@article{GottschollWagenhoeferKlimmeretal.2022, author = {Gottscholl, Andreas and Wagenh{\"o}fer, Maximilian and Klimmer, Manuel and Scherbel, Selina and Kasper, Christian and Baianov, Valentin and Astakhov, Georgy V. and Dyakonov, Vladimir and Sperlich, Andreas}, title = {Superradiance of spin defects in silicon carbide for maser applications}, series = {Frontiers in Photonics}, volume = {3}, journal = {Frontiers in Photonics}, issn = {2673-6853}, doi = {10.3389/fphot.2022.886354}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284698}, year = {2022}, abstract = {Masers as telecommunication amplifiers have been known for decades, yet their application is strongly limited due to extreme operating conditions requiring vacuum techniques and cryogenic temperatures. Recently, a new generation of masers has been invented based on optically pumped spin states in pentacene and diamond. In this study, we pave the way for masers based on spin S = 3/2 silicon vacancy (V\(_{Si}\)) defects in silicon carbide (SiC) to overcome the microwave generation threshold and discuss the advantages of this highly developed spin hosting material. To achieve population inversion, we optically pump the V\(_{Si}\) into their m\(_S\) = ±1/2 spin sub-states and additionally tune the Zeeman energy splitting by applying an external magnetic field. In this way, the prerequisites for stimulated emission by means of resonant microwaves in the 10 GHz range are fulfilled. On the way to realising a maser, we were able to systematically solve a series of subtasks that improved the underlying relevant physical parameters of the SiC samples. Among others, we investigated the pump efficiency as a function of the optical excitation wavelength and the angle between the magnetic field and the defect symmetry axis in order to boost the population inversion factor, a key figure of merit for the targeted microwave oscillator. Furthermore, we developed a high-Q sapphire microwave resonator (Q ≈ 10\(^4\)-10\(^5\)) with which we find superradiant stimulated microwave emission. In summary, SiC with optimized spin defect density and thus spin relaxation rates is well on its way of becoming a suitable maser gain material with wide-ranging applications.}, language = {en} } @article{LodhaErhardDoelkenetal.2022, author = {Lodha, Manivel and Erhard, Florian and D{\"o}lken, Lars and Prusty, Bhupesh K.}, title = {The hidden enemy within: non-canonical peptides in virus-induced autoimmunity}, series = {Frontiers in Microbiology}, volume = {13}, journal = {Frontiers in Microbiology}, issn = {1664-302X}, doi = {10.3389/fmicb.2022.840911}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-263053}, year = {2022}, abstract = {Viruses play a key role in explaining the pathogenesis of various autoimmune disorders, whose underlying principle is defined by the activation of autoreactive T-cells. In many cases, T-cells escape self-tolerance due to the failure in encountering certain MHC-I self-peptide complexes at substantial levels, whose peptides remain invisible from the immune system. Over the years, contribution of unstable defective ribosomal products (DRiPs) in immunosurveillance has gained prominence. A class of unstable products emerge from non-canonical translation and processing of unannotated mammalian and viral ORFs and their peptides are cryptic in nature. Indeed, high throughput sequencing and proteomics have revealed that a substantial portion of our genomes comprise of non-canonical ORFs, whose generation is significantly modulated during disease. Many of these ORFs comprise short ORFs (sORFs) and upstream ORFs (uORFs) that resemble DRiPs and may hence be preferentially presented. Here, we discuss how such products, normally "hidden" from the immune system, become abundant in viral infections activating autoimmune T-cells, by discussing their emerging role in infection and disease. Finally, we provide a perspective on how these mechanisms can explain several autoimmune disorders in the wake of the COVID-19 pandemic.}, language = {en} } @article{SperlichAuthDyakonov2022, author = {Sperlich, Andreas and Auth, Michael and Dyakonov, Vladimir}, title = {Charge transfer in ternary solar cells employing two fullerene derivatives: where do electrons go?}, series = {Israel Journal of Chemistry}, volume = {62}, journal = {Israel Journal of Chemistry}, number = {7-8}, doi = {10.1002/ijch.202100064}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257506}, year = {2022}, abstract = {Earlier reports demonstrated that ternary organic solar cells (OSC) made of donor polymers (D) blended with different mixtures of fullerene acceptors (A : A) performed very similarly. This finding is surprising, as the corresponding fullerene LUMO levels are slightly different, which might result in decisive differences in the charge transfer step. We investigate ternary OSC (D : A : A) made of the donor polymer P3HT with stoichiometric mixtures of different fullerene derivatives, PC\(_{60}\)BM : PC\(_{70}\)BM and PC\(_{70}\)BM : IC\(_{60}\)BA, respectively. Using quantitative electron paramagnetic resonance (EPR) we can distinguish between positive and negative polarons, localized on the specific molecules. We found that after the initial charge transfer step, the electrons are re-distributed over two nearby acceptors in agreement with their stoichiometry and their relative LUMO energy difference. Remarkably, the measured ΔLUMO differences in fullerene mixtures are reduced by an order of magnitude compared to that of the pristine materials, i. e., below 1 meV for PC\(_{60}\)BM : PC\(_{70}\)BM and (20±5) meV for PC\(_{70}\)BM : IC\(_{60}\)BA. Furthermore, we found that this reduced ΔLUMO explains the shift in open circuit voltage for D : A : A organic solar cells. We attribute these findings to hybridization, leading to an effective fullerene LUMO. Consequently, multi-acceptor blends are indeed a viable option for photodetectors and solar cells, as they combine the best electron acceptor and light absorbing properties.}, language = {en} } @article{PozziPalmisanoReichetal.2022, author = {Pozzi, Nicol{\´o} G. and Palmisano, Chiara and Reich, Martin M. and Capetian, Philip and Pacchetti, Claudio and Volkmann, Jens and Isaias, Ioannis U.}, title = {Troubleshooting gait disturbances in Parkinson's disease with deep brain stimulation}, series = {Frontiers in Human Neuroscience}, volume = {16}, journal = {Frontiers in Human Neuroscience}, issn = {1662-5161}, doi = {10.3389/fnhum.2022.806513}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-274007}, year = {2022}, abstract = {Deep brain stimulation (DBS) of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson's disease (PD) that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD encompass a variety of clinical manifestations and rely on different pathophysiological bases. While gait disturbances arising years after DBS surgery can be related to disease progression, early impairment of gait may be secondary to treatable causes and benefits from DBS reprogramming. In this review, we tackle the issue of gait disturbances in PD patients with DBS by discussing their neurophysiological basis, providing a detailed clinical characterization, and proposing a pragmatic programming approach to support their management.