle}, language = {en} } @article{WeberLassalleHaukeRamseretal.2018, author = {Weber-Lassalle, Nana and Hauke, Jan and Ramser, Juliane and Richters, Lisa and Groß, Eva and Bl{\"u}mcke, Britta and Gehrig, Andrea and Kahlert, Anne-Karin and M{\"u}ller, Clemens R. and Hackmann, Karl and Honisch, Ellen and Weber-Lassalle, Konstantin and Niederacher, Dieter and Borde, Julika and Thiele, Holger and Ernst, Corinna and Altm{\"u}ller, Janine and Neidhardt, Guido and N{\"u}rnberg, Peter and Klaschik, Kristina and Schroeder, Christopher and Platzer, Konrad and Volk, Alexander E. and Wang-Gohrke, Shan and Just, Walter and Auber, Bernd and Kubisch, Christian and Schmidt, Gunnar and Horvath, Judit and Wappenschmidt, Barbara and Engel, Christoph and Arnold, Norbert and Dworniczak, Bernd and Rhiem, Kerstin and Meindl, Alfons and Schmutzler, Rita K. and Hahnen, Eric}, title = {BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer}, series = {Breast Cancer Research}, volume = {20}, journal = {Breast Cancer Research}, doi = {10.1186/s13058-018-0935-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233433}, year = {2018}, abstract = {Background Germline mutations in the BRIP1 gene have been described as conferring a moderate risk for ovarian cancer (OC), while the role of BRIP1 in breast cancer (BC) pathogenesis remains controversial. Methods To assess the role of deleterious BRIP1 germline mutations in BC/OC predisposition, 6341 well-characterized index patients with BC, 706 index patients with OC, and 2189 geographically matched female controls were screened for loss-of-function (LoF) mutations and potentially damaging missense variants. All index patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germline testing and tested negative for pathogenic BRCA1/2 variants. Results BRIP1 LoF mutations confer a high OC risk in familial index patients (odds ratio (OR) = 20.97, 95\% confidence interval (CI) = 12.02-36.57, P < 0.0001) and in the subgroup of index patients with late-onset OC (OR = 29.91, 95\% CI = 14.99-59.66, P < 0.0001). No significant association of BRIP1 LoF mutations with familial BC was observed (OR = 1.81 95\% CI = 1.00-3.30, P = 0.0623). In the subgroup of familial BC index patients without a family history of OC there was also no apparent association (OR = 1.42, 95\% CI = 0.70-2.90, P = 0.3030). In 1027 familial BC index patients with a family history of OC, the BRIP1 mutation prevalence was significantly higher than that observed in controls (OR = 3.59, 95\% CI = 1.43-9.01; P = 0.0168). Based on the negative association between BRIP1 LoF mutations and familial BC in the absence of an OC family history, we conclude that the elevated mutation prevalence in the latter cohort was driven by the occurrence of OC in these families. Compared with controls, predicted damaging rare missense variants were significantly more prevalent in OC (P = 0.0014) but not in BC (P = 0.0693) patients. Conclusions To avoid ambiguous results, studies aimed at assessing the impact of candidate predisposition gene mutations on BC risk might differentiate between BC index patients with an OC family history and those without. In familial cases, we suggest that BRIP1 is a high-risk gene for late-onset OC but not a BC predisposition gene, though minor effects cannot be excluded.}, language = {en} } @unpublished{AuerhammerArrowsmithBoehnkeetal.2018, author = {Auerhammer, Dominic and Arrowsmith, Merle and B{\"o}hnke, Julian and Braunschweig, Holger and Dewhurst, Rian D. and Kupfer, Thomas}, title = {Brothers from Another Mother: a Borylene and its Dimer are Non-Interconvertible but Connected through Reactivity}, series = {Chemical Science}, journal = {Chemical Science}, doi = {10.1039/C7SC04789D}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157125}, year = {2018}, abstract = {The self-stabilizing, tetrameric cyanoborylene [(cAAC)B(CN)]4 (I, cAAC = 1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene) and its diborene relative, [(cAAC)(CN)B=B(CN)(cAAC)] (II), both react with disulfides and diselenides to yield the corresponding cAAC-supported cyanoboron bis(chalcogenides). Furthermore, reactions of I or II with elemental sulfur and selenium in various stoichiometries provided access to a variety of cAAC- stabilized cyanoboron-chalcogen heterocycles, including a unique dithiaborirane, a diboraselenirane, 1,3-dichalcogena-2,4-diboretanes, 1,3,4-trichalcogena- 2,5-diborolanes and a rare six-membered 1,2,4,5-tetrathia-3,6-diborinane. Stepwise addition reactions and solution stability studies provided insights into the mechanism of these reactions and the subtle differences in reactivity observed between I and II.}, language = {en} } @phdthesis{Halboth2018, author = {Halboth, Florian}, title = {Building behavior and nest climate control in leaf-cutting ants: How environmental cues affect the building responses of workers of \(Atta\) \(vollenweideri\)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161701}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {The present work investigates the influence of environmental stimuli on the building behavior of workers of the leaf-cutting ant Atta vollenweideri. It focuses on cues related to the airflow-driven ventilation of their giant underground nests, i.e., air movements and their direction, carbon dioxide concentrations and humidity levels of the nest air. First, it is shown that workers are able to use airflow and its direction as learned orientation cue by performing learning experiments with individual foragers using a classical conditioning paradigm. This ability is expected to allow workers to also navigate inside the nest tunnels using the prevailing airflow directions for orientation, for example during tasks related to nest construction and climate control. Furthermore, the influence of carbon dioxide on the digging behavior of workers is investigated. While elevated CO2 levels hardly affect the digging rate of the ants, workers prefer to excavate at locations with lower concentrations and avoid higher CO2 levels when given a choice. Under natural conditions, shifting their digging activity to soil layers containing lower carbon dioxide levels might help colonies to excavate new or to broaden existing nest openings, if the CO2 concentration in the underground rises. It is also shown that workers preferably transport excavated soil along tunnels containing high CO2 concentrations, when carbon dioxide levels in the underground are elevated as well. In addition, workers prefer to carry soil pellets along outflow tunnels instead of inflow tunnels, at least for high humidity levels of the air. The material transported along tunnels providing outflow of CO2-rich air might be used by workers for the construction of ventilation turrets on top of the nest mound, which is expected to promote the wind-induced ventilation and the removal of carbon dioxide from the underground. The climatic conditions inside the nest tunnels also influence the structural features of the turrets constructed by workers on top the nest. While airflow and humidity have no effect on turret structure, outflow of CO2-rich air from the nest causes workers to construct turrets with additional openings and increased aperture, potentially enhancing the airflow-driven gas exchanges within the nest. Finally, the effect of airflow and ventilation turrets on the gas exchanges in Atta vollenweideri nests is tested experimentally on a physical model of a small nest consisting of a single chamber and two nest tunnels. The carbon dioxide clearance rate from the underground was measured depending on both the presence of airflow in the nest and the structural features of the built turrets. Carbon dioxide is removed faster from the physical nest model when air moves through the nest, confirming the contribution of wind-induced flow inside the nest tunnels to the ventilation of Atta vollenweideri nests. In addition, turrets placed on top of one of the tunnel openings of the nest further enhance the CO2 clearance rate and the effect is positively correlated with turret aperture. Taken together, climatic variables like airflow, carbon dioxide and humidity levels strongly affect the building responses of Atta vollenweideri leaf-cutting ants. Workers use these environmental stimuli as orientation cue in the nest during tasks related to excavation, soil transport and turret construction. Although the effects of these building responses on the microclimatic conditions inside the nest remain elusive so far, the described behaviors are expected to allow ant colonies to restore and maintain a proper nest climate in the underground.}, subject = {Verhalten}, language = {en} } @article{LangenhorstHaackGoebetal.2018, author = {Langenhorst, Daniela and Haack, Stephanie and G{\"o}b, Selina and Uri, Anna and L{\"u}hder, Fred and Vanhove, Bernhard and H{\"u}nig, Thomas and Beyersdorf, Niklas}, title = {CD28 costimulation of T helper 1 cells enhances cytokine release in vivo}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {1060}, doi = {10.3389/fimmu.2018.01060}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176726}, year = {2018}, abstract = {Compared to naive T cells, differentiated T cells are thought to be less dependent on CD28 costimulation for full activation. To revisit the role of CD28 costimulation in mouse T cell recall responses, we adoptively transferred in vitro generated OT-II T helper (Th) 1 cells into C57BL/6 mice (Thy1.2\(^{+}\)) and then either blocked CD28-ligand interactions with Fab fragments of the anti-CD28 monoclonal antibody (mAb) E18 or deleted CD28 expression using inducible CD28 knock-out OT-II mice as T cell donors. After injection of ovalbumin protein in adjuvant into the recipient mice we observed that systemic interferon (IFN)γ release strongly depended on CD28 costimulation of the Th1 cells, while secondary clonal expansion was not reduced in the absence of CD28 costimulation. For human memory CD4\(^{+}\) T cell responses we also noted that cytokine release was reduced upon inhibition of CD28 costimulation. Together, our data highlight the so far underestimated role of CD28 costimulation for the reactivation of fully differentiated CD4\(^{+}\) T cells.}, language = {en} } @article{RauertWunderlichBerberichRosenwaldetal.2018, author = {Rauert-Wunderlich, Hilka and Berberich, Ingolf and Rosenwald, Andreas and Rudelius, Martina}, title = {CD40L mediated alternative NF kappa B-signaling induces resistance to BCR-inhibitors in patients with mantle cell lymphoma}, series = {Cell Death \& Disease}, journal = {Cell Death \& Disease}, number = {9}, doi = {10.1038/s41419-017-0157-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225027}, pages = {86, 1-9}, year = {2018}, abstract = {Drug resistance is a significant obstacle in cancer treatment and therefore a frequent subject of research. Developed or primary resistance limits the treatment success of inhibitors of the B cell receptor (BCR) pathway in mantle cell lymphoma (MCL) patients. Recent research has highlighted the role of the nuclear factor-kappa B (NF kappa B) pathway in the context of resistance to BCR inhibitors in MCL. In this study, we analyzed the dependency of MCL cell lines on NF kappa B signaling and illustrated the ability of CD40L to activate the alternative NF kappa B pathway in MCL. This activation leads to independency of classical NF kappa B signaling and results in resistance to BCR inhibitors. Therefore, ligands (such as CD40L) and their activation of the alternative NF kappa B pathway have a major impact on the drug response in MCL. Furthermore, this study indicates a protective role for cells expressing specific ligands as microenvironmental niches for MCL cells and underlines the significance of therapeutically targeting alternative NF kappa B signaling in MCL.}, language = {en} } @article{ZeinerZinkeKowalewskietal.2018, author = {Zeiner, P. S. and Zinke, J. and Kowalewski, D. J. and Bernatz, S. and Tichy, J. and Ronellenfitsch, M. W. and Thorsen, F. and Berger, A. and Forster, M. T. and Muller, A. and Steinbach, J. P. and Beschorner, R. and Wischhusen, J. and Kvasnicka, H. M. and Plate, K. H. and Stefanović, S. and Weide, B. and Mittelbronn, M. and Harter, P. N.}, title = {CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival}, series = {Acta Neuropathologica Communications}, volume = {6}, journal = {Acta Neuropathologica Communications}, doi = {10.1186/s40478-018-0521-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233882}, year = {2018}, abstract = {Abstract Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity. We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival. Additionally, we assessed whole DNA methylome profiles including CD74 promoter methylation and differential methylation in 21 brain metastases. We analyzed the effects of a siRNA mediated CD74 knockdown on HLA-expression and HLA peptidome composition in a brain metastatic melanoma cell line. We observed that CD74 expression on tumor cells is a strong positive prognostic marker in brain metastasis patients and positively associated with tumor-infiltrating T-lymphocytes (TILs). Whole DNA methylome analysis suggested that CD74 tumor cell expression might be regulated epigenetically via CD74 promoter methylation. CD74\(^{high}\) and TIL\(^{high}\) tumors displayed a differential DNA methylation pattern with highest enrichment scores for antigen processing and presentation. Furthermore, CD74 knockdown in vitro lead to a reduction of HLA class II peptidome complexity, while HLA class I peptidome remained unaffected. In summary, our results demonstrate that a functional HLA class II processing machinery in brain metastatic tumor cells, reflected by a high expression of CD74 and a complex tumor cell HLA peptidome, seems to be crucial for better patient prognosis.