@article{TianeSchepersRombautetal.2019, author = {Tiane, Assia and Schepers, Melissa and Rombaut, Ben and Hupperts, Raymond and Prickaerts, Jos and Hellings, Niels and van den Hove, Daniel and Vanmierlo, Tim}, title = {From OPC to oligodendrocyte: an epigenetic journey}, series = {Cells}, volume = {8}, journal = {Cells}, number = {10}, issn = {2073-4409}, doi = {10.3390/cells8101236}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193267}, year = {2019}, abstract = {Oligodendrocytes provide metabolic and functional support to neuronal cells, rendering them key players in the functioning of the central nervous system. Oligodendrocytes need to be newly formed from a pool of oligodendrocyte precursor cells (OPCs). The differentiation of OPCs into mature and myelinating cells is a multistep process, tightly controlled by spatiotemporal activation and repression of specific growth and transcription factors. While oligodendrocyte turnover is rather slow under physiological conditions, a disruption in this balanced differentiation process, for example in case of a differentiation block, could have devastating consequences during ageing and in pathological conditions, such as multiple sclerosis. Over the recent years, increasing evidence has shown that epigenetic mechanisms, such as DNA methylation, histone modifications, and microRNAs, are major contributors to OPC differentiation. In this review, we discuss how these epigenetic mechanisms orchestrate and influence oligodendrocyte maturation. These insights are a crucial starting point for studies that aim to identify the contribution of epigenetics in demyelinating diseases and may thus provide new therapeutic targets to induce myelin repair in the long run.}, language = {en} } @article{TiffeMorbachRueckeretal.2019, author = {Tiffe, Theresa and Morbach, Caroline and R{\"u}cker, Viktoria and Gelbrich, G{\"o}tz and Wagner, Martin and Faller, Hermann and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Impact of patient beliefs on blood pressure control in the general population: findings from the population-based STAAB cohort study}, series = {International Journal of Hypertension}, volume = {2019}, journal = {International Journal of Hypertension}, doi = {10.1155/2019/9385397}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200992}, pages = {9385397}, year = {2019}, abstract = {Background. Effective antihypertensive treatment depends on patient compliance regarding prescribed medications. We assessed the impact of beliefs related towards antihypertensive medication on blood pressure control in a population-based sample treated for hypertension. Methods. We used data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) study investigating 5000 inhabitants aged 30 to 79 years from the general population of W{\"u}rzburg, Germany. The Beliefs about Medicines Questionnaire German Version (BMQ-D) was provided in a subsample without established cardiovascular diseases (CVD) treated for hypertension. We evaluated the association between inadequately controlled hypertension (systolic RR >140/90 mmHg; >140/85 mmHg in diabetics) and reported concerns about and necessity of antihypertensive medication. Results. Data from 293 participants (49.5\% women, median age 64 years [quartiles 56.0; 69.0]) entered the analysis. Despite medication, half of the participants (49.8\%) were above the recommended blood pressure target. Stratified for sex, inadequately controlled hypertension was less frequent in women reporting higher levels of concerns (OR 0.36; 95\%CI 0.17-0.74), whereas no such association was apparent in men. We found no association for specific-necessity in any model. Conclusion. Beliefs regarding the necessity of prescribed medication did not affect hypertension control. An inverse association between concerns about medication and inappropriately controlled hypertension was found for women only. Our findings highlight that medication-related beliefs constitute a serious barrier of successful implementation of treatment guidelines and underline the role of educational interventions taking into account sex-related differences.