}, language = {en} } @article{SchickSchlegel2022, author = {Schick, Martin Alexander and Schlegel, Nicolas}, title = {Clinical implication of phosphodiesterase-4-inhibition}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {3}, issn = {1422-0067}, doi = {10.3390/ijms23031209}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284511}, year = {2022}, abstract = {The pleiotropic function of 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent pathways in health and disease led to the development of pharmacological phosphodiesterase inhibitors (PDE-I) to attenuate cAMP degradation. While there are many isotypes of PDE, a predominant role of PDE4 is to regulate fundamental functions, including endothelial and epithelial barrier stability, modulation of inflammatory responses and cognitive and/or mood functions. This makes the use of PDE4-I an interesting tool for various therapeutic approaches. However, due to the presence of PDE4 in many tissues, there is a significant danger for serious side effects. Based on this, the aim of this review is to provide a comprehensive overview of the approaches and effects of PDE4-I for different therapeutic applications. In summary, despite many obstacles to use of PDE4-I for different therapeutic approaches, the current data warrant future research to utilize the therapeutic potential of phosphodiesterase 4 inhibition.}, language = {en} } @article{MihatschBeissertPomperetal.2022, author = {Mihatsch, Patrick W. and Beissert, Matthias and Pomper, Martin G. and Bley, Thorsten A. and Seitz, Anna K. and K{\"u}bler, Hubert and Buck, Andreas K. and Rowe, Steven P. and Serfling, Sebastian E. and Hartrampf, Philipp E. and Werner, Rudolf A.}, title = {Changing threshold-based segmentation has no relevant impact on semi-quantification in the context of structured reporting for PSMA-PET/CT}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {2}, issn = {2072-6694}, doi = {10.3390/cancers14020270}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254782}, year = {2022}, abstract = {Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with \(^{18}\)F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUV\(_{max}\), SUV\(_{peak}\), SUV\(_{mean}\)) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50\%). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUV\(_{max}\) and SUV\(_{peak}\) compared to the entire PSMA-RADS-4 or -5 cohort (p < 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p < 0.0001), but not to the PSMA-RADS-4 cohort (SUV\(_{max}\), p = 0.07; SUV\(_{peak}\), p = 0.08). SUV\(_{mean}\) (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50\% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in \(^{18}\)F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUV\(_{mean}\) and TL-PSMA in contrast to PSMA-TV.}, language = {en} } @article{HankirBruneauJr2022, author = {Hankir, Mohammed Khair and Bruneau Jr., Michael}, title = {Periphery-brain interactions and leptin in the regulation of whole-body energy metabolism}, series = {Nutrients}, volume = {14}, journal = {Nutrients}, number = {8}, issn = {2072-6643}, doi = {10.3390/nu14081594}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270581}, year = {2022}, abstract = {No abstract available}, language = {en} } @phdthesis{Hofstetter2022, author = {Hofstetter, Julia Eva Ines}, title = {MYC shapes the composition of RNA polymerase II through direct recruitment of transcription elongation factors}, doi = {10.25972/OPUS-24035}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240358}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {The transcription factor MYC is a onco-protein, found to be deregulated in many human cancers. High MYC levels correlate with an aggressive tumor outcome and poor survival rates. Despite MYC being discovered as an oncogene already in the 1970s, how MYC regulates transcription of its target genes, which are involved in cellular growth and proliferation, is not fully understood yet. In this study, the question how MYC influences factors interacting with the RNA polymerase II ensuring productive transcription of its target genes was addressed using quantitative mass spectrometry. By comparing the interactome of RNA polymerase II under varying MYC levels, several potential factors involved in transcriptional elongation were identified. Furthermore, the question which of those factors interact with MYC was answered by employing quantitative mass spectrometry of MYC itself. Thereby, the direct interaction of MYC with the transcription elongation factor SPT5, a subunit of the DRB-sensitivity inducing factor, was discovered and analyzed in greater detail. SPT5 was shown to be recruited to chromatin by MYC. In addition, the interaction site of MYC on SPT5 was narrowed down to its evolutionary conserved NGN-domain, which is the known binding site for SPT4, the earlier characterized second subunit of the DRB-sensitivity inducing factor. This finding suggests a model in which MYC and SPT4 compete for binding the NGN-domain of SPT5. Investigations of the SPT5-interacting region on MYC showed binding of SPT5 to MYC's N-terminus including MYC-boxes 0, I and II. In order to analyze proteins interacting specifically with the N-terminal region of MYC, a truncated MYC-mutant was used for quantitative mass spectrometric analysis uncovering reduced binding for several proteins including the well-known interactor TRRAP and TRRAP-associated complexes. Summarized, ...}, subject = {Transkription }, language = {en} } @phdthesis{Vardapour2022, author = {Vardapour, Romina}, title = {Mutations in the DROSHA/DGCR8 microprocessor complex in high-risk blastemal Wilms tumor}, doi = {10.25972/OPUS-23140}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231404}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Wilms tumor (WT) or nephroblastoma is the most common kidney tumor in childhood. Several genetic alterations have been identified in WT over the past years. However, a clear-cut underlying genetic defect has remained elusive. Growing evidence suggests that miRNA processing genes play a major role in the formation of pediatric tumors, including WT. We and others have identified the microprocessor genes DROSHA and DGCR8 as key players in Wilms tumorigenesis. Exome sequence analysis of a cohort of blastemal-type WTs revealed the recurrent hotspot mutations DROSHA E1147K and DGCR8 E518K mapping to regions important for catalyic activity and RNA-binding. These alterations were expected to affect processing of miRNA precursors, ultimately leading to altered miRNA expression. Indeed, mutated tumor samples were characterized by distinct miRNA patterns. Notably, these mutations have been observed almost exclusively in WT, suggesting that they play a specific role in WT formation. The aim of the present work was to first examine the mutation frequency of DROSHA E1147K and DGCR8 E518K in a larger cohort of WTs, and to further characterize these microprocessor gene mutations as potential oncogenic drivers for WT formation. Screening of additional 700 WT samples by allele-specific PCR revealed a high frequency of DROSHA E1147K and DGCR8 E518K mutations, with the highest incidence found in tumors of high-risk histology. DROSHA E1147K was heterozygously expressed in all cases, which strongly implies a dominant negative effect. In contrast, DGCR8 E518K exclusively exhibited homozygous expression, suggestive for the mutation to act recessive. To functionally assess the mutations of the microprocessor complex in vitro, I generated stable HEK293T cell lines with inducible overexpression of DROSHA E1147K, and stable mouse embryonic stem cell (mESC) lines with inducible overexpression of DGCR8 E518K. To mimic the homozygous expression observed in WT, DGCR8 mESC lines were generated on a DGCR8 knockout background. Inducible overexpression of wild-type or mutant DROSHA in HEK293T cells showed that DROSHA E1147K leads to a global downregulation of miRNA expression. It has previously been