@article{BiedermannBilloniDenneretal.2016, author = {Biedermann, B. and Billoni, M. and Denner, A. and Dittmaier, S. and Hofer, L. and J{\"a}ger, B. and Salfelder, L.}, title = {Next-to-leading-order electroweak corrections to pp -> W\(^{+}\)W\(^{-}\) -> 4 leptons at the LHC}, series = {JOURNAL OF HIGH ENERGY PHYSICS}, volume = {06}, journal = {JOURNAL OF HIGH ENERGY PHYSICS}, number = {065}, doi = {10.1007/JHEP06(2016)065}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167790}, year = {2016}, abstract = {We present results of the first calculation of next-to-leading-order electroweak corrections to W-boson pair production at the LHC that fully takes into account leptonic W-boson decays and off-shell effects. Employing realistic event selections, we discuss the corrections in situations that are typical for the study of W-boson pairs as a signal process or of Higgs-boson decays H → WW∗, to which W-boson pair production represents an irreducible background. In particular, we compare the full off-shell results, obtained treating the W-boson resonances in the complex-mass scheme, to previous results in the so-called double-pole approximation, which is based on an expansion of the loop amplitudes about the W resonance poles. At small and intermediate scales, i.e. in particular in angular and rapidity distributions, the two approaches show the expected agreement at the level of fractions of a percent, but larger differences appear in the TeV range. For transverse-momentum distributions, the differences can even exceed the 10\% level in the TeV range where "background diagrams" with one instead of two resonant W bosons gain in importance because of recoil effects.}, language = {en} } @article{BialasZitzlerKunkelKirchneretal.2016, author = {Bialas, David and Zitzler-Kunkel, Andr{\´e} and Kirchner, Eva and Schmidt, David and W{\"u}rthner, Frank}, title = {Structural and quantum chemical analysis of exciton coupling in homo- and heteroaggregate stacks of merocyanines}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms12949}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170200}, year = {2016}, abstract = {Exciton coupling is of fundamental importance and determines functional properties of organic dyes in (opto-)electronic and photovoltaic devices. Here we show that strong exciton coupling is not limited to the situation of equal chromophores as often assumed. Quadruple dye stacks were obtained from two bis(merocyanine) dyes with same or different chromophores, respectively, which dimerize in less-polar solvents resulting in the respective homo- and heteroaggregates. The structures of the quadruple dye stacks were assigned by NMR techniques and unambiguously confirmed by single-crystal X-ray analysis. The heteroaggregate stack formed from the bis(merocyanine) bearing two different chromophores exhibits remarkably different ultraviolet/vis absorption bands compared with those of the homoaggregate of the bis(merocyanine) comprising two identical chromophores. Quantum chemical analysis based on an extension of Kasha's exciton theory appropriately describes the absorption properties of both types of stacks revealing strong exciton coupling also between different chromophores within the heteroaggregate.}, language = {en} } @article{BhavsarSinghSharmaetal.2016, author = {Bhavsar, Shefalee K. and Singh, Yogesh and Sharma, Piyush and Khairnar, Vishal and Hosseinzadeh, Zohreh and Zhang, Shaqiu and Palmada, Monica and Sabolic, Ivan and Koepsell, Hermann and Lang, Karl S. and Lang, Philipp A. and Lang, Florian}, title = {Expression of JAK3 Sensitive Na\(^+\) Coupled Glucose Carrier SGLT1 in Activated Cytotoxic T Lymphocytes}, series = {Cellular Physiology and Biochemistry}, volume = {39}, journal = {Cellular Physiology and Biochemistry}, number = {3}, doi = {10.1159/000447827}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164900}, pages = {1209-1228}, year = {2016}, abstract = {Background: Similar to tumor cells, activated T-lymphocytes generate ATP mainly by glycolytic degradation of glucose. Lymphocyte glucose uptake involves non-concentrative glucose carriers of the GLUT family. In contrast to GLUT isoforms, Na+-coupled glucose-carrier SGLT1 accumulates glucose against glucose gradients and is effective at low extracellular glucose concentrations. The present study explored expression and regulation of SGLT1 in activated murine splenic cytotoxic T cells (CTLs) and human Jurkat T cells. Methods: FACS analysis, immunofluorescence, confocal microscopy, chemiluminescence and Western blotting were employed to estimate SGLT1 expression, function and regulation in lymphocytes, as well as dual electrode voltage clamp in SGLT1 ± JAK3 expressing Xenopus oocytes to quantify the effect of janus kinase3 (JAK3) on SGLT1 function. Results: SGLT1 is expressed in murine CTLs and also in human Jurkat T cells. 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake was significantly decreased by SGLT1-blocker phloridzin (0.2 mM) and by pharmacological inhibition of JAK3 with WHI-P131 (156 µM), WHI-P154 (11.2 µM) and JAK3 inhibitor VI (0.5 µM). Electrogenic glucose transport (Iglucose) in Xenopus oocytes expressing human SGLT1 was increased by additional expression of human wild type JAK3, active A568VJAK3 but not inactive K851AJAK3. Coexpression of JAK3 enhanced the maximal transport rate without significantly modifying affinity of the carrier. Iglucose in SGLT1+JAK3 expressing oocytes was significantly decreased by WHI-P154 (11.2 µM). JAK3 increased the SGLT1 protein abundance in the cell membrane. Inhibition of carrier insertion by brefeldin A (5 µM) in SGLT1+JAK3 expressing oocytes resulted in a decline of Iglucose, which was similar in presence and absence of JAK3. Conclusions: SGLT1 is expressed in murine cytotoxic T cells and human Jurkat T cells and significantly contributes to glucose uptake in those cells post activation. JAK3 up-regulates SGLT1 activity by increasing the carrier protein abundance in the cell membrane, an effect enforcing cellular glucose uptake into activated lymphocytes and thus contributing to the immune response.}, language = {en} } @article{BeykanDamEberleinetal.2016, author = {Beykan, Seval and Dam, Jan S. and Eberlein, Uta and Kaufmann, Jens and Kj{\ae}rgaard, Benedict and J{\o}dal, Lars and Bouterfa, Hakim and Bejot, Romain and Lassmann, Michael and Jensen, Svend Borup}, title = {\(^{177}\)Lu-OPS201 targeting somatostatin receptors: in vivo biodistribution and dosimetry in a pig model}, series = {EJNMMI Research}, volume = {6}, journal = {EJNMMI Research}, number = {50}, doi = {10.1186/s13550-016-0204-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146888}, year = {2016}, abstract = {Background \(^{177}\)Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of \(^{177}\)Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications. Results \(^{177}\)Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 \% in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 \% of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq \(^{177}\)Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of 177Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels. Conclusions The \(^{177}\)Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range.}, language = {en} } @article{BertChmielewskaBergmannetal.2016, author = {Bert, Bettina and Chmielewska, Justyna and Bergmann, Sven and Busch, Maximilian and Driever, Wolfgang and Finger-Baier, Karin and H{\"o}ßler, Johanna and K{\"o}hler, Almut and Leich, Nora and Misgeld, Thomas and N{\"o}ldner, Torsten and Reiher, Annegret and Schartl, Manfred and Seebach-Sproedt, Anja and Thumberger, Thomas and Sch{\"o}nfelder, Gilbert and Grune, Barbara}, title = {Considerations for a European animal welfare standard to evaluate adverse phenotypes in teleost fish}, series = {The EMBO Journal}, volume = {35}, journal = {The EMBO Journal}, number = {11}, doi = {10.15252/embj.201694448}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188783}, pages = {1151-1154}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{BerntRangrezEdenetal.2016, author = {Bernt, Alexander and Rangrez, Ashraf Y. and Eden, Matthias and Jungmann, Andreas and Katz, Sylvia and Rohr, Claudia and M{\"u}ller, Oliver J. and Katus, Hugo A. and Sossalla, Samuel T. and Williams, Tatjana and Ritter, Oliver and Frank, Derk and Frey, Norbert}, title = {Sumoylation-independent activation of Calcineurin-NFAT-signaling via SUMO2 mediates cardiomyocyte hypertrophy}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, number = {35758}, doi = {10.1038/srep35758}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167525}, year = {2016}, abstract = {The objective of this study was to identify unknown modulators of Calcineurin (Cn)-NFAT signaling. Measurement of NFAT reporter driven luciferase activity was therefore utilized to screen a human cardiac cDNA-library (~10\(^{7}\) primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated in the identification of SUMO2 as a most efficient Cn-NFAT activator. SUMO2-mediated activation of Cn-NFAT signaling in cardiomyocytes translated into a hypertrophic phenotype. Prohypertrophic effects were also observed in mice expressing SUMO2 in the heart using AAV9 (Adeno-associated virus), complementing the in vitro findings. In addition, increased SUMO2-mediated sumoylation in human cardiomyopathy patients and in mouse models of cardiomyopathy were observed. To decipher the underlying mechanism, we generated a sumoylation-deficient SUMO2 mutant (ΔGG). Surprisingly, ΔGG replicated Cn-NFAT-activation and the prohypertrophic effects of native SUMO2, both in vitro and in vivo, suggesting a sumoylation-independent mechanism. Finally, we discerned a direct interaction between SUMO2 and CnA, which promotes CnA nuclear localization. In conclusion, we identified SUMO2 as a novel activator of Cn-NFAT signaling in cardiomyocytes. In broader terms, these findings reveal an unexpected role for SUMO2 in cardiac hypertrophy and cardiomyopathy, which may open the possibility for therapeutic manipulation of this pathway.