}, language = {en} } @article{TiwarekarFehrholzSchneiderSchaulies2019, author = {Tiwarekar, Vishakha and Fehrholz, Markus and Schneider-Schaulies, J{\"u}rgen}, title = {KDELR2 competes with measles virus envelope proteins for cellular chaperones reducing their chaperone-mediated cell surface transport}, series = {Viruses}, volume = {11}, journal = {Viruses}, number = {1}, issn = {1999-4915}, doi = {10.3390/v11010027}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197468}, pages = {27}, year = {2019}, abstract = {Recently, we found that the cytidine deaminase APOBEC3G (A3G) inhibits measles (MV) replication. Using a microarray, we identified differential regulation of several host genes upon ectopic expression of A3G. One of the up-regulated genes, the endoplasmic reticulum (ER) protein retention receptor KDELR2, reduced MV replication ~5 fold when it was over-expressed individually in Vero and CEM-SS T cells. Silencing of KDELR2 in A3G-expressing Vero cells abrogated the antiviral activity induced by A3G, confirming its role as an A3G-regulated antiviral host factor. Recognition of the KDEL (Lys-Asp-Glu-Leu) motif by KDEL receptors initiates the retrograde transport of soluble proteins that have escaped the ER and play an important role in ER quality control. Although KDELR2 over-expression reduced MV titers in cell cultures, we observed no interaction between KDELR2 and the MV hemagglutinin (H) protein. Instead, KDELR2 retained chaperones in the ER, which are required for the correct folding and transport of the MV envelope glycoproteins H and fusion protein (F) to the cell surface. Our data indicate that KDELR2 competes with MV envelope proteins for binding to calnexin and GRP78/Bip, and that this interaction limits the availability of the chaperones for MV proteins, causing the reduction of virus spread and titers.}, language = {en} } @phdthesis{Tiwarekar2019, author = {Tiwarekar, Vishakha Rakesh}, title = {The APOBEC3G-regulated host factors REDD1 and KDELR2 restrict measles virus replication}, doi = {10.25972/OPUS-17952}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179526}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Measles is an extremely contagious vaccine-preventable disease responsible for more than 90000 deaths worldwide annually. The number of deaths has declined from 8 million in the pre-vaccination era to few thousands every year due to the highly efficacious vaccine. However, this effective vaccine is still unreachable in many developing countries due to lack of infrastructure, while in developed countries too many people refuse vaccination. Specific antiviral compounds are not yet available. In the current situation, only an extensive vaccination approach along with effective antivirals could help to have a measles-free future. To develop an effective antiviral, detailed knowledge of viral-host interaction is required. This study was undertaken to understand the interaction between MV and the innate host restriction factor APOBEC3G (A3G), which is well-known for its activity against human immunodeficiency virus (HIV). Restriction of MV replication was not attributed to the cytidine deaminase function of A3G, instead, we identified a novel role of A3G in regulating cellular gene functions. Among two of the A3G regulated host factors, we found that REDD1 reduced MV replication, whereas, KDELR2 hampered MV haemagglutinin (H) surface transport thereby affecting viral release. REDD1, a negative regulator of mTORC1 signalling impaired MV replication by inhibiting mTORC1. A3G regulated REDD1 expression was demonstrated to inversely correlate with MV replication. siRNA mediated silencing of A3G in primary human blood lymphocytes (PBL) reduced REDD1 levels and simultaneously increased MV titres. Also, direct depletion of REDD1 improved MV replication in PBL, indicating its role in A3G mediated restriction of MV. Based on these finding, a new role of rapamycin, a pharmacological inhibitor of mTORC1, was uncovered in successfully diminishing MV replication in Vero as well as in human PBL. The ER and Golgi resident receptor KDELR2 indirectly affected MV by competing with MV-H for cellular chaperones. Due to the sequestering of chaperones by KDELR2, they can no longer assist in MV-H folding and subsequent surface expression. Taken together, the two A3G-regulated host factors REDD1 and KDELR2 are mainly responsible for mediating its antiviral activity against MV.