@article{VeldhoenBehzadiLenzetal.2017, author = {Veldhoen, Simon and Behzadi, Cyrus and Lenz, Alexander and Henes, Frank Oliver and Rybczynski, Meike and von Kodolitsch, Yskert and Bley, Thorsten Alexander and Adam, Gerhard and Bannas, Peter}, title = {Non-contrast MR angiography at 1.5 Tesla for aortic monitoring in Marfan patients after aortic root surgery}, series = {Journal of Cardiovascular Magnetic Resonance}, volume = {19}, journal = {Journal of Cardiovascular Magnetic Resonance}, number = {82}, doi = {10.1186/s12968-017-0394-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158693}, year = {2017}, abstract = {Background: Contrast-enhanced cardiovascular magnetic resonance angiography (CE-CMRA) is the established imaging modality for patients with Marfan syndrome requiring life-long annual aortic imaging before and after aortic root replacement. Contrast-free CMRA techniques avoiding side-effects of contrast media are highly desirable for serial imaging but have not been evaluated in the postoperative setup of Marfan patients. The purpose of this study was to assess the feasibility of non-contrast balanced steady-state free precession (bSSFP) magnetic resonance imaging for aortic monitoring of postoperative patients with Marfan syndrome. Methods: Sixty-four adult Marfan patients after aortic root replacement were prospectively included. Fourteen patients (22\%) had a residual aortic dissection after surgical treatment of type A dissection. bSSFP imaging and CE-CMRA were performed at 1.5 Tesla. Two radiologists evaluated the images regarding image quality (1 = poor, 4 = excellent), artifacts (1 = severe, 4 = none) and aortic pathologies. Readers measured the aortic diameters at defined levels in both techniques. Statistics included observer agreement for image scoring and diameter measurements and ROC analyses for comparison of the diagnostic performance of bSSFP and CE-CMRA. Results: Both readers observed no significant differences in image quality between bSSFP and CE-CMRA and found a median image quality score of 4 for both techniques (all p > .05). No significant differences were found regarding the frequency of image artifacts in both sequences (all p > .05). Sensitivity and specificity for detection of aortic dissections was 100\% for both readers and techniques. Compared to bSSFP imaging, CE-CMRA resulted in higher diameters (mean bias, 0.9 mm; p < .05). The inter-observer biases of diameter measurements were not significantly different (all p > .05), except for the distal graft anastomosis (p = .001). Using both techniques, the readers correctly identified a graft suture dehiscence with aneurysm formation requiring surgery. Conclusion: Unenhanced bSSFP CMR imaging allows for riskless aortic monitoring with high diagnostic accuracy in Marfan patients after aortic root surgery.}, language = {en} } @article{VargasCasanovaRodriguezGuerraUmanaPerezetal.2017, author = {Vargas Casanova, Yerly and Rodr{\´i}guez Guerra, Jorge Antonio and Uma{\~n}a P{\´e}rez, Yadi Adriana and Leal Castro, Aura Luc{\´i}a and Almanzar Reina, Giovanni and Garc{\´i}a Casta{\~n}eda, Javier Eduardo and Rivera Monroy, Zuly Jenny}, title = {Antibacterial synthetic peptides derived from bovine lactoferricin exhibit cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines}, series = {Molecules}, volume = {22}, journal = {Molecules}, number = {10}, doi = {10.3390/molecules22101641}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173887}, year = {2017}, abstract = {Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)\(_2\)K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.}, language = {en} } @article{VangeelPishvaHompesetal.2017, author = {Vangeel, Elise Beau and Pishva, Ehsan and Hompes, Titia and van den Hove, Daniel and Lambrechts, Diether and Allegaert, Karel and Freson, Kathleen and Izzi, Benedetta and Claes, Stephan}, title = {Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for \(GABBR1\)}, series = {Clinical Epigenetics}, volume = {9}, journal = {Clinical Epigenetics}, doi = {10.1186/s13148-017-0408-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173825}, year = {2017}, abstract = {Background: There is increasing evidence for the role of prenatal stress in shaping offspring DNA methylation and disease susceptibility. In the current study, we aimed to identify genes and pathways associated with pregnancy anxiety using a genome-wide DNA methylation approach. Methods: We selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to the lowest or highest degree of maternal pregnancy anxiety, respectively. Cord blood genome-wide