}, language = {en} } @article{BergesKerkauWerneretal.2016, author = {Berges, Carsten and Kerkau, Thomas and Werner, Sandra and Wolf, Nelli and Winter, Nadine and H{\"u}nig, Thomas and Einsele, Hermann and Topp, Max S. and Beyersdorf, Niklas}, title = {Hsp90 inhibition ameliorates CD4\(^{+}\) T cell-mediated acute Graft versus Host disease in mice}, series = {Immunity, Inflammation and Disease}, volume = {4}, journal = {Immunity, Inflammation and Disease}, number = {4}, doi = {10.1002/iid3.127}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168318}, pages = {463-473}, year = {2016}, abstract = {Introduction: For many patients with leukemia only allogeneic bone marrow transplantion provides a chance of cure. Co-transplanted mature donor T cells mediate the desired Graft versus Tumor (GvT) effect required to destroy residual leukemic cells. The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)—a potentially life-threatening complication. Methods: Therefore, we used the well established C57BL/6 into BALB/c mouse aGvHD model to evaluate whether pharmacological inhibition of heat shock protein 90 (Hsp90) would protect the mice from aGvHD. Results: Treatment of the BALB/c recipient mice from day 0 to +2 after allogeneic CD4\(^{+}\) T cell transplantation with the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG) partially protected the mice from aGvHD. DMAG treatment was, however, insufficient to prolong overall survival of leukemia-bearing mice after transplantation of allogeneic CD4\(^{+}\) and CD8\(^{+}\) T cells. Ex vivo analyses and in vitro experiments revealed that DMAG primarily inhibits conventional CD4\(^{+}\) T cells with a relative resistance of CD4\(^{+}\) regulatory and CD8\(^{+}\) T cells toward Hsp90 inhibition. Conclusions: Our data, thus, suggest that Hsp90 inhibition might constitute a novel approach to reduce aGvHD in patients without abrogating the desired GvT effect.}, language = {en} } @article{BenoitAdelmanReinhardtetal.2016, author = {Benoit, Joshua B. and Adelman, Zach N. and Reinhardt, Klaus and Dolan, Amanda and Poelchau, Monica and Jennings, Emily C. and Szuter, Elise M. and Hagan, Richard W. and Gujar, Hemant and Shukla, Jayendra Nath and Zhu, Fang and Mohan, M. and Nelson, David R. and Rosendale, Andrew J. and Derst, Christian and Resnik, Valentina and Wernig, Sebastian and Menegazzi, Pamela and Wegener, Christian and Peschel, Nicolai and Hendershot, Jacob M. and Blenau, Wolfgang and Predel, Reinhard and Johnston, Paul R. and Ioannidis, Panagiotis and Waterhouse, Robert M. and Nauen, Ralf and Schorn, Corinna and Ott, Mark-Christoph and Maiwald, Frank and Johnston, J. Spencer and Gondhalekar, Ameya D. and Scharf, Michael E. and Raje, Kapil R. and Hottel, Benjamin A. and Armis{\´e}n, David and Crumi{\`e}re, Antonin Jean Johan and Refki, Peter Nagui and Santos, Maria Emilia and Sghaier, Essia and Viala, S{\`e}verine and Khila, Abderrahman and Ahn, Seung-Joon and Childers, Christopher and Lee, Chien-Yueh and Lin, Han and Hughes, Daniel S.T. and Duncan, Elizabeth J. and Murali, Shwetha C. and Qu, Jiaxin and Dugan, Shannon and Lee, Sandra L. and Chao, Hsu and Dinh, Huyen and Han, Yi and Doddapaneni, Harshavardhan and Worley, Kim C. and Muzny, Donna M. and Wheeler, David and Panfilio, Kristen A. and Jentzsch, Iris M. Vargas and Jentzsch, IMV and Vargo, Edward L. and Booth, Warren and Friedrich, Markus and Weirauch, Matthew T. and Anderson, Michelle A.E. and Jones, Jeffery W. and Mittapalli, Omprakash and Zhao, Chaoyang and Zhou, Jing-Jiang and Evans, Jay D. and Attardo, Geoffrey M. and Robertson, Hugh M. and Zdobnov, Evgeny M. and Ribeiro, Jose M.C. and Gibbs, Richard A. and Werren, John H. and Palli, Subba R. and Schal, Coby and Richards, Stephen}, title = {Unique features of a global human ectoparasite identified through sequencing of the bed bug genome}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, number = {10165}, doi = {10.1038/ncomms10165}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166221}, year = {2016}, abstract = {The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human-bed bug and symbiont-bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.}, language = {en} } @article{BeningHamoudaLeyh2016, author = {Bening, C. and Hamouda, K. and Leyh, R.}, title = {Sex differences in volume overload in skinned fibers}, series = {BMC Cardiovascular Disorders}, volume = {16}, journal = {BMC Cardiovascular Disorders}, number = {197}, doi = {10.1186/s12872-016-0370-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147896}, year = {2016}, abstract = {Background The impact of sex on cardiac morphology and function in chronic volume overload has been described in detail. However, the relation between sex and contractile properties at the actin-myosin level has not been well defined. Therefore, we evaluated the influence of sex on the contractile capacities of patients with chronic volume overload. Methods In 36 patients (18 males, 65 ± 9 years; 18 females, 65 ± 13 years) scheduled for elective mitral valve surgery due to severe mitral regurgitation (MR) with preserved left ventricular function, right auricle samples were obtained prior to extracorporal circulation. The fibers were prepared and skinned and exposed to a gradual increase in the calcium concentration (from pCa of 6.5-4.0) for calcium-induced force-developing measurements. Calcium sensitivity was also measured and recorded. Results The pCa-force relationship of the fibers obtained from males and females was significantly different, with the force values of the female fibers greater than those of male fibers at maximum calcium concentrations (pCa of 4.0: 3.6 ± 0.3 mN versus 3.2 ± 0.4 mN, p 0.02) and pCa of 4.5 2.6 ± 0.6 versus 2.0 ± 0.5, p 0.002). In contrast, the force values of female fibers were lower at mean calcium concentrations compared to those of male fibers (at 5.5 and pCa of 6.0: 1.0 ± 0.3 mN versus 1.2 ± 0.5 mN, p 0.04; 0.61 ± 0.05 versus 0.88 ± 0.09, p 0.04). Calcium sensitivity was observed at pCa of 5.0 in females and pCa of 4.5 in males. Conclusion This study demonstrated that female fibers from patients exposed to chronic volume overload developed higher force values at a given calcium concentration compared to fibers from male patients. We assume that female patients might tap the full force potential, which is required when exposed to the highest calcium concentrations in our experimental cycle. The calcium sensitivity among genders was significantly different, with the results suggesting that males have higher calcium sensitivity and might compensate for lower force values at maximal calcium concentrations by a higher affinity for calcium. Hence, female patients with MR seem to work more "energy efficient".}, language = {en} } @article{BenAmiTongBhuiyanetal.2016, author = {Ben Ami, Tal and Tong, Yuehong and Bhuiyan, Alauddin and Huisingh, Carrie and Ablonczy, Zsolt and Ach, Thomas and Curcio, Christine A. and Smith, R. Theodore}, title = {Spatial and Spectral Characterization of Human Retinal Pigment Epithelium Fluorophore Families by Ex Vivo Hyperspectral Autofluorescence Imaging}, series = {Translational Vision Science \& Technology}, volume = {5}, journal = {Translational Vision Science \& Technology}, number = {3}, doi = {10.1167/tvst.5.3.5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168328}, pages = {5}, year = {2016}, abstract = {Purpose: Discovery of candidate spectra for abundant fluorophore families in human retinal pigment epithelium (RPE) by ex vivo hyperspectral imaging. Methods: Hyperspectral autofluorescence emission images were captured between 420 and 720 nm (10-nm intervals), at two excitation bands (436-460, 480-510 nm), from three locations (fovea, perifovea, near-periphery) in 20 normal RPE/Bruch's membrane (BrM) flatmounts. Mathematical factorization extracted a BrM spectrum (S0) and abundant lipofuscin/melanolipofuscin (LF/ML) spectra of RPE origin (S1, S2, S3) from each tissue. Results: Smooth spectra S1 to S3, with perinuclear localization consistent with LF/ML at all three retinal locations and both excitations in 14 eyes (84 datasets), were included in the analysis. The mean peak emissions of S0, S1, and S2 at λ\(_{ex}\) 436 nm were, respectively, 495 ± 14, 535 ± 17, and 576 ± 20 nm. S3 was generally trimodal, with peaks at either 580, 620, or 650 nm (peak mode, 650 nm). At λ\(_{ex}\) 480 nm, S0, S1, and S2 were red-shifted to 526 ± 9, 553 ± 10, and 588 ± 23 nm, and S3 was again trimodal (peak mode, 620 nm). S1 often split into two spectra, S1A and S1B. S3 strongly colocalized with melanin. There were no significant differences across age, sex, or retinal location. Conclusions: There appear to be at least three families of abundant RPE fluorophores that are ubiquitous across age, retinal location, and sex in this sample of healthy eyes. Further molecular characterization by imaging mass spectrometry and localization via super-resolution microscopy should elucidate normal and abnormal RPE physiology involving fluorophores. Translational Relevance: Our results help establish hyperspectral autofluorescence imaging of the human retinal pigment epithelium as a useful tool for investigating retinal health and disease.}, language = {en} } @article{BemmBeckerLarischetal.2016, author = {Bemm, Felix and Becker, Dirk and Larisch, Christina and Kreuzer, Ines and Escalante-Perez, Maria and Schulze, Waltraud X. and Ankenbrand, Markus and Van de Weyer, Anna-Lena and Krol, Elzbieta and Al-Rasheid, Khaled A. and Mith{\"o}fer, Axel and Weber, Andreas P. and Schultz, J{\"o}rg and Hedrich, Rainer}, title = {Venus flytrap carnivorous lifestyle builds on herbivore defense strategies}, series = {Genome Research}, volume = {26}, journal = {Genome Research}, number = {6}, doi = {10.1101/gr.202200.115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188799}, pages = {812-825}, year = {2016}, abstract = {Although the concept of botanical carnivory has been known since Darwin's time, the molecular mechanisms that allow animal feeding remain unknown, primarily due to a complete lack of genomic information. Here, we show that the transcriptomic landscape of the Dionaea trap is dramatically shifted toward signal transduction and nutrient transport upon insect feeding, with touch hormone signaling and protein secretion prevailing. At the same time, a massive induction of general defense responses is accompanied by the repression of cell death-related genes/processes. We hypothesize that the carnivory syndrome of Dionaea evolved by exaptation of ancient defense pathways, replacing cell death with nutrient acquisition.