shown that the knockout of DGCR8 in mESCs also results in a significant downregulation of canonical miRNAs. Inducible overexpression of wild type DGCR8 rescued this processing defect. DGCR8 E518K on the other hand, only led to a partial rescue. Differentially expressed miRNAs comprised members of the ESC cell cycle (ESCC) and let-7 miRNA families whose antagonism is known to play a pivotal role in the regulation of stem cell properties. Along with altered miRNA expression, DGCR8-E518K mESCs exhibited alterations in target gene expression potentially affecting various biological processes. We could observe decreased proliferation rates, most likely due to reduced cell viability. DGCR8-E518K seemed to be able to overcome the block of G1-S transition and to rescue the cell cycle defect in DGCR8-KO mESCs, albeit not to the full extent like DGCR8-wild-type. Moreover, DGCR8-E518K appeared to be unable to completely block epithelial-to-mesenchymal transition (EMT). Embryoid bodies (EBs) with the E518K mutation, however, were still able to silence the self-renewal program rescuing the differentiation defect in DGCR8-KO mESCs. Taken together, I could show that DROSHA E1147K and DGCR8 E518K are frequent events in WT with the highest incidence in high-risk tumor entities. Either mutation led to altered miRNA expression in vitro confirming our previous findings in tumor samples. While the DROSHA E1147K mutation resulted in a global downregulation of canonical miRNAs, DGCR8 E518K was able to retain significant activity of the microprocessor complex, suggesting that partial reduction of activity or altered specificity may be critical in Wilms tumorigenesis. Despite the significant differences found in the miRNA and mRNA profiles of DGCR8 E518K and DGCR8-wild-type mESCs, functional analysis showed that DGCR8 E518K could mostly restore important cellular functions in the knockout and only slightly differed from the wild-type situation. Further studies in a rather physiological environment, such as in a WT blastemal model system, may additionally help to better assess the subtle differences between DGCR8 E518K and DGCR8 wild-type observed in our mESC lines. Together with our findings, these model systems may thus contribute to better understand the role of these microprocessor mutations in the formation of WT.}, subject = {Nephroblastom}, language = {en} } @phdthesis{Berger2022, author = {Berger, Sarina Maria}, title = {Influence of Charge and Its Distribution on Biological Applications of Bis-Triarylboranes and Preliminary Investigations on H\(_2\)O\(_2\)-Cleavable Aryl Boronate Esters}, doi = {10.25972/OPUS-24314}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243147}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {This dissertation describes the synthesis of an unsymmetrically-substituted triarylborane. This term describes a three-coordinate boron atom that is bound to three different aromatic systems, namely 2,6-dimethylphenyl, mesityl, and 4-(N,N-dimethylamino)-2,6-dimethylphenyl. It is also demonstrated that the amine functionality can be converted with methyl triflate into an ammonium moiety. The investigation of photophysical and electrochemical properties of this compound in comparison with the non-aminated and di-aminated analogues of the triarylborane is described besides other investigations of e. g. singlet oxygen sensitization, rotational barriers, and fundamental DFT calculations. Based on these investigations, selectively mono-, bis- and tris-dimethylamino- and trimethylammonium-substituted bis-triarylborane bithiophene chromophores were synthesized and their photophysical, and electrochemical properties were investigated together with the water solubility and singlet oxygen sensitizing efficiency of the cationic compounds Cat1+, Cat2+, Cat(i)2+, and Cat3+. Comparing these properties with the results obtained for the mono-triarylboranes reveals a large influence of the bridging unit on the investigated properties of the bis-triarylboranes. In addition, the interaction of the cationic bis-triarylboranes with different polynucleotides were investigated in buffered solutions as well as the ability of these selectively charged compounds to enter and localize within organelles of human lung carcinoma and normal lung cells. All these investigations demonstrate that the number of charges and their distribution influences the interactions and staining properties as well as most of the other properties investigated. In addition, preliminary investigations on H2O2-cleavable boronate esters in the presence of stochiometric amounts of H2O2 are described for three different aryl boronate esters.}, subject = {Triarylborane}, language = {en} } @phdthesis{Youssef2022, author = {Youssef, Almoatazbellah}, title = {Fabrication of Micro-Engineered Scaffolds for Biomedical Application}, doi = {10.25972/OPUS-23545}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235457}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Thermoplastic polymers have a history of decades of safe and effective use in the clinic as implantable medical devices. In recent years additive manufacturing (AM) saw increased clinical interest for the fabrication of customizable and implantable medical devices and training models using the patients' own radiological data. However, approval from the various regulatory bodies remains a significant hurdle. A possible solution is to fabricate the AM scaffolds using materials and techniques with a clinical safety record, e.g. melt processing of polymers. Melt Electrowriting (MEW) is a novel, high resolution AM technique which uses thermoplastic polymers. MEW produces scaffolds with microscale fibers and precise fiber placement, allowing the control of the scaffold microarchitecture. Additionally, MEW can process medical-grade thermoplastic polymers, without the use of solvents paving the way for the production of medical devices for clinical applications. This pathway is investigated in this thesis, where the layout is designed to resemble the journey of a medical device produced via MEW from conception to early in vivo experiments. To do so, first, a brief history of the development of medical implants and the regenerative capability of the human body is given in Chapter 1. In Chapter 2, a review of the use of thermoplastic polymers in medicine, with a focus on poly(ε-caprolactone) (PCL), is illustrated, as this is the polymer used in the rest of the thesis. This review is followed by a comparison of the state of the art, regarding in vivo and clinical experiments, of three polymer melt AM technologies: melt-extrusion, selective laser sintering and MEW. The first two techniques already saw successful translation to the bedside, producing patient-specific, regulatory-approved AM implants. To follow in the footsteps of these two technologies, the MEW device parameters need to be optimized. The MEW process parameters and their interplay are further discussed in Chapter 3 focusing on the importance of a steady mass flow rate of the polymer during printing. MEW reaches a balance between polymer flow, the stabilizing electric field and moving collector to produce reproducible, high-resolution scaffolds. An imbalance creates phenomena like fiber pulsing or arcing which result in defective scaffolds and potential printer damage. Chapter 4 shows the use of X-ray microtomography (µCT) as a non-destructive method to characterize the pore-related features: total porosity and the pore size distribution. MEW scaffolds are three-dimensional (3D) constructs but have long been treated in the literature as two-dimensional (2D) ones and