@phdthesis{Laqua2024, author = {Laqua, Caroline}, title = {Association of myocardial tissue characteristics and functional outcome in biopsy-verified myocarditis assessed by cardiac magnetic resonance imaging}, doi = {10.25972/OPUS-36390}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363903}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {The relation between LV function and cardiac MRI tissue characteristics in separate myocardial segments and their change over time has yet to be explored in myocarditis. Thus, our research aimed to investigate possible associations between global and regional myocardial T1 and T2 times and peak strain in patients with suspected myocarditis. From 2012 to 2015, 129 patients with clinically suspected myocarditis of the prospective, observational MyoRacer-Trial underwent systematic biventricular EMB at baseline and cardiac MRI at baseline and after three months as a follow-up. We divided the LV myocardium into 17 segments and estimated the segmental myocardial strain using FT. We registered T1 and T2 maps to the cine sequences and transferred the segmentations used for FT to ensure conformity of the myocardial segments. Multi-level multivariable linear mixed effects regression was applied to investigate the relation of segmental myocardial strain to relaxation times and their respective change from baseline to follow-up. We found a significant improvement in myocardial peak strain from baseline to follow-up (p < 0.001; all p-values given for likelihood ratio tests) and significant associations between higher T1 and T2 times and lower segmental myocardial peak strain (p ranging from < 0.001 to 0.049). E.g., regression coefficient (Reg. coef.) for segmental radial peak strain in short axis view (SRPS_SAX) and T1 time: -1.9, 95\% CI (-2.6;-1.2) \%/100 ms, p < 0.001. A decrease in T1 and T2 times from baseline to follow-up was also significantly related to a recovery of segmental peak strains (p ranging from < 0.001 to 0.050). E.g., Reg. coef. for SRPS_SAX per ΔT1: -1.8, 95\% CI (-2.5;-1.0) \%/100 ms, p < 0.001. Moreover, the higher the baseline T1 time, the more substantial the functional recovery from baseline to follow-up (p ranging from 0.004 to 0.042, e.g., for SRPS_SAX: Reg. coef. 1.3, 95\% CI (0.4;2.1) \%/100 ms, p 0.004). We did not find an effect modification by the presence of myocarditis in the EMB (p > 0.1). Our cross-sectional and longitudinal analyses provide evidence of dose-dependent correlations between T1 and T2 relaxation times and myocardial peak strain in patients with clinical presentation of myocarditis, regardless of the EMB result. Thus, assessing strain values and mapping relaxation times helps estimate the functional prognosis in patients with clinically suspected myocarditis.}, subject = {Myokarditis}, language = {en} } @article{ŽutićMatosAbiagueScharfetal.2019, author = {Žutić, Igor and Matos-Abiague, Alex and Scharf, Benedikt and Dery, Hanan and Belashchenko, Kirill}, title = {Proximitized materials}, series = {Materials Today}, volume = {22}, journal = {Materials Today}, doi = {10.1016/j.mattod.2018.05.003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233972}, pages = {85-107}, year = {2019}, abstract = {Advances in scaling down heterostructures and having an improved interface quality together with atomically thin two-dimensional materials suggest a novel approach to systematically design materials. A given material can be transformed through proximity effects whereby it acquires properties of its neighbors, for example, becoming superconducting, magnetic, topologically nontrivial, or with an enhanced spin-orbit coupling. Such proximity effects not only complement the conventional methods of designing materials by doping or functionalization but also can overcome their various limitations. In proximitized materials, it is possible to realize properties that are not present in any constituent region of the considered heterostructure. While the focus is on magnetic and spin-orbit proximity effects with their applications in spintronics, the outlined principles also provide a broader framework for employing other proximity effects to tailor materials and realize novel phenomena.}, language = {en} } @article{BaluapuriHofstetterDudvarskiStankovicetal.2019, author = {Baluapuri, Apoorva and Hofstetter, Julia and Dudvarski Stankovic, Nevenka and Endres, Theresa and Bhandare, Pranjali and Vos, Seychelle Monique and Adhikari, Bikash and Schwarz, Jessica Denise and Narain, Ashwin and Vogt, Markus and Wang, Shuang-Yan and D{\"u}ster, Robert and Jung, Lisa Anna and Vanselow, Jens Thorsten and Wiegering, Armin and Geyer, Matthias and Maric, Hans Michael and Gallant, Peter and Walz, Susanne and Schlosser, Andreas and Cramer, Patrick and Eilers, Martin and Wolf, Elmar}, title = {MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation}, series = {Molecular Cell}, volume = {74}, journal = {Molecular Cell}, doi = {10.1016/j.molcel.2019.02.031}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221438}, pages = {674-687}, year = {2019}, abstract = {The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elongation factor DSIF. MYC directly binds SPT5, recruits SPT5 to promoters, and enables the CDK7-dependent transfer of SPT5 onto Pol II. Consistent with known functions of SPT5, MYC is required for fast and processive transcription elongation. Intriguingly, the high levels of MYC that are expressed in tumors sequester SPT5 into non-functional complexes, thereby decreasing the expression of growth-suppressive genes. Altogether, these results argue that MYC controls the productive assembly of processive Pol II elongation complexes and provide insight into how oncogenic levels of MYC permit uncontrolled cellular growth.