}, language = {en} } @article{BekesFriedlKoehleretal.2016, author = {Bekes, Inga and Friedl, Thomas W. P. and K{\"o}hler, Tanja and M{\"o}bus, Volker and Janni, Wolfgang and W{\"o}ckel, Achim and Wulff, Christine}, title = {Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer?}, series = {Molecular Cancer}, volume = {15}, journal = {Molecular Cancer}, number = {13}, doi = {10.1186/s12943-016-0497-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169298}, year = {2016}, abstract = {Background Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types. Methods Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition. Results VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5. Conclusions Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.}, language = {en} } @article{BeerSteffanDewenterHaerteletal.2016, author = {Beer, Katharina and Steffan-Dewenter, Ingolf and H{\"a}rtel, Stephan and Helfrich-F{\"o}rster, Charlotte}, title = {A new device for monitoring individual activity rhythms of honey bees reveals critical effects of the social environment on behavior}, series = {Journal of Comparative Physiology A}, volume = {202}, journal = {Journal of Comparative Physiology A}, number = {8}, doi = {10.1007/s00359-016-1103-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188030}, pages = {555-565}, year = {2016}, abstract = {Chronobiological studies of individual activity rhythms in social insects can be constrained by the artificial isolation of individuals from their social context. We present a new experimental set-up that simultaneously measures the temperature rhythm in a queen-less but brood raising mini colony and the walking activity rhythms of singly kept honey bees that have indirect social contact with it. Our approach enables monitoring of individual bees in the social context of a mini colony under controlled laboratory conditions. In a pilot experiment, we show that social contact with the mini colony improves the survival of monitored young individuals and affects locomotor activity patterns of young and old bees. When exposed to conflicting Zeitgebers consisting of a light-dark (LD) cycle that is phase-delayed with respect to the mini colony rhythm, rhythms of young and old bees are socially synchronized with the mini colony rhythm, whereas isolated bees synchronize to the LD cycle. We conclude that the social environment is a stronger Zeitgeber than the LD cycle and that our new experimental set-up is well suited for studying the mechanisms of social entrainment in honey bees.}, language = {en} } @article{BeckerKucharskiRoessleretal.2016, author = {Becker, Nils and Kucharski, Robert and R{\"o}ssler, Wolfgang and Maleszka, Ryszard}, title = {Age-dependent transcriptional and epigenomic responses to light exposure in the honey bee brain}, series = {FEBS Open Bio}, volume = {6}, journal = {FEBS Open Bio}, number = {7}, doi = {10.1002/2211-5463.12084}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147080}, pages = {622-639}, year = {2016}, abstract = {Light is a powerful environmental stimulus of special importance in social honey bees that undergo a behavioral transition from in-hive to outdoor foraging duties. Our previous work has shown that light exposure induces structural neuronal plasticity in the mushroom bodies (MBs), a brain center implicated in processing inputs from sensory modalities. Here, we extended these analyses to the molecular level to unravel light-induced transcriptomic and epigenomic changes in the honey bee brain. We have compared gene expression in brain compartments of 1- and 7-day-old light-exposed honey bees with age-matched dark-kept individuals. We have found a number of differentially expressed genes (DEGs), both novel and conserved, including several genes with reported roles in neuronal plasticity. Most of the DEGs show age-related changes in the amplitude of light-induced expression and are likely to be both developmentally and environmentally regulated. Some of the DEGs are either known to be methylated or are implicated in epigenetic processes suggesting that responses to light exposure are at least partly regulated at the epigenome level. Consistent with this idea light alters the DNA methylation pattern of bgm, one of the DEGs affected by light exposure, and the expression of microRNA miR-932. This confirms the usefulness of our approach to identify candidate genes for neuronal plasticity and provides evidence for the role of epigenetic processes in driving the molecular responses to visual stimulation.}, language = {en} } @article{Beck2016, author = {Beck, Lukas}, title = {Zur Funktionsweise der Prokura als handelsrechtliche Vollmacht}, series = {JURA - Juristische Ausbildung}, volume = {38}, journal = {JURA - Juristische Ausbildung}, number = {9}, publisher = {De Gruyter}, issn = {1612-7021}, doi = {10.1515/jura-2016-0200}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195109}, pages = {969-984}, year = {2016}, abstract = {Kein Abstract verf{\"u}gbar.}, language = {de} } @article{BechtleCamargoMolinaDeschetal.2016, author = {Bechtle, Philip and Camargo-Molina, Jos{\´e} Eliel and Desch, Klaus and Dreiner, Herbert K. and Hamer, Matthias and Kr{\"a}mer, Michael and O'Leary, Ben and Porod, Werner and Sarrazin, Bj{\"o}rn and Stefaniak, Tim and Uhlenbrock, Mathias and Wienemann, Peter}, title = {Killing the cMSSM softly}, series = {The European Physical Journal C}, volume = {76}, journal = {The European Physical Journal C}, number = {96}, doi = {10.1140/epjc/s10052-015-3864-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165045}, year = {2016}, abstract = {We investigate the constrained Minimal Supersymmetric Standard Model (cMSSM) in the light of constraining experimental and observational data from precision measurements, astrophysics, direct supersymmetry searches at the LHC and measurements of the properties of the Higgs boson, by means of a global fit using the program Fittino. As in previous studies, we find rather poor agreement of the best fit point with the global data. We also investigate the stability of the electro-weak vacuum in the preferred region of parameter space around the best fit point. We find that the vacuum is metastable, with a lifetime significantly longer than the age of the Universe. For the first time in a global fit of supersymmetry, we employ a consistent methodology to evaluate the goodness-of-fit of the cMSSM in a frequentist approach by deriving p values from large sets of toy experiments. We analyse analytically and quantitatively the impact of the choice of the observable set on the p value, and in particular its dilution when confronting the model with a large number of barely constraining measurements. Finally, for the preferred sets of observables, we obtain p values for the cMSSM below 10 \%, i.e. we exclude the cMSSM as a model at the 90 \% confidence level.}, language = {en} } @article{BaurRitterGermeretal.2016, author = {Baur, Johannes and Ritter, Christian O. and Germer, Christoph-Thomas and Klein, Ingo and Kickuth, Ralph and Steger, Ulrich}, title = {Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma}, series = {Hepatic Medicine}, volume = {2016}, journal = {Hepatic Medicine}, number = {8}, doi = {10.2147/HMER.S105395}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146553}, pages = {69-74}, year = {2016}, abstract = {Purpose: In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE). Patients and methods: In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever. Results: No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1\% vs 12.5\%, P=0.0281). The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference. Conclusion: No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE.}, language = {en} } @article{BaumeisterStrifflerBrandtetal.2016, author = {Baumeister, Joachim and Striffler, Albrecht and Brandt, Marc and Neumann, Michael}, title = {Collaborative Decision Support and Documentation in Chemical Safety with KnowSEC}, series = {Journal of Cheminformatics}, volume = {8}, journal = {Journal of Cheminformatics}, number = {21}, doi = {10.1186/s13321-016-0132-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146575}, year = {2016}, abstract = {To protect the health of human and environment, the European Union implemented the REACH regulation for chemical substances. REACH is an acronym for Registration, Evaluation, Authorization, and Restriction of Chemicals. Under REACH, the authorities have the task of assessing chemical substances, especially those that might pose a risk to human health or environment. The work under REACH is scientifically, technically and procedurally a complex and knowledge-intensive task that is jointly performed by the European Chemicals Agency and member state authorities in Europe. The assessment of substances under REACH conducted in the German Environment Agency is supported by the knowledge-based system KnowSEC, which is used for the screening, documentation, and decision support when working on chemical substances. The software KnowSEC integrates advanced semantic technologies and strong problem solving methods. It allows for the collaborative work on substances in the context of the European REACH regulation. We discuss the applied methods and process models and we report on experiences with the implementation and use of the system.