}, language = {en} } @article{LeichtWeinigMayeretal.2018, author = {Leicht, Hans Benno and Weinig, Elke and Mayer, Beate and Viebahn, Johannes and Geier, Andreas and Rau, Monika}, title = {Ceftriaxone-induced hemolytic anemia with severe renal failure: a case report and review of literature}, series = {BMC Pharmacology and Toxicology}, volume = {19}, journal = {BMC Pharmacology and Toxicology}, number = {67}, doi = {10.1186/s40360-018-0257-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176637}, year = {2018}, abstract = {Background: Drug induced immune hemolytic anemia (DIIHA) is a rare complication and often underdiagnosed. DIIHA is frequently associated with a bad outcome, including organ failure and even death. For the last decades, ceftriaxone has been one of the most common drugs causing DIIHA, and ceftriaxone-induced immune hemolytic anemia (IHA) has especially been reported to cause severe complications and fatal outcomes. Case Presentation: A 76-year-old male patient was treated with ceftriaxone for cholangitis. Short time after antibiotic exposure the patient was referred to intensive care unit due to cardiopulmonary instability. Hemolysis was observed on laboratory testing and the patient developed severe renal failure with a need for hemodialysis for 2 weeks. Medical history revealed that the patient had been previously exposed to ceftriaxone less than 3 weeks before with subsequent hemolytic reaction. Further causes for hemolytic anemia were excluded and drug-induced immune hemolytic (DIIHA) anemia to ceftriaxone could be confirmed. Conclusions: The case demonstrates the severity of ceftriaxone-induced immune hemolytic anemia, a rare, but immediately life-threatening condition of a frequently used antibiotic in clinical practice. Early and correct diagnosis of DIIHA is crucial, as immediate withdrawal of the causative drug is essential for the patient prognosis. Thus, awareness for this complication must be raised among treating physicians.}, language = {en} } @phdthesis{Lorenz2018, author = {Lorenz, Viola}, title = {Cellular regulation of the hemITAM-coupled platelet receptor C-type lectin-like receptor 2 (CLEC-2): In vitro and in vivo studies in mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116724}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Platelet aggregation at sites of vascular injury is essential to limit posttraumatic blood loss, but may also cause acute ischemic disease states such as myocardial infarction or stroke. Stable thrombus formation requires a series of molecular events involving platelet receptors and intracellular signal transduction, which contribute to adhesion, activation and aggregation of platelets. In this thesis, the cellular regulation of platelet surface receptors and their involvement in thrombus formation was investigated using genetically modified mice. In the first part of the study, the functional relevance of the immunoreceptor tyrosine-based activation motif (ITAM)-coupled collagen receptor GPVI and of the recently identified hemITAM-bearing C-type lectin-like receptor 2 (CLEC-2) for in vivo thrombus formation was analyzed. Megakaryocyte/ platelet-specific CLEC-2 knock out mice displayed a defective lymphatic development and were protected from occlusive arterial thrombus formation. These phenotypes were more pronounced in mice with a GPVI/CLEC-2 double deficiency. Hemostasis was not compromised in CLEC-2 or GPVI single-deficient animals, as they showed only mildly prolonged tail bleeding times. Combined depletion of both receptors resulted in markedly prolonged bleeding times revealing an unexpected redundant function of the two receptors in hemostasis as well as thrombosis. These findings might have important implications for the development of anti-CLEC-2/ anti-GPVI agents as therapeutics. In the second part, mechanisms underlying the cellular regulation of CLEC-2 were studied. Previous studies have shown that injection of the anti-CLEC-2 antibody INU1 results in complete immunodepletion of platelet CLEC-2 in mice, which is preceded by a severe transient thrombocytopenia thereby limiting its potential therapeutic use. It is demonstrated that INU1-induced CLEC-2 immunodepletion occurs through Src family kinase (SFK)-dependent receptor internalization in vitro and in vivo, presumably followed by intracellular degradation. In mice with spleen tyrosine kinase (Syk) deficiency, INU1-induced CLEC-2 internalization/ degradation was fully preserved, whereas the associated thrombocytopenia was largely prevented. These results show that CLEC-2 can be downregulated from the platelet surface through internalization in vitro and in vivo and that this can be mechanistically uncoupled from the associated antibody-induced thrombocytopenia. Since INU1 IgG induced a pronounced thrombocytopenia, the in vivo effects of monovalent INU1 F(ab) fragments were analyzed. Very unexpectedly, injection of the F(ab) fragments resulted in widespread thrombus formation leading to persistent neurological deficits of the animals. This intravascular thrombus formation is the result of CLEC-2-dependent platelet activation and aggregation. The mechanism underlying the thrombus formation is still unknown and depends potentially on binding of a yet unidentified ligand to F(ab)-opsonized CLEC-2 on platelets.}, subject = {Thrombozytenaggregation}, language = {en} } @phdthesis{Lerch2018, author = {Lerch, Maike Franziska}, title = {Characterisation of a novel non-coding RNA and its involvement in polysaccharide intercellular adhesin (PIA)-mediated biofilm formation of \(Staphylococcus\) \(epidermidis\)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155777}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, have been recognised as an important cause of health care-associated infections due to catheterisation, and livestock-associated infections. The colonisation of indwelling medical devices is achieved by the formation of biofilms, which are large cell-clusters surrounded by an extracellular matrix. This extracellular matrix consists mainly of PIA (polysaccharide intercellular adhesin), which is encoded by the icaADBC-operon. The importance of icaADBC in clinical strains provoking severe infections initiated numerous investigations of this operon and its regulation within the last two decades. The discovery of a long transcript being located next to icaADBC, downstream of the regulator gene icaR, led to the hypothesis of a possible involvement of this transcript in the regulation of biofilm formation (Eckart, 2006). Goal of this work was to characterise this transcript, named ncRNA IcaZ, in molecular detail and to uncover its functional role in S. epidermidis. The ~400 nt long IcaZ is specific for ica-positive S. epidermidis and is transcribed in early- and mid-exponential growth phase as primary transcript. The promotor sequence and the first nucleotides of icaZ overlap with the 3' UTR of the preceding icaR gene, whereas the terminator sequence is shared by tRNAThr-4, being located convergently to icaZ. Deletion of icaZ resulted in a macroscopic biofilm-negative phenotype with highly diminished PIA-biofilm. Biofilm composition was analysed in vitro by classical crystal violet assays and in vivo by confocal laser scanning microscopy under flow conditions to display biofilm formation in real-time. The mutant showed clear defects in initial adherence and decreased cell-cell adherence, and was therefore not able to form a proper biofilm under flow in contrast to the wildtype. Restoration of PIA upon providing icaZ complementation from plasmids revealed inconsistent results in the various mutant backgrounds. To uncover the functional role of IcaZ, transcriptomic and proteomic analysis was carried out, providing some hints on candidate targets, but the varying biofilm phenotypes of wildtype and icaZ mutants made it difficult to identify direct IcaZ mRNA targets. Pulse expression of icaZ was then used as direct fishing method and computational target predictions were executed with candidate mRNAs from aforesaid approaches. The combined data of these analyses suggested an involvement of icaR in IcaZ-mediated biofilm control. Therefore, RNA binding assays were established for IcaZ and icaR mRNA. A positive gel shift was maintained with icaR 3' UTR and with 5'/3' icaR mRNA fusion product, whereas no gel shift was obtained with icaA mRNA. From these assays, it was assumed that IcaZ regulates icaR mRNA expression in S. epidermidis. S. aureus instead lacks ncRNA IcaZ and its icaR mRNA was shown to undergo autoregulation under so far unknown circumstances by intra- or intermolecular binding of 5' UTR and 3' UTR (Ruiz de los Mozos et al., 2013). Here, the Shine-Dalgarno sequence is blocked through 5'/3' UTR base pairing and RNase III, an endoribonuclease, degrades icaR mRNA, leading to translational blockade. In this work, icaR mRNA autoregulation was therefore analysed experimentally in S. epidermidis and results showed that this specific autoregulation does not take place in this organism. An involvement of RNase III in the degradation process could not be verified here. GFP-reporter plasmids were generated to visualise the interaction, but have to be improved for further investigations. In conclusion, IcaZ was found to interact with icaR mRNA, thereby conceivably interfering with translation initiation of repressor IcaR, and thus to promote PIA synthesis and biofilm formation. In addition, the environmental factor ethanol was found to induce icaZ expression, while only weak or no effects were obtained with NaCl and glucose. Ethanol, actually is an ingredient of disinfectants in hospital settings and known as efficient effector for biofilm induction. As biofilm formation on medical devices is a critical factor hampering treatment of S. epidermidis infections in clinical care, the results of this thesis do not only contribute to better understanding of the complex network of biofilm regulation in staphylococci, but may also have practical relevance in the future.}, subject = {Biofilm}, language = {en} } @article{OPUS4-22774, title = {Characterisation of the Hamamatsu photomultipliers for the KM3NeT Neutrino Telescope}, series = {Journal of Instrumentation}, volume = {13}, journal = {Journal of Instrumentation}, organization = {The KM3NeT collaboration}, doi = {10.1088/1748-0221/13/05/P05035}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227744}, pages = {1-14}, year = {2018}, abstract = {The Hamamatsu R12199-023-inch photomultiplier tube is the photodetector chosen for the first phase of the KM3NeT neutrino telescope. About 7000 photomultipliers have been characterised for dark count rate, timing spread and spurious pulses. The quantum efficiency, the gain and the peak-to-valley ratio have also been measured for a sub-sample in order to determine parameter values needed as input to numerical simulations of the detector.}, language = {en} } @phdthesis{Bargul2018, author = {Bargul, Joel Ltilitan}, title = {Characterization of motility and erythrocyte adherence as virulence factors in African trypanosomes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115053}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Pathogens causing African animal trypanosomiasis (AAT), the major livestock disease in sub-Saharan Africa, belong to the salivarian group of the African trypanosomes, which are transmitted by the bite of the tsetse fly (Glossina spec.). T. vivax, T. congolense and T. brucei brucei are major pathogens of cattle in particular, causing nagana, with dramatic socio-economic consequences for the affected regions. The parasites additionally have a huge reservoir of other livestock and wild animal hosts. T. brucei, the species which also includes the subspecies pathogenic to humans causing sleeping sickness, has been extensively studied as the cultivatable model trypanosome. But less is known about the other salivarian species, which are not routinely held in culture, if at all possible. A hallmark of trypanosomal lifestyle is the protozoan flagellates incessant motility, which enables them to populate an enormous range of habitats in very diverse hosts. We were now able to characterize, for the first time with high spatiotemporal resolution microscopy, the swimming behaviour and mechanism of the most relevant salivarian species isolated directly from blood. We show the influence of viscosity on the motility of bloodstream form (BSF) cells and simulate their movement between erythrocytes, giving a clear picture of how all analyzed species move under varying environmental conditions. We show that although the basic mechanism of flagellar motility applies to all analyzed species, there are clear morphological differences that produce different reactions to the physical environment. We could define specific conditions for highly increased swimming persistence and speed for compared to the behaviour in standard culture. These results have important implications for the parasites survival strategies in the host, e.g. regarding the capacity for antibody clearance. Although we show all species to effectively remove antibodies from the cell surface, T. congolense differed markedly in its motility behaviour, which gives rise to interesting questions about this species behaviour in the bloodstream. Most of the T. congolense parasites (and to a lesser extent T. vivax) adhere to sheep erythrocytes. Further in vitro studies showed that T. congolense and T. vivax adhered to rabbit, goat, pig and cattle erythrocytes- but binding behaviour was absent in murine blood. Notably, both T. brucei and T. evansi lacked adherence to all studied host erythrocytes. Generally, attachment to blood cells caused reduction of swimming velocities. Judging from its cell architecture, as well as the motility studies in higher media viscosity and in micropillar arrays, T. congolense is not adapted to swim at high speeds in the mammalian bloodstream. Low swimming speeds could allow these purely intravascular parasites to remain bound to the host erythrocytes.