}, language = {en} } @article{McCollGrollJungstetal.2018, author = {McColl, Erin and Groll, J{\"u}rgen and Jungst, Tomasz and Dalton, Paul D.}, title = {Design and fabrication of melt electrowritten tubes using intuitive software}, series = {Materials and Design}, volume = {155}, journal = {Materials and Design}, doi = {10.1016/j.matdes.2018.05.036}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223891}, pages = {46-58}, year = {2018}, abstract = {This study approaches the accurate continuous direct-writing onto a cylindrical collector from a mathematical perspective, taking into account the winding angle, cylinder diameter and length required for the final 3D printed tube. Using an additive manufacturing process termed melt electrowriting (MEW), porous tubes intended for tissue engineering applications are fabricated from medical-grade poly(ε-caprolactone) (PCL), validating the mathematically-derived method. For the fabricated tubes in this study, the pore size, winding angle and printed length can all be planned in advance and manufactured as designed. The physical dimensions of the tubes matched theoretical predictions and mechanical testing performed demonstrated that variations in the tubular morphology have a direct impact on their strength. MEWTubes, the web-based application developed and described here, is a particularly useful tool for planning the complex continuous direct writing path required for MEW onto a rotating, cylindrical build surface.}, language = {en} } @phdthesis{Bossert2024, author = {Bossert, Patrick}, title = {Statistical structure and inference methods for discrete high-frequency observations of SPDEs in one and multiple space dimensions}, doi = {10.25972/OPUS-36113}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361130}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {The focus of this thesis is on analysing a linear stochastic partial differential equation (SPDE) with a bounded domain. The first part of the thesis commences with an examination of a one-dimensional SPDE. In this context, we construct estimators for the parameters of a parabolic SPDE based on discrete observations of a solution in time and space on a bounded domain. We establish central limit theorems for a high-frequency asymptotic regime, showing substantially smaller asymptotic variances compared to existing estimation methods. Moreover, asymptotic confidence intervals are directly feasible. Our approach builds upon realized volatilities and their asymptotic illustration as the response of a log-linear model with a spatial explanatory variable. This yields efficient estimators based on realized volatilities with optimal rates of convergence and minimal variances. We demonstrate our results by Monte Carlo simulations. Extending this framework, we analyse a second-order SPDE model in multiple space dimensions in the second part of this thesis and develop estimators for the parameters of this model based on discrete observations in time and space on a bounded domain. While parameter estimation for one and two spatial dimensions was established in recent literature, this is the first work that generalizes the theory to a general, multi-dimensional framework. Our methodology enables the construction of an oracle estimator for volatility within the underlying model. For proving central limit theorems, we use a high-frequency observation scheme. To showcase our results, we conduct a Monte Carlo simulation, highlighting the advantages of our novel approach in a multi-dimensional context.}, subject = {Stochastische partielle Differentialgleichung}, language = {en} } @phdthesis{KuklovskyformerFinke2024, author = {Kuklovsky [former Finke], Valerie}, title = {Are some bees smarter than others? An examination of consistent individual differences in the cognitive abilities of honey bees}, doi = {10.25972/OPUS-32301}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323012}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Cognition refers to the ability to of animals to acquire, process, store and use vital information from the environment. Cognitive processes are necessary to predict the future and reduce the uncertainty of the ever-changing environment. Classically, research on animal cognition focuses on decisive cognitive tests to determine the capacity of a species by the testing the ability of a few individuals. This approach views variability between these tested key individuals as unwanted noise and is thus often neglected. However, inter-individual variability provides important insights