DNA methylation was assayed using the HumanMethylation450 BeadChip (HM450, n = 45) and candidate gene methylation using EpiTYPER (n = 80). Cortisol levels were measured at 2, 4, and 12 months of age to test infant stress system (re)activity. Results: Data showed ten differentially methylated regions (DMR) when comparing newborns exposed to low versus high pregnancy anxiety scores. We validated a top DMR in the GABA-B receptor subunit 1 gene (GABBR1) revealing the association with pregnancy anxiety particularly in male newborns (most significant CpG Pearson R = 0.517, p = 0.002; average methylation Pearson R = 0.332, p = 0.039). Cord blood GABBR1 methylation was associated with infant cortisol levels in response to a routine vaccination at 4 months old. Conclusions: In conclusion, our results show that pregnancy anxiety is associated with differential DNA methylation patterns in newborns and that our candidate gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. Our findings reveal a potential role for GABBR1 methylation in association with stress and provide grounds for further research.}, language = {en} } @article{VanSteenbergenBalteauGinionetal.2017, author = {Van Steenbergen, Anne and Balteau, Magali and Ginion, Audrey and Fert{\´e}, Laura and Battault, Sylvain and de Meester de Ravenstein, Christophe and Balligand, Jean-Luc and Daskalopoulos, Evangelos-Panagiotis and Gilon, Patrick and Despa, Florin and Despa, Sanda and Vanoverschelde, Jean-Louis and Horman, Sandrine and Koepsell, Hermann and Berry, Gerard and Hue, Louis and Bertrand, Luc and Beauloye, Christophe}, title = {Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/srep41166}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180891}, pages = {14}, year = {2017}, abstract = {Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to HG. In contrast, myo-inositol (transported through SMIT1) reproduced the toxic effects of HG. SMIT1 overexpression exacerbated glucotoxicity and sensitized cardiomyocytes to HG, whereas its deletion prevented HG-induced NOX2 activation. In conclusion, our results show that heart SMIT1 senses HG and triggers NOX2 activation. This could participate in the redox signaling in hyperglycemic heart and contribute to the pathophysiology of diabetic cardiomyopathy.}, language = {en} } @article{UriWernerLuehderetal.2017, author = {Uri, Anna and Werner, Sandra and L{\"u}hder, Fred and H{\"u}nig, Thomas and Kerkau, Thomas and Beyersdorf, Niklas}, title = {Protection of mice from acute graft-versus-host disease requires CD28 co-stimulation on donor CD4\(^{+}\) Foxp3\(^{+}\) regulatory T Cells}, series = {Frontiers in Immunology}, volume = {8}, journal = {Frontiers in Immunology}, number = {721}, doi = {10.3389/fimmu.2017.00721}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158469}, year = {2017}, abstract = {Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4\(^{+}\) conventional (CD4\(^{+}\)CD25\(^{-}\)Foxp3\(^{-}\), Tconv) and regulatory (CD4\(^{+}\)CD25\(^{+}\)Foxp3\(^{+}\), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4\(^{+}\) Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4\(^{+}\) Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice. Selective depletion of CD28 on donor Treg did not abrogate protection of recipient mice from aGvHD until about day 20 after allo-HSCT. Later, however, the pool of CD28-depleted Treg drastically declined as compared to wt Treg. Consequently, only wt, but not CD28-deficient, Treg were able to continuously suppress aGvHD and induce long-term survival of the recipient mice. To our knowledge, this is the first study that specifically evaluates the impact of CD28 expression on donor Treg in aGvHD. Moreover, the delayed kinetics of aGvHD lethality after transplantation of iCD28KO Treg provides a novel animal model for similar disease courses found in patients after allo-HSCT.}, language = {en} } @article{UllmannBanksSchmittetal.2017, author = {Ullmann, Tobias and Banks, Sarah N. and Schmitt, Andreas and Jagdhuber, Thomas}, title = {Scattering characteristics of X-, C- and L-Band PolSAR data examined for the tundra environment of the Tuktoyaktuk Peninsula, Canada}, series = {Applied Sciences}, volume = {7}, journal = {Applied Sciences}, number = {6}, doi = {10.3390/app7060595}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158362}, pages = {595}, year = {2017}, abstract = {In this study, polarimetric Synthetic Aperture Radar (PolSAR) data at X-, C- and L-Bands, acquired by the satellites: TerraSAR-X (2011), Radarsat-2 (2011), ALOS (2010) and ALOS-2 (2016), were used to characterize the tundra