}, language = {en} } @article{BatschingWolfHeisenberg2016, author = {Batsching, Sophie and Wolf, Reinhard and Heisenberg, Martin}, title = {Inescapable Stress Changes Walking Behavior in Flies - Learned Helplessness Revisited}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0167066}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178640}, year = {2016}, abstract = {Like other animals flies develop a state of learned helplessness in response to unescapable aversive events. To show this, two flies, one 'master', one 'yoked', are each confined to a dark, small chamber and exposed to the same sequence of mild electric shocks. Both receive these shocks when the master fly stops walking for more than a second. Behavior in the two animals is differently affected by the shocks. Yoked flies are transiently impaired in place learning and take longer than master flies to exit from the chamber towards light. After the treatment they walk more slowly and take fewer and shorter walking bouts. The low activity is attributed to the fly's experience that its escape response, an innate behavior to terminate the electric shocks, does not help anymore. Earlier studies using heat pulses instead of electric shocks had shown similar effects. This parallel supports the interpretation that it is the uncontrollability that induces the state.}, language = {en} } @article{BartelheimNemesSeeringeretal.2016, author = {Bartelheim, Kerstin and Nemes, Karolina and Seeringer, Angela and Kerl, Kornelius and Buechner, Jochen and Boos, Joachim and Graf, Norbert and D{\"u}rken, Matthias and Gerss, Joachim and Hasselblatt, Martin and Kortmann, Rolf-Dieter and Teichert von Luettichau, Irene and Nagel, Inga and Nygaard, Randi and Oyen, Florian and Quiroga, Eduardo and Schlegel, Paul-Gerhardt and Schmid, Irene and Schneppenheim, Reinhard and Siebert, Reiner and Solano-Paez, Palma and Timmermann, Beate and Warmuth-Metz, Monika and Fr{\"u}hwald, Michael Christoph}, title = {Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007}, series = {Cancer Medicine}, volume = {5}, journal = {Cancer Medicine}, number = {8}, doi = {10.1002/cam4.741}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164799}, pages = {1765-1775}, year = {2016}, abstract = {Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64\% (genetic analyses, FISH, MLPA, sequencing) up to 97\% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46\% (±0.10) and 45\% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials.}, language = {en} } @article{BarquistMayhoCumminsetal.2016, author = {Barquist, Lars and Mayho, Matthew and Cummins, Carla and Cain, Amy K. and Boinett, Christine J. and Page, Andrew J. and Langridge, Gemma C. and Quail, Michael A. and Keane, Jacqueline A. and Parkhill, Julian}, title = {The TraDIS toolkit: sequencing and analysis for dense transposon mutant libraries}, series = {Bioinformatics}, volume = {32}, journal = {Bioinformatics}, number = {7}, doi = {10.1093/bioinformatics/btw022}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189667}, pages = {1109-1111}, year = {2016}, abstract = {Transposon insertion sequencing is a high-throughput technique for assaying large libraries of otherwise isogenic transposon mutants providing insight into gene essentiality, gene function and genetic interactions. We previously developed the Transposon Directed Insertion Sequencing (TraDIS) protocol for this purpose, which utilizes shearing of genomic DNA followed by specific PCR amplification of transposon-containing fragments and Illumina sequencing. Here we describe an optimized high-yield library preparation and sequencing protocol for TraDIS experiments and a novel software pipeline for analysis of the resulting data. The Bio-Tradis analysis pipeline is implemented as an extensible Perl library which can either be used as is, or as a basis for the development of more advanced analysis tools. This article can serve as a general reference for the application of the TraDIS methodology.}, language = {en} } @article{BargulJungMcOdimbaetal.2016, author = {Bargul, Joel L. and Jung, Jamin and McOdimba, Francis A. and Omogo, Collins O. and Adung'a, Vincent O. and Kr{\"u}ger, Timothy and Masiga, Daniel K. and Engstler, Markus}, title = {Species-Specific Adaptations of Trypanosome Morphology and Motility to the Mammalian Host}, series = {PLoS Pathogens}, volume = {12}, journal = {PLoS Pathogens}, number = {2}, doi = {10.1371/journal.ppat.1005448}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146513}, pages = {e1005448}, year = {2016}, abstract = {African trypanosomes thrive in the bloodstream and tissue spaces of a wide range of mammalian hosts. Infections of cattle cause an enormous socio-economic burden in sub-Saharan Africa. A hallmark of the trypanosome lifestyle is the flagellate's incessant motion. This work details the cell motility behavior of the four livestock-parasites Trypanosoma vivax, T. brucei, T. evansi and T. congolense. The trypanosomes feature distinct swimming patterns, speeds and flagellar wave frequencies, although the basic mechanism of flagellar propulsion is conserved, as is shown by extended single flagellar beat analyses. Three-dimensional analyses of the trypanosomes expose a high degree of dynamic pleomorphism, typified by the 'cellular waveform'. This is a product of the flagellar oscillation, the chirality of the flagellum attachment and the stiffness of the trypanosome cell body. The waveforms are characteristic for each trypanosome species and are influenced by changes of the microenvironment, such as differences in viscosity and the presence of confining obstacles. The distinct cellular waveforms may be reflective of the actual anatomical niches the parasites populate within their mammalian host. T. vivax displays waveforms optimally aligned to the topology of the bloodstream, while the two subspecies T. brucei and T. evansi feature distinct cellular waveforms, both additionally adapted to motion in more confined environments such as tissue spaces. T. congolense reveals a small and stiff waveform, which makes these parasites weak swimmers and destined for cell adherence in low flow areas of the circulation. Thus, our experiments show that the differential dissemination and annidation of trypanosomes in their mammalian hosts may depend on the distinct swimming capabilities of the parasites.}, language = {en} } @article{BarbieriGardonRuizCastelletal.2016, author = {Barbieri, Flavia L. and Gardon, Jacques and Ruiz-Castell, Mar{\´i}a and Paco V., Pamela and Muckelbauer, Rebecca and Casiot, Corinne and Freydier, R{\´e}mi and Duprey, Jean-Louis and Chen, Chih-Mei and M{\"u}ller-Nordhorn, Jacqueline and Keil, Thomas}, title = {Toxic trace elements in maternal and cord blood and social determinants in a Bolivian mining city}, series = {International Journal of Environmental Health Research}, volume = {26}, journal = {International Journal of Environmental Health Research}, number = {2}, doi = {10.1080/09603123.2015.1061114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150385}, pages = {158-174}, year = {2016}, abstract = {This study assessed lead, arsenic, and antimony in maternal and cord blood, and associations between maternal concentrations and social determinants in the Bolivian mining city of Oruro using the baseline assessment of the ToxBol/Mine-Ni{\~n}o birth cohort. We recruited 467 pregnant women, collecting venous blood and sociodemographic information as well as placental cord blood at birth. Metallic/semimetallic trace elements were measured using inductively coupled plasma mass spectrometry. Lead medians in maternal and cord blood were significantly correlated (Spearman coefficient = 0.59; p < 0.001; 19.35 and 13.50 μg/L, respectively). Arsenic concentrations were above detection limit (3.30 μg/L) in 17.9 \% of maternal and 34.6 \% of cord blood samples. They were not associated (Fischer's p = 0.72). Antimony medians in maternal and cord blood were weakly correlated (Spearman coefficient = 0.15; p < 0.03; 9.00 and 8.62 μg/L, respectively). Higher concentrations of toxic elements in maternal blood were associated with maternal smoking, low educational level, and partner involved in mining.}, language = {en} } @article{BarbieriGardonRuizCastelletal.2016, author = {Barbieri, Flavia L. and Gardon, Jacques and Ruiz-Castell, Mar{\´i}a and Paco V., Pamela and Muckelbauer, Rebecca and Casiot, Corinne and Freydier, R{\´e}mi and Duprey, Jean-Louis and Chen, Chih-Mei and M{\"u}ller-Nordhorn, Jacqueline and Keil, Thomas}, title = {Toxic trace elements in maternal and cord blood and social determinants in a Bolivian mining city}, series = {International Journal of Environmental Health Research}, volume = {26}, journal = {International Journal of Environmental Health Research}, number = {2}, doi = {10.1080/09603123.2015.1061114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190703}, pages = {158-174}, year = {2016}, abstract = {This study assessed lead, arsenic, and antimony in maternal and cord blood, and associations between maternal concentrations and social determinants in the Bolivian mining city of Oruro using the baseline assessment of the ToxBol/Mine-Nino birth cohort. We recruited 467 pregnant women, collecting venous blood and sociodemographic information as well as placental cord blood at birth. Metallic/semimetallic trace elements were measured using inductively coupled plasma mass spectrometry. Lead medians in maternal and cord blood were significantly correlated (Spearman coefficient=0.59; p<0.001; 19.35 and 13.50 μg/L, respectively). Arsenic concentrations were above detection limit (3.30 μg/L) in 17.9\% of maternal and 34.6\% of cord blood samples. They were not associated (Fischer's p=0.72). Antimony medians in maternal and cord blood were weakly correlated (Spearman coefficient=0.15; p<0.03; 9.00 and 8.62 μg/L, respectively). Higher concentrations of toxic elements in maternal blood were associated with maternal smoking, low educational level, and partner involved in mining.}, language = {en} } @article{BaptistaKeszeiOliveiraetal.2016, author = {Baptista, Marisa A.P. and Keszei, Marton and Oliveira, Mariana and Sunahara, Karen K.S. and Andersson, John and Dahlberg, Carin I.M. and Worth, Austen J. and Lied{\´e}n, Agne and Kuo, I-Chun and Wallin, Robert P.A. and Snapper, Scott B. and Eidsmo, Liv and Scheynius, Annika and Karlsson, Mikael C.I. and Bouma, Gerben and Burns, Siobhan O. and Forsell, Mattias N.E. and Thrasher, Adrian J. and Nyl{\´e}n, Susanne and Westerberg, Lisa S.