@phdthesis{Wagner2019,
  author    = {Wagner, Wolfgang},
  title     = {Supramolecular Block Copolymers by Seeded Living Supramolecular Polymerization of Perylene Bisimides},
  doi       = {10.25972/OPUS-19300},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193004},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The research on supramolecular polymerization has undergone a rapid development in the last two decades, particularly since supramolecular polymers exhibit a broad variety of functionalities and applications in organic electronics, biological science or as functional materials (Chapter 2.1). Although former studies have focused on investigation of the thermodynamics of supramolecular polymerization (Chapter 2.2), the academic interest in the recent years shifted towards gaining insight into kinetically controlled self-assembly and pathway complexity to generate novel out-of-equilibrium architectures with interesting nanostructures and features (Chapter 2.3). Along this path, the concepts of seeded and living supramolecular polymerization were recently developed to enable the formation of supramolecular polymers with controlled length and low polydispersity under precise kinetic control (Chapter 2.4). Besides that, novel strategies were developed to achieve supramolecular copolymerization resulting in complex multicomponent nanostructures with different structural motives. The classification of these supramolecular copolymers on the basis of literature examples and an overview of previously reported principles to create such supramolecular architectures are provided in Chapter 2.5. The aim of the thesis was the non-covalent synthesis of highly desirable supramolecular block copolymers by the approach of living seeded supramolecular polymerization and to study the impact of the molecular shape of the monomeric building blocks on the supramolecular copolymerization. Based on the structure of the previously investigated PBI organogelator H-PBI a series of novel PBIs, bearing identical hydrogen-bonding amide side-groups in imide-position and various kind or number of substituents in bay-position, was synthesized and analyzed within this thesis. The new PBIs were successfully obtained in three steps starting from the respective bromo-substituted perylene-3,4:9,10-tetracarboxylic acid tetrabutylesters or from the N,N'-dicyclohexyl-1,7-dibromoperylene-3,4:9,10-tetracarboxylic acid bisimide. All target compounds were obtained in the final step by imidization reactions of the respective perylene tetracarboxylic acid bisanhydride precursors with N-(2-aminoethyl)-3,4,5-tris(dodecyloxy)-benzamide and were fully characterized by 1H and 13C NMR spectroscopy as well as high resolution mass spectrometry. The variation of bay-substituents strongly changes the optical properties of the monomeric PBIs which were investigated by UV/vis and fluorescence spectroscopy. The increase of the number of the methoxy-substituents provokes, for example, a red-shift of the absorption maxima concomitant with a decrease of extinction coefficients and leads to a drastic increase of the fluorescence quantum yields. Furthermore, the molecular geometry of the PBIs is also affected by variations of the bay-substituents. Thus, increasing the steric demand of the bay-substituents leads to an enlargement of the twist angles of the PBI cores as revealed by DFT calculations. Especially the 1,7-dimethoxy bay-substituted MeO-PBI proved to be very well-suited for the studies envisioned within this thesis. The self-assembly of this PBI derivative was analyzed in detail by UV/vis, fluorescence and FT-IR spectroscopy as well as atomic force microscopy (Chapter 3). These studies revealed that MeO-PBI forms in a solvent mixture of methylcyclohexane and toluene (2:1, v/v) kinetically trapped off-pathway H-aggregated nanoparticles upon fast cooling of a monomeric solution from 90 to 20 °C. However, upon slow cooling of the monomer solution fluorescent J-type nanofibers are formed by π π interactions and intermolecular hydrogen-bonding. The kinetically metastable off-pathway H-aggregates can be transformed