land cover of a test site located close to the town of Tuktoyaktuk, NWT, Canada. Using available in situ ground data collected in 2010 and 2012, we investigate PolSAR scattering characteristics of common tundra land cover classes at X-, C- and L-Bands. Several decomposition features of quad-, co-, and cross-polarized data were compared, the correlation between them was investigated, and the class separability offered by their different feature spaces was analyzed. Certain PolSAR features at each wavelength were sensitive to the land cover and exhibited distinct scattering characteristics. Use of shorter wavelength imagery (X and C) was beneficial for the characterization of wetland and tundra vegetation, while L-Band data highlighted differences of the bare ground classes better. The Kennaugh Matrix decomposition applied in this study provided a unified framework to store, process, and analyze all data consistently, and the matrix offered a favorable feature space for class separation. Of all elements of the quad-polarized Kennaugh Matrix, the intensity based elements K0, K1, K2, K3 and K4 were found to be most valuable for class discrimination. These elements contributed to better class separation as indicated by an increase of the separability metrics squared Jefferys Matusita Distance and Transformed Divergence. The increase in separability was up to 57\% for Radarsat-2 and up to 18\% for ALOS-2 data.}, language = {en} } @article{TymoshenkoOnykiienkoMuelleretal.2017, author = {Tymoshenko, Y. V. and Onykiienko, Y. A. and M{\"u}ller, T. and Thomale, R. and Rachel, S. and Cameron, A. S. and Portnichenko, P. Y. and Efremov, D. V. and Tsurkan, V. and Abernathy, D. L. and Ollivier, J. and Schneidewind, A. and Piovano, A. and Felea, V. and Loidl, A. and Inosov, D. S.}, title = {Pseudo-Goldstone magnons in the frustrated \(S=3/2\) Heisenberg helimagnet \(ZnCr_2Se_4\) with a pyrochlore magnetic sublattice}, series = {Physical Review X}, volume = {7}, journal = {Physical Review X}, number = {4}, doi = {10.1103/PhysRevX.7.041049}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172770}, year = {2017}, abstract = {Low-energy spin excitations in any long-range ordered magnetic system in the absence of magnetocrystalline anisotropy are gapless Goldstone modes emanating from the ordering wave vectors. In helimagnets, these modes hybridize into the so-called helimagnon excitations. Here we employ neutron spectroscopy supported by theoretical calculations to investigate the magnetic excitation spectrum of the isotropic Heisenberg helimagnet \({ZnCr_2Se_4}\) with a cubic spinel structure, in which spin\(-3/2\) magnetic \({Cr^{3+}}\) ions are arranged in a geometrically frustrated pyrochlore sublattice. Apart from the conventional Goldstone mode emanating from the \((0~ 0~ {q_h})\) ordering vector, low-energy magnetic excitations in the single-domain proper-screw spiral phase show soft helimagnon modes with a small energy gap of \({∼0.17~ meV}\), emerging from two orthogonal wave vectors \(({q_h}~ 0~ 0)\) and \({(0~ {q_h}~ 0)}\) where no magnetic Bragg peaks are present. We term them pseudo-Goldstone magnons, as they appear gapless within linear spinwave theory and only acquire a finite gap due to higher-order quantum-fluctuation corrections. Our results are likely universal for a broad class of symmetric helimagnets, opening up a new way of studying weak magnon-magnon interactions with accessible spectroscopic methods.}, language = {en} } @article{TuanScharfŽutičetal.2017, author = {Tuan, Dinh Van and Scharf, Benedikt and Žutič, Igor and Dery, Hanan}, title = {Marrying excitons and plasmons in monolayer transition-metal dichalcogenides}, series = {Physical Review X}, volume = {7}, journal = {Physical Review X}, number = {4}, doi = {10.1103/PhysRevX.7.041040}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173030}, year = {2017}, abstract = {Just as photons are the quanta of light, plasmons are the quanta of orchestrated charge-density oscillations in conducting media. Plasmon phenomena in normal metals, superconductors, and doped semiconductors are often driven by long-wavelength Coulomb interactions. However, in crystals whose Fermi surface is comprised of disconnected pockets in the Brillouin zone, collective electron excitations can also attain a shortwave component when electrons transition between these pockets. In this work, we show that the band structure of monolayer transition-metal dichalcogenides gives rise to an intriguing mechanism through which shortwave plasmons are paired up with excitons. The coupling elucidates the origin for the optical sideband that is observed repeatedly in monolayers of WSe\(_2\) and WS\(_2\) but not understood. The theory makes it clear why exciton-plasmon coupling has the right conditions to manifest itself distinctly only in the optical spectra of electron-doped tungsten-based monolayers.