}, language = {en} } @phdthesis{Trabel2019, author = {Trabel, Mirko}, title = {Growth and Characterization of Epitaxial Manganese Silicide Thin Films}, doi = {10.25972/OPUS-18472}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184720}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {This thesis describes the growth and characterization of epitaxial MnSi thin films on Si substrates. The interest in this material system stems from the rich magnetic phase diagram resulting from the noncentrosymmetric B20 crystal structure. Here neighboring spins prefer a tilted relative arrangement in contrast to ferro- and antiferromagnets, which leads to a helical ground state where crystal and spin helix chirality are linked [IEM+85]. This link makes the characterization and control of the crystal chirality the main goal of this thesis. After a brief description of the material properties and applied methods, the thesis itself is divided into four main parts. In the first part the advancement of the MBE growth process of MnSi on Si\((111)\) substrate as well as the fundamental structural characterization are described. Here the improvement of the substrate interface by an adjusted substrate preparation process is demonstrated, which is the basis for well ordered flat MnSi layers. On this foundation the influence of Mn/Si flux ratio and substrate temperature on the MnSi layer growth is investigated via XRD and clear boundaries to identify the optimal growth conditions are determined. The nonstoichiometric phases outside of this optimal growth window are identified as HMS and Mn\(_5\)Si\(_3\). Additionally, a regime at high substrate temperatures and low Mn flux is discovered, where MnSi islands are growing incorporated in a Si layer, which could be interesting for further investigations as a size confinement can change the magnetic phase diagram [DBS+18]. XRD measurements demonstrate the homogeneity of the grown MnSi layers over most of the 3 inch wafer diameter and a small \(\omega\)-FWHM of about 0.02° demonstrates the high quality of the layers. XRD and TEM measurements also show that relaxation of the layers happens via misfit dislocations at the interface to the substrate. The second part of the thesis is concerned with the crystal chirality. Here azimuthal \(\phi\)-scans of asymmetric XRD reflections reveal twin domains with a \(\pm\)30° rotation to the substrate. These twin domains seem to consist of left and right-handed MnSi, which are connected by a mirror operation at the \((\bar{1}10)\) plane. For some of the asymmetric XRD reflections this results in different intensities for the different twin domains, which reveals that one of the domains is rotated +30° and the other is rotated -30°. From XRD and TEM measurements an equal volume fraction of both domains is deduced. Different mechanisms to suppress these twin domains are investigated and successfully achieved with the growth on chiral Si surfaces, namely Si\((321)\) and Si\((531)\). Azimuthal \(\phi\)-scans of asymmetric XRD reflections demonstrate a suppression of up to 92\%. The successful twin suppression is an important step in the use of MnSi for the proposed spintronics applications with skyrmions as information carriers, as discussed in the introduction. Because of this achievement, the third part of the thesis on the magnetic properties of the MnSi thin films is not only concerned with the principal behavior, but also with the difference between twinned and twin suppressed layers. Magnetometry measurements are used to demonstrate, that the MnSi layers behave principally as expected from the literature. The analysis of saturation and residual magnetization hints to the twin suppression on Si\((321)\) and Si\((531)\) substrates and further investigations with more samples can complete this picture. For comparable layers on Si\((111)\), Si\((321)\) and Si\((531)\) the Curie-Weiss temperature is identical within 1 K and the critical field within 0.1 T. Temperature dependent magnetoresistivity measurements also demonstrate the expected \(T^2\) behavior not only on Si\((111)\) but also on Si\((321)\) substrates. This demonstrates the successful growth of MnSi on Si\((321)\) and Si\((531)\) substrates. The latter measurements also reveal a residual resistivity of less then half for MnSi on Si\((321)\) in comparison to Si\((111)\). This can be explained with the reduced number of domain boundaries demonstrating the successful suppression of one of the twin domains. The homogeneity of the residual resistivity as well as the charge carrier density over a wide area of the Si\((111)\) wafer is also demonstrated with these measurements as well as Hall effect measurements. The fourth part shows the AMR and PHE of MnSi depending on the angle between in plane current and magnetic field direction with respect to the crystal direction. This was proposed as a tool to identify skyrmions [YKT+15]. The influence of the higher C\(_{3\mathrm{v}}\) symmetry of the twinned system instead of the C\(_3\) symmetry of a B20 single crystal is demonstrated. The difference could serve as a