into the thermodynamically more favored J-type aggregates by addition of seeds, which are produced by ultrasonication of the polymeric nanofibers. Interestingly, the living character of this seed-induced supramolecular polymerization process was proven by a newly designed multicycle polymerization experimental protocol. This living polymerization experiment clearly proves, that the polymerization can only occur at the "active" ends of the polymeric seed and that almost no recombination or chain termination processes are present. Hence, the approach of living supramolecular polymerization enables the formation of supramolecular polymers with controlled length and narrow polydispersity. In Chapter 4 the copolymerization of MeO-PBI with the structurally similar 1,7-dichloro (Cl-PBI) and 1,7-dimethylthio (MeS-PBI) bay-substituted PBIs is studied in detail. Both PBIs form analogous to MeO-PBI kinetically trapped off-pathway aggregates, which can be converted into the thermodynamically stable supramolecular polymers by seed-induced living supramolecular polymerization under precise kinetic control. However, the stability of the kinetically trapped aggregates of Cl-PBI and MeS-PBI is distinctly reduced compared to that of MeO-PBI, because the π-π-interactions of the kinetically metastable aggregates are hampered through the increased twisting of the PBI-cores of the former PBIs. UV/vis studies revealed that the two-component seeded copolymerization of the kinetically trapped state of MeO-PBI with seeds of Cl-PBI leads to the formation of unprecedented supramolecular block copolymers with A-B-A pattern by a living supramolecular polymerization process at the termini of the seeds. Remarkably, the resulting A-B-A block pattern of the obtained copolymers was clearly confirmed by atomic force microscopy studies as the respective blocks formed by the individual monomeric units could be distinguished by the pitches of the helical nanofibers. Moreover, detailed UV/vis and AFM studies have shown that by inverted two-component seed-induced polymerization, e.g., upon addition of seeds of MeO-PBI to the kinetically trapped aggregates of Cl-PBI, triblock supramolecular copolymers with B-A-B pattern can be generated. The switching of the block pattern could only be achieved because of the perfectly matching conditions for the copolymerization process and the tailored molecular geometry of the individual building blocks of both PBIs. These studies have demonstrated for the first time, that the block pattern of a supramolecular copolymer can be modulated by the experimental protocol through the approach of living supramolecular polymerization. Furthermore, by UV/vis analysis of the living copolymerization of MeO-PBI and MeS-PBI similar results were obtained showing also the formation of both A-B-A and B-A-B type supramolecular block copolymers. Although for these two PBIs the individual blocks could not be identified by AFM because the helical nanofibers of both PBIs exhibit identical helical pitches, these studies revealed for the first time that the approach of seeded living polymerization is not limited to a special pair of monomeric building blocks. In the last part of the thesis (Chapter 5) a systematic study on the two-component living copolymerization of PBIs with various sterical demanding bay-substituents is provided. Thus, a series of PBIs containing identical hydrogen-bonding amide groups in imide position but variable number (1-MeO-PBI, MeO-PBI, 1,6,7-MeO-PBI, 1,6,7,12-MeO-PBI) or size (EtO-PBI, iPrO-PBI) of alkoxy bay-substituents was investigated. The molecular geometry of the monomeric building blocks has a strong impact on the thermodynamically and even more pronounced on the kinetically controlled aggregation in solvent mixtures of MCH and Tol. While the mono- and dialkoxy-substituted PBIs form kinetically metastable species, the self-assembly of the tri- and tetramethoxy-substituted PBIs (1,6,7-MeO-PBI and 1,6,7,12-MeO-PBI) is completely thermodynamically controlled. The two 1,7-alkoxy substituted PBIs (EtO-PBI, iPrO-PBI) form very similar to MeO-PBI kinetically off-pathway