}, title = {Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms12175}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165966}, pages = {12175}, year = {2016}, abstract = {Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in theWASp gene. Decreased cellular responses in WASp-deficient cells have been interpreted to mean that WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an exception to this concept and show that WASp-deficient dendritic cells have increased activation of Rac2 that support cross-presentation to CD8þ T cells. Using two different skin pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin and increased expansion of IFNg-producing CD8þ T cells in the draining lymph node and spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8þ T cells at the expense of CD4þ T cells. WASp-deficient dendritic cells induce increased cross-presentation to CD8þ T cells by activating Rac2 that maintains a near neutral pH of phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2 signalling pathways in dendritic cells.}, language = {en} } @article{BankogluTschoppSchmittetal.2016, author = {Bankoglu, Ezgi Eyluel and Tschopp, Oliver and Schmitt, Johannes and Burkard, Philipp and Jahn, Daniel and Geier, Andreas and Stopper, Helga}, title = {Role of PTEN in Oxidative Stress and DNA Damage in the Liver of Whole-Body Pten Haplodeficient Mice}, series = {PLoS One}, volume = {11}, journal = {PLoS One}, number = {11}, doi = {10.1371/journal.pone.0166956}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146970}, pages = {e0166956}, year = {2016}, abstract = {Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular mechanisms of carcinogenesis in this context are only partially understood. High blood insulin levels are typical in early T2DM and excessive insulin can cause elevated reactive oxygen species (ROS) production and genomic instability. ROS are important for various cellular functions in signaling and host defense. However, elevated ROS formation is thought to be involved in cancer induction. In the molecular events from insulin receptor binding to genomic damage, some signaling steps have been identified, pointing at the PI3K/AKT pathway. For further elucidation Phosphatase and Tensin homolog (Pten), a tumour suppressor phosphatase that plays a role in insulin signaling by negative regulation of PI3K/AKT and its downstream targets, was investigated here. Dihydroethidium (DHE) staining was used to detect ROS formation in immortalized human hepatocytes. Comet assay and micronucleus test were performed to investigate genomic damage in vitro. In liver samples, DHE staining and western blot detection of HSP70 and HO-1 were performed to evaluate oxidative stress response. DNA double strand breaks (DSBs) were detected by immunohistostaining. Inhibition of PTEN with the pharmacologic inhibitor VO-OHpic resulted in increased ROS production and genomic damage in a liver cell line. Knockdown of Pten in a mouse model yielded increased oxidative stress levels, detected by ROS levels and expression of the two stress-proteins HSP70 and HO-1 and elevated genomic damage in the liver, which was significant in mice fed with a high fat diet. We conclude that PTEN is involved in oxidative stress and genomic damage induction in vitro and that this may also explain the in vivo observations. This further supports the hypothesis that the PI3K/AKT pathway is responsible for damaging effects of high levels of insulin.}, language = {en} } @article{BanalesCardinaleCarpinoetal.2016, author = {Banales, Jesus M. and Cardinale, Vincenzo and Carpino, Guido and Marzioni, Marco and Andersen, Jesper B. and Invernizzi, Pietro and Lind, Guro E. and Folseraas, Trine and Forbes, Stuart J. and Fouassier, Laura and Geier, Andreas and Calvisi, Diego F. and Mertens, Joachim C. and Trauner, Michael and Benedetti, Antonio and Maroni, Luca and Vaquero, Javier and Macias, Rocio I. R. and Raggi, Chiara and Perugorria, Maria J. and Gaudio, Eugenio and Boberg, Kirsten M. and Marin, Jose J. G. and Alvaro, Domenico}, title = {Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)}, series = {Nature Reviews Gastroenterology \& Hepatology}, volume = {13}, journal = {Nature Reviews Gastroenterology \& Hepatology}, number = {5}, doi = {10.1038/nrgastro.2016.51}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189077}, pages = {261-280}, year = {2016}, abstract = {Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.}, language = {en} } @article{BaierBaierSaipSchillingetal.2016, author = {Baier, Pablo A. and Baier-Saip, J{\"u}rgen A. and Schilling, Klaus and Oliveira, Jauvane C.}, title = {Simulator for Minimally Invasive Vascular Interventions: Hardware and Software}, series = {Presence}, volume = {25}, journal = {Presence}, number = {2}, issn = {1531-3263}, doi = {10.1162/PRES_a_00250}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140580}, pages = {108-128}, year = {2016}, abstract = {In the present work, a simulation system is proposed that can be used as an educational tool by physicians in training basic skills of minimally invasive vascular interventions. In order to accomplish this objective, initially the physical model of the wire proposed by Konings has been improved. As a result, a simpler and more stable method was obtained to calculate the equilibrium configuration of the wire. In addition, a geometrical method is developed to perform relaxations. It is particularly useful when the wire is hindered in the physical method because of the boundary conditions. Then a recipe is given to merge the physical and the geometrical methods, resulting in efficient relaxations. Moreover, tests have shown that the shape of the virtual wire agrees with the experiment. The proposed algorithm allows real-time executions, and furthermore, the hardware to assemble the simulator has a low cost.}, language = {en} } @article{BahnikStrack2016, author = {Bahn{\´i}k, Štěp{\´a}n and Strack, Fritz}, title = {Overlap of accessible information undermines the anchoring effect}, series = {Judgment and Decision Making}, volume = {11}, journal = {Judgment and Decision Making}, number = {1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169287}, pages = {92-98}, year = {2016}, abstract = {According to the Selective Accessibility Model of anchoring, the comparison question in the standard anchoring paradigm activates information that is congruent with an anchor. As a consequence, this information will be more likely to become the basis for the absolute judgment which will therefore be assimilated toward the anchor. However, if the activated information overlaps with information that is elicited by the absolute judgment itself, the preceding comparative judgment should not exert an incremental effect and should fail to result in an anchoring effect. The present studies find this result when the comparative judgment refers to a general category and the absolute judgment refers to a subset of the general category that was activated by the anchor value. For example, participants comparing the average annual temperature in New York City to a high 102 °F judged the average winter, but not summer temperature to be higher than participants making no comparison. On the other hand, participants comparing the annual temperature to a low -4 °F judged the average summer, but not winter temperature to be lower than control participants. This pattern of results was shown also in another content domain. It is consistent with the Selective Accessibility Model but difficult to reconcile with other main explanations of the anchoring effect.}, language = {en} } @article{BabskiHaasNaetherSchindleretal.2016, author = {Babski, Julia and Haas, Karina A. and N{\"a}ther-Schindler, Daniela and Pfeiffer, Friedhelm and F{\"o}rstner, Konrad U. and Hammelmann, Matthias and Hilker, Rolf and Becker, Anke and Sharma, Cynthia M. and Marchfelder, Anita and Soppa, J{\"o}rg}, title = {Genome-wide identification of transcriptional start sites in the haloarchaeon Haloferax volcanii based on differential RNA-Seq (dRNA-Seq)}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, number = {629}, doi = {10.1186/s12864-016-2920-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164553}, year = {2016}, abstract = {Background Differential RNA-Seq (dRNA-Seq) is a recently developed method of performing primary transcriptome analyses that allows for the genome-wide mapping of transcriptional start sites (TSSs) and the identification of novel transcripts. Although the transcriptomes of diverse bacterial species have been characterized by dRNA-Seq, the transcriptome analysis of archaeal species is still rather limited. Therefore, we used dRNA-Seq to characterize the primary transcriptome of the model archaeon Haloferax volcanii. Results Three independent cultures of Hfx. volcanii grown under optimal conditions to the mid-exponential growth phase were used to determine the primary transcriptome and map the 5′-ends of the transcripts. In total, 4749 potential TSSs were detected. A position weight matrix (PWM) was derived for the promoter predictions, and the results showed that 64 \% of the TSSs were preceded by stringent or relaxed basal promoters. Of the identified TSSs, 1851 belonged to protein-coding genes. Thus, fewer than half (46 \%) of the 4040 protein-coding genes were expressed under optimal growth conditions. Seventy-two percent of all protein-coding transcripts were leaderless, which emphasized that this pathway is the major pathway for translation initiation in haloarchaea. A total of 2898 of the TSSs belonged to potential non-coding RNAs, which accounted for an unexpectedly high fraction (61 \%) of all transcripts. Most of the non-coding TSSs had not been previously described (2792) and represented novel sequences (59 \% of all TSSs). A large fraction of the potential novel non-coding transcripts were cis-antisense RNAs (1244 aTSSs). A strong negative correlation between the levels of antisense transcripts and cognate sense mRNAs was found, which suggested that the negative regulation of gene expression via antisense RNAs may play an important role in haloarchaea. The other types of novel non-coding transcripts corresponded to internal transcripts overlapping with mRNAs (1153 iTSSs) and intergenic small RNA (sRNA) candidates (395 TSSs). Conclusion This study provides a comprehensive map of the primary transcriptome of Hfx. volcanii grown under optimal conditions. Fewer than half of all protein-coding genes have been transcribed under these conditions. Unexpectedly, more than half of the detected TSSs belonged to several classes of non-coding RNAs. Thus, RNA-based regulation appears to play a more important role in haloarchaea than previously anticipated.