useful additional tool to prove the twin suppression on the chiral substrates. But this is only possible for rotations with specific symmetry surfaces and not for the studied unsymmetrical Si\((321)\) surface. Measurements for MnSi layers on Si\((111)\) above the critical magnetic field demonstrate the attenuation of AMR and PHE parameters for increasing resistivity, as expected from literature [WC67]. Even if a direct comparison to the parameters on Si\((321)\) is not possible, the higher values of the parameters on Si\((321)\) can be explained considering the reduced charge carrier scattering from domain boundaries. Below the critical magnetic field, which would be the region where a skyrmion lattice could be expected, magnetic hysteresis complicates the analysis. Only one phase transition at the critical magnetic field can be clearly observed, which leaves the existence of a skyrmion lattice in thin epitaxial MnSi layers open. The best method to solve this question seems to be a more direct approach in the form of Lorentz-TEM, which was also successfully used to visualize the skyrmion lattice for thin plates of bulk MnSi [TYY+12]. For the detection of in plane skyrmions, lamellas would have to be prepared for a side view, which seems in principle possible. The demonstrated successful twin suppression for MnSi on Si\((321)\) and Si\((531)\) substrates may also be applied to other material systems. Suppressing the twinning in FeGe on Si\((111)\) would lead to a single chirality skyrmion lattice near room temperature [HC12]. This could bring the application of skyrmions as information carriers in spintronics within reach. Glossary: MBE Molecular Beam Epitaxy XRD X-Ray Diffraction HMS Higher Manganese Silicide FWHM Full Width Half Maximum TEM Tunneling Electron Microscopy AMR Anisotropic MagnetoResistance PHE Planar Hall Effect Bibliography: [IEM+85] M. Ishida, Y. Endoh, S. Mitsuda, Y. Ishikawa, and M. Tanaka. Crystal Chirality and Helicity of the Helical Spin Density Wave in MnSi. II. Polarized Neutron Diffraction. Journal of the Physical Society of Japan, 54(8):2975, 1985. [DBS+18] B. Das, B. Balasubramanian, R. Skomski, P. Mukherjee, S. R. Valloppilly, G. C. Hadjipanayis, and D. J. Sellmyer. Effect of size confinement on skyrmionic properties of MnSi nanomagnets. Nanoscale, 10(20):9504, 2018. [YKT+15] T. Yokouchi, N. Kanazawa, A. Tsukazaki, Y. Kozuka, A. Kikkawa, Y. Taguchi, M. Kawasaki, M. Ichikawa, F. Kagawa, and Y. Tokura. Formation of In-plane Skyrmions in Epitaxial MnSi Thin Films as Revealed by Planar Hall Effect. Journal of the Physical Society of Japan, 84(10):104708, 2015. [WC67] R. H. Walden and R. F. Cotellessa. Magnetoresistance of Nickel-Copper Single-Crystal Thin Films. Journal of Applied Physics, 38(3):1335, 1967. [TYY+12] A. Tonomura, X. Yu, K. Yanagisawa, T. Matsuda, Y. Onose, N. Kanazawa, H. S. Park, and Y. Tokura. Real-Space Observation of Skyrmion Lattice in Helimagnet MnSi Thin Samples. Nano Letters, 12(3):1673, 2012. [HC12] S. X. Huang and C. L. Chien. Extended Skyrmion Phase in Epitaxial FeGe(111) Thin Films. Physical Review Letters, 108(26):267201, 2012.}, subject = {Molekularstrahlepitaxie}, language = {en} } @article{TrappeKneisel2019, author = {Trappe, Julian and Kneisel, Christof}, title = {Geophysical and sedimentological investigations of Peatlands for the assessment of lithology and subsurface water pathways}, series = {Geosciences}, volume = {9}, journal = {Geosciences}, number = {3}, doi = {10.3390/geosciences9030118}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201699}, pages = {118}, year = {2019}, abstract = {Peatlands located on slopes (herein called slope bogs) are typical landscape units in the Hunsrueck, a low mountain range in Southwestern Germany. The pathways of the water feeding the slope bogs have not yet been documented and analyzed. The identification of the different mechanisms allowing these peatlands to originate and survive requires a better understanding of the subsurface lithology and hydrogeology. Hence, we applied a multi-method approach to two case study sites in order to characterize the subsurface lithology and to image the variable spatio-temporal hydrological conditions. The combination of Electrical Resistivity Tomography (ERT) and an ERT-Monitoring and Ground Penetrating Radar (GPR), in conjunction with direct methods and data (borehole drilling and meteorological data), allowed us to gain deeper insights into the subsurface characteristics and dynamics of the peatlands and their catchment area. The precipitation influences the hydrology of the peatlands as well as the interflow in the subsurface. Especially, the geoelectrical monitoring data, in combination with the precipitation and temperature data, indicate that there are several forces driving the hydrology and hydrogeology of the peatlands. While the water content of the uppermost layers changes with the weather conditions, the bottom layer seems to be more stable and changes to a lesser extent. At the selected case study sites, small differences in subsurface properties can have a huge impact on the subsurface hydrogeology and the water paths. Based on the collected data, conceptual models have been deduced for the two case study sites.