H-aggregates and thermodynamically more favored J-type aggregates. However, the stability of the kinetically metastable state is drastically lower and the conversion into the thermodynamically favored state much faster than for MeO-PBI. In contrast, the monomethoxy-substituted PBI derivative (1-MeO-PBI) forms a kinetically trapped species by intramolecular hydrogen-bonding of the monomers, which can be transformed into the thermodynamically favored nanofibers by seeded polymerization. Importantly, the two-component seeded copolymerization of the kinetically trapped MeO PBI with seeds of other PBIs of the present series was studied by UV/vis and AFM revealing that the formation of supramolecular block copolymers is only possible for appropriate combinations of PBI building blocks. Thus, the seeded polymerization of the trapped state of the moderately core-twisted MeO-PBI with the, according to DFT-calculations, structurally similar PBIs (EtO-PBI and iPrO-PBI) leads to the formation of A-B-A block copolymers, like in the seeded copolymerization of MeO-PBItrapped with seeds of Cl-PBI and MeS-PBI already described in Chapter 4. However, by addition of seeds of the almost planar PBIs (H-PBI and 1-MeO-PBI) or seeds of the strongly core-twisted PBIs (1,6,7-MeO-PBI and 1,6,7,12-MeO-PBI) to the kinetically trapped state of MeO-PBI no block copolymers can be obtained. The mismatching geometry of these molecular building blocks strongly hampers both the intermolecular hydrogen-bonding and the π-π-interactions between the two different PBIs and consequently prevents the copolymerization process. Furthermore, the studies of the two-component seeded copolymerization of the kinetically trapped species of 1-MeO-PBI with seeds of the other PBIs also corroborated that a precise shape complementarity is crucial to generate supramolecular block copolymers. Thus, by addition of seeds of H-PBI to the kinetically trapped monomers of 1-MeO-PBI supramolecular block copolymers were generated. Both PBIs exhibit an almost planar PBI core according to DFT-calculations leading to strong non-covalent interactions between these PBIs. This perfectly matching geometry of both PBIs also enables the inverted seeded copolymerization of the kinetically trapped monomers of H-PBI with 1-MeO-PBIseed concomitant with a switching of the block pattern of the supramolecular copolymer from A-B-A to B-A-B type. In contrast, the seeding with the moderately twisted (MeO-PBI, EtO-PBI and iPrO-PBI) and the strongly twisted PBIs (1,6,7-MeO-PBI and 1,6,7,12 MeO-PBI) has no effect on the kinetically trapped state of 1-MeO-PBI, because the copolymerization of these PBIs is prevented by the mismatching geometry of the molecular building blocks. In conclusion, the supramolecular polymerization and two-component seeded copolymerization of a series of PBI monomers was investigated within this thesis. The studies revealed that the thermodynamically and kinetically controlled self-assembly can be strongly modified by subtle changes of the monomeric building blocks. Moreover, the results have shown that living supramolecular polymerization is an exceedingly powerful method to generate unprecedented supramolecular polymeric nanostructures with controlled block pattern and length distribution. The formation of supramolecular block copolymers can only be achieved under precise kinetic control of the polymerization process and is strongly governed by the shape complementarity already imparted in the individual components. Thus, these insightful studies might enable a more rational design of monomeric building blocks for the non-covalent synthesis of highly complex supramolecular architectures with interesting properties for possible future applications, e.g., as novel functional materials.},
  subject      = {Supramolekulare Chemie},
  language  = {en}
}
@article{NguyenKerstenSenmaoetal.2015,
  author    = {Nguyen, Duy Ba and Kersten, Clauss and Senmao, Cao and Vahid, Naeimi and Kuenzer, Claudia and Wagner, Wolfgang},
  title     = {Mapping Rice Seasonality in the Mekong Delta with Multi-Year Envisat ASAR WSM Data},