characterized mainly by microscopy, including stereo- and scanning electron microscopy, where pore size was simply reported as the distance between the fibers in a single layer. These methods, together with the trend of producing scaffolds with symmetrical pores in the 0/90° and 0/60/120° laydown patterns, disregarded the lateral connections between pores and the potential of MEW to be used for more complex 3D structures, mimicking the extracellular matrix. Here we characterized scaffolds in the aforementioned symmetrical laydown patterns, along with the more complex 0/45/90/135° and 0/30/60/90/120/150° ones. A 2D pore size estimation was done first using stereomicroscopy, followed by and compared to µCT scanning. The scaffolds with symmetrical laydown patterns resulted in the predominance of one pore size, while those with more complex patterns had a broader distribution, which could be better shown by µCT scans. Moreover, in the symmetrical scaffolds, the size of 3D pores was not able to reach the value of the fiber spacing due to a flattening effect of the scaffold, where the thickness of the scaffold was less than the fiber spacing, further restricting the pore size distribution in such scaffolds. This method could be used for quality assurance of fabricated scaffolds prior to use in in vitro or in vivo experiments and would be important for a clinical translation. Chapter 5 illustrates a proof of principle subcutaneous implantation in vivo experiment. MEW scaffolds were already featured in small animal in vivo experiments, but to date, no analysis of the foreign body reaction (FBR) to such implants was performed. FBR is an immune reaction to implanted foreign materials, including medical devices, aimed at protecting the host from potential adverse effects and can interfere with the function of some medical implants. Medical-grade PCL was used to melt electrowrite scaffolds with 50 and 60 µm fiber spacing for the 0/90° and 0/60/120° laydown patterns, respectively. These implants were implanted subcutaneously in immunocompetent, outbred mice, with appropriate controls, and explanted after 2, 4, 7 and 14 days. A thorough characterization of the scaffolds before implantation was done, followed by a full histopathological analysis of the FBR to the implants after excision. The scaffolds, irrespective of their pore geometry, induced an extensive FBR in the form of accumulation of foreign body giant cells around the fiber walls, in a manner that almost occluded available pore spaces with little to no neovascularization. This reaction was not induced by the material itself, as the same reaction failed to develop in the PCL solid film controls. A discussion of the results was given with special regard to the literature available on flat surgical meshes, as well as other hydrogel-based porous scaffolds with similar pore sizes. Finally, a general summary of the thesis in Chapter 6 recapitulates the most important points with a focus on future directions for MEW.}, language = {en} } @phdthesis{Schmeller2022, author = {Schmeller, Christof}, title = {Uniform distribution of zero ordinates of Epstein zeta-functions}, doi = {10.25972/OPUS-25199}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251999}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {The dissertation investigates the wide class of Epstein zeta-functions in terms of uniform distribution modulo one of the ordinates of their nontrivial zeros. Main results are a proof of a Landau type theorem for all Epstein zeta-functions as well as uniform distribution modulo one for the zero ordinates of all Epstein zeta-functions asscoiated with binary quadratic forms.}, subject = {Zetafunktion}, language = {en} } @techreport{LhamoNguyenFitzek2022, type = {Working Paper}, author = {Lhamo, Osel and Nguyen, Giang T. and Fitzek, Frank H. P.}, title = {Virtual Queues for QoS Compliance of Haptic Data Streams in Teleoperation}, series = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, journal = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, doi = {10.25972/OPUS-28076}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280762}, pages = {4}, year = {2022}, abstract = {Tactile Internet aims at allowing perceived real-time interactions between humans and machines. This requires satisfying a stringent latency requirement of haptic data streams whose data rates vary drastically as the results of perceptual codecs. This introduces a complex problem for the underlying network infrastructure to fulfill the pre-defined level of Quality of Service (QoS). However, novel networking hardware with data plane programming capability allows processing packets differently and opens up a new opportunity. For example, a dynamic and network-aware resource management strategy can help satisfy the QoS requirements of different priority flows without wasting precious bandwidth. This paper introduces virtual queues for service differentiation between different types of traffic streams, leveraging protocol independent switch architecture (PISA). We propose coordinating the management of all the queues and dynamically adapting their sizes to minimize packet loss and delay due to network congestion and ensure QoS compliance.}, subject = {Datennetz}, language = {en} } @article{HartrampfKrebsPeteretal.2022, author = {Hartrampf, Philipp E. and Krebs, Markus and Peter, Lea and Heinrich, Marieke and Ruffing, Julia and Kalogirou, Charis and Weinke, Maximilian and Brumberg, Joachim and K{\"u}bler, Hubert and Buck, Andreas K. and Werner, Rudolf A. and Seitz, Anna Katharina}, title = {Reduced segmentation of lesions is comparable to whole-body segmentation for response assessment by PSMA PET/CT: initial experience with the keyhole approach}, series = {Biology}, volume = {11}, journal = {Biology}, number = {5}, issn = {2079-7737}, doi = {10.3390/biology11050660}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271191}, year = {2022}, abstract = {Simple Summary The calculation of PSMA-positive tumor volume (PSMA-TV) of the whole body from PSMA PET scans for response evaluation remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative tumor lesions. Changes in the whole-body PSMA-TV of 65 patients were comparable to the changes in PSMA-TV after including only the ten largest lesions. Moreover, changes in PSMA-TV correlated well with changes in PSA levels, as did the changes in PSMA-TV with the reduced number of lesions. We conclude that a response assessment using PSMA-TV with a reduced number of lesions is feasible and could lead to a simplified process for evaluating PSMA PET/CT. Abstract (1) Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-derived parameters, such as the commonly used standardized uptake value (SUV) and PSMA-positive tumor volume (PSMA-TV), have been proposed for response assessment in metastatic prostate cancer (PCa) patients. However, the calculation of whole-body PSMA-TV remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative lesions. (2) Methods: Sixty-five patients classified into different disease stages were assessed by PSMA PET/CT for staging and restaging after therapy. Whole-body PSMA-TV and whole-body SUV\(_{max}\) were calculated. We then repeated this calculation only including the five or ten hottest or largest lesions. The corresponding serum levels of prostate-specific antigen (PSA) were also determined. The derived delta between baseline and follow-up values provided the following parameters: ΔSUV\(_{maxall}\), ΔSUV\(_{max10}\), ΔSUV\(_{max5}\), ΔPSMA-TV\(_{all}\), ΔPSMA-TV\(_{10}\), ΔPSMA-TV\(_{5}\), ΔPSA. Finally, we compared the findings from our whole-body