}, subject = {Motili{\"a}t}, language = {en} } @phdthesis{Sidiropoulou2018, author = {Sidiropoulou, Ourania}, title = {Characterization of the ATLAS-type Micromegas Detectors}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167323}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Micromegas are parallel-plate gaseous detectors with micro-pattern readout structures that are able to measure precisely and efficiently at high particle rates. Their difference with respect to other gaseous detectors is that the space in which particles ionise the gas and create electrons is separated from the region in which these electrons are multiplied (or amplified) by a thin metallic mesh. In the ionisation region, typically a few mm thick, a moderate field of a few hundred V/cm is applied. The amplification region with a homogeneous electrical field of 40--50~kV/cm is only 100--150~\$\upmu\$m thick. The latter guarantees that the positive ions produced in the amplification process are rapidly evacuated and the possibility to build up space charge at high rate is reduced. Critical in micromegas detectors are sparks in the thin amplification region in the presence of the high electrical field. This problem was solved in 2011 by introducing a spark protection scheme. It consists of a layer of resistive strips on top of the readout strips, separated from the latter by a thin insulation layer. Micromegas with the spark protection scheme were selected as instrumentation of the first ATLAS forward muon station (NSW) in the upgrade of the ATLAS detector for the operation of the Large Hadron Collider (LHC) at high luminosity (HL-LHC), expected for 2026. The main subjects of this thesis are: the characterisation of the first micromegas quadruplet prototypes for the NSW detectors; the characterisation of the materials used in the spark-protection system; and the study of the influence of the mesh distance holders (pillars) on the detector performance. The thesis starts with a brief introduction into the LHC and ATLAS projects, followed by a chapter that explains the reason for the upgrade of the ATLAS muon system and shows the layout of the NSW. The first of the three main chapters covers the construction and the characterisation of the first two prototypes for the NSW detectors. These detectors comprise four detection layers and have the same mechanical structure as the NSW detectors. The mechanical precision as well as the homogeneity of the detector response are discussed. The latter has been measured using X-rays and cosmic rays. The spatial resolution that can be achieved with these detectors precision has been measured at the MAMI accelerator at Mainz with low-energy electrons. The chapter is completed by a section that describes the successful integration of a data acquisition system (DAQ) into the official ATLAS DAQ system that was required for an initially planned installation of one of the prototypes on the existing Small Wheel. The next chapter presents a study of the influence of temperature and humidity changes on the resistive strips used in the spark protection system. In addition the long-term stability of the resistive material has been measured accumulating charge equivalent to 100 years of operation in the HL-LHC and exposing the samples to intense gamma irradiation equivalent to 10 years of HL-LHC operation. The third part covers the impact of the mesh distance holders (pillars) on the performance of the detector. This study has been performed with a 10 x 10 cm\$^2\$ bulk-micromegas with two different pillar shapes. Both 5.9 keV gammas from a \$^{55}\$Fe and 8 keV X-rays from a Cu target were used. In this context also the electrostatic charge-up of the detector is discussed. In the Appendices one finds a summary of the fundamental physics relevant for gaseous detectors as well as some supporting material for the topics covered in the main part of the thesis.}, subject = {ATLAS }, language = {en} } @phdthesis{Heidenreich2018, author = {Heidenreich, Julius Frederik}, title = {Characterization of the widely used Rac1-inhibitors NSC23766 and EHT1864 in mouse platelets}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165453}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Platelet activation and aggregation at sites of vascular injury is critical to prevent excessive blood loss, but may also lead to life-threatening ischemic diseases, such as myocardial infarction and stroke. Extracellular agonists induce platelet activation by stimulation of platelet membrane receptors. Signal transduction results in reorganization of the cytoskeleton, shape change, platelet adhesion and aggregation, cumulating in thrombus formation. Several Rho GTPases, including Rac1, Cdc42 and RhoA, are essential mediators of subsequent intracellular transduction of ITAM- and GPCR-signaling. Therefore, inhibition or knockout can result in severely defective platelet signaling. Mice with platelet specific Rac1-deficiency are protected from arterial thrombosis. This benefit highlights further investigation of Rac1-specific functions and its potential as a new pharmacological target for prevention of cardiovascular diseases. Two newly developed synthetic compounds, NSC23766 and EHT1864, were proposed to provide highly specific inhibition of Rac1 activity, but both drugs have never been tested in Rac1-deficient cell systems to rule out potential Rac1-independent effects. This study revealed significant off-target effects of NSC23766 and EHT1864 that occurred in a dose-dependent fashion in both wild-type and Rac1-deficient platelets. Both inhibitors individually affected resting platelets after treatment, either by altering membrane protein expression (NSC23766) or by a marked decrease of platelet viability (EHT1864). Platelet apoptosis could be confirmed by enhanced levels of phosphatidylserine exposure and decreased mitochondrial membrane potential. Phosphorylation studies of the major effector proteins of Rac1 revealed that NSC23766 and EHT1864 abolish PAK1/PAK2 activation independently of Rac1 in wild-type and knockout platelets, which may contribute to the observed off-target effects. Additionally, this study demonstrated the involvement of Rac1 in G protein-coupled receptor-mediated platelet activation and GPIb-induced signaling. Furthermore, the data revealed that Rac1 is dispensable in the process of integrin IIb 3-mediated clot retraction. This study unveiled that new pharmacological approaches in antithrombotic therapy with Rac1 as molecular target have to be designed carefully in order to obtain high specificity and minimize potential off-target effects.}, subject = {Thrombozyt}, language = {en} } @article{KoepingShehataDielerSchneideretal.2018, author = {K{\"o}ping, Maria and Shehata-Dieler, Wafaa and Schneider, Dieter and Cebulla, Mario and Oder, Daniel and M{\"u}ntze, Jonas and Nordbeck, Peter and Wanner, Christoph and Hagen, Rudolf and Schraven, Sebastian P.}, title = {Characterization of vertigo and hearing loss in patients with Fabry disease}, series = {Orphanet Journal of Rare Diseases}, volume = {13}, journal = {Orphanet Journal of Rare Diseases}, doi = {10.1186/s13023-018-0882-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222818}, year = {2018}, abstract = {Background Fabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ involvement, patients commonly complain about vestibulocochlear symptoms like high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data especially on vertigo remain scarce. The aim of this study was to examine the prevalence and characteristics of vertigo and hearing loss in patients with FD, depending on renal and cardiac parameters and get hints about the site and the pattern of the lesions. Methods Single-center study with 57 FD patients. Every patient underwent an oto-rhino-laryngological examination as well as videonystagmography and vestibular evoked myogenic potentials (VEMPs) and audiological measurements using pure tone audiometry and auditory brainstem response audiometry (ABR). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class. Results More than one out of three patients (35.1\%) complained about hearing loss, 54.4\% about vertigo and 28.1\% about both symptom. In 74\% a sensorineural hearing loss of at least 25 dB was found, ABR could exclude any retrocochlear lesion. Caloric testing showed abnormal values in 71.9\%, VEMPs were pathological in 68\%. A correlation between the side or the shape of hearing loss and pathological vestibular testing could not be revealed. Conclusions Hearing loss and vertigo show a high prevalence in FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as well as central nervous pathologies cause vertigo. Thus, both the site of lesion and the pathophysiological patterns seem to differ.}, language = {en} } @unpublished{StennettMattockPentecostetal.2018, author = {Stennett, Tom and Mattock, James and Pentecost, Leanne and Vargas, Alfredo and Braunschweig, Holger}, title = {Chelated Diborenes and their Inverse-Electron-Demand Diels- Alder Reactions with Dienes}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201809217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178268}, year = {2018}, abstract = {A doubly base-stabilized diborane based on a benzylphosphine linker was prepared by a salt elimination reaction between 2-LiC\(_6\)H\(_4\)CH\(_2\)PCy\(_2\).Et\(_2\)O and B\(_2\)Br\(_4\). This compound was reduced with KC8 to its corresponding diborene, with the benzylphosphine forming a five-membered chelate. The diborene reacts with butadiene, 2-trimethylsiloxy-1,3-butadiene and isoprene to form 4,5-diboracyclohexenes, which interconvert between their 1,1- (geminal) and 1,2- (vicinal) chelated isomers. The 1,1-chelated diborene undergoes a halide-catalysed isomerisation into its thermodynamically favoured 1,2-isomer, which undergoes Diels-Alder reactions more slowly than the kinetic product.}, language = {en} } @article{ReilingKrohneFriedrichetal.2018, author = {Reiling, Sarah J. and Krohne, Georg and Friedrich, Oliver and Geary, Timothy G. and Rohrbach, Petra}, title = {Chloroquine exposure triggers distinct cellular responses in sensitive versus resistant Plasmodium falciparum parasites}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {11137}, doi = {10.1038/s41598-018-29422-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225123}, pages = {1-11}, year = {2018}, abstract = {Chloroquine (CQ) treatment failure in Plasmodium falciparum parasites has been documented for decades, but the pharmacological explanation of this phenotype is not fully understood. Current concepts attribute CQ resistance to reduced accumulation of the drug at a given external CQ concentration ([CQ] ex) in resistant compared to sensitive parasites. The implication of this explanation is that the mechanisms of CQ-induced toxicity in resistant and sensitive strains are similar once lethal internal concentrations have been reached. To test this hypothesis, we investigated the mechanism of CQ-induced toxicity in CQ-sensitive (CQS) versus CQ-resistant (CQR) parasites by analyzing the time-course of cellular responses in these strains after exposure to varying [CQ] ex as determined in 72 h toxicity assays. Parasite killing was delayed in CQR parasites for up to 10 h compared to CQS parasites when exposed to equipotent [CQ] ex. In striking contrast, brief exposure (1 h) to lethal [CQ] ex in CQS but not CQR parasites caused the appearance of hitherto undescribed hemozoin (Hz)-containing compartments in the parasite cytosol. Hz-containing compartments were very rarely observed in CQR parasites even after CQ exposures sufficient to cause irreversible cell death. These findings challenge current concepts that CQ killing of malaria parasites is solely concentration-dependent, and instead suggest that CQS and CQR strains fundamentally differ in the consequences of CQ exposure.}, language = {en} } @article{RasaNoraKrukleHenningetal.2018, author = {Rasa, Santa and Nora-Krukle, Zaiga and Henning, Nina and Eliassen, Eva and Shikova, Evelina and Harrer, Thomas and Scheibenbogen, Carmen and Murovska, Modra and Prusty, Bhupesh K.}, title = {Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)}, series = {Journal of Translational Medicine}, volume = {16}, journal = {Journal of Translational Medicine}, number = {268}, doi = {10.1186/s12967-018-1644-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224960}, pages = {1-25}, year = {2018}, abstract = {Background and main text: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. Conclusions: This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.}, language = {en} } @article{SchulzeHuttererSaboetal.2018, author = {Schulze, Markus and Hutterer, Maria and Sabo, Anja and Hoja, Sabine and Lorenz, Julia and Rothhammer-Hampl, Tanja and Herold-Mende, Christel and Floßbach, Lucia and Monoranu, Camelia and Riemenschneider, Markus J.