}, language = {en} } @article{TrautzFrankeBohnertetal.2019, author = {Trautz, Florian and Franke, Heike and Bohnert, Simone and Hammer, Niels and M{\"u}ller, Wolf and Stassart, Ruth and Tse, Rexson and Zwirner, Johann and Dreßler, Jan and Ondruschka, Benjamin}, title = {Survival-time dependent increase in neuronal IL-6 and astroglial GFAP expression in fatally injured human brain tissue}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-48145-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229037}, year = {2019}, abstract = {Knowledge on trauma survival time prior to death following a lethal traumatic brain injury (TBI) may be essential for legal purposes. Immunohistochemistry studies might allow to narrow down this survival interval. The biomarkers interleukin-6 (IL-6) and glial fibrillary acidic protein (GFAP) are well known in the clinical setting for their usability in TBI prediction. Here, both proteins were chosen in forensics to determine whether neuronal or glial expression in various brain regions may be associated with the cause of death and the survival time prior to death following TBI. IL-6 positive neurons, glial cells and GFAP positive astrocytes all concordantly increase with longer trauma survival time, with statistically significant changes being evident from three days post-TBI (p < 0.05) in the pericontusional zone, irrespective of its definite cortical localization. IL-6 staining in neurons increases significantly in the cerebellum after trauma, whereas increasing GFAP positivity is also detected in the cortex contralateral to the focal lesion. These systematic chronological changes in biomarkers of pericontusional neurons and glial cells allow for an estimation of trauma survival time. Higher numbers of IL-6 and GFAP-stained cells above threshold values in the pericontusional zone substantiate the existence of fatal traumatic changes in the brain with reasonable certainty.}, language = {en} } @article{TreffWinkertSarebanetal.2019, author = {Treff, Gunnar and Winkert, Kay and Sareban, Mahdi and Steinacker, J{\"u}rgen M. and Sperlich, Billy}, title = {The Polarization-Index: A Simple Calculation to Distinguish Polarized From Non-polarized Training Intensity Distributions}, series = {Frontiers in Physiology}, volume = {10}, journal = {Frontiers in Physiology}, doi = {10.3389/fphys.2019.00707}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229040}, year = {2019}, abstract = {The training intensity distribution (TID) of endurance athletes has retrieved substantial scientific interest since it reflects a vital component of training prescription: (i) the intensity of exercise and its distribution over time are essential components for adaptation to endurance training and (ii) the training volume (at least for most endurance disciplines) is already near or at maximum, so optimization of training procedures including TID have become paramount for success. This paper aims to elaborate the polarization-index (PI) which is calculated as log10(Zone 1/Zone 2∗Zone 3∗100), where Zones 1-3 refer to aggregated volume (time or distance) spent with low, mid, or high intensity training. PI allows to distinguish between non-polarized and polarized TID using a cut-off > 2.00 a.U. and to quantify the level of a polarized TID. Within this hypothesis paper, examples from the literature illustrating the usefulness of PI-calculation are discussed as well as its limitations. Further it is elucidated how the PI may contribute to a more precise definition of TID descriptors.