}, language = {en} } @article{AurastGradlPernesetal.2016, author = {Aurast, Anna and Gradl, Tobias and Pernes, Stefan and Pielstr{\"o}m, Steffen}, title = {Big Data und Smart Data in den Geisteswissenschaften}, series = {Bibliothek Forschung und Praxis}, volume = {40}, journal = {Bibliothek Forschung und Praxis}, number = {2}, issn = {1865-7648}, doi = {10.1515/bfp-2016-0033}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195237}, pages = {200-206}, year = {2016}, abstract = {Kein Abstract verf{\"u}gbar.}, language = {de} } @article{AudehmSchmidtBruecketal.2016, author = {Audehm, P. and Schmidt, M. and Br{\"u}ck, S. and Tietze, T. and Gr{\"a}fe, J. and Macke, S. and Sch{\"u}tz, G. and Goering, E.}, title = {Pinned orbital moments - A new contribution to magnetic anisotropy}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, number = {25517}, doi = {10.1038/srep25517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167727}, year = {2016}, abstract = {Reduced dimensionality and symmetry breaking at interfaces lead to unusual local magnetic configurations, such as glassy behavior, frustration or increased anisotropy. The interface between a ferromagnet and an antiferromagnet is such an example for enhanced symmetry breaking. Here we present detailed X-ray magnetic circular dichroism and X-ray resonant magnetic reflectometry investigations on the spectroscopic nature of uncompensated pinned magnetic moments in the antiferromagnetic layer of a typical exchange bias system. Unexpectedly, the pinned moments exhibit nearly pure orbital moment character. This strong orbital pinning mechanism has not been observed so far and is not discussed in literature regarding any theory for local magnetocrystalline anisotropy energies in magnetic systems. To verify this new phenomenon we investigated the effect at different temperatures. We provide a simple model discussing the observed pure orbital moments, based on rotatable spin magnetic moments and pinned orbital moments on the same atom. This unexpected observation leads to a concept for a new type of anisotropy energy.}, language = {en} } @article{AsthanaBrunhuberMuehlbergeretal.2016, author = {Asthana, Manish Kumar and Brunhuber, Bettina and M{\"u}hlberger, Andreas and Reif, Andreas and Schneider, Simone and Herrmann, Martin J.}, title = {Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism}, series = {International Journal of Neuropsychopharmacology}, volume = {19}, journal = {International Journal of Neuropsychopharmacology}, number = {6}, doi = {10.1093/ijnp/pyv137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166217}, year = {2016}, abstract = {Background: Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans. Methods: An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265. Results: The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation. Conclusions: Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans.}, language = {en} } @article{ArrowsmithBoehnkeBraunschweigetal.2016, author = {Arrowsmith, Merle and B{\"o}hnke, Julian and Braunschweig, Holger and Celik, Mehmet and Dellermann, Theresa and Hammond, Kai}, title = {Uncatalyzed Hydrogenation of First-Row Main Group Multiple Bonds}, series = {Chemistry, A European Journal}, volume = {22}, journal = {Chemistry, A European Journal}, number = {48}, doi = {10.1002/chem.201604094}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139364}, pages = {17169 -- 17172}, year = {2016}, abstract = {Room temperature hydrogenation of an SIDep-stabilized diboryne (SIDep = 1,3-bis(diethylphenyl)-4,5-dihydroimidazol-2-ylidene) and a CAAC-supported diboracumulene (CAAC = 1-(2,6- diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene) provided the first selective route to the corresponding 1,2-dihydrodiborenes. DFT calculations showed an overall exothermic (ΔG = 19.4 kcal mol\(^{-1}\) two-step asynchronous H\(_2\) addition mechanism proceeding via a bridging hydride.}, subject = {Diborane}, language = {en} } @article{ArrowsmithBoehnkeBraunschweigetal.2016, author = {Arrowsmith, Merle and B{\"o}hnke, Julian and Braunschweig, Holger and Celik, Mehmet and Claes, Christina and Ewing, William and Krummenacher, Ivo and Lubitz, Katharina and Schneider, Christoph}, title = {Neutral Diboron Analogues of Archetypal Aromatic Species by Spontaneous Cycloaddition}, series = {Angewandte Chemie, International Edition}, volume = {55}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201602384}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138226}, pages = {11271-11275}, year = {2016}, abstract = {Among the numerous routes organic chemists have developed to synthesize benzene derivatives and heteroaro- matic compounds, transition-metal-catalyzed cycloaddition reactions are the most elegant. In contrast, cycloaddition reactions of heavier alkene and alkyne analogues, though limited in scope, proceed uncatalyzed. In this work we present the first spontaneous cycloaddition reactions of lighter alkene and alkyne analogues. Selective addition of unactivated alkynes to boron-boron multiple bonds under ambient con- ditions yielded diborocarbon equivalents of simple aromatic hydrocarbons, including the first neutral 6 π-aromatic dibora- benzene compound, a 2  π-aromatic triplet biradical 1,3-dibor- ete, and a phosphine-stabilized 2  π-homoaromatic 1,3-dihydro- 1,3-diborete. DFT calculations suggest that all three com- pounds are aromatic and show frontier molecular orbitals matching those of the related aromatic hydrocarbons, C\(_6\)H\(_6\) and C\(_4\)H\(_4\)\(^{2+}\), and homoaromatic C\(_4\)H\(_5\)\(^+\).}, language = {en} } @article{ArimanyNardiMinuesaPastorAngladaetal.2016, author = {Arimany-Nardi, Cristina and Minuesa, Gerard and Pastor-Anglada, Mar{\c{c}}al and Keller, Thorsten and Erkizia, Itziar and Koepsell, Hermann and Martinez-Picado, Javier}, title = {Role of Human Organic Cation Transporter 1 (hOCT1) Polymorphisms in Lamivudine (3TC) Uptake and Drug-Drug Interactions}, series = {Frontiers in Pharmacology}, volume = {7}, journal = {Frontiers in Pharmacology}, number = {175}, doi = {10.3389/fphar.2016.00175}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165236}, year = {2016}, abstract = {Lamivudine (3TC), a drug used in the treatment of HIV infection, needs to cross the plasma membrane to exert its therapeutic action. Human Organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is the transporter responsible for its uptake into target cells. As SLC22A1 is a highly polymorphic gene, the aim of this study was to determine how SNPs in the OCT1-encoding gene affected 3TC internalization and its interaction with other co-administered drugs. HEK293 cells stably transfected with either the wild type form or the polymorphic variants of hOCT1 were used to perform kinetic and drug-drug interaction studies. Protein co-immunoprecipitation was used to assess the impact of selected polymorphic cysteines on the oligomerization of the transporter. Results showed that 3TC transport efficiency was reduced in all polymorphic variants tested (R61C, C88R, S189L, M420del, and G465R). This was not caused by lack of oligomerization in case of variants located at the transporter extracellular loop (R61C and C88R). Drug-drug interaction measurements showed that co-administered drugs [abacavir (ABC), zidovudine (AZT), emtricitabine (FTC), tenofovir diproxil fumarate (TDF), efavirenz (EFV) and raltegravir (RAL)], differently inhibited 3TC uptake depending upon the polymorphic variant analyzed. These data highlight the need for accurate analysis of drug transporter polymorphic variants of clinical relevance, because polymorphisms can impact on substrate (3TC) translocation but even more importantly they can differentially affect drug-drug interactions at the transporter level.}, language = {en} } @article{AppelScholzKocabeyetal.2016, author = {Appel, Mirjam and Scholz, Claus-J{\"u}rgen and Kocabey, Samet and Savage, Sinead and K{\"o}nig, Christian and Yarali, Ayse}, title = {Independent natural genetic variation of punishment- versus relief-memory}, series = {Biology Letters}, volume = {12}, journal = {Biology Letters}, number = {12}, doi = {10.1098/rsbl.2016.0657}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186554}, pages = {20160657}, year = {2016}, abstract = {A painful event establishes two opponent memories: cues that are associated with pain onset are remembered negatively, whereas cues that coincide with the relief at pain offset acquire positive valence. Such punishment-versus relief-memories are conserved across species, including humans, and the balance between them is critical for adaptive behaviour with respect to pain and trauma. In the fruit fly, Drosophila melanogaster as a study case, we found that both punishment-and relief-memories display natural variation across wild-derived inbred strains, but they do not covary, suggesting a considerable level of dissociation in their genetic effectors. This provokes the question whether there may be heritable inter-individual differences in the balance between these opponent memories in man, with potential psycho-clinical implications.