}, title = {Chronophin regulates active vitamin B6 levels and transcriptomic features of glioblastoma cell lines cultured under non-adherent, serum-free conditions}, series = {BMC Cancer}, volume = {18}, journal = {BMC Cancer}, doi = {10.1186/s12885-018-4440-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234645}, year = {2018}, abstract = {Background The phosphatase chronophin (CIN/PDXP) has been shown to be an important regulator of glioma cell migration and invasion. It has two known substrates: p-Ser3-cofilin, the phosphorylated form of the actin binding protein cofilin, and pyridoxal 5′-phosphate, the active form of vitamin B6. Phosphoregulation of cofilin, among other functions, plays an important role in cell migration, whereas active vitamin B6 is a cofactor for more than one hundred enzymatic reactions. The role of CIN has yet only been examined in glioblastoma cell line models derived under serum culture conditions. Results We found that CIN is highly expressed in cells cultured under non-adherent, serum-free conditions that are thought to better mimic the in vivo situation. Furthermore, the substrates of CIN, p-Ser3-cofilin and active vitamin B6, were significantly reduced as compared to cell lines cultured in serum-containing medium. To further examine its molecular role we stably knocked down the CIN protein with two different shRNA hairpins in the glioblastoma cell lines NCH421k and NCH644. Both cell lines did not show any significant alterations in proliferation but expression of differentiation markers (such as GFAP or TUBB3) was increased in the knockdown cell lines. In addition, colony formation was significantly impaired in NCH644. Of note, in both cell lines CIN knockdown increased active vitamin B6 levels with vitamin B6 being known to be important for S-adenosylmethionine biosynthesis. Nevertheless, global histone and DNA methylation remained unaltered as was chemoresistance towards temozolomide. To further elucidate the role of phosphocofilin in glioblastoma cells we applied inhibitors for ROCK1/2 and LIMK1/2 to our model. LIMK- and ROCK-inhibitor treatment alone was not toxic for glioblastoma cells. However, it had profound, but antagonistic effects in NCH421k and NCH644 under chemotherapy. Conclusion In non-adherent glioblastoma cell lines cultured in serum-free medium, chronophin knockdown induces phenotypic changes, e.g. in colony formation and transcription, but these are highly dependent on the cellular background. The same is true for phenotypes observed after treatment with inhibitors for kinases regulating cofilin phosphorylation (ROCKs and LIMKs). Targeting the cofilin phosphorylation pathway might therefore not be a straightforward therapeutic option in glioblastoma.}, language = {en} } @article{SaundersDavisKrankeetal.2018, author = {Saunders, Rhodri and Davis, Jason A. and Kranke, Peter and Weissbrod, Rachel and Whitaker, David K and Lightdale, Jenifer R}, title = {Clinical and economic burden of procedural sedation-related adverse events and their outcomes: analysis from five countries}, series = {Therapeutics and Clinical Risk Management}, volume = {14}, journal = {Therapeutics and Clinical Risk Management}, doi = {10.2147/TCRM.S154720}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227508}, pages = {393-401}, year = {2018}, abstract = {Background: Studies have reported on the incidence of sedation-related adverse events (AEs), but little is known about their impact on health care costs and resource use. Methods: Health care providers and payers in five countries were recruited for an online survey by independent administrators to ensure that investigators and respondents were blinded to each other. Surveys were conducted in the local language and began with a "screener" to ensure that respondents had relevant expertise and experience. Responses were analyzed using Excel and R, with the Dixon's Q statistic used to identify and remove outliers. Global and country-specific average treatment patterns were calculated via bootstrapping; costs were mean values. The sum product of costs and intervention probability gave a cost per AE. Results: Responses were received from 101 providers and 26 payers, the majority having. 5 years of experience. At a minimum, the respondents performed a total of 3,430 procedural sedations per month. All AEs detailed occurred in clinical practice in the last year and were reported to cause procedural delays and cancellations in some patients. Standard procedural sedation costs ranged from (sic)74 (Germany) to \$2,300 (US). Respondents estimated that AEs would increase costs by between 16\% (Italy) and 179\% (US). Hypotension was reported as the most commonly observed AE with an associated global mean cost (interquartile range) of \$43 (\$27-\$68). Other frequent AEs, including mild hypotension, bradycardia, tachycardia, mild oxygen desaturation, hypertension, and brief apnea, were estimated to increase health care spending on procedural sedation by \$2.2 billion annually in the US. Conclusion: All sedation-related AEs can increase health care costs and result in substantial delays or cancellations of subsequent procedures. The prevention of even minor AEs during procedural sedation may be crucial to ensuring its value as a health care service.}, language = {en} } @article{GilbertSchneemannScholzetal.2018, author = {Gilbert, F. and Schneemann, C. and Scholz, C. J. and Kickuth, R. and Meffert, R. H. and Wildenauer, R. and Lorenz, U. and Kellersmann, R. and Busch, A.}, title = {Clinical implications of fracture-associated vascular damage in extremity and pelvic trauma}, series = {BMC Muscuskeletal Disorders}, volume = {19}, journal = {BMC Muscuskeletal Disorders}, number = {404}, doi = {10.1186/s12891-018-2333-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176252}, year = {2018}, abstract = {Background: Vascular damage in polytrauma patients is associated with high mortality and morbidity. Therefore, specific clinical implications of vascular damage with fractures in major trauma patients are reassessed. Methods: This comprehensive nine-year retrospective single center cohort study analyzed demography, laboratory, treatment and outcome data from 3689 patients, 64 patients with fracture-associated vascular injuries were identified and were compared to a control group. Results: Vascular damage occurred in 7\% of patients with upper and lower limb and pelvic fractures admitted to the trauma room. Overall survival was 80\% in pelvic fracture and 97\% in extremity fracture patients and comparable to non-vascular trauma patients. Additional arterial damage required substantial fluid administration and was visible as significantly anemia and disturbed coagulation tests upon admission. Open procedures were done in over 80\% of peripheral extremity vascular damage. Endovascular procedures were predominant (87\%) in pelvic injury. Conclusion: Vascular damage is associated with high mortality rates especially in combination with pelvic fractures. Initial anemia, disturbed coagulation tests and the need for extensive pre-clinical fluid substitution were observed in the cohort with vascular damage. Therefore, fast diagnosis and early interventional and surgical procedures are necessary to optimize patient-specific outcome.}, language = {en} } @unpublished{StoyBoehnkeJiménezHallaetal.2018, author = {Stoy, Andreas and B{\"o}hnke, Julian and Jiménez-Halla, J. Oscar C. and Dewhurst, Rian D. and Thiess, Torsten and Braunschweig, Holger}, title = {CO\(_2\) Binding and Splitting by Boron-Boron Multiple Bonds}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201802117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164265}, year = {2018}, abstract = {CO\(_2\) is found to undergo room-temperature, ambient- pressure reactions with two species containing boron-boron multiple bonds, leading to incorporation of either one or two CO\(_2\) molecules. In one case, a thermally-unstable intermediate was structurally characterized, indicating the operation of an initial 2+2 cycloaddition mechanism in the reaction.}, language = {en} } @misc{Breitenbach2018, author = {Breitenbach, Tim}, title = {Codes of examples for SQH method}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167587}, year = {2018}, abstract = {Code examples for the paper "On the SQH Scheme to Solve Nonsmooth PDE Optimal Control Problems" by Tim Breitenbach and Alfio Borz{\`i} published in the journal "Numerical Functional Analysis and Optimization", in 2019, DOI: 10.1080/01630563.2019.1599911}, language = {en} } @misc{Breitenbach2018, author = {Breitenbach, Tim}, title = {Codes of examples for SQH method}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165669}, year = {2018}, abstract = {Code examples for the paper "On the SQH Scheme to Solve Nonsmooth PDE Optimal Control Problems" by Tim Breitenbach and Alfio Borz{\`i} published in the journal "Numerical Functional Analysis and Optimization", in 2019, DOI: 10.1080/01630563.2019.1599911}, language = {en} } @phdthesis{Wannagat2018, author = {Wannagat, Wienke Charlotte}, title = {Cognitive Processes of Discourse Comprehension in Children and Adults - Comparisons between Written, Auditory, and Audiovisual Modes of Presentation -}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162515}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {In drei Studien wurde untersucht, wie sich unterschiedliche Darbietungsformate (schriftlich, auditiv, audiovisuell (auditiv + Bilder) auf das Verst{\"a}ndnis semantisch identischer Inhalte auswirken. Dabei interessierte insbesondere der Entwicklungsverlauf von der ersten Klasse bis zum Erwachsenenalter. Dass sich Bilder f{\"o}rderlich auf die Verst{\"a}ndnisleistung auswirken k{\"o}nnen, gilt als gut untersucht (z.B. Carney \& Levin, 2002). Anders als viele bisherige Studien erfassen wir Textverstehen mit impliziten Maßen, die differenziertere R{\"u}ckschl{\"u}sse auf die, g{\"a}ngigen Theorien zufolge, zugrundeliegenden Prozesse zulassen: Textverstehen geht mit der Konstruktion von drei Ebenen mentaler Repr{\"a}sentationen einher (vgl. Kintsch, 1998). Weiterhin bedeutet erfolgreiches Textverstehen, eine auf lokaler und globaler Ebene koh{\"a}rente mentale Repr{\"a}sentation zu konstruieren (z.B. Schnotz \& Dutke, 2004). Mit einem Satz-Rekognitionstest (vgl. Schmalhofer \& Glavanov, 1986) untersuchten wir, ob sich das Ged{\"a}chtnis f{\"u}r die Textoberfl{\"a}che, die Textbasis und das Situationsmodell bei 103 8- und 10-J{\"a}hrigen zwischen schriftlicher, auditiver und audiovisueller (Studie 1) und bei 106 7-, 9- und 11-J{\"a}hrigen zwischen auditiver und audiovisueller Darbietung narrativer Texte (Studie 2) unterscheidet. Weiterhin (Studie 3) untersuchten wir mit 155 9- und 11-J{\"a}hrigen, inwieweit sich die F{\"a}higkeit der Inferenzbildung zur Herstellung lokaler und globaler Koh{\"a}renz zwischen schriftlicher, auditiver und audiovisueller Darbietung unterscheidet. Als Indikator dienten die Reaktionszeiten auf W{\"o}rter, die mit einem {\"u}ber (global)- oder untergeordneten (lokal) Protagonistenziel assoziiert sind. Insgesamt zeigte sich, dass Sch{\"u}ler bis zu einem Alter von 11 Jahren nicht nur die Textoberfl{\"a}che besser erinnern, sondern auch besser in der Lage sind ein Situationsmodell zu konstruieren, wenn einem Text Bilder beigef{\"u}gt sind. Dies zeigte sich sowohl im Vergleich mit auditiver als auch mit schriftlicher Darbietung. Bei Erwachsenen zeigte sich kein Effekt der Darbietungsform. Sowohl 9- als auch 11-J{\"a}hrigen gelingt außerdem die Herstellung globaler Koh{\"a}renz bei audiovisueller Darbietung besser als bei auditiver. Die schriftliche Darbietung zeigte sich im Vergleich zur auditiven sowohl im Hinblick auf lokale als auch auf globale Koh{\"a}renz {\"u}berlegen.}, subject = {Textverstehen}, language = {en} } @phdthesis{Roeding2018, author = {R{\"o}ding, Sebastian}, title = {Coherent Multidimensional Spectroscopy in Molecular Beams and Liquids Using Incoherent Observables}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156726}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Das Ziel der vorliegenden Arbeit war die Umsetzung einer experimentellen Herangehensweise, welche die koh{\"a}rente zweidimensionale (2D) Spektroskopie an Proben in unterschiedlichen Aggregatzust{\"a}nden erm{\"o}glicht. Hierzu wurde zun{\"a}chst ein Aufbau f{\"u}r fl{\"u}ssige Proben realisiert, in welchem die emittierte Fluoreszenz als Messsignal zur Aufnahme der 2D Spektren genutzt wird. Im Gegensatz zu dieser bereits etablierten Methode in der fl{\"u}ssigen Phase stellt die in dieser Arbeit außerdem vorgestellte 2D Spektroskopie an gasf{\"o}rmigen Proben in einem Molekularstrahl einen neuen Ansatz dar. Hierbei werden zum ersten Mal Kationen mittels eines Flugzeitmassenspektrometers als Signal verwendet und somit ionen-spezifische 2D Spektren isolierter Molek{\"u}le erhalten. Zus{\"a}tzlich zu den experimentellen Entwicklungen wurde in dieser Arbeit ein neues Konzept zur Datenerfassung in der 2D Spektroskopie entworfen, welches mit Hilfe einer optimierten Signalabtastung und eines Compressed-Sensing Rekonstruktionsalgorithmus die Aufnahmezeit der Daten deutlich reduziert. Charakteristisch f{\"u}r die in dieser Arbeit eingesetzte Variante der 2D Spektroskopie ist die Verwendung einer phasenkoh{\"a}renten Sequenz bestehend aus vier Laserimpulsen in einer kollinearen Laserstrahlgeometrie zur Anregung der Probe. Diese Impulssequenz wurde durch einen Laserimpulsformer erzeugt, der durch {\"A}nderung der relevanten Laserimpulsparameter mit der Wiederholrate des Lasers eine schnelle Datenerfassung erm{\"o}glicht. Die Antwort der Probe auf diese Anregung wurde durch inkoh{\"a}rente Observablen gemessen, welche proportional zur Population des angeregten Zustandes sind, wie zum Beispiel Fluoreszenz oder Ionen. Um aus diesem Signal w{\"a}hrend der Datenanalyse die gew{\"u}nschten nichtlinearen Beitr{\"a}ge zu extrahieren, wurde die Messung mit verschiedenen Kombinationen der relativen Phase zwischen den Laserimpulsen wiederholt ("Phase Cycling"). Der Aufbau zur 2D Spektroskopie in fl{\"u}ssiger Phase mit Fluoreszenz-Detektion wurde an Hand von 2D Spektren des Laserfarbstoffes Cresyl Violett charakterisiert. Hierbei wurden Oszillationen in verschiedenen Bereichen des 2D Spektrums beobachtet, welche durch vibronische Koh{\"a}renzen hervorgerufen werden und mit fr{\"u}heren Beobachtungen in der Literatur {\"u}bereinstimmen. Mit dem gleichen Datensatz wurde im n{\"a}chsten Schritt das neue Konzept zur optimierten Datenerfassung demonstriert. Um ein optimiertes Schema f{\"u}r die Signalabtastung zu finden, wurde ein genetischer Algorithmus implementiert, wobei nur ein Viertel der eigentlichen Datenpunkte zur Messwerterfassung verwendet werden sollte. Dies reduziert die Zeitdauer der Datenerfassung auf ein Viertel der urspr{\"u}nglichen Messzeit. Die Rekonstruktion des vollst{\"a}ndigen Signales erfolgte mit Hilfe einer neuartigen, kompakten Darstellung von 2D Spektren basierend auf der von Neumann Basis. Diese Herangehensweise ben{\"o}tigte im Vergleich zur {\"u}blicherweise verwendeten Fourier Basis nur ein Sechstel der Koeffizienten um das Signal vollst{\"a}ndig darzustellen und erm{\"o}glichte so die erfolgreiche Rekonstruktion der Oszillationen in Cresyl Violett aus einem reduzierten Datensatz. Mit Hilfe der neuartigen koh{\"a}renten 2D Spektroskopie an Molekularstrahlen wurden {\"U}berg{\"a}nge von hoch angeregten Rydberg-Zust{\"a}nden ins ionische Kontinuum in Stickstoffdioxid untersucht. Als dominierender Beitrag stellte sich hierbei der {\"U}bergang in auto-ionisierende Zust{\"a}nde heraus. Ein wesentlicher Vorteil der Datenerfassung {\"u}ber ein Flugzeitmassenspektrometer ist die M{\"o}glichkeit der gleichzeitigen Aufnahme von 2D Spektren der Edukte und Produkte einer chemischen Reaktion. Dies wurde in Experimenten zur Mehrphotonenionisation gezeigt, in denen deutliche Unterschiede in den 2D Spektren des Stickstoffdioxid-Kations und des Stickstoffmonoxid-Fragmentes sichtbar wurden, welche auf unterschiedliche Antwortfunktionen zur{\"u}ckzuf{\"u}hren sind. Die in dieser Arbeit entwickelten experimentellen Techniken erm{\"o}glichen die schnelle Aufnahme von 2D Spektren f{\"u}r Proben in unterschiedlichen Aggregatzust{\"a}nden und erlauben einen zuverl{\"a}ssigen, direkten Vergleich der Ergebnisse. Sie sind deshalb ein Wegbereiter f{\"u}r zuk{\"u}nftige Untersuchungen der Eigenschaften quantenmechanischer Koh{\"a}renzen in photophysikalischen Prozessen oder w{\"a}hrend photochemischer Reaktionen in unterschiedlichen Aggregatzust{\"a}nden.