}, language = {en} } @article{TsonevaMinevFrentzenetal.2017, author = {Tsoneva, Desislava and Minev, Boris and Frentzen, Alexa and Zhang, Qian and Wege, Anja K. and Szalay, Aladar A.}, title = {Humanized Mice with Subcutaneous Human Solid Tumors for Immune Response Analysis of Vaccinia Virus-Mediated Oncolysis}, series = {Molecular Therapy Oncolytics}, volume = {5}, journal = {Molecular Therapy Oncolytics}, doi = {10.1016/j.omto.2017.03.001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170786}, pages = {41-61}, year = {2017}, abstract = {Oncolytic vaccinia virus (VACV) therapy is an alternative cancer treatment modality that mediates targeted tumor destruction through a tumor-selective replication and an induction of anti-tumor immunity. We developed a humanized tumor mouse model with subcutaneous human tumors to analyze the interactions of VACV with the developing tumors and human immune system. A successful systemic reconstitution with human immune cells including functional T cells as well as development of tumors infiltrated with human T and natural killer (NK) cells was observed. We also demonstrated successful in vivo colonization of such tumors with systemically administered VACVs. Further, a new recombinant GLV-1h376 VACV encoding for a secreted human CTLA4-blocking single-chain antibody (CTLA4 scAb) was tested. Surprisingly, although proving CTLA4 scAb's in vitro binding ability and functionality in cell culture, beside the significant increase of CD56\(^{bright}\) NK cell subset, GLV-1h376 was not able to increase cytotoxic T or overall NK cell levels at the tumor site. Importantly, the virus-encoded β-glucuronidase as a measure of viral titer and CTLA4 scAb amount was demonstrated. Therefore, studies in our "patient-like" humanized tumor mouse model allow the exploration of newly designed therapy strategies considering the complex relationships between the developing tumor, the oncolytic virus, and the human immune system.}, language = {en} } @article{TshitengeFeineisMudogoetal.2017, author = {Tshitenge, Dieudonn{\´e} Tshitenge and Feineis, Doris and Mudogo, Virima and Kaiser, Marcel and Brun, Reto and Bringmann, Gerhard}, title = {Antiplasmodial Ealapasamines A-C,'Mixed' Naphthylisoquinoline Dimers from the Central African Liana Ancistrocladus ealaensis}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {5767}, doi = {10.1038/s41598-017-05719-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170645}, year = {2017}, abstract = {Three unusual heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A-C (1-3), were isolated from the leaves of the tropical plant Ancistrocladus ealaensis J. L{\´e}onard. These 'mixed', constitutionally unsymmetric dimers are the first stereochemically fully assigned cross-coupling products of a 5,8′- and a 7,8′-coupled naphthylisoquinoline linked via C-6′ in both naphthalene portions. So far, only two other West and Central Ancistrocladus species were known to produce dimers with a central 6,6″-axis, yet, in contrast to the ealapasamines, usually consisting of two 5,8′-coupled monomers, like e.g., in michellamine B. The new dimers 1-3 contain six elements of chirality, four stereogenic centers and the two outer axes, while the central biaryl axis is configurationally unstable. The elucidation of the complete stereostructures of the ealapasamines was achieved by the interplay of spectroscopic methods including HRESIMS, 1D and 2D NMR (in particular ROESY measurements), in combination with chemical (oxidative degradation) and chiroptical (electronic circular dichroism) investigations. The ealapasamines A-C display high antiplasmodial activities with excellent half-maximum inhibition concentration values in the low nanomolar range.