}, language = {en} } @phdthesis{Tscharn2019, author = {Tscharn, Robert}, title = {Innovative And Age-Inclusive Interaction Design with Image-Schematic Metaphors}, doi = {10.25972/OPUS-17576}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175762}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {The field of human-computer interaction (HCI) strives for innovative user interfaces. Innovative and novel user interfaces are a challenge for a growing population of older users and endanger older adults to be excluded from an increasingly digital world. This is because older adults often have lower cognitive abilities and little prior experiences with technology. This thesis aims at resolving the tension between innovation and age-inclusiveness by developing user interfaces that can be used regardless of cognitive abilities and technology-dependent prior knowledge. The method of image-schematic metaphors holds promises for innovative and age-inclusive interaction design. Image-schematic metaphors represent a form of technology-independent prior knowledge. They reveal basic mental models and can be gathered in language (e.g. bank account is container from "I put money into my bank account"). Based on a discussion of previous applications of image-schematic metaphors in HCI, the present work derives three empirical research questions regarding image-schematic metaphors for innovative and age-inclusive interaction design. The first research question addresses the yet untested assumption that younger and older adults overlap in their technology-independent prior knowledge and, therefore, their usage of image-schematic metaphors. In study 1, a total of 41 participants described abstract concepts from the domains of online banking and everyday life. In study 2, ten contextual interviews were conducted. In both studies, younger and older adults showed a substantial overlap of 70\% to 75\%, indicating that also their mental models overlap substantially. The second research question addresses the applicability and potential of image-schematic metaphors for innovative design from the perspective of designers. In study 3, 18 student design teams completed an ideation process with either an affinity diagram as the industry standard, image-schematic metaphors or both methods in combination and created paper prototypes. The image-schematic metaphor method alone, but not the combination of both methods, was readily adopted and applied just as a well as the more familiar standard method. In study 4, professional interaction designers created prototypes either with or without image-schematic metaphors. In both studies, the method of image-schematic metaphors was perceived as applicable and creativity stimulating. The third research question addresses whether designs that explicitly follow image-schematic metaphors are more innovative and age-inclusive regarding differences in cognitive abilities and prior technological knowledge. In two experimental studies (study 5 and 6) involving a total of 54 younger and 53 older adults, prototypes that were designed with image-schematic metaphors were perceived as more innovative compared to those who were designed without image-schematic metaphors. Moreover, the impact of prior technological knowledge on interaction was reduced for prototypes that had been designed with image-schematic metaphors. However, participants' cognitive abilities and age still influenced the interaction significantly. The present work provides empirical as well as methodological findings that can help to promote the method of image-schematic metaphors in interaction design. As a result of these studies it can be concluded that the image-schematic metaphors are an applicable and effective method for innovative user interfaces that can be used regardless of prior technological knowledge.}, subject = {Mensch-Maschine-Kommunikation}, language = {en} } @phdthesis{TshitengeTshitenge2019, author = {Tshitenge Tshitenge, Dieudonn{\´e}}, title = {Isolation and Structural Elucidation of Novel Anti-Infective Naphthylisoquinoline Alkaloids from Ancistrocladus ealaensis, and Phytochemical Analysis of Two Congolese Medicinal Plants}, doi = {10.25972/OPUS-15417}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154175}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Herein described are the isolation, structural elucidation, and biological evaluation of highly thrilling monomeric and dimeric new naphthylisoquinoline alkaloids from A. ealaensis. The separation, chiral resolution, and characterization of a series of stereoisomeric 2,3-dihydrobenzofuran neolignans are also reported. The analytical and phytochemical analysis on two Congolese antimalarial herbal drugs is part of the last chapter of the results. In this last case, major concerns on widely used Congolese herbal drugs are discussed.}, subject = {Naphthylisochinolinalkaloide}, language = {en} }