segmentation with the results from our keyhole approach (focusing on a limited number of lesions) and correlated all values with the biochemical response (ΔPSA). (3) Results: Among patients with metastatic hormone-sensitive PCa (mHSPC), none showed a relevant deviation for ΔSUV\(_{max10}\)/ΔSUV\(_{max5}\) or ΔPSMA-TV\(_{10}\)/ΔPSMA-TV\(_{5}\) compared to ΔSUV\(_{maxall}\) and ΔPSMA-TV\(_{all}\). For patients treated with taxanes, up to 6/21 (28.6\%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only up to 2/21 (9.5\%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). For patients treated with radioligand therapy (RLT), up to 5/28 (17.9\%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only 1/28 (3.6\%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). The highest correlations with ΔPSA were found for ΔPSMA-TV\(_{all}\) (r ≥ 0.59, p ≤ 0.01), followed by ΔPSMA-TV\(_{10}\) (r ≥ 0.57, p ≤ 0.01) and ΔPSMA-TV\(_{5}\) (r ≥ 0.53, p ≤ 0.02) in all cohorts. ΔPSA only correlated with ΔSUV\(_{maxall}\) (r = 0.60, p = 0.02) and with ΔSUV\(_{max10}\) (r = 0.53, p = 0.03) in the mHSPC cohort, as well as with ΔSUV\(_{maxall}\) (r = 0.51, p = 0.01) in the RLT cohort. (4) Conclusion: Response assessment using PSMA-TV with a reduced number of lesions is feasible, and may allow for a simplified evaluation process for PSMA PET/CT.}, language = {en} } @article{TucaBernardellideMattosFunketal.2022, author = {Tuca, Alexandru-Cristian and Bernardelli de Mattos, Ives and Funk, Martin and Winter, Raimund and Palackic, Alen and Groeber-Becker, Florian and Kruse, Daniel and Kukla, Fabian and Lemarchand, Thomas and Kamolz, Lars-Peter}, title = {Orchestrating the dermal/epidermal tissue ratio during wound healing by controlling the moisture content}, series = {Biomedicines}, volume = {10}, journal = {Biomedicines}, number = {6}, issn = {2227-9059}, doi = {10.3390/biomedicines10061286}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275115}, year = {2022}, abstract = {A balanced and moist wound environment and surface increases the effect of various growth factors, cytokines, and chemokines, stimulating cell growth and wound healing. Considering this fact, we tested in vitro and in vivo water evaporation rates from the cellulose dressing epicite\(^{hydro}\) when combined with different secondary dressings as well as the resulting wound healing efficacy in a porcine donor site model. The aim of this study was to evaluate how the different rates of water evaporation affected wound healing efficacy. To this end, epicite\(^{hydro}\) primary dressing, in combination with different secondary dressing materials (cotton gauze, JELONET\(^◊\), AQUACEL\(^®\) Extra\(^™\), and OPSITE\(^◊\) Flexifix), was placed on 3 × 3 cm-sized dermatome wounds with a depth of 1.2 mm on the flanks of domestic pigs. The healing process was analyzed histologically and quantified by morphometry. High water evaporation rates by using the correct secondary dressing, such as cotton gauze, favored a better re-epithelialization in comparison with the low water evaporation resulting from an occlusive secondary dressing, which favored the formation of a new and intact dermal tissue that nearly fully replaced all the dermis that was removed during wounding. This newly available evidence may be of great benefit to clinical wound management.}, language = {en} } @article{NagaiFoersterDote2022, author = {Nagai, Michiaki and F{\"o}rster, Carola Yvette and Dote, Keigo}, title = {Sex hormone-specific neuroanatomy of Takotsubo syndrome: is the insular cortex a moderator?}, series = {Biomolecules}, volume = {12}, journal = {Biomolecules}, number = {1}, issn = {2218-273X}, doi = {10.3390/biom12010110}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254776}, year = {2022}, abstract = {Takotsubo syndrome (TTS), a transient form of dysfunction in the heart's left ventricle, occurs predominantly in postmenopausal women who have emotional stress. Earlier studies support the concept that the human circulatory system is modulated by a cortical network (consisting of the anterior cingulate gyrus, amygdala, and insular cortex (Ic)) that plays a pivotal role in the central autonomic nervous system in relation to emotional stressors. The Ic plays a crucial role in the sympathovagal balance, and decreased levels of female sex hormones have been speculated to change functional cerebral asymmetry, with a possible link to autonomic instability. In this review, we focus on the Ic as an important moderator of the human brain-heart axis in association with sex hormones. We also summarize the current knowledge regarding the sex-specific neuroanatomy in TTS.}, language = {en} } @article{TrifaultMamontovaBurger2022, author = {Trifault, Barbara and Mamontova, Victoria and Burger, Kaspar}, title = {In vivo proximity labeling of nuclear and nucleolar proteins by a stably expressed, DNA damage-responsive NONO-APEX2 fusion protein}, series = {Frontiers in Molecular Biosciences}, volume = {9}, journal = {Frontiers in Molecular Biosciences}, issn = {2296-889X}, doi = {10.3389/fmolb.2022.914873}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276707}, year = {2022}, abstract = {Cellular stress can induce DNA lesions that threaten the stability of genes. The DNA damage response (DDR) recognises and repairs broken DNA to maintain genome stability. Intriguingly, components of nuclear paraspeckles like the non-POU domain containing octamer-binding protein (NONO) participate in the repair of DNA double-strand breaks (DSBs). NONO is a multifunctional RNA-binding protein (RBP) that facilitates the retention and editing of messenger (m)RNA as well as pre-mRNA processing. However, the role of NONO in the DDR is poorly understood. Here, we establish a novel human U2OS cell line that expresses NONO fused to the engineered ascorbate peroxidase 2 (U2OS:NONO-APEX2-HA). We show that NONO-APEX2-HA accumulates in the nucleolus in response to DNA damage. Combining viability assays, subcellular localisation studies, coimmunoprecipitation experiments and in vivo proximity labeling, we demonstrate that NONO-APEX2-HA is a stably expressed fusion protein that mimics endogenous NONO in terms of expression, localisation and bona fide interactors. We propose that in vivo proximity labeling in U2OS:NONO-APEX2-HA cells is capable for the assessment of NONO interactomes by downstream assays. U2OS:NONO-APEX2-HA cells will likely be a valuable resource for the investigation of NONO interactome dynamics in response to DNA damage and other stimuli.}, language = {en} } @incollection{LiaqatSednevHoebartner2022, author = {Liaqat, Anam and Sednev, Maksim V. and H{\"o}bartner, Claudia}, title = {In Vitro Selection of Deoxyribozymes for the Detection of RNA Modifications}, series = {Ribosome Biogenesis: Methods and Protocols}, booktitle = {Ribosome Biogenesis: Methods and Protocols}, publisher = {Humana Press}, isbn = {978-1-0716-2501-9}, doi = {10.1007/978-1-0716-2501-9_10}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279208}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {167-179}, year = {2022}, abstract = {Deoxyribozymes are artificially evolved DNA molecules with catalytic abilities. RNA-cleaving deoxyribozymes have been recognized as an efficient tool for detection of modifications in target RNAs and provide an alternative to traditional and modern methods for detection of ribose or nucleobase methylation. However, there are only few examples of DNA enzymes that specifically reveal the presence of a certain type of modification, including N6-methyladenosine, and the knowledge about how DNA enzymes recognize modified RNAs is still extremely limited. Therefore, DNA enzymes cannot be easily engineered for the analysis of desired RNA modifications, but are instead identified by in vitro selection from random DNA libraries using synthetic modified RNA substrates. This protocol describes a general in vitro selection stagtegy to evolve new RNA-cleaving DNA enzymes that can efficiently differentiate modified RNA substrates from their unmodified counterpart.