}, subject = {Femtosekundenspektroskopie}, language = {en} } @article{RoedingBrixner2018, author = {Roeding, Sebastian and Brixner, Tobias}, title = {Coherent two-dimensional electronic mass spectrometry}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, number = {2519}, doi = {10.1038/s41467-018-04927-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226458}, pages = {1-9}, year = {2018}, abstract = {Coherent two-dimensional (2D) optical spectroscopy has revolutionized our ability to probe many types of couplings and ultrafast dynamics in complex quantum systems. The dynamics and function of any quantum system strongly depend on couplings to the environment. Thus, studying coherent interactions for different environments remains a topic of tremendous interest. Here we introduce coherent 2D electronic mass spectrometry that allows 2D measurements on effusive molecular beams and thus on quantum systems with minimum system-bath interaction and employ this to identify the major ionization pathway of 3d Rydberg states in NO2. Furthermore, we present 2D spectra of multiphoton ionization, disclosing distinct differences in the nonlinear response functions leading to the ionization products. We also realize the equivalent of spectrally resolved transient-absorption measurements without the necessity for acquiring weak absorption changes. Using time-of-flight detection introduces cations as an observable, enabling the 2D spectroscopic study on isolated systems of photophysical and photochemical reactions.}, language = {en} } @phdthesis{Lichtenstein2018, author = {Lichtenstein, Leonie}, title = {Color vision and retinal development of the compound eye in bees}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150997}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {The superfamiliy of bees, Apiformes, comprises more than 20,000 species. Within the group, the eusocial species like honeybees and bumblebees are receiving increased attention due to their outstanding importance for pollination of many crop and wild plants, their exceptional eusocial lifestyle and complex behavioral repertoire, which makes them an interesting invertebrate model to study mechanisms of sensory perception, learning and memory. In bees and most animals, vision is one of the major senses since almost every living organism and many biological processes depend on light energy. Bees show various forms of vision, e.g. color vision, achromatic vision or polarized vision in order to orientate in space, recognize mating partners, detect suitable nest sites and search for rewarding food sources. To catch photons and convert light energy into electric signals, bees possess compound eyes which consists of thousands of single ommatidia comprising a fixed number of photoreceptors; they are characterized by a specific opsin protein with distinct spectral sensitivity. Different visual demands, e.g. the detection of a single virgin queen by a drone, or the identification and discrimination of flowers during foraging bouts by workers, gave rise to the exceptional sex-specific morphology and physiology of male and female compound eyes in honeybees. Since Karl von Frisch first demonstrated color vision in honeybees more than 100 years ago, much effort has been devoted to gain insight into the molecular, morphological and physiological characteristics of (sex-specific) bee compound eyes and the corresponding photoreceptors. However, to date, almost nothing is known about the underlying mechanisms during pupal development which pattern the retina and give rise to the distinct photoreceptor distribution. Hence, in Chapter 2 and 3 I aimed to better understand the retinal development and photoreceptor determination in the honeybee eye. In a first step, the intrinsic temporal expression pattern of opsins within the retina was evaluated by quantifying opsin mRNA expression levels during the pupal phase of honeybee workers and drones. First results revealed that honeybee workers and drones express three different opsin genes, UVop, BLop and Lop1 during pupal development which give rise to an ultraviolet, blue, and green-light sensitive photoreceptor. Moreover, opsin expression patterns differed between both sexes and the onset of a particular opsin occurred at different time points during retinal development. Immunostainings of the developing honeybee retina in Chapter 2 showed that at the beginning of pupation the retina consist only of a thin hypodermis. However, at this stage all retinal structures are already present. From about mid of pupation, opsin expression levels increase and goes hand in hand with the differentiation of the rhabdoms, suggesting a two-step process in photoreceptor development and differentiation in the honeybee compound eye. In a first step the photoreceptor cells meet its fate during late pupation; in a second step, the quantity of opsin expression in each photoreceptor strongly increase up to the 25-fold shortly after eclosion. To date, the underlying mechanisms leading to different photoreceptor types have been intensively studied in the fruit fly, Drosophila melanogaster, and to some extend in butterflies. Interestingly, the molecular mechanisms seemed to be conserved within insects and e.g. the two transcription factors, spalt and spineless, which have been shown to be essential for photoreceptor determination in flies and butterflies, have been also identified in the honeybee. In chapter 3, I investigated the expression patterns of both transcription factors during pupal development of honeybee workers and showed that spalt is mainly expressed during the first few pupal stages which might correlate with the onset of BLop expression. Further, spineless showed a prominent peak at mid of pupation which might initiates the expression of Lop1. However, whether spalt and spineless are also essential for photoreceptor determination in the honeybee has still to be investigated, e.g. by a knockdown/out of the respective transcription factor during retinal development which leads to a spectral phenotype, e.g. a dichromatic eye. Such spectral phenotypes can then be tested in behavioral experiments in order to test the function of specific photoreceptors for color perception and the entrainment of the circadian clock. In order to evaluate the color discrimination capabilities of bees and the quality of color perception, a reliable behavioral experiment under controlled conditions is a prerequisite. Hence, in chapter 4, I aimed to establish the visual PER paradigm as a suitable method for behaviorally testing color vision in bees. Since PER color vision has considered to be difficult in bees and was not successful in Western honeybees without ablating the bee's antennae or presenting color stimuli in combination with other cues for several decades, the experimental setup was first established in bumblebees which have been shown to be robust and reliable, e.g. during electrophysiological recordings. Workers and drones of the bufftailed bumblebee, Bombus terrestris were able to associate different monochromatic light stimuli with a sugar reward and succeeded in discriminating a rewarded color stimulus from an unrewarded color stimulus. They were also able to retrieve the learned stimulus after two hours, and workers successfully transferred the learned information to a new behavioral context. In the next step, the experimental setup was adapted to honeybees. In chapter 5, I tested the setup in two medium-sized honeybees, the Eastern honeybee, Apis cerana and the Western honeybee, Apis mellifera. Both honeybee species were able to associate and discriminate between two monochromatic light stimuli, blue and green light, with peak sensitivities of 435 nm and 528 nm. Eastern and Western honeybees also successfully retrieve the learned stimulus after two hours, similar to the bumblebees. Visual conditioning setups and training protocols in my study significantly differed from previous studies using PER conditioning. A crucial feature found to be important for a successful visual PER conditioning is the duration of the conditioned stimulus presentation. In chapter 6, I systematically tested different length of stimuli presentations, since visual PER conditioning in earlier studies tended to be only successful when the conditioned stimulus is presented for more than 10 seconds. In this thesis, intact honeybee workers could successfully discriminate two monochromatic lights when the stimulus was presented 10 s before reward was offered, but failed, when the duration of stimulus presentation was shorter than 4 s. In order to allow a more comparable conditioning, I developed a new setup which includes a shutter, driven by a PC based software program. The revised setup allows a more precise and automatized visual PER conditioning, facilitating performance levels comparable to olfactory conditioning and providing now an excellent method to evaluate visual perception and cognition of bees under constant and controlled conditions in future studies.}, subject = {Biene}, language = {en} } @phdthesis{Huang2018, author = {Huang, Hua}, title = {Comparative investigation of the chemical composition and the water permeability of fruit and leaf cuticles}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152948}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {The plant cuticle is a continuous extracellular protective layer covering the outermost surfaces of higher plants that are in contact with the surrounding atmosphere. The primary function of the cuticular lipid membrane, which is mainly composed of biopolymer cutin and cuticular waxes, is to protect the plant organs against uncontrolled water loss. The chemical composition and the biophysical properties of cuticular waxes affect the rate of water diffusion across the cuticle. Fruit transpiration plays an important role in the development and the maintenance of fruit quality. The fruit has been suggested to present better dehydration stress tolerance than the leaf. However, the differences in transpiration and the chemical composition of cuticular waxes between fruit and leaf have yet to be comprehensively investigated. The present study aims to investigate the water permeability and cuticular wax composition of fruit and leaf cuticles of a wide range of plant species and to elucidate the different roles of the cuticular wax components in the transpiration barrier. To address these objectives, fruit and leaf samples from 17 species were investigated. The cuticular transpiration of intact fruits and astomatous adaxial leaf surfaces and the minimum leaf conductance obtained by leaf drying curves for intact leaves were gravimetrically determined for a variety of plant species. The chemical composition of cuticular waxes of fruits and leaves was thoroughly analysed by gas chromatography with flame ionization and mass spectrometry. The water permeability of fruits ranged from 3.7 x 10-5 m s-1 (Prunus domestica subsp. syriaca) to 37.4 x 10-5 m s-1 (Coffea arabica), whereas permeability for leaves varied between 1.6 x 10-5 m s-1 (Cornus officinalis) and 4.5 x 10-5 m s-1 (Prunus domestica subsp. syriaca (L.)). The interspecies range of water permeability of fruits was significantly higher than that of leaves. Chemical analyses of the cuticular waxes demonstrated that fatty acids, primary alcohols, n-alkanes, aldehydes and alkyl esters were the predominant very-long-chain aliphatic compound classes of fruit and leaf surfaces. Sterols, such as β-sitosterol and campesterol, and triterpenoids, such as oleanolic acid, ursolic acid, α-amyrin and ß-amyrin, were the major cyclic compound classes in the cuticular wax membrane. The amount and composition of cuticular waxes of both fruits and leaves varied at an intraspecific level. There were no significant correlations between the total cuticular wax load or the individual cuticular wax composition and the water permeability of fruits or leaves independently or together. After combining the fruit and leaf data set, a significant correlation between the average chain length of very-long-chain aliphatic compounds and permeabilities was detected, i.e. the longer the average chain length, the lower the water permeability. Interestingly, n-Nonacosane (C29) was abundantly detected in fruit waxes of Rosaceae species. These fruits exhibited a relatively low transpiration level, which was very close to their leaf cuticular permeability. The present study suggests that the lower cuticular permeability of leaves, in comparison to that of fruits, may be attributed to the longer average chain length of aliphatic compounds. The accumulation of total wax, triterpenoids and aliphatic compounds may not contribute to the transpiration barrier directly. The present results are highly consistent with the previous model assumptions for the cuticular structure and transport barrier. Furthermore, this comparative study on leaf and fruit cuticles provides further insights linking the cuticular wax chemistry to the physiological properties of the plant cuticle.