}, language = {en} } @article{TsamadouFuerstVucinicetal.2017, author = {Tsamadou, Chrysanthi and F{\"u}rst, Daniel and Vucinic, Vladan and Bunjes, Donald and Neuchel, Christine and Mytilineos, Daphne and Gramatzki, Martin and Arnold, Renate and Wagner, Eva Maria and Einsele, Hermann and M{\"u}ller, Carlheinz and Schrezenmeier, Hubert and Mytilineos, Joannis}, title = {Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients}, series = {Haematologica}, volume = {102}, journal = {Haematologica}, number = {11}, doi = {10.3324/haematol.2017.169805}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173325}, pages = {1947-1955}, year = {2017}, abstract = {The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53\% vs. 38\%, P=0.002, 5-year OS) and multivariate (hazard ratio (HR)=0.63, confidence interval (CI) 95\%=0.48-0.83, P=0.001) analyses. Further subgroup analysis demonstrated that the positive effect of HLA-E mismatch was significant and pronounced in advanced disease patients (n=120) (5-year OS: 50\% vs. 18\%, P=0.005; HR=0.40, CI 95\%=0.22-0.72, P=0.002; results from univariate and multivariate analyses, respectively). The study herein is the first to report an association between HLA-E incompatibility and improved post-transplant prognosis in AL patients who have undergone matched unrelated HSCT. Combined NK and T cell HLA-E-mediated mechanisms may account for the better outcomes observed. Notwithstanding the necessity for in vitro and confirmational studies, our findings highlight the clinical relevance of HLA-E matching and strongly support prospective HLA-E screening upon donor selection for matched AL unrelated HSCTs.}, language = {en} } @article{TriphanJobstAnjorinetal.2017, author = {Triphan, Simon M. F. and Jobst, Bertram J. and Anjorin, Angela and Sedlaczek, Oliver and Wolf, Ursula and Terekhov, Maxim and Hoffmann, Christian and Ley, Sebastian and D{\"u}ber, Christoph and Biederer, J{\"u}rgen and Kauczor, Hans-Ulrich and Jakob, Peter M. and Wielp{\"u}tz, Mark O.}, title = {Reproducibility and comparison of oxygen-enhanced T\(_1\) quantification in COPD and asthma patients}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0172479}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171833}, year = {2017}, abstract = {T\(_1\) maps have been shown to yield useful diagnostic information on lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma, both for native T\(_1\) and ΔT\(_1\), the relative reduction while breathing pure oxygen. As parameter quantification is particularly interesting for longitudinal studies, the purpose of this work was both to examine the reproducibility of lung T\(_1\) mapping and to compare T\(_1\) found in COPD and asthma patients using IRSnapShotFLASH embedded in a full MRI protocol. 12 asthma and 12 COPD patients (site 1) and further 15 COPD patients (site 2) were examined on two consecutive days. In each patient, T\(_1\) maps were acquired in 8 single breath-hold slices, breathing first room air, then pure oxygen. Maps were partitioned into 12 regions each to calculate average values. In asthma patients, the average T\(_{1,RA}\) = 1206ms (room air) was reduced to T\(_{1,O2}\) = 1141ms under oxygen conditions (ΔT\(_1\) = 5.3\%, p < 5⋅10\(^{-4})\), while in COPD patients both native T\(_{1,RA}\) = 1125ms was significantly shorter (p < 10\(^{-3})\) and the relative reduction to T\(_{1,O2}\) = 1081ms on average ΔT\(_1\) = 4.2\%(p < 10\(^{-5}\)). On the second day, with T\(_{1,RA}\) = 1186ms in asthma and T\(_{1,RA}\) = 1097ms in COPD, observed values were slightly shorter on average in all patient groups. ΔT\(_1\) reduction was the least repeatable parameter and varied from day to day by up to 23\% in individual asthma and 30\% in COPD patients. While for both patient groups T\(_1\) was below the values reported for healthy subjects, the T\(_1\) and ΔT\(_1\) found in asthmatics lies between that of the COPD group and reported values for healthy subjects, suggesting a higher blood volume fraction and better ventilation. However, it could be demonstrated that lung T\(_1\) quantification is subject to notable inter-examination variability, which here can be attributed both to remaining contrast agent from the previous day and the increased dependency of lung T\(_1\) on perfusion and thus current lung state.}, language = {en} } @article{TiffeWagnerRueckeretal.2017, author = {Tiffe, Theresa and Wagner, Martin and R{\"u}cker, Viktoria and Morbach, Caroline and Gelbrich, G{\"o}tz and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Control of cardiovascular risk factors and its determinants in the general population - findings from the STAAB cohort study}, series = {BMC Cardiovascular Disorders}, volume = {17}, journal = {BMC Cardiovascular Disorders}, number = {276}, doi = {10.1186/s12872-017-0708-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159391}, year = {2017}, abstract = {Background: While data from primary care suggest an insufficient control of vascular risk factors, little is known about vascular risk factor control in the general population. We therefore aimed to investigate the adoption of adequate risk factor control and its determinants