}, language = {en} } @article{EndresJungblutDivyapicigiletal.2022, author = {Endres, Leo M. and Jungblut, Marvin and Divyapicigil, Mustafa and Sauer, Markus and Stigloher, Christian and Christodoulides, Myron and Kim, Brandon J. and Schubert-Unkmeir, Alexandra}, title = {Development of a multicellular in vitro model of the meningeal blood-CSF barrier to study Neisseria meningitidis infection}, series = {Fluids and Barriers of the CNS}, volume = {19}, journal = {Fluids and Barriers of the CNS}, number = {1}, doi = {10.1186/s12987-022-00379-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300208}, year = {2022}, abstract = {Background Bacterial meningitis is a life-threatening disease that occurs when pathogens such as Neisseria meningitidis cross the meningeal blood cerebrospinal fluid barrier (mBCSFB) and infect the meninges. Due to the human-specific nature of N. meningitidis, previous research investigating this complex host-pathogen interaction has mostly been done in vitro using immortalized brain endothelial cells (BECs) alone, which often do not retain relevant barrier properties in culture. Here, we developed physiologically relevant mBCSFB models using BECs in co-culture with leptomeningeal cells (LMCs) to examine N. meningitidis interaction. Methods We used BEC-like cells derived from induced pluripotent stem cells (iBECs) or hCMEC/D3 cells in co-culture with LMCs derived from tumor biopsies. We employed TEM and structured illumination microscopy to characterize the models as well as bacterial interaction. We measured TEER and sodium fluorescein (NaF) permeability to determine barrier tightness and integrity. We then analyzed bacterial adherence and penetration of the cell barrier and examined changes in host gene expression of tight junctions as well as chemokines and cytokines in response to infection. Results Both cell types remained distinct in co-culture and iBECs showed characteristic expression of BEC markers including tight junction proteins and endothelial markers. iBEC barrier function as determined by TEER and NaF permeability was improved by LMC co-culture and remained stable for seven days. BEC response to N. meningitidis infection was not affected by LMC co-culture. We detected considerable amounts of BEC-adherent meningococci and a relatively small number of intracellular bacteria. Interestingly, we discovered bacteria traversing the BEC-LMC barrier within the first 24 h post-infection, when barrier integrity was still high, suggesting a transcellular route for N. meningitidis into the CNS. Finally, we observed deterioration of barrier properties including loss of TEER and reduced expression of cell-junction components at late time points of infection. Conclusions Here, we report, for the first time, on co-culture of human iPSC derived BECs or hCMEC/D3 with meningioma derived LMCs and find that LMC co-culture improves barrier properties of iBECs. These novel models allow for a better understanding of N. meningitidis interaction at the mBCSFB in a physiologically relevant setting.}, language = {en} } @article{HerbertFickHeydarianetal.2022, author = {Herbert, Saskia-Laureen and Fick, Andrea and Heydarian, Motaharehsadat and Metzger, Marco and W{\"o}ckel, Achim and Rudel, Thomas and Kozjak-Pavlovic, Vera and Wulff, Christine}, title = {Establishment of the SIS scaffold-based 3D model of human peritoneum for studying the dissemination of ovarian cancer}, series = {Journal of Tissue Engineering}, volume = {13}, journal = {Journal of Tissue Engineering}, issn = {2041-7314}, doi = {10.1177/20417314221088514}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301311}, pages = {1}, year = {2022}, abstract = {Ovarian cancer is the second most common gynecological malignancy in women. More than 70\% of the cases are diagnosed at the advanced stage, presenting as primary peritoneal metastasis, which results in a poor 5-year survival rate of around 40\%. Mechanisms of peritoneal metastasis, including adhesion, migration, and invasion, are still not completely understood and therapeutic options are extremely limited. Therefore, there is a strong requirement for a 3D model mimicking the in vivo situation. In this study, we describe the establishment of a 3D tissue model of the human peritoneum based on decellularized porcine small intestinal submucosa (SIS) scaffold. The SIS scaffold was populated with human dermal fibroblasts, with LP-9 cells on the apical side representing the peritoneal mesothelium, while HUVEC cells on the basal side of the scaffold served to mimic the endothelial cell layer. Functional analyses of the transepithelial electrical resistance (TEER) and the FITC-dextran assay indicated the high barrier integrity of our model. The histological, immunohistochemical, and ultrastructural analyses showed the main characteristics of the site of adhesion. Initial experiments using the SKOV-3 cell line as representative for ovarian carcinoma demonstrated the usefulness of our models for studying tumor cell adhesion, as well as the effect of tumor cells on endothelial cell-to-cell contacts. Taken together, our data show that the novel peritoneal 3D tissue model is a promising tool for studying the peritoneal dissemination of ovarian cancer.}, language = {en} } @article{WangBachoferKoehleretal.2022, author = {Wang, Zhiyuan and Bachofer, Felix and Koehler, Jonas and Huth, Juliane and Hoeser, Thorsten and Marconcini, Mattia and Esch, Thomas and Kuenzer, Claudia}, title = {Spatial modelling and prediction with the spatio-temporal matrix: a study on predicting future settlement growth}, series = {Land}, volume = {11}, journal = {Land}, number = {8}, issn = {2073-445X}, doi = {10.3390/land11081174}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281856}, year = {2022}, abstract = {In the past decades, various Earth observation-based time series products have emerged, which have enabled studies and analysis of global change processes. Besides their contribution to understanding past processes, time series datasets hold enormous potential for predictive modeling and thereby meet the demands of decision makers on future scenarios. In order to further exploit these data, a novel pixel-based approach has been introduced, which is the spatio-temporal matrix (STM). The approach integrates the historical characteristics of a specific land cover at a high temporal frequency in order to interpret the spatial and temporal information for the neighborhood of a given target pixel. The provided information can be exploited with common predictive models and algorithms. In this study, this approach was utilized and evaluated for the prediction of future urban/built-settlement growth. Random forest and multi-layer perceptron were employed for the prediction. The tests have been carried out with training strategies based on a one-year and a ten-year time span for the urban agglomerations of Surat (India), Ho-Chi-Minh City (Vietnam), and Abidjan (Ivory Coast). The slope, land use, exclusion, urban, transportation, hillshade (SLEUTH) model was selected as a baseline indicator for the performance evaluation. The statistical results from the receiver operating characteristic curve (ROC) demonstrate a good ability of the STM to facilitate the prediction of future settlement growth and its transferability to different cities, with area under the curve (AUC) values greater than 0.85. Compared with SLEUTH, the STM-based model achieved higher AUC in all of the test cases, while being independent of the additional datasets for the restricted and the preferential development areas.