}, language = {en} } @article{AnsellKostakisBraunschweigetal.2016, author = {Ansell, Melvyn B. and Kostakis, George E. and Braunschweig, Holger and Navarro, Oscar and Spencer, John}, title = {Synthesis of functionalized hydrazines: facile homogeneous (N-heterocyclic carbene)-palladium(0)-catalyzed diboration and silaboration of azobenzenes}, series = {Advanced Synthesis \& Catalysis}, volume = {358}, journal = {Advanced Synthesis \& Catalysis}, number = {23}, doi = {10.1002/adsc.201601106}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186582}, pages = {3765-3769}, year = {2016}, abstract = {The bis(N-heterocyclic carbene)(diphenylacetylene)palladium complex Pd(ITMe)\(_2\)(PhCCPh)] (ITMe=1,3,4,5-tetramethylimidazol-2-ylidene) acts as a highly active pre-catalyst in the diboration and silaboration of azobenzenes to synthesize a series of novel functionalized hydrazines. The reactions proceed using commercially available diboranes and silaboranes under mild reaction conditions.}, language = {en} } @article{AnkenbrandWeberBeckeretal.2016, author = {Ankenbrand, Markus J. and Weber, Lorenz and Becker, Dirk and F{\"o}rster, Frank and Bemm, Felix}, title = {TBro: visualization and management of de novo transcriptomes}, series = {Database}, volume = {2016}, journal = {Database}, doi = {10.1093/database/baw146}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147954}, pages = {baw146}, year = {2016}, abstract = {RNA sequencing (RNA-seq) has become a powerful tool to understand molecular mechanisms and/or developmental programs. It provides a fast, reliable and cost-effective method to access sets of expressed elements in a qualitative and quantitative manner. Especially for non-model organisms and in absence of a reference genome, RNA-seq data is used to reconstruct and quantify transcriptomes at the same time. Even SNPs, InDels, and alternative splicing events are predicted directly from the data without having a reference genome at hand. A key challenge, especially for non-computational personnal, is the management of the resulting datasets, consisting of different data types and formats. Here, we present TBro, a flexible de novo transcriptome browser, tackling this challenge. TBro aggregates sequences, their annotation, expression levels as well as differential testing results. It provides an easy-to-use interface to mine the aggregated data and generate publication-ready visualizations. Additionally, it supports users with an intuitive cart system, that helps collecting and analysing biological meaningful sets of transcripts. TBro's modular architecture allows easy extension of its functionalities in the future. Especially, the integration of new data types such as proteomic quantifications or array-based gene expression data is straightforward. Thus, TBro is a fully featured yet flexible transcriptome browser that supports approaching complex biological questions and enhances collaboration of numerous researchers.}, language = {en} } @article{AnisimovSiminSoltamovetal.2016, author = {Anisimov, A. N. and Simin, D. and Soltamov, V. A. and Lebedev, S. P. and Baranov, P. G. and Astakhov, G. V. and Dyakonov, V.}, title = {Optical thermometry based on level anticrossing in silicon carbide}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, number = {33301}, doi = {10.1038/srep33301}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147809}, year = {2016}, abstract = {We report a giant thermal shift of 2.1 MHz/K related to the excited-state zero-field splitting in the silicon vacancy centers in 4H silicon carbide. It is obtained from the indirect observation of the optically detected magnetic resonance in the excited state using the ground state as an ancilla. Alternatively, relative variations of the zero-field splitting for small temperature differences can be detected without application of radiofrequency fields, by simply monitoring the photoluminescence intensity in the vicinity of the level anticrossing. This effect results in an all-optical thermometry technique with temperature sensitivity of 100 mK/Hz\(^{1/2}\) for a detection volume of approximately 10\(^{-6}\) mm\(^3\). In contrast, the zero-field splitting in the ground state does not reveal detectable temperature shift. Using these properties, an integrated magnetic field and temperature sensor can be implemented on the same center.}, language = {en} } @article{AlrefaiMuhammadRudolfetal.2016, author = {Alrefai, Hani and Muhammad, Khalid and Rudolf, Ronald and Pham, Duong Anh Thuy and Klein-Hessling, Stefan and Patra, Amiya K. and Avots, Andris and Bukur, Valesca and Sahin,, Ugur and Tenzer, Stefan and Goebeler, Matthias and Kerstan, Andreas and Serfling, Edgar}, title = {NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms11724}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173053}, year = {2016}, abstract = {Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.}, language = {en} } @article{AlnawaisehSchubertNelisetal.2016, author = {Alnawaiseh, Maged and Schubert, Friederike and Nelis, Pieter and Wirths, Gabriele and Rosentreter, Andr{\´e} and Eter, Nicole}, title = {Optical coherence tomography (OCT) angiography findings in retinal arterial macroaneurysms}, series = {BMC Ophthalmology}, volume = {16}, journal = {BMC Ophthalmology}, number = {120}, doi = {10.1186/s12886-016-0293-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164702}, year = {2016}, abstract = {Background Optical coherence tomography angiography is a novel imaging technique that allows dyeless in vivo visualization of the retinal and choroidal vasculature. The purpose of this study was to describe optical coherence tomography (OCT) angiography findings in patients with retinal arterial macroaneurysms (RAMs). Methods Three eyes of three patients with RAMs were retrospectively included. Fundus photography, OCT, fluorescein angiography (FA), and OCT angiography were performed. The entire imaging data was analyzed in detail. Results OCT angiography could detect the RAMs noninvasively without dye injection. By simultaneously observing the OCT scans, it was possible to determine the depth of the RAMs in the retina, to detect the exact localization in relation to the main vessel, and to determine the level of blood flow in the RAMs. Conclusions OCT angiography can clearly visualize RAMs without use of a dye. It also allows layer-specific observation of blood flow in each layer of the RAM. OCT angiography provides additional dynamic information on RAMs, which is not obtained with FA and facilitates a better understanding of its morphology and activity. This information in combination with ICG and fluorescein angiography can help to optimize direct laser treatment.}, language = {en} } @article{AlmanzarKleinSchmalzingetal.2016, author = {Almanzar, Giovanni and Klein, Matthias and Schmalzing, Marc and Hilligardt, Deborah and El Hajj, Nady and Kneitz, Hermann and Wild, Vanessa and Rosenwald, Andreas and Benoit, Sandrine and Hamm, Henning and Tony, Hans-Peter and Haaf, Thomas and Goebeler, Matthias and Prelog, Martina}, title = {Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis}, series = {International Archives of Allergy and Immunology}, volume = {171}, journal = {International Archives of Allergy and Immunology}, number = {2}, issn = {1018-2438}, doi = {10.1159/000450949}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196577}, pages = {141-154}, year = {2016}, abstract = {Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.}, language = {en} } @article{AlmadeJongJelusicetal.2016, author = {Alma, Harma and de Jong, Corina and Jelusic, Danijel and Wittmann, Michael and Schuler, Michael and Flokstra-de Blok, Bertine and Kocks, Janwillem and Schultz, Konrad and van der Molen, Thys}, title = {Health status instruments for patients with COPD in pulmonary rehabilitation: defining a minimal clinically important difference}, series = {npj Primary Care Respiration Medicine}, volume = {26}, journal = {npj Primary Care Respiration Medicine}, number = {16041}, doi = {10.1038/npjpcrm.2016.41}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166327}, year = {2016}, abstract = {The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects. This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George's Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches. In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65\% male, 43 pack-years, GOLD stage II/III/IV 50/39/11\%). Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.). Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ). Questionnaire-referencing suggested MCID ranges of 0.28-0.61 (CCQ), 1.46-3.08 (CAT) and 6.86-9.47 (SGRQ). The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ). Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement. MCID estimates differed depending on the method used. Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients. The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD.}, language = {en} } @article{AliMontenegro2016, author = {Ali, Qasim and Montenegro, Sergio}, title = {Decentralized control for scalable quadcopter formations}, series = {International Journal of Aerospace Engineering}, volume = {2016}, journal = {International Journal of Aerospace Engineering}, doi = {10.1155/2016/9108983}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146704}, pages = {9108983}, year = {2016}, abstract = {An innovative framework has been developed for teamwork of two quadcopter formations, each having its specified formation geometry, assigned task, and matching control scheme. Position control for quadcopters in one of the formations has been implemented through a Linear Quadratic Regulator Proportional Integral (LQR PI) control scheme based on explicit model following scheme. Quadcopters in the other formation are controlled through LQR PI servomechanism control scheme. These two control schemes are compared in terms of their performance and control effort. Both formations are commanded by respective ground stations through virtual leaders. Quadcopters in formations are able to track desired trajectories as well as hovering at desired points for selected time duration. In case of communication loss between ground station and any of the quadcopters, the neighboring quadcopter provides the command data, received from the ground station, to the affected unit. Proposed control schemes have been validated through extensive simulations using MATLAB®/Simulink® that provided favorable results.