in the general population free of cardiovascular disease (CVD). Methods: Data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) Cohort Study, a population-based study of inhabitants aged 30 to 79 years from the general population of W{\"u}rzburg (Germany), were used. Proportions of participants without established CVD meeting targets for risk factor control recommended by 2016 ESC guideline were identified. Determinants of the accumulation of insufficiently controlled vascular risk factors (three or more) were assessed. Results: Between December 2013 and April 2015, 1379 participants without CVD were included; mean age was 53.1 ± 11.9 years and 52.9\% were female; 30.8\% were physically inactive, 55.2\% overweight, 19.3\% current smokers. Hypertension, dyslipidemia, and diabetes mellitus were prevalent in 31.8\%, 57.6\%, and 3.9\%, respectively. Treatment goals were not reached despite medication in 52.7\% of hypertensive, in 37.3\% of hyperlipidemic and in 44.0\% of diabetic subjects. Insufficiently controlled risk was associated with male sex (OR 1.94, 95\%CI 1.44-2.61), higher age (OR for 30-39 years vs. 70-79 years 4.01, 95\%CI 1.94-8.31) and lower level of education (OR for primary vs. tertiary 2.15, 95\%CI 1.48-3.11). Conclusions: In the general population, prevalence of vascular risk factors was high. We found insufficient identification and control of vascular risk factors and a considerable potential to improve adherence to cardiovascular guidelines for primary prevention. Further studies are needed to identify and overcome patient- and physician-related barriers impeding successful control of vascular risk factors in the general population.}, language = {en} } @article{Thalhammer2017, author = {Thalhammer, Johanna}, title = {L'art de bien chanter und Von der Kunst zierlich zu singen und zu spielen - Eine kontrastive Analyse von Texten der musikalischen Fachsprache im 18. Jahrhundert anhand von Ausz{\"u}gen aus Code de musique pratique, Rameau (1760) und Der vollkommene Capellmeister, Mattheson (1739)}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {3}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2510-2613}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172958}, pages = {203-224}, year = {2017}, abstract = {This article is an analysis and a comparison of German and French special language of music in the 18th century, more precisely about the terms used to describe the activity of singing. The analysis is based on two treatises about music theory. The first writing, Der Vollkommene Capellmeister, was written by Johann Mattheson in 1739 and the second, Code de musique pratique by Jean-Philippe Rameau was published in 1760. Both texts contain a chapter which gives explanations how to sing. The treatises include different types of technical words: specific terms easy identified as special language terms like names of ornaments in the music, special verbs standing for singing, and words and anaphors to describe tonality and dynamics. By having a look on the terms of music language, the influence of Italian and French words on German vocabulary of music becomes obvious. The vocabulary is often similar in both languages, but not always defined as a part of the special language of music.}, language = {de} } @article{TemmeFriebeSchmidtetal.2017, author = {Temme, Sebastian and Friebe, Daniela and Schmidt, Timo and Poschmann, Gereon and Hesse, Julia and Steckel, Bodo and St{\"u}hler, Kai and Kunz, Meik and Dandekar, Thomas and Ding, Zhaoping and Akhyari, Payam and Lichtenberg, Artur and Schrader, J{\"u}rgen}, title = {Genetic profiling and surface proteome analysis of human atrial stromal cells and rat ventricular epicardium-derived cells reveals novel insights into their cardiogenic potential}, series = {Stem Cell Research}, volume = {25}, journal = {Stem Cell Research}, doi = {10.1016/j.scr.2017.11.006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172716}, pages = {183-190}, year = {2017}, abstract = {Epicardium-derived cells (EPDC) and atrial stromal cells (ASC) display cardio-regenerative potential, but the molecular details are still unexplored. Signals which induce activation, migration and differentiation of these cells are largely unknown. Here we have isolated rat ventricular EPDC and rat/human ASC and performed genetic and proteomic profiling. EPDC and ASC expressed epicardial/mesenchymal markers (WT-1, Tbx18, CD73,CD90, CD44, CD105), cardiac markers (Gata4, Tbx5, troponin T) and also contained phosphocreatine. We used cell surface biotinylation to isolate plasma membrane proteins of rEPDC