  series = {Remote Sensing},
  volume    = {7},
  journal   = {Remote Sensing},
  number    = {12},
  doi       = {10.3390/rs71215808},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137554},
  pages     = {15868-15893},
  year      = {2015},
  abstract  = {Rice is the most important food crop in Asia, and the timely mapping and monitoring of paddy rice fields subsequently emerged as an important task in the context of food security and modelling of greenhouse gas emissions. Rice growth has a distinct influence on Synthetic Aperture Radar (SAR) backscatter images, and time-series analysis of C-band images has been successfully employed to map rice fields. The poor data availability on regional scales is a major drawback of this method. We devised an approach to classify paddy rice with the use of all available Envisat ASAR WSM (Advanced Synthetic Aperture Radar Wide Swath Mode) data for our study area, the Mekong Delta in Vietnam. We used regression-based incidence angle normalization and temporal averaging to combine acquisitions from multiple tracks and years. A crop phenology-based classifier has been applied to this time series to detect single-, double- and triple-cropped rice areas (one to three harvests per year), as well as dates and lengths of growing seasons. Our classification has an overall accuracy of 85.3\% and a kappa coefficient of 0.74 compared to a reference dataset and correlates highly with official rice area statistics at the provincial level (R-2 of 0.98). SAR-based time-series analysis allows accurate mapping and monitoring of rice areas even under adverse atmospheric conditions.},
  language  = {en}
}
@article{NaeimiLeinenkugelSabeletal.2013,
  author    = {Naeimi, Vahid and Leinenkugel, Patrick and Sabel, Daniel and Wagner, Wolfgang and Apel, Heiko and Kuenzer, Claudia},
  title     = {Evaluation of Soil Moisture Retrieval from the ERS and Metop Scatterometers in the Lower Mekong Basin},
  series = {Remote Sensing},
  volume    = {5},
  journal   = {Remote Sensing},
  number    = {4},
  doi       = {10.3390/rs5041603},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130480},
  pages     = {1603-1623},
  year      = {2013},
  abstract  = {The natural environment and livelihoods in the Lower Mekong Basin (LMB) are significantly affected by the annual hydrological cycle. Monitoring of soil moisture as a key variable in the hydrological cycle is of great interest in a number of Hydrological and agricultural applications. In this study we evaluated the quality and spatiotemporal variability of the soil moisture product retrieved from C-band scatterometers data across the LMB sub-catchments. The soil moisture retrieval algorithm showed reasonable performance in most areas of the LMB with the exception of a few sub-catchments in the eastern parts of Laos, where the land cover is characterized by dense vegetation. The best performance of the retrieval algorithm was obtained in agricultural regions. Comparison of the available in situ evaporation data in the LMB and the Basin Water Index (BWI), an indicator of the basin soil moisture condition, showed significant negative correlations up to R = -0.85. The inter-annual variation of the calculated BWI was also found corresponding to the reported extreme hydro-meteorological events in the Mekong region. The retrieved soil moisture data show high correlation (up to R = 0.92) with monthly anomalies of precipitation in non-irrigated regions. In general, the seasonal variability of soil moisture in the LMB was well captured by the retrieval method. The results of analysis also showed significant correlation between El Ni{\~n}o events and the monthly BWI anomaly measurements particularly for the month May with the maximum correlation of R = 0.88.},
  language  = {en}
}
@article{BenzMerkelOffneretal.2013,
  author    = {Benz, Peter M. and Merkel, Carla J. and Offner, Kristin and Abeßer, Marco and Ullrich, Melanie and Fischer, Tobias and Bayer, Barbara and Wagner, Helga and Gambaryan, Stepan and Ursitti, Jeanine A. and Adham, Ibrahim M. and Linke, Wolfgang A. and Feller, Stephan M. and Fleming, Ingrid and Renn{\´e}, Thomas and Frantz, Stefan and Unger, Andreas and Schuh, Kai},