to behavioral plasticity, cognitive specialization and brain modularity. Honey bees Apis mellifera are a robust and traditional model for the study of learning, memory and cognition due to their impressive capabilities and rich behavioral repertoire. In this thesis I have applied a novel view on the learning abilities of honey bees by looking explicitly at individual differences in a variety of learning tasks. Are some individual bees consistently smarter than some of her sisters? If so, will a smart individual always perform good independent of the time, the context and the cognitive requirements or do bees show distinct isolated 'cognitive modules'? My thesis presents the first comprehensive investigation of consistent individual differences in the cognitive abilities of honey bees. To speak of an individual as behaving consistently, a crucial step is to test the individual multiple times to examine the repeatability of a behavior. I show that free-flying bees remain consistent in a visual discrimination task for three consecutive days. Successively, I explored individual consistency in cognitive proficiency across tasks involving different sensory modalities, contexts and cognitive requirements. I found that free-flying bees show a cognitive specialization between visual and olfactory learning but remained consistent across a simple discrimination task and a complex concept learning task. I wished to further explore individual consistency with respect to tasks of different cognitive complexity, a question that has never been tackled before in an insect. I thus performed a series of four experiments using either visual or olfactory stimuli and a different training context (free-flying and restrained) and tested bees in a discrimination task, reversal learning and negative patterning. Intriguingly, across all these experiments I evidenced the same results: The bees' performances were consistent across the discrimination task and reversal learning and negative patterning respectively. No association was evidenced between reversal learning and negative patterning. After establishing the existence of consistent individual differences in the cognitive proficiency of honey bees I wished to determine factors which could underlie these differences. Since genetic components are known to underlie inter-individual variability in learning abilities, I studied the effects of genetics on consistency in cognitive proficiency by contrasting bees originating from either from a hive with a single patriline (low genetic diversity) or with multiple patrilines (high genetic diversity). These two groups of bees showed differences in the patterns of individually correlated performances, indicating a genetic component accounts for consistent cognitive individuality. Another major factor underlying variability in learning performances is the individual responsiveness to sucrose solution and to visual stimuli, as evidenced by many studies on restrained bees showing a positive correlation between responsiveness to task relevant stimuli and learning performances. I thus tested whether these relationships between sucrose/visual responsiveness and learning performances are applicable for free-flying bees. Free-flying bees were again subjected to reversal learning and negative patterning and subsequently tested in the laboratory for their responsiveness to sucrose and to light. There was no evidence of a positive relationship between sucrose/visual responsiveness and neither performances of free-flying bees in an elemental discrimination, reversal learning and negative patterning. These findings indicate that relationships established between responsiveness to task relevant stimuli and learning proficiency established in the laboratory with restrained bees might not hold true for a completely different behavioral context i.e. for free-flying bees in their natural environment. These results show that the honey bee is an excellent insect model to study consistency in cognitive proficiency and to identify the underlying factors. I mainly discuss the results with respect to the question of brain modularity in insects and the adaptive significance of individuality in cognitive abilities for honey bee colonies. I also provide a proposition of research questions which tie in this theme of consistent cognitive proficiency and could provide fruitful areas for future research.