}, language = {en} } @misc{Gross2022, type = {Master Thesis}, author = {Groß, Lennart}, title = {Point-spread function engineering for single-molecule localization microscopy in brain slices}, doi = {10.25972/OPUS-28259}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282596}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Single-molecule localization microscopy (SMLM) is the method of choice to study biological specimens on a nanoscale level. Advantages of SMLM imply its superior specificity due to targeted molecular fluorescence labeling and its enhanced tissue preservation compared to electron microscopy, while reaching similar resolution. To reveal the molecular organization of protein structures in brain tissue, SMLM moves to the forefront: Instead of investigating brain slices with a thickness of a few µm, measurements of intact neuronal assemblies (up to 100 µm in each dimension) are required. As proteins are distributed in the whole brain volume and can move along synapses in all directions, this method is promising in revealing arrangements of neuronal protein markers. However, diffraction-limited imaging still required for the localization of the fluorophores is prevented by sample-induced distortion of emission pattern due to optical aberrations in tissue slices from non-superficial planes. In particular, the sample causes wavefront dephasing, which can be described as a summation of Zernike polynomials. To recover an optimal point spread function (PSF), active shaping can be performed by the use of adaptive optics. The aim of this thesis is to establish a setup using a deformable mirror and a wavefront sensor to actively shape the PSF to correct the wavefront phases in a super-resolution microscope setup. Therefore, fluorescence-labeled proteins expressed in different anatomical regions in brain tissue will be used as experiment specimen. Resolution independent imaging depth in slices reaching tens of micrometers is aimed.}, subject = {Einzelmolek{\"u}lmikroskopie}, language = {en} } @article{WolfDoellingerMaletal.2022, author = {Wolf, Erik and D{\"o}llinger, Nina and Mal, David and Wenninger, Stephan and Bartl, Andrea and Botsch, Mario and Latoschik, Marc Erich and Wienrich, Carolin}, title = {Does distance matter? Embodiment and perception of personalized avatars in relation to the self-observation distance in virtual reality}, series = {Frontiers in Virtual Reality}, volume = {3}, journal = {Frontiers in Virtual Reality}, issn = {2673-4192}, doi = {10.3389/frvir.2022.1031093}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299415}, year = {2022}, abstract = {Virtual reality applications employing avatar embodiment typically use virtual mirrors to allow users to perceive their digital selves not only from a first-person but also from a holistic third-person perspective. However, due to distance-related biases such as the distance compression effect or a reduced relative rendering resolution, the self-observation distance (SOD) between the user and the virtual mirror might influence how users perceive their embodied avatar. Our article systematically investigates the effects of a short (1 m), middle (2.5 m), and far (4 m) SOD between users and mirror on the perception of their personalized and self-embodied avatars. The avatars were photorealistic reconstructed using state-of-the-art photogrammetric methods. Thirty participants repeatedly faced their real-time animated self-embodied avatars in each of the three SOD conditions, where they were repeatedly altered in their body weight, and participants rated the 1) sense of embodiment, 2) body weight perception, and 3) affective appraisal towards their avatar. We found that the different SODs are unlikely to influence any of our measures except for the perceived body weight estimation difficulty. Here, the participants perceived the difficulty significantly higher for the farthest SOD. We further found that the participants' self-esteem significantly impacted their ability to modify their avatar's body weight to their current body weight and that it positively correlated with the perceived attractiveness of the avatar. Additionally, the participants' concerns about their body shape affected how eerie they perceived their avatars. The participants' self-esteem and concerns about their body shape influenced the perceived body weight estimation difficulty. We conclude that the virtual mirror in embodiment scenarios can be freely placed and varied at a distance of one to four meters from the user without expecting major effects on the perception of the avatar.}, language = {en} } @article{ForsterKohlmorgenHaasetal.2022, author = {Forster, Johannes and Kohlmorgen, Britta and Haas, Julian and Weis, Philipp and Breunig, Lukas and Turnwald, Doris and Mizaikoff, Boris and Schoen, Christoph}, title = {A streamlined method for the fast and cost-effective detection of bacterial pathogens from positive blood cultures for the BacT/ALERT blood culture system using the Vitek MS mass spectrometer}, series = {PLoS ONE}, volume = {17}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0267669}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300213}, year = {2022}, abstract = {Background and objective Prompt pathogen identification of blood stream infections is essential to provide appropriate antibiotic treatment. Therefore, the objective of this prospective single centre study was to establish an inexpensive, fast and accurate protocol for bacterial species identification with SDS protein-extraction directly from BacT/Alert® blood culture (BC) bottles by VitekMS®. Results Correct species identification was obtained for 198/266 (74.4\%, 95\%-CI = [68.8\%, 79.6\%]) of pathogens. The protocol was more successful in identifying 87/96 (91.4\%, 95\%-CI = [83.8\%, 93.2\%]) gram-negative bacteria than 110/167 (65.9\%, 95\%-CI = [58.1\%, 73.0\%]) gram-positive bacteria. The hands-on time for sample preparation and measurement was about 15 min for up to five samples. This is shorter than for most other protocols using a similar lysis-centrifugation approach for the combination of BacT/Alert® BC bottles and the Vitek® MS mass spectrometer. The estimated costs per sample were approx. 1.80€ which is much cheaper than for commercial kits. Conclusion This optimized protocol allows for accurate identification of bacteria directly from blood culture bottles for laboratories equipped with BacT/Alert® blood culture bottles and VitekMS® mass spectrometer.