and hASC, Nano-liquid chromatography with subsequent mass spectrometry and bioinformatics analysis identified 396 rat and 239 human plasma membrane proteins with 149 overlapping proteins. Functional GO-term analysis revealed several significantly enriched categories related to extracellular matrix (ECM), cell migration/differentiation, immunology or angiogenesis. We identified receptors for ephrin and growth factors (IGF, PDGF, EGF, anthrax toxin) known to be involved in cardiac repair and regeneration. Functional category enrichment identified clusters around integrins, PI3K/Akt-signaling and various cardiomyopathies. Our study indicates that EPDC and ASC have a similar molecular phenotype related to cardiac healing/regeneration. The cell surface proteome repository will help to further unravel the molecular details of their cardio-regenerative potential and their role in cardiac diseases.}, language = {en} } @article{TemmeAdamAhnenetal.2017, author = {Temme, Fabian and Adam, Jan and Ahnen, Max L. and Baack, Dominik and Balbo, Matteo and Bergmann, Matthias and Biland, Adrian and Blank, Michael and Bretz, Thomas and Br{\"u}gge, Kai A. and Buss, Jens and Dmytriiev, Anton and Dorner, Daniela and Einecke, Sabrina and Hempfling, Christina and Hildebrand, Dorothee and Hughes, Gareth and Linhoff, Lena and Mannheim, Karl and M{\"u}ller, Sebastian and Neise, Dominik and Neronov, Andrii and N{\"o}the, Max and Paravac, Aleksander and Pauss, Felicitas and Rhode, Wolfgang and Shukla, Amit and Thaele, Julia and Walter, Roland}, title = {Long-Term monitoring of bright blazars in the multi-GeV to TeV range with FACT}, series = {Galaxies}, volume = {5}, journal = {Galaxies}, number = {1}, publisher = {MDPI}, issn = {2075-4434}, doi = {10.3390/galaxies5010018}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198088}, pages = {18}, year = {2017}, abstract = {Blazars like Markarian 421 or Markarian 501 are active galactic nuclei (AGN), with their jets orientated towards the observer. They are among the brightest objects in the very high energy (VHE) gamma ray regime (>100 GeV). Their emitted gamma-ray fluxes are extremely variable, with changing activity levels on timescales between minutes, months, and even years. Several questions are part of the current research, such as the question of the emission regions or the engine of the AGN and the particle acceleration. A dedicated longterm monitoring program is necessary to investigate the properties of blazars in detail. A densely sampled and unbiased light curve allows for observation of both high and low states of the sources, and the combination with multi-wavelength observation could contribute to the answer of several questions mentioned above. FACT (First G-APD Cherenkov Telescope) is the first operational telescope using silicon photomultiplier (SiPM, also known as Geigermode—Avalanche Photo Diode, G-APD) as photon detectors. SiPM have a very homogenous and stable longterm performance, and allow operation even during full moon without any filter, leading to a maximal duty cycle for an Imaging Air Cherenkov Telescope (IACT). Hence, FACT is an ideal device for such a longterm monitoring of bright blazars. A small set of sources (e.g., Markarian 421, Markarian 501, 1ES 1959+650, and 1ES 2344+51.4) is currently being monitored. In this contribution, the FACT telescope and the concept of longterm monitoring of bright blazars will be introduced. The results of the monitoring program will be shown, and the advantages of densely sampled and unbiased light curves will be discussed.}, language = {en} } @article{Teichmann2017, author = {Teichmann, Christoph}, title = {Die GmbH im europ{\"a}ischen Wettbewerb der Rechtsformen}, series = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, volume = {46}, journal = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, number = {5}, issn = {1612-7048}, doi = {10.1515/zgr-2017-0024}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194060}, pages = {543 -- 582}, year = {2017}, abstract = {In den 125 Jahren seit ihrer Einf{\"u}hrung im Jahre 1892 hat die deutsche GmbH einerseits einen Siegeszug um die ganze Welt angetreten und musste sich andererseits im eigenen Heimatland der scharfen Konkurrenz der englischen Limited erwehren. Dieser Wettbewerb setzte im Internationalen Gesellschaftsrecht einen Wechsel von der Sitz- zur Gr{\"u}ndungstheorie voraus. Seine negativen Auswirkungen lassen sich, wie die j{\"u}ngere EuGH-Rechtsprechung zeigt, durch eine am Sachproblem orientierte Anwendung inl{\"a}ndischer Drittschutzregeln zielgerichtet eingrenzen. Im europ{\"a}ischen Ideenwettbewerb ist das deutsche GmbH-Recht derweil deutlich zur{\"u}ckgefallen. Das liegt weniger an der vermeintlichen Dominanz des englischen Rechts als am Ideenreichtum der kleineren EU-Staaten, denen es mit gut durchdachten Reformprojekten gelingt, international Aufmerksamkeit auf sich zu ziehen.