}, subject = {Lernen}, language = {en} } @phdthesis{Endres2024, author = {Endres, Erik}, title = {Kovalente Inhibitoren: Modellierung und Design}, doi = {10.25972/OPUS-35933}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359330}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Kovalente Inhibition stellt einen effektiven Weg dar, die Verweildauer des Liganden innerhalb einer Bindetasche zu erh{\"o}hen. In dieser Arbeit wurden theoretische Methoden angewendet, um die Reaktivit{\"a}t und den nichtkovalenten Zustand vor der Reaktion zu modellieren. Im Rahmen einer Fallstudie zu Cathepsin K wurden nichtkovalente Modelle von kovalenten Inhibitoren generiert. F{\"u}r verschiedene Komplexe aus Cathepsin K und einem kovalent gebundenem Liganden wurde der Zustand vor der Reaktion modelliert und dessen Stabilit{\"a}t im Rahmen einer klassischen MD-Simulation {\"u}berpr{\"u}ft. Die Stabilit{\"a}t des Warheads in der Bindetasche hing haupts{\"a}chlich vom gew{\"a}hlten Protonierungszustand der katalytischen Aminos{\"a}uren ab. F{\"u}r eine Reihe von Inhibitoren der ChlaDUB1 wurde ein Protokoll aus quantenmechanischen Rechnungen genutzt, um die Reaktivit{\"a}t verschiedener Warheads abzusch{\"a}tzen. Die erhaltenen Aktivierungsenergien korrelierten mit experimentell bestimmten Raten zur Inaktivierung des Enzyms. Im Rahmen eines Wirkstoffdesign-Projektes zur Deubiquitinase USP28 wurden von unpublizierten Kristallstrukturen ausgehend erste Docking-Experimente durchgef{\"u}hrt. Es konnte gezeigt werden, dass ein literaturbekannter Inhibitor von USP28 mit einem Warhead so modifiziert werden kann, dass die reaktive Einheit in direkter Nachbarschaft zu einem Cystein positioniert wird. F{\"u}r diese Warheads wurden ebenfalls quantenmechanische Rechnungen zur Bestimmung der Aktivierungsenergie durchgef{\"u}hrt. Um besser nachvollziehen zu k{\"o}nnen, warum bei einem Photoswitch-Inhibitor der Butyrylcholin-Esterase der cis-Zustand des Molek{\"u}ls besser inhibiert als der trans-Zustand, wurde eine Docking-Studie des Zustandes vor der Reaktion durchgef{\"u}hrt. Es konnte ein qualitatives Modell aufgestellt werden, das zeigt, dass der trans-Zustand aufgrund seiner l{\"a}ngeren Form mit wichtigen Aminos{\"a}uren am Eingang der Bindungstasche kollidiert.}, subject = {Molekulardynamik}, language = {de} } @article{OPUS4-37080, title = {Interview mit Prof. Dr. Marina Ortrud Hertrampf}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {9}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, editor = {Hesselbach, Robert}, issn = {2510-2613}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370808}, pages = {7-13}, year = {2023}, abstract = {Interview mit Prof. Dr. Marina Ortrud Hertrampf}, language = {de} } @article{ColungaHayworthKressetal.2019, author = {Colunga, Thomas and Hayworth, Miranda and Kreß, Sebastian and Reynolds, David M. and Chen, Luoman and Nazor, Kristopher L. and Baur, Johannes and Singh, Amar M. and Loring, Jeanne F. and Metzger, Marco and Dalton, Stephen}, title = {Human Pluripotent Stem Cell-Derived Multipotent Vascular Progenitors of the Mesothelium Lineage Have Utility in Tissue Engineering and Repair}, series = {Cell Reports}, volume = {26}, journal = {Cell Reports}, doi = {10.1016/j.celrep.2019.02.016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223217}, pages = {2566-2579}, year = {2019}, abstract = {In this report we describe a human pluripotent stem cell-derived vascular progenitor (MesoT) cell of the mesothelium lineage. MesoT cells are multipotent and generate smooth muscle cells, endothelial cells, and pericytes and self-assemble into vessel-like networks in vitro. MesoT cells transplanted into mechanically damaged neonatal mouse heart migrate into the injured tissue and contribute to nascent coronary vessels in the repair zone. When seeded onto decellularized vascular scaffolds, MesoT cells differentiate into the major vascular lineages and self-assemble into vasculature capable of supporting peripheral blood flow following transplantation. These findings demonstrate in vivo functionality and the potential utility of MesoT cells in vascular engineering applications.}, language = {en} } @article{BecherAndresPonsRomanovetal.2018, author = {Becher, Isabelle and Andr{\´e}s-Pons, Amparo and Romanov, Natalie and Stein, Frank and Schramm, Maike and Baudin, Florence and Helm, Dominic and Kurzawa, Nils and Mateus, Andr{\´e} and Mackmull, Marie-Therese and Typas, Athanasios and M{\"u}ller, Christoph W. and Bork, Peer and Beck, Martin and Savitski, Mikhail M.}, title = {Pervasive Protein Thermal Stability Variation during the Cell Cycle}, series = {Cell}, volume = {173}, journal = {Cell}, doi = {10.1016/j.cell.2018.03.053}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221565}, pages = {1495-1507}, year = {2018}, abstract = {Quantitative mass spectrometry has established proteome-wide regulation of protein abundance and post-translational modifications in various biological processes. Here, we used quantitative mass spectrometry to systematically analyze the thermal stability and solubility of proteins on a proteome-wide scale during the eukaryotic cell cycle. We demonstrate pervasive variation of these biophysical parameters with most changes occurring in mitosis and G1. Various cellular pathways and components vary in thermal stability, such as cell-cycle factors, polymerases, and chromatin remodelers. We demonstrate that protein thermal stability serves as a proxy for enzyme activity, DNA binding, and complex formation in situ. Strikingly, a large cohort of intrinsically disordered and mitotically phosphorylated proteins is stabilized and solubilized in mitosis, suggesting a fundamental remodeling of the biophysical environment of the mitotic cell. Our data represent a rich resource for cell, structural, and systems biologists interested in proteome regulation during biological transitions.}, language = {en} }