  title     = {Mena/VASP and alphaII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy},
  series = {Cell Communication and Signaling},
  volume    = {11},
  journal   = {Cell Communication and Signaling},
  number    = {56},
  doi       = {10.1186/1478-811X-11-56},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128760},
  year      = {2013},
  abstract  = {Background: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. Results: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Conclusions: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.},
  language  = {en}
}
@article{MorbachWagnerGuentneretal.2017,
  author    = {Morbach, Caroline and Wagner, Martin and G{\"u}ntner, Stefan and Malsch, Carolin and Oezkur, Mehmet and Wood, David and Kotseva, Kornelia and Leyh, Rainer and Ertl, Georg and Karmann, Wolfgang and Heuschmann, Peter U and St{\"o}rk, Stefan},
  title     = {Heart failure in patients with coronary heart disease: Prevalence, characteristics and guideline implementation - Results from the German EuroAspire IV cohort},
  series = {BMC Cardiovascular Disorders},
  volume    = {17},
  journal   = {BMC Cardiovascular Disorders},
  number    = {108},
  doi       = {10.1186/s12872-017-0543-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157738},
  year      = {2017},
  abstract  = {Background: Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation. Methods: Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40\%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered. Results: 509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9\%), stage B in n = 264 (51.9\%), and stage C in n = 225 (44.2\%) patients; 94/225 patients were diagnosed with HFrEF (42\%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19\%). Overall GAI-3 of HFrEF patients was 96.4\% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription. Conclusions: In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists. Trial registration: This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial.},
  language  = {en}
}
@article{DumontWeberLassalleJolyBeauparlantetal.2022,
  author    = {Dumont, Martine and Weber-Lassalle, Nana and Joly-Beauparlant, Charles and Ernst, Corinna and Droit, Arnaud and Feng, Bing-Jian and Dubois, St{\´e}phane and Collin-Deschesnes, Annie-Claude and Soucy, Penny and Vall{\´e}e, Maxime and Fournier, Fr{\´e}d{\´e}ric and Lema{\c{c}}on, Audrey and Adank, Muriel A. and Allen, Jamie and Altm{\"u}ller, Janine and Arnold, Norbert and Ausems, Margreet G. E. M. and Berutti, Riccardo and Bolla, Manjeet K. and Bull, Shelley and Carvalho, Sara and Cornelissen, Sten and Dufault, Michael R. and Dunning, Alison M. and Engel, Christoph and Gehrig, Andrea and Geurts-Giele, Willemina R. R. and Gieger, Christian and Green, Jessica and Hackmann, Karl and Helmy, Mohamed and Hentschel, Julia and Hogervorst, Frans B. L. and Hollestelle, Antoinette and Hooning, Maartje J. and Horv{\´a}th, Judit and Ikram, M. Arfan and Kaulfuß, Silke and Keeman, Renske and Kuang, Da and Luccarini, Craig and Maier, Wolfgang and Martens, John W. M. and Niederacher, Dieter and N{\"u}rnberg, Peter and Ott, Claus-Eric and Peters, Annette and Pharoah, Paul D. P. and Ramirez, Alfredo and Ramser, Juliane and Riedel-Heller, Steffi and Schmidt, Gunnar and Shah, Mitul and Scherer, Martin and St{\"a}bler, Antje and Strom, Tim M. and Sutter, Christian and Thiele, Holger and van Asperen, Christi J. and van der Kolk, Lizet and van der Luijt, Rob B. and Volk, Alexander E. and Wagner, Michael and Waisfisz, Quinten and Wang, Qin and Wang-Gohrke, Shan and Weber, Bernhard H. F. and Devilee, Peter and Tavtigian, Sean and Bader, Gary D. and Meindl, Alfons and Goldgar, David E. and Andrulis, Irene L. and Schmutzler, Rita K. and Easton, Douglas F. and Schmidt, Marjanka K. and Hahnen, Eric and Simard, Jacques},
  title     = {Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {14},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14143363},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281768},
  year      = {2022},