}, subject = {Cuticle}, language = {en} } @article{ZoltnerKrienitzFieldetal.2018, author = {Zoltner, Martin and Krienitz, Nina and Field, Mark C. and Kramer, Susanne}, title = {Comparative proteomics of the two T. brucei PABPs suggests that PABP2 controls bulk mRNA}, series = {PLoS Neglected Tropical Diseases}, volume = {12}, journal = {PLoS Neglected Tropical Diseases}, number = {7}, doi = {10.1371/journal.pntd.0006679}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177126}, pages = {e0006679}, year = {2018}, abstract = {Poly(A)-binding proteins (PABPs) regulate mRNA fate by controlling stability and translation through interactions with both the poly(A) tail and eIF4F complex. Many organisms have several paralogs of PABPs and eIF4F complex components and it is likely that different eIF4F/PABP complex combinations regulate distinct sets of mRNAs. Trypanosomes have five eIF4G paralogs, six of eIF4E and two PABPs, PABP1 and PABP2. Under starvation, polysomes dissociate and the majority of mRNAs, most translation initiation factors and PABP2 reversibly localise to starvation stress granules. To understand this more broadly we identified a protein interaction cohort for both T. brucei PABPs by cryo-mill/affinity purification-mass spectrometry. PABP1 very specifically interacts with the previously identified interactors eIF4E4 and eIF4G3 and few others. In contrast PABP2 is promiscuous, with a larger set of interactors including most translation initiation factors and most prominently eIF4G1, with its two partners TbG1-IP and TbG1-IP2. Only RBP23 was specific to PABP1, whilst 14 RNA-binding proteins were exclusively immunoprecipitated with PABP2. Significantly, PABP1 and associated proteins are largely excluded from starvation stress granules, but PABP2 and most interactors translocate to granules on starvation. We suggest that PABP1 regulates a small subpopulation of mainly small-sized mRNAs, as it interacts with a small and distinct set of proteins unable to enter the dominant pathway into starvation stress granules and localises preferentially to a subfraction of small polysomes. By contrast PABP2 likely regulates bulk mRNA translation, as it interacts with a wide range of proteins, enters stress granules and distributes over the full range of polysomes.}, language = {en} } @article{OPUS4-22596, title = {Comparison between simulated and observed LHC beam backgrounds in the ATLAS experiment at \(E\)\(_{beam}\)=4 TeV}, series = {Journal of Instrumentation}, volume = {13}, journal = {Journal of Instrumentation}, organization = {The ATLAS Collaboration}, doi = {10.1088/1748-0221/13/12/P12006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225966}, pages = {1-40}, year = {2018}, abstract = {Results of dedicated Monte Carlo simulations of beam-induced background (BIB) in the ATLAS experiment at the Large Hadron Collider (LHC) are presented and compared with data recorded in 2012. During normal physics operation this background arises mainly from scattering of the 4 TeV protons on residual gas in the beam pipe. Methods of reconstructing the BIB signals in the ATLAS detector, developed and implemented in the simulation chain based on the FLUKA Monte Carlo simulation package, are described. The interaction rates are determined from the residual gas pressure distribution in the LHC ring in order to set an absolute scale on the predicted rates of BIB so that they can be compared quantitatively with data. Through these comparisons the origins of the BIB leading to different observables in the ATLAS detectors are analysed. The level of agreement between simulation results and BIB measurements by ATLAS in 2012 demonstrates that a good understanding of the origin of BIB has been reached.}, language = {en} } @article{BoelchRuecklFuchsetal.2018, author = {Boelch, Sebastian P. and Rueckl, Kilian and Fuchs, Clara and Jordan, Martin and Knauer, Markus and Steinert, Andre and Rudert, Maximilian and Luedemann, Martin}, title = {Comparison of elution characteristics and compressive strength of biantibiotic-loaded PMMA bone cement for spacers: Copal\(^®\) spacem with gentamicin and vancomycin versus Palacos\(^®\) R+G with vancomycin}, series = {BioMed Research International}, volume = {2018}, journal = {BioMed Research International}, number = {4323518}, doi = {10.1155/2018/4323518}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177435}, year = {2018}, abstract = {Purpose. Copal\(^®\) spacem is a new PMMA bone cement for fabricating spacers. This study compares elution of gentamicin, elution of vancomycin, and compressive strength of Copal\(^®\) spacem and of Palacos\(^®\) R+G at different vancomycin loadings in the powder of the cements. We hypothesized that antibiotic elution of Copal\(^®\) spacem is superior at comparable compressive strength. Methods. Compression test specimens were fabricated using Copal\(^®\) spacem manually loaded with 0.5 g gentamicin and additionally 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (COP specimens) and using 0.5 g gentamicin premixed Palacos\(^®\) R+G manually loaded with 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (PAL specimens). These specimens were used for determination of gentamicin and vancomycin elution (in fetal calf serum, at 22°C) and for determination of compressive strength both prior and following the elution tests. Results. Cumulative gentamicin concentrations (p < 0.005) and gentamicin concentration after 28 days (p ≤ 0.043) were significantly lower for COP specimens compared to PAL specimens. Cumulative vancomycin concentrations were significantly higher (p ≤ 0.043) for COP specimens after the second day. Vancomycin concentrations after 28 days were not significantly higher for the Copal specimens loaded with 2 g and 4 g of vancomycin. Compressive strength was not significantly different between COP specimens and PAL specimens before elution tests. Compressive strength after the elution tests was significantly lower (p = 0.005) for COP specimens loaded with 2 g of vancomycin. Conclusion. We could not demonstrate consistent superior antibiotic elution from Copal\(^®\) spacem compared to Palacos\(^®\) R+G for fabricating gentamicin and vancomycin loaded spacers. The results do not favor Copal\(^®\) spacem over Palacos\(^®\) R+G for the use as a gentamicin and vancomycin biantibiotic-loaded spacer.}, language = {en} } @article{RosenbaumBlumSchweizeretal.2018, author = {Rosenbaum, David and Blum, Leonore and Schweizer, Paul and Fallgatter, Andreas J. and Herrmann, Martin J. and Ehlis, Ann-Christine and Metzger, Florian G.}, title = {Comparison of speed versus complexity effects on the hemodynamic response of the trail making test in block designs}, series = {Neurophotonics}, volume = {5}, journal = {Neurophotonics}, number = {4}, doi = {10.1117/1.NPh.5.4.045007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226982}, pages = {045007, 1-9}, year = {2018}, abstract = {The use of functional near-infrared spectroscopy (fNIRS) in block designs provides measures of cortical activity in ecologically valid environments. However, in some cases, the use of block designs may be problematic when data are not corrected for performance in a time-restricted block. We sought to investigate the effects of task complexity and processing speed on hemodynamic responses in an fNIRS block design. To differentiate the effects of task complexity and processing speed, 20 subjects completed the trail making test (TMT) in two versions (TMT-A versus TMT-B) and three different speed levels (slow versus moderate versus fast). During TMT-A, subjects are asked to connect encircled numbers in numerically ascending order (1-2-3 ... ). In the more complex TMT-B, subjects are instructed to connect encircled numbers and letters in alternating ascending order (1-A-2-B ... ). To illustrate the obscuring effects of processing speed on task complexity, we perform two different analyses. First, we analyze the classical measures of oxygenated blood, and second, we analyze the measures corrected for the number of processed items. Our results show large effects for processing speed within the bilateral inferior frontal gyrus, left dorsolateral prefrontal cortex, and superior parietal lobule (SPL). The TMT contrast did not show significant effects with classical measures, although trends are observed for higher activation during TMT-B. When corrected for processed items, higher activity for TMT-B in comparison to TMT-A is found within the SPL. The results are discussed in light of recent research designs, and simple to use correction methods are suggested. (c) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.}, language = {en} } @article{ChenLotzRoeweretal.2018, author = {Chen, Shasha and Lotz, Christopher and Roewer, Norbert and Broscheit, Jens-Albert}, title = {Comparison of volatile anesthetic-induced preconditioning in cardiac and cerebral system: molecular mechanisms and clinical aspects}, series = {European Journal of Medical Research}, volume = {23}, journal = {European Journal of Medical Research}, number = {10}, doi = {10.1186/s40001-018-0308-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175509}, year = {2018}, abstract = {Volatile anesthetic-induced preconditioning ( APC) has shown to have cardiac and cerebral protective properties in both pre-clinical models and clinical trials. Interestingly, accumulating evidences demonstrate that, except from some specific characters, the underlying molecular mechanisms of APC-induced protective effects in myocytes and neurons are very similar; they share several major intracellular signaling pathways, including mediating mitochondrial function, release of inflammatory cytokines and cell apoptosis. Among all the experimental results, cortical spreading depolarization is a relative newly discovered cellular mechanism of APC, which, however, just exists in central nervous system. Applying volatile anesthetic preconditioning to clinical practice seems to be a promising cardio- and neuroprotective strategy. In this review, we also summarized and discussed the results of recent clinical research of APC. Despite all the positive experimental evidences, large-scale, long-term, more precisely controlled clinical trials focusing on the perioperative use of volatile anesthetics for organ protection are still needed.}, language = {en} } @article{HerrmannMuenstermannStrobeletal.2018, author = {Herrmann, Johannes and Muenstermann, Marcel and Strobel, Lea and Schubert-Unkmeir, Alexandra and Woodruff, Trent M. and Gray-Owen, Scott D. and Klos, Andreas and Johswich, Kay O.}, title = {Complement C5a receptor 1 exacerbates the pathophysiology of N. meningitidis sepsis and is a potential target for disease treatment}, series = {mBio}, volume = {9}, journal = {mBio}, number = {1}, doi = {10.1128/mBio.01755-17}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175792}, pages = {e01755-17}, year = {2018}, abstract = {Sepsis caused by Neisseria meningitidis (meningococcus) is a rapidly progressing, life-threatening disease. Because its initial symptoms are rather unspecific, medical attention is often sought too late, i.e., when the systemic inflammatory response is already unleashed. This in turn limits the success of antibiotic treatment. The complement system is generally accepted as the most important innate immune determinant against invasive meningococcal disease since it protects the host through the bactericidal membrane attack complex. However, complement activation concomitantly liberates the C5a peptide, and it remains unclear whether this potent anaphylatoxin contributes to protection and/or drives the rapidly progressing immunopathogenesis associated with meningococcal disease. Here, we dissected the specific contribution of C5a receptor 1 (C5aR1), the canonical receptor for C5a, using a mouse model of meningococcal sepsis. Mice lacking C3 or C5 displayed susceptibility that was enhanced by >1,000-fold or 100-fold, respectively, consistent with the contribution of these components to protection. In clear contrast, C5ar1\(^{-/-}\) mice resisted invasive meningococcal infection and cleared N. meningitidis more rapidly than wild-type (WT) animals. This favorable outcome stemmed from an ameliorated inflammatory cytokine response to N. meningitidis in C5ar1\(^{-/-}\) mice in both in vivo and ex vivo whole-blood infections. In addition, inhibition of C5aR1 signaling without interference with the complement bactericidal activity reduced the inflammatory response also in human whole blood. Enticingly, pharmacologic C5aR1 blockade enhanced mouse survival and lowered meningococcal burden even when the treatment was administered after sepsis induction. Together, our findings demonstrate that C5aR1 drives the pathophysiology associated with meningococcal sepsis and provides a promising target for adjunctive therapy. Importance: The devastating consequences of N. meningitidis sepsis arise due to the rapidly arising and self-propagating inflammatory response that mobilizes antibacterial defenses but also drives the immunopathology associated with meningococcemia. The complement cascade provides innate broad-spectrum protection against infection by directly damaging the envelope of pathogenic microbes through the membrane attack complex and triggers an inflammatory response via the C5a peptide and its receptor C5aR1 aimed at mobilizing cellular effectors of immunity. Here, we consider the potential of separating the bactericidal activities of the complement cascade from its immune activating function to improve outcome of N. meningitidis sepsis. Our findings demonstrate that the specific genetic or pharmacological disruption of C5aR1 rapidly ameliorates disease by suppressing the pathogenic inflammatory response and, surprisingly, allows faster clearance of the bacterial infection. This outcome provides a clear demonstration of the therapeutic benefit of the use of C5aR1-specific inhibitors to improve the outcome of invasive meningococcal disease.