}, language = {en} } @article{RoeschPlank2022, author = {R{\"o}sch, Moritz and Plank, Simon}, title = {Detailed mapping of lava and ash deposits at Indonesian volcanoes by means of VHR PlanetScope change detection}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {5}, issn = {2072-4292}, doi = {10.3390/rs14051168}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262232}, year = {2022}, abstract = {Mapping of lava flows in unvegetated areas of active volcanoes using optical satellite data is challenging due to spectral similarities of volcanic deposits and the surrounding background. Using very high-resolution PlanetScope data, this study introduces a novel object-oriented classification approach for mapping lava flows in both vegetated and unvegetated areas during several eruptive phases of three Indonesian volcanoes (Karangetang 2018/2019, Agung 2017, Krakatau 2018/2019). For this, change detection analysis based on PlanetScope imagery for mapping loss of vegetation due to volcanic activity (e.g., lava flows) is combined with the analysis of changes in texture and brightness, with hydrological runoff modelling and with analysis of thermal anomalies derived from Sentinel-2 or Landsat-8. Qualitative comparison of the mapped lava flows showed good agreement with multispectral false color time series (Sentinel-2 and Landsat-8). Reports of the Global Volcanism Program support the findings, indicating the developed lava mapping approach produces valuable results for monitoring volcanic hazards. Despite the lack of bands in infrared wavelengths, PlanetScope proves beneficial for the assessment of risk and near-real-time monitoring of active volcanoes due to its high spatial (3 m) and temporal resolution (mapping of all subaerial volcanoes on a daily basis).}, language = {en} } @article{BetzSegerNieding2022, author = {Betz, Ann-Katrin and Seger, Benedikt T. and Nieding, Gerhild}, title = {How can carbon labels and climate-friendly default options on restaurant menus contribute to the reduction of greenhouse gas emissions associated with dining?}, series = {PLOS Climate}, volume = {1}, journal = {PLOS Climate}, number = {5}, doi = {10.1371/journal.pclm.0000028}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301039}, year = {2022}, abstract = {In this study, we aimed to understand how restaurants can contribute to climate change mitigation via menu design. We investigated two types of interventions: changing the configuration of menu entries with variable side dishes so that the most climate-friendly option is set as the default and indicating the greenhouse gas emission of each dish via carbon labels. In an online simulation experiment, 265 participants were shown the menus of nine different restaurants and had to choose exactly one dish per menu. In six menus, the main dishes were presented with different default options: the side dish was associated either with the highest or with the lowest greenhouse gas emissions. The other three menus consisted of unitary dishes for which the default rules did not apply. All menus were presented either with or without carbon labels for each dish option. The results indicated that more climate-friendly dish choices resulting in lower greenhouse gas emissions were made with the low-emission than the high-emission default condition, and when carbon labels were present rather than absent. The effects of both interventions interacted, which indicates that the interventions partly overlap with regard to cognitive predecessors of choice behavior, such as attentional focus and social norms. The results suggest that the design of restaurant menus has a considerable effect on the carbon footprint of dining.}, language = {en} } @article{ChaianunpornHovestadt2022, author = {Chaianunporn, Thotsapol and Hovestadt, Thomas}, title = {Emergence of spatially structured populations by area-concentrated search}, series = {Ecology and Evolution}, volume = {12}, journal = {Ecology and Evolution}, number = {12}, doi = {10.1002/ece3.9528}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311939}, year = {2022}, abstract = {The idea that populations are spatially structured has become a very powerful concept in ecology, raising interest in many research areas. However, despite dispersal being a core component of the concept, it typically does not consider the movement behavior underlying any dispersal. Using individual-based simulations in continuous space, we explored the emergence of a spatially structured population in landscapes with spatially heterogeneous resource distribution and with organisms following simple area-concentrated search (ACS); individuals do not, however, perceive or respond to any habitat attributes per se but only to their foraging success. We investigated the effects of different resource clustering pattern in landscapes (single large cluster vs. many small clusters) and different resource density on the spatial structure of populations and movement between resource clusters of individuals. As results, we found that foraging success increased with increasing resource density and decreasing number of resource clusters. In a wide parameter space, the system exhibited attributes of a spatially structured populations with individuals concentrated in areas of high resource density, searching within areas of resources, and "dispersing" in straight line between resource patches. "Emigration" was more likely from patches that were small or of low quality (low resource density), but we observed an interaction effect between these two parameters. With the ACS implemented, individuals tended to move deeper into a resource cluster in scenarios with moderate resource density than in scenarios with high resource density. "Looping" from patches was more likely if patches were large and of high quality. Our simulations demonstrate that spatial structure in populations may emerge if critical resources are heterogeneously distributed and if individuals follow simple movement rules (such as ACS). Neither the perception of habitat nor an explicit decision to emigrate from a patch on the side of acting individuals is necessary for the emergence of such spatial structure.}, language = {en} } @article{WagenhaeuserRickertSommeretal.2022, author = {Wagenh{\"a}user, Laura and Rickert, Vanessa and Sommer, Claudia and Wanner, Christoph and Nordbeck, Peter and Rost, Simone and {\"U}{\c{c}}eyler, Nurcan}, title = {X-chromosomal inactivation patterns in women with Fabry disease}, series = {Molecular Genetics \& Genomic Medicine}, volume = {10}, journal = {Molecular Genetics \& Genomic Medicine}, number = {9}, doi = {10.1002/mgg3.2029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312795}, year = {2022}, abstract = {Background Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women. Patients and Methods We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X-chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity. Results 43/95 (45\%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., ≥75:25\% distribution) in 6/87 (7\%) mouth epithelial cell samples, 31/88 (35\%) blood samples, and 9/27 (33\%) skin fibroblast samples. Clinical phenotype, α-galactosidase A (GAL) activity, and lyso-Gb3 levels did not show intergroup differences when stratified for X-chromosomal skewing and activity status of the mutated X-chromosome. Conclusions X-inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.}, language = {en} } @article{KaethnerEidelHaegeetal.2022, author = {K{\"a}thner, Ivo and Eidel, Matthias and H{\"a}ge, Anne-Sophie and Gram, Annika and Pauli, Paul}, title = {Observing physicians acting with different levels of empathy modulates later assessed pain tolerance}, series = {British Journal of Health Psychology}, volume = {27}, journal = {British Journal of Health Psychology}, number = {2}, doi = {10.1111/bjhp.12553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258368}, pages = {434-448}, year = {2022}, abstract = {Objectives The patient-physician relationship is essential for treatment success. Previous studies demonstrated that physicians who behave empathic in their interaction with patients have a positive effect on health outcomes. In this study, we investigated if the mere perception of physicians as empathic/not empathic modulates pain despite an emotionally neutral interaction with the patients. Methods N = 60 women took part in an experimental study