  abstract  = {Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.},
  language  = {en}
}
@article{YurdadoganMalschKotsevaetal.2021,
  author    = {Yurdadogan, Tino and Malsch, Carolin and Kotseva, Kornelia and Wood, David and Leyh, Rainer and Ertl, Georg and Karmann, Wolfgang and M{\"u}ller-Scholden, Lara and Morbach, Caroline and Breuning, Margret and Wagner, Martin and Gelbrich, G{\"o}tz and Bots, Michiel L. and Heuschmann, Peter U. and St{\"o}rk, Stefan},
  title     = {Functional versus morphological assessment of vascular age in patients with coronary heart disease},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-96998-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265810},
  year      = {2021},
  abstract  = {Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VA(PWVao) in 68\% of patients; for VA\(_{AIao}\) in 52\% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VA\(_{total-cIMT}\) accelerated vascular aging in 75\% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.},
  language  = {en}
}
@article{HollaenderSchwenderBoehmeetal.2021,
  author    = {Holl{\"a}nder, Olivia and Schwender, Kristina and B{\"o}hme, Petra and Fleckhaus, Jan and Haas, Cordula and Han, Yang and Heidorn, Frank and Klein-Unseld, Rachel and Lichtenwald, Julia and Naue, Jana and Neubauer, Jacqueline and Poetsch, Micaela and Schneider, Peter M. and Wagner, Wolfgang and Vennemann, Marielle},
  title     = {Forensische DNA-Methylierungsanalyse},
  series = {Rechtsmedizin},
  volume    = {31},
  journal   = {Rechtsmedizin},
  number    = {3},
  organization    = {Arbeitsgemeinschaft Molekulare Alterssch{\"a}tzung der Deutschen Gesellschaft f{\"u}r Rechtsmedizin (DGRM)},
  issn      = {0937-9819},
  doi       = {10.1007/s00194-021-00492-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307131},
  pages     = {192-201},
  year      = {2021},
  abstract  = {Die quantitative Analyse der relativen DNA-Methylierung gilt als eine der vielversprechendsten Methoden der molekularen Alterssch{\"a}tzung. Viele Studien der letzten Jahre identifizierten geeignete Positionen im Genom, deren DNA-Methylierung sich altersabh{\"a}ngig ver{\"a}ndert. F{\"u}r den Einsatz dieser Methode in der Routine- bzw. Fallarbeit ist es von großer Bedeutung, angewandte Analysetechniken zu validieren. Als ein Teilaspekt dieser Validierung sollte die Vergleichbarkeit der Analyseergebnisse zur DNA-Methylierung mithilfe der Mini- und Pyrosequenzierung zwischen verschiedenen Laboren evaluiert werden. Die Arbeitsgruppe „Molekulare Alterssch{\"a}tzung" der Deutschen Gesellschaft f{\"u}r Rechtsmedizin (DGRM) f{\"u}hrte hierzu den ersten, technischen Ringversuch durch, der 4 Positionen in den Genen PDE4C, EDARADD, SST und KLF14 umfasste. Diese Marker waren in vorangegangenen Studien als altersabh{\"a}ngige Biomarker charakterisiert worden. Am Ringversuch nahmen 12 Labore teil, wobei jedes die Wahl zwischen der Minisequenzierung und/oder der Pyrosequenzierung f{\"u}r die quantitative Methylierungsanalyse hatte. Jedem teilnehmenden Labor wurden Blut- und Speichelproben von 3 Personen unterschiedlichen Alters {\"u}bersandt. Die Wahl der Reagenzien f{\"u}r die Probenbearbeitung wurde den Teilnehmern freigestellt. Die Ergebnisse der Minisequenzierung zeigten systematische Abweichungen zwischen den Laboren, die am ehesten auf die Verwendung unterschiedlicher Reagenzien und Analyseplattformen zur{\"u}ckzuf{\"u}hren sein k{\"o}nnen. Die Resultate der Pyrosequenzierung hingegen wiesen nicht auf systematische Abweichungen zwischen den Laboren hin, hier zeigte sich jedoch die Tendenz einer markerabh{\"a}ngigen Abweichung. Dar{\"u}ber hinaus konnten Unterschiede hinsichtlich technischer Probleme zwischen Laboren mit mehr Erfahrung in der jeweiligen Sequenzierungsmethode und Laboren mit weniger Erfahrung festgestellt werden. Sowohl die Beobachtung von systematischen als auch die von markerabh{\"a}ngigen Abweichungen l{\"a}sst den Schluss zu, dass eine {\"U}bertragung von Analysemethoden zwischen Laboren grunds{\"a}tzlich m{\"o}glich ist, eine Anpassung des jeweiligen Modells zur Alterssch{\"a}tzung jedoch notwendig sein kann.},
  language  = {de}
}