}, language = {en} } @phdthesis{Toepfer2018, author = {Toepfer, Franziska Helene}, title = {Component selectivity and multistability in a \(Drosophila\) orientation paradigm using incoherent motion stimuli}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153346}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Visual information is essential for Drosophila to navigate its environment. The visual system of the fly has been studied for many decades and has yielded many insights about vision in general. However, visual information can be ambiguous and the system processing it needs to be able to cope with that. In this study, the visual orientation behavior of Drosophila is challenged by panoramic incoherent motion stimuli to which the fly can respond in three different, equally adaptive ways. The study is conducted in a well-established setup, the so-called flight simulator (Heisenberg and Wolf, 1993), where the fly can control its visual surroundings in stationary flight with its yaw torque, which is simultaneously recorded. The fly can either use one of two incoherently moving panorama patterns or the integrated motion of both as its reference for straight flight. It is observed that flies use all three of these behavioral alternatives for orientation. Previous models of fly motion vision do not predict a bimodal tuning to incoherent wide-field motion stimuli (Joesch et al., 2008, Borst et al., 1995), however, a recent study on blowflies could suggests that they show component selectivity to the individual moving gratings in a compound plaid stimulus (Saleem et al., 2012). Here, it can be shown that the same bimodal tuning manifests in Drosophila, although the stimuli used are different and most of the experiments are conducted in closed loop. It is found that the extent to which the Drosophila expresses this component selectivity in its orientation behavior, i.e. how often it stabilizes a single panorama pattern instead of the integrated motion of both, depends on two properties of the panorama stimuli, pattern contrast and horizontal pattern element distance. Single pattern stabilization decreases with increasing contrast and increasing pattern element distance. In the latter case, it increases again when there are very few horizontal pattern elements, although that appears to be the result of a lack of rivalry between the patterns due to the low number of pattern elements. Both increased pattern contrast and pattern element distance increase the salience of the single pattern elements. A single element in a compound visual stimulus, like a dot within a dot pattern, can be interpreted as a standalone figure or a part of a bigger unit. Previous studies on Drosophila vision have concentrated on how the fly discriminates a figure from the background (Heisenberg and Wolf, 1984, Bahl et al., 2013, Aptekar et al., 2012), but have hardly touched the question of what qualifies a figure or a background (i.e. a panorama) stimulus as such. In the present study, it is observed that, when exposed to incoherent panoramic motion stimuli, the flies prefer to orient themselves towards the average of the two motions when the panorama stimuli possess strong figure features and towards the single patterns when they do not and single pattern elements are therefore less salient. The above-mentioned plaid stimuli are a well-known multistable percept in human psychophysics. Multistability is a property of higher visual systems and considered an indicator of endogenous activity in vision. As Drosophila expresses behavioral multistability in the IPMP, it is evaluated in this respect. The results show several parallels to human multistable perception. For one, the frequency and duration with which a behavior occurs, can be influenced, but the occurrence of the behaviors is non-deterministic and not coupled to the stimulus. It can also be shown that the switches between behaviors do not stem from a rivalry of the two visual hemispheres of the fly, although monocularity does also influence the likelihood with which the behaviors occur. Secondly, like in human perceptual rivalry, individual flies exhibit strong idiosyncrasies regarding the overall durations they spend with the different behaviors and the frequencies with which they switch between them. Finally, the distribution of the durations between the behavioral switches can be fit to the same function as the distribution of percept durations in human multistable perception, the gamma function, although it has a different shape and therefore also differing parameters. The Drosophila mutant radish, which has been shown to have attention-like deficits (van Swinderen and Brembs, 2010, Koenig et al., 2016a), does also express an altered behavior in the IPMP compared to wildtype flies. As these behavioral alterations resemble effects on multistable perception found in humans suffering from ADHD (Amador-Campos et al., 2015) and perceptual multistability is generally considered to be closely related to attention (Leopold and Logothetis, 1999), attentional processes are also very likely to play a role in the flies' behavior in the IPMP. In conclusion, the visual system of Drosophila is capable disentangle incoherent motion stimuli even if they overlap and cover the entire visual field, i.e. it shows component selectivity of wide-field motion. Whether it uses a single wide-field motion component or the average of two as its reference for straight flight depends on pattern contrast and horizontal pattern element density, which indicates an involvement of a figure-background rivalry. This rivalry and the one between the two wide-field motion components elicit a multistability in the orientation behavior of the fly the temporal dynamics of which partially resemble the temporal dynamics of human multistable perception and which also suggests the involvement of attentional processes.}, subject = {Drosophila}, language = {en} } @article{RosentreterLappasWidderetal.2018, author = {Rosentreter, Andr{\´e} and Lappas, Alexandra and Widder, Randolf Alexander and Alnawaiseh, Maged and Dietlein, Thomas Stefan}, title = {Conjunctival repair after glaucoma drainage device exposure using collagen-glycosaminoglycane matrices}, series = {BMC Ophthalmology}, volume = {18}, journal = {BMC Ophthalmology}, number = {60}, doi = {10.1186/s12886-018-0721-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175534}, year = {2018}, abstract = {Background: To report the results of the repair of conjunctival erosions resulting from glaucoma drainage device surgery using collagen-glycosaminoglycane matrices (CGM). Methods: Case series of 8 patients who underwent revision surgery due to conjunctival defects with exposed tubes through necrosis of the overlying scleral flap and conjunctiva after Baerveldt drainage device surgery. The defects were repaired by lateral displacement of the tube towards the sclera, with a slice of a CGM as a patch, covered by adjacent conjunctiva. Result: Successful, lasting closure (follow-up of 12 to 42 months) of the conjunctival defects was achieved without any side-effects or complications in all eight cases. Conclusions: Erosion of the drainage tube, creating buttonholes in the conjunctiva after implantation of glaucoma drainage devices, is a potentially serious problem. It can be managed successfully using a biodegradable CGM as a patch.}, language = {en} } @misc{Schaper2018, type = {Master Thesis}, author = {Schaper, Anna-Katharina}, title = {Conquering China's Second-Tier Cities: An Empirical Analysis of the Relationship between a City's Degree of Internationalization and Foreign Companies' Market Entry Decisions in China's Second-Tier Cities}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161329}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {China's emerging second-tier cities attract more and more foreign companies that are looking for business opportunities. Although much has been written about companies' internationalization strategies, including companies' market entry decisions and market entry mode strategies, research on the relationship between a city's degree of internationalization and foreign companies' market entry decisions and market entry mode strategies in second-tier cities in China is still relatively scarce. Thus, the central research question of this study is: Why and how does a second-tier city's degree of internationalization influence foreign companies' market entry decisions and market entry mode strategies in second-tier China? This study is based on a qualitative research approach; an embedded multiple-case study is applied and interviews with two different target groups are conducted. The first target group consists of foreign companies having established business operations in China's second-tier cities directly and have had no previous business operations in first-tier cites. The second group is made up of foreign companies that initially operated in first-tier China, and then moved to second-tier cities. The company sample compromises small- and medium-sized foreign companies with various industry backgrounds and market entry modes in Chengdu and Chongqing. Since 2015, Maxxelli has been publishing its China International City Index (CICI) on a yearly basis in which it measures and compares China's cities' degree of internationalization. Because Maxxelli revised this year's CICI methodology comprehensively, this study also aims at feedback to improve the overall CICI. This study concludes that a second-tier city's degree of internationalization is particularly important to foreign companies having first set up in Chinese first-tier cities. Companies having established themselves in second-tier cities directly, do not pay a lot of direct attention to a city's degree of internationalization and tend to base their market entry decisions more on business opportunities they identify in a city. In addition, this study argues that in most cases a city's degree of internationalization does not influence the type of market entry mode companies choose to enter second-tier China.}, subject = {China}, language = {en} } @article{OPUS4-34679, title = {Constraints on off-shell Higgs boson production and the Higgs boson total width in \(ZZ\) → 4l and \(ZZ\) → 2l2ν final states with the ATLAS detector}, series = {Physics Letters B}, volume = {786}, journal = {Physics Letters B}, organization = {The ATLAS Collaboration}, doi = {10.1016/j.physletb.2018.09.048}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346791}, pages = {223-244}, year = {2018}, abstract = {A measurement of off-shell Higgs boson production in the ZZ -> 4l and ZZ -> 2l2v decay channels, where stands for either an electron or a muon, is performed using data from proton-proton collisions at a centre-of-mass energy of root s = 13 TeV. The data were collected by the ATLAS experiment in 2015 and 2016 at the Large Hadron Collider, and they correspond to an integrated luminosity of 36.1 fb(-1). An observed (expected) upper limit on the off-shell Higgs signal strength, defined as the event yield normalised to the Standard Model prediction, of 3.8 (3.4) is obtained at 95\% confidence level (CL). Assuming the ratio of the Higgs boson couplings to the Standard Model predictions is independent of the momentum transfer of the Higgs production mechanism considered in the analysis, a combination with the on-shell signal-strength measurements yields an observed (expected) 95\% CL upper limit on the Higgs boson total width of 14.4 (15.2) MeV.}, language = {en} } @unpublished{StennettBertermannBraunschweig2018, author = {Stennett, Tom and Bertermann, R{\"u}diger and Braunschweig, Holger}, title = {Construction of Linear and Branched Tetraboranes via 1,1- and 1,2-Diboration of Diborenes}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201809976}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178276}, year = {2018}, abstract = {Sterically unencumbered diborenes based on a benzylphosphine chelate undergo diboration reactions with bis(catecholato)diboron in the absence of a catalyst to yield tetraboranes. The symmetrical diborenes studied undergo 1,2- diborations, whereas an unsymmetrical derivative was found to yield a triborylborane-phosphine adduct as the result of a formal 1,1-diboration. A related borylborylene compound also underwent a 1,2-diboration to produce a borylene-borane adduct.