}, language = {en} } @article{AliMontenegro2016, author = {Ali, Qasim and Montenegro, Sergio}, title = {Explicit Model Following Distributed Control Scheme for Formation Flying of Mini UAVs}, series = {IEEE Access}, volume = {4}, journal = {IEEE Access}, number = {397-406}, doi = {10.1109/ACCESS.2016.2517203}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146061}, year = {2016}, abstract = {A centralized heterogeneous formation flight position control scheme has been formulated using an explicit model following design, based on a Linear Quadratic Regulator Proportional Integral (LQR PI) controller. The leader quadcopter is a stable reference model with desired dynamics whose output is perfectly tracked by the two wingmen quadcopters. The leader itself is controlled through the pole placement control method with desired stability characteristics, while the two followers are controlled through a robust and adaptive LQR PI control method. Selected 3-D formation geometry and static stability are maintained under a number of possible perturbations. With this control scheme, formation geometry may also be switched to any arbitrary shape during flight, provided a suitable collision avoidance mechanism is incorporated. In case of communication loss between the leader and any of the followers, the other follower provides the data, received from the leader, to the affected follower. The stability of the closed-loop system has been analyzed using singular values. The proposed approach for the tightly coupled formation flight of mini unmanned aerial vehicles has been validated with the help of extensive simulations using MATLAB/Simulink, which provided promising results.}, language = {en} } @article{AlbersBernsteinBrachmannetal.2016, author = {Albers, Gregory W. and Bernstein, Richard A. and Brachmann, Johannes and Camm, John and Easton, J. Donald and Fromm, Peter and Goto, Shinya and Granger, Christopher B. and Hohnloser, Stefan H. and Hylek, Elaine and Jaffer, Amir K. and Krieger, Derk W. and Passman, Rod and Pines, Jesse M. and Reed, Shelby D. and Rothwell, Peter M. and Kowey, Peter R.}, title = {Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report}, series = {Journal of the American Heart Association}, volume = {5}, journal = {Journal of the American Heart Association}, number = {e00294}, doi = {10.1161/JAHA.115.002944}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165709}, pages = {1-11}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{AhmedZeeshanDandekar2016, author = {Ahmed, Zeeshan and Zeeshan, Saman and Dandekar, Thomas}, title = {Mining biomedical images towards valuable information retrieval in biomedical and life sciences}, series = {Database - The Journal of Biological Databases and Curation}, volume = {2016}, journal = {Database - The Journal of Biological Databases and Curation}, doi = {10.1093/database/baw118}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162697}, pages = {baw118}, year = {2016}, abstract = {Biomedical images are helpful sources for the scientists and practitioners in drawing significant hypotheses, exemplifying approaches and describing experimental results in published biomedical literature. In last decades, there has been an enormous increase in the amount of heterogeneous biomedical image production and publication, which results in a need for bioimaging platforms for feature extraction and analysis of text and content in biomedical images to take advantage in implementing effective information retrieval systems. In this review, we summarize technologies related to data mining of figures. We describe and compare the potential of different approaches in terms of their developmental aspects, used methodologies, produced results, achieved accuracies and limitations. Our comparative conclusions include current challenges for bioimaging software with selective image mining, embedded text extraction and processing of complex natural language queries.}, language = {en} } @article{AdrianMartinezAlbertAndreetal.2016, author = {Adri{\´a}n-Mart{\´i}nez, S. and Albert, A. and Andr{\´e}, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Avgitas, T. and Baret, B. and Barrios-Mart{\´i}, J. and Basa, S. and Bertin, V. and Biagi, S. and Bormuth, R. and Bouwhuis, M.C. and Bruijn, R. and Brunner, J. and Busto, J. and Capone, A. and Caramete, L. and Carr, J. and Celli, S. and Chiarusi, T. and Circella, M. and Coleiro, A. and Coniglione, R. and Costantini, H. and Coyle, P. and Creusot, A. and Deschamps, A. and De Bonis, G. and Distefano, C. and Donzaud, C. and Dornic, D. and Drouhin, D. and Eberl, T. and El Bojaddaini, I. and Els{\"a}sser, D. and Enzenh{\"o}fer, A. and Fehn, K. and Felis, I. and Fusco, L.A. and Galat{\`a}, S. and Gay, P. and Geißels{\"o}der, S. and Geyer, K. and Giordano, V. and Gleixner, A. and Glotin, H. and Gracia-Ruiz, R. and Graf, K. and Hallmann, S. and van Haren, H. and Heijboer, A.J. and Hello, Y. and Hern{\´a}ndez-Rey, J.J. and H{\"o}ßl, J. and Hofest{\"a}dt, J. and Hugon, C. and Illuminati, G. and James, C.W. and de Jong, M. and Jongen, M. and Kadler, M. and Kalekin, O. and Katz, U. and Kießling, D. and Kouchner, A. and Kreter, M. and Kreykenbohm, I. and Kulikovskiy, V. and Lachaud, C. and Lahmann, R. and Lef{\`e}vre, D. and Leonora, E. and Loucatos, S. and Marcelin, M. and Margiotta, A. and Marinelli, A. and Mart{\´i}nez-Mora, J.A. and Mathieu, A. and Melis, K. and Michael, T. and Migliozzi, P. and Moussa, A. and Mueller, C. and Nezri, E. and Pavalas, G.E. and Pellegrino, C. and Perrina, C. and Piattelli, P. and Popa, V. and Pradier, T. and Racca, C. and Riccobene, G. and Roensch, K. and Salda{\~n}a, M. and Samtleben, D.F.E. and S{\´a}nchez-Losa, A. and Sanguineti, M. and Sapienza, P. and Schnabel, J. and Sch{\"u}ssler, F. and Seitz, T. and Sieger, C. and Spurio, M. and Stolarczyk, Th. and Taiuti, M. and T{\"o}nnis, C. and Trovato, A. and Tselengidou, M. and Turpin, D. and Vallage, B. and Vall{\´e}e, C. and Van Elewyck, V. and Vivolo, D. and Wagner, S. and Wilms, J. and Zornoza, J.D. and Z{\´u}{\~n}iga, J.}, title = {Limits on dark matter annihilation in the sun using the ANTARES neutrino telescope}, series = {Physics Letters B}, volume = {759}, journal = {Physics Letters B}, doi = {10.1016/j.physletb.2016.05.019}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166642}, pages = {69-74}, year = {2016}, abstract = {A search for muon neutrinos originating from dark matter annihilations in the Sun is performed using the data recorded by the ANTARES neutrino telescope from 2007 to 2012. In order to obtain the best possible sensitivities to dark matter signals, an optimisation of the event selection criteria is performed taking into account the background of atmospheric muons, atmospheric neutrinos and the energy spectra of the expected neutrino signals. No significant excess over the background is observed and 90\% C.L. upper limits on the neutrino flux, the spin-dependent and spin-independent WIMP-nucleon cross-sections are derived for WIMP masses ranging from 50 GeV to 5 TeV for the annihilation channels WIMP + WIMP→ b\(\overline{b}\), W\(^{+}\)W\(^{-}\) and τ\(^{+}\)τ\(^{-}\).}, language = {en} } @article{AdrianMartinezAlbertAndreetal.2016, author = {Adri{\´a}n-Mart{\´i}nez, S. and Albert, A. and Andr{\´e}, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Avgitas, T. and Baret, B. and Barrios-Mart{\´i}, J. and Basa, S. and Bertin, V. and Biagi, S. and Bormuth, R. and Bou-Cabo, M. and Bouwhuis, M.C. and Bruijn, R. and Brunner, J. and Busto, J. and Capone, A. and Caramete, L. and Carr, J. and Celli, S. and Chiarusi, T. and Circella, M. and Coleiro, A. and Coniglione, R. and Costantini, H. and Coyle, P. and Creusot, A. and Deschamps, A. and De Bonis, G. and Distefano, C. and Donzaud, C. and Dornic, D. and Drouhin, D. and Eberl, T. and El Bojaddaini, I. and Els{\"a}sser, D. and Enzenh{\"o}fer, A. and Fehn, K. and Felis, I. and Fusco, L.A. and Galat{\`a}, S. and Gay, P. and Geißels{\"o}der, S. and Geyer, K. and Giordano, V. and Gleixner, A. and Glotin, H. and Gracia-Ruiz, R. and Graf, K. and Hallmann, S. and van Haren, H. and Heijboer, A.J. and Hello, Y. and Hern{\´a}ndez-Rey, J.-J. and H{\"o}ßl, J. and Hofest{\"a}dt, J. and Hugon, C. and Illuminati, G. and James, C.W. and de Jong, M. and Kadler, M. and Kalekin, O. and Katz, U. and Kießling, D. and Kouchner, A. and Kreter, M. and Kreykenbohm, I. and Kulikovskiy, V. and Lachaud, C. and Lahmann, R. and Lef{\`e}vre, D. and Leonora, E. and Loucatos, S. and Marcelin, M. and Margiotta, A. and Marinelli, A. and Mart{\´i}nez-Mora, J.A. and Mathieu, A. and Michael, T. and Migliozzi, P. and Moussa, A. and Mueller, C. and Nezri, E. and Păvălaș, G.E. and Pellegrino, C. and Perrina, C. and Piattelli, P. and Popa, V. and Pradier, T. and Racca, C. and Riccobene, G. and Roensch, K. and Salda{\~n}a, M. and Samtleben, D.F.E. and Sanguineti, M. and Sapienza, P. and Schnabel, J. and Sch{\"u}ssler, F. and Seitz, T. and Sieger, C. and Spurio, M. and Stolarczyk, Th. and S{\´a}nchez-Losa, A. and Taiuti, M. and Trovato, A. and Tselengidou, M. and Turpin, D. and T{\"o}nnis, C. and Vallage, B. and Vall{\´e}e, C. and Van Elewyck, V. and Vivolo, D. and Wagner, S. and Wilms, J. and Zornoza, J.D. and Z{\´u}{\~n}iga, J.}, title = {A search for Secluded Dark Matter in the Sun with the ANTARES neutrino telescope}, series = {Journal of Cosmology and Astroparticle Physics}, volume = {2016}, journal = {Journal of Cosmology and Astroparticle Physics}, number = {5}, organization = {The ANTARES collaboration}, doi = {10.1088/1475-7516/2016/05/016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189035}, pages = {12}, year = {2016}, abstract = {A search for Secluded Dark Matter annihilation in the Sun using 2007-2012 data of the ANTARES neutrino telescope is presented. Three different cases are considered: a) detection of dimuons that result from the decay of the mediator, or neutrino detection from: b) mediator that decays into a dimuon and, in turn, into neutrinos, and c) mediator that decays directly into neutrinos. As no significant excess over background is observed, constraints are derived on the dark matter mass and the lifetime of the mediator.}, language = {en} }