}, language = {de} } @article{Teichmann2017, author = {Teichmann, Christoph}, title = {Die grenz{\"u}berschreitende Unternehmensgruppe im Compliance-Zeitalter}, series = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, volume = {46}, journal = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, number = {4}, issn = {1612-7048}, doi = {10.1515/zgr-2017-0021}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194940}, pages = {485 -- 508}, year = {2017}, abstract = {Die europ{\"a}ische Konzernorganisation und die „Europa GmbH" (SPE) bilden zwei wichtige Forschungsschwerpunkte im Werk von Peter Hommelhoff. Beide Projekte haben sich {\"u}ber die Jahre als außerordentlich dicke Bretter erwiesen. Doch davon l{\"a}sst sich der Jubilar nicht beirren. R{\"u}ckschl{\"a}ge und Umwege geh{\"o}ren in der Wissenschaft zum kollektiven Lernprozess, der neue Erkenntnisse bringt. Ganz in diesem Sinne m{\"u}nden die Erfahrungen aus der Diskussion um ein europ{\"a}isches Konzernrecht und um die SPE im vorliegenden Beitrag in die Konzeption eines supranationalen Konzernbausteins f{\"u}r europ{\"a}ische Unternehmensgruppen.}, language = {de} } @article{TawkSharanEulalioetal.2017, author = {Tawk, Caroline and Sharan, Malvika and Eulalio, Ana and Vogel, J{\"o}rg}, title = {A systematic analysis of the RNA-targeting potential of secreted bacterial effector proteins}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-09527-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158815}, pages = {9328}, year = {2017}, abstract = {Many pathogenic bacteria utilize specialized secretion systems to deliver proteins called effectors into eukaryotic cells for manipulation of host pathways. The vast majority of known effector targets are host proteins, whereas a potential targeting of host nucleic acids remains little explored. There is only one family of effectors known to target DNA directly, and effectors binding host RNA are unknown. Here, we take a two-pronged approach to search for RNA-binding effectors, combining biocomputational prediction of RNA-binding domains (RBDs) in a newly assembled comprehensive dataset of bacterial secreted proteins, and experimental screening for RNA binding in mammalian cells. Only a small subset of effectors were predicted to carry an RBD, indicating that if RNA targeting was common, it would likely involve new types of RBDs. Our experimental evaluation of effectors with predicted RBDs further argues for a general paucity of RNA binding activities amongst bacterial effectors. We obtained evidence that PipB2 and Lpg2844, effector proteins of Salmonella and Legionella species, respectively, may harbor novel biochemical activities. Our study presenting the first systematic evaluation of the RNA-targeting potential of bacterial effectors offers a basis for discussion of whether or not host RNA is a prominent target of secreted bacterial proteins.}, language = {en} } @article{SanchezThierschmannMolenkamp2017, author = {S{\´a}nchez, Rafael and Thierschmann, Holger and Molenkamp, Laurens W.}, title = {Single-electron thermal devices coupled to a mesoscopic gate}, series = {New Journal of Physics}, volume = {19}, journal = {New Journal of Physics}, doi = {10.1088/1367-2630/aa8b94}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172982}, year = {2017}, abstract = {We theoretically investigate the propagation of heat currents in a three-terminal quantum dot engine. Electron-electron interactions introduce state-dependent processes which can be resolved by energy-dependent tunneling rates. We identify the relevant transitions which define the operation of the system as a thermal transistor or a thermal diode. In the former case, thermal-induced charge fluctuations in the gate dot modify the thermal currents in the conductor with suppressed heat injection, resulting in huge amplification factors and the possible gating with arbitrarily low energy cost. In the latter case, enhanced correlations of the state-selective tunneling transitions redistribute heat flows giving high rectification coefficients and the unexpected cooling of one conductor terminal by heating the other one. We propose quantum dot arrays as a possible way to achieve the extreme tunneling asymmetries required for the different operations.}, language = {en} }