}, language = {en} } @phdthesis{Coban2018, author = {Coban, Mustafa}, title = {Contributions to the Empirics of Immigration, Redistribution and Social Mobility}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148934}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {In recent decades the international migration has increased worldwide. The influx of people from different cultures and ethnic groups poses new challenges to the labor market and the welfare state of the host countries and causes changes in the social fabric. In general, immigration benefits the economy of the host country. However, these gains from immigration are unevenly distributed among the native population. Natives who are in direct competition with the new workers expect wage losses and a higher probability of getting unemployed, whereas remaining natives foresee either no feedback effects or even wage gains. On the other hand, the tax and transfer system benefits disproportionally from an influx of highly skilled immigrants. Examinations of 20 European countries in 2010 show that a higher proportion of low-skilled immigrants in the immediate neighborhood of the natives increases the difference in the demand for redistribution between high-skilled and low-skilled natives. Thus, high-skilled natives are more opposed to an expansion of the governmental redistribution. On the one hand, a higher proportion of low-skilled immigrants generates a higher fiscal burden on the welfare state. On the other hand, high-skilled natives' wages increase due to an influx of low-skilled immigrants, since relative supply of high-skilled labor increases. In addition to the economic impact of immigration, the inflow of new citizens is accompanied by natives' fear of changes in the social environment as well as in symbolic values, such as cultural identity or natives' set of values. The latter might generate negative attitudes towards immigrants and increase the demand for a more restrictive immigration policy. On the other hand, more interethnic contact due to a higher ethnic diversity could reduce natives' information gaps, prejudices and stereotypes. This, in turn, could enhance more tolerance and solidarity towards immigrants among natives. Examinations of 18 European countries in 2014 show that more interethnic contact during everyday life reduces both the natives' social distance from immigrants and their fear of social upheaval by the presence of immigrants. However, natives' social distance from immigrants has no effect on their preference for redistribution, but their perceived threat to the national culture and social life by the presence of immigrants has a significantly negative impact on their demand for redistribution. Thus, natives' concern about the preservation of symbolic norms and values affects the solidarity channel of their redistribution preference. An individual's upward mobility over time or in relation to his or her parents determines his or her attitude towards the welfare state as well as the transfer of his or her opinions to his or her own children. With regard to intergenerational income mobility, Germany shows a value in the international midfield; higher than the United States (lower mobility) and lower than the Scandinavian countries (higher mobility). For example, if a father's lifetime income increases by 10 percent, his son's lifetime income increases by 4.9 percent in the United States and by 3.1 percent in Germany. Additionally, in Germany, fathers' lifetime income tends to show a higher impact on their sons' income if their incomes are higher. In the United States, fathers' lifetime incomes have a stronger influence on their sons' income at the lower and the upper end of the income distribution compared to the middle. Taking a closer look at the intragenerational wage mobility and wage inequality in Germany, the development at the current edge is rather sobering. Since 2000 there is a steady decline in wage mobility. Furthermore, wage mobility in the services sector has been significantly lower than in the manufacturing sector since the beginning of the 2000s. This result is mainly driven by the decrease of wage mobility in the health care and social services sector. Moreover, a worker's unemployment spells and occupation have become more important in the meantime. Since 2006 the increase in the German wage inequality has markedly slowed down and wage growth between 2006 and 2013 has been even polarized, i.e. wages at the lower and at the upper end of the wage distribution have increased more than wages in the middle. However, this development can be partly attributed to the computerization and automation of the production processes. Although, there was substitution of manual routine tasks between 2001 and 2013, cognitive routine tasks are still more pronounced in the middle and at the upper end of the wage distribution. Furthermore, the latter experienced an increase in wage mobility since 2000. On the other hand, manual non-routine tasks are localized disproportionally in the middle and at the lower end of the wage distribution. Thus, the wage gains of these occupations at the lower end were compensated for by the wage losses in the middle.}, subject = {Einwanderung}, language = {en} } @phdthesis{Schoetz2018, author = {Sch{\"o}tz, Matthias}, title = {Convergent Star Products and Abstract O*-Algebras}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174355}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Diese Dissertation behandelt ein Problem aus der Deformationsquantisierung: Nachdem man die Quantisierung eines klassischen Systems konstruiert hat, w{\"u}rde man gerne ihre mathematischen Eigenschaften verstehen (sowohl die des klassischen Systems als auch die des Quantensystems). Falls beide Systeme durch *-Algebren {\"u}ber dem K{\"o}rper der komplexen Zahlen beschrieben werden, bedeutet dies dass man die Eigenschaften bestimmter *-Algebren verstehen muss: Welche Darstellungen gibt es? Was sind deren Eigenschaften? Wie k{\"o}nnen die Zust{\"a}nde in diesen Darstellungen beschrieben werden? Wie kann das Spektrum der Observablen beschrieben werden? Um eine hinreichend allgemeine Behandlung dieser Fragen zu erm{\"o}glichen, wird das Konzept von abstrakten O*-Algebren entwickelt. Dies sind im Wesentlichen *-Algebren zusammen mit einem Kegel positiver linearer Funktionale darauf (z.B. die stetigen positiven linearen Funktionale wenn man mit einer *-Algebra startet, die mit einer gutartigen Topologie versehen ist). Im Anschluss daran wird dieser Ansatz dann auf zwei Beispiele aus der Deformationsquantisierung angewandt, die im Detail untersucht werden.}, subject = {Deformationsquantisierung}, language = {en} } @phdthesis{Munzert2018, author = {Munzert, Stefanie Martina}, title = {Coordination of dynamic metallosupramolecular polymers (MEPEs)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-160650}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Several transition metal ions, like Fe2+, Co2+, Ni2+, and Zn2+ complex to the ditopic ligand 1,4-bis(2,2':6',2''-terpyridin-4'-yl)benzene. Due to the high association constant, metal ion induced self-assembly of Fe2+, Co2+, and Ni2+ leads to extended, rigid-rod like metallo-supramolecular coordination polyelectrolytes (MEPEs) even in aqueous solution. Here, the kinetics of coordination and the kinetics of growth of MEPEs are presented. The species in solutions are analyzed by stopped-flow fluorescence spectroscopy, light scattering, viscometry and cryogenic transmission electron microscopy. At near-stoichiometric amounts of the reactants, high molar masses are obtained, which follow the order Ni-MEPE ~ Co-MEPE < Fe-MEPE. Furthermore, a way is presented to adjust the average molar mass, chain-length and viscosity of MEPEs using the monotopic chain stopper 4'-(phenyl)-2,2':6',2''-terpyridine.}, subject = {Supramolekulare Chemie}, language = {en} } @phdthesis{Eichhorn2018, author = {Eichhorn, Antonius}, title = {Copper(I) catalyzed borylation and cross-coupling reactions}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167332}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {The present thesis comprises synthesis and stoichiometric model reactions of well-defined NHC-stabilized copper(I) complexes (NHC = N-heterocyclic carbene) in order to understand their basic reactivity in borylation and cross-coupling reactions. This also includes the investigations of the reactivity of the ligands used (NHCs and CaaCs = cyclic alkyl(amino)carbenes) with the substrates, i.e. diboron(4) esters and arylboronates, which are addressed in the second part of the thesis.}, subject = {Copper}, language = {en} } @article{SchuhmannEberleinMuelleretal.2018, author = {Schuhmann, Sarah and Eberlein, Uta and M{\"u}ller, Jessica and Scherthan, Harry and Lassmann, Michael}, title = {Correlation of the absorbed dose to the blood and DNA damage in leukocytes after internal ex-vivo irradiation of blood samples with Ra-224}, series = {EJNMMI Research}, volume = {8}, journal = {EJNMMI Research}, number = {77}, doi = {10.1186/s13550-018-0422-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176593}, year = {2018}, abstract = {Background: Irradiation with α-particles creates densely packed damage tracks along particle trajectories in exposed cells, including complex DNA damage and closely spaced double-strand breaks (DSBs) in hit nuclei. Here, we investigated the correlation of the absorbed dose to the blood and the number of α-induced DNA damage tracks elicited in human blood leukocytes after ex-vivo in-solution exposure with Ra-224. The aim was to compare the data to previously published data on Ra-223 and to investigate differences in DNA damage induction between the two radium isotopes. Results: Blood samples from three healthy volunteers were exposed ex-vivo to six different concentrations of Ra-224 dichloride. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the Ra-224 decay chain, ranging from 0 to 127 mGy. γ-H2AX + 53BP1 DNA damage co-staining and analysis was performed on ethanol-fixed leukocytes isolated from the irradiated blood samples. For damage quantification, α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci were enumerated in the exposed leukocytes. This revealed a linear relationship between the frequency of α-induced γ-H2AX damage tracks and the absorbed dose to the blood, while the frequency of small γ-H2AX + 53BP1 DSB foci indicative of β-irradiation was similar to baseline values. Conclusions: Our data provide a first estimation of the DNA damage induced by Ra-224 in peripheral blood mononuclear cells. A comparison with our previously published Ra-223 data suggests that there is no difference in the induction of radiation-induced DNA damage between the two radium isotopes due to their similar decay properties.}, language = {en} } @article{SchlichtingRiegerCusumanoetal.2018, author = {Schlichting, Matthias and Rieger, Dirk and Cusumano, Paola and Grebler, Rudi and Costa, Rodolfo and Mazzotta, Gabriella M. and Helfrich-F{\"o}rster, Charlotte}, title = {Cryptochrome interacts with actin and enhances eye-mediated light sensitivity of the circadian clock in Drosophila melanogaster}, series = {Frontiers in Molecular Neuroscience}, volume = {11}, journal = {Frontiers in Molecular Neuroscience}, number = {238}, doi = {10.3389/fnmol.2018.00238}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177086}, year = {2018}, abstract = {Cryptochromes (CRYs) are a class of flavoproteins that sense blue light. In animals, CRYs are expressed in the eyes and in the clock neurons that control sleep/wake cycles and are implied in the generation and/or entrainment of circadian rhythmicity. Moreover, CRYs are sensing magnetic fields in insects as well as in humans. Here, we show that in the fruit fly Drosophila melanogaster CRY plays a light-independent role as "assembling" protein in the rhabdomeres of the compound eyes. CRY interacts with actin and appears to increase light sensitivity of the eyes by keeping the "signalplex" of the phototransduction cascade close to the membrane. By this way, CRY also enhances light-responses of the circadian clock.}, language = {en} } @phdthesis{Maas2018, author = {Maas, Daniel Peter}, title = {Currency Areas, Monetary Policy, and the Macroeconomy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168037}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Hauptgegenstand der Dissertation ist die Analyse der makro{\"o}konomischen Auswirkungen der Gr{\"u}ndung der Eurozone auf die Mitgliedsstaaten. Diese Analyse umfasst zwei Studien, die sich der Fragestellung aus verschiedenen Perspektiven n{\"a}hern. Die erste Studie unternimmt einen Vergleich der Geldpolitik von EZB und von ausgew{\"a}hlten Zentralbanken des Europ{\"a}ischen W{\"a}hrungssystems (EWS). Es wird untersucht, inwiefern sich bei makro{\"o}konomischen Nachfrage- und Angebotsschocks die systematischen Reaktionen der EZB von denen der vier wichtigsten nationalen Zentralbanken des EWS (Deutschland, Frankreich, Italien und Spanien) unterscheiden. In der zweiten Studie werden die Ursachen f{\"u}r den Aufbau interner und externer Ungleichgewichte in Spanien, d.h. auf dem Immobilienmarkt und in der Leistungsbilanz, im Vorfeld der Finanzkrise 2007/08 analysiert. Dabei wird zwischen Spanien-spezifischen und Eurozonen-spezifischen Ursachen unterschieden und deren Erkl{\"a}rungsgehalt empirisch quantifiziert. In der dritten und letzten Studie der Dissertation wird ein preistheoretisches Kreditangebotsmodell entwickelt und empirisch gesch{\"a}tzt. Als Basis f{\"u}r die empirische Sch{\"a}tzung werden Daten des Kreditmarktes f{\"u}r deutsche Unternehmen verwendet. Die methodische Vorgehensweise beinhaltet in allen Studien zeitreihen{\"o}konometrische Ans{\"a}tze wie beispielsweise (Mehrl{\"a}nder-)Vektorautoregressionen (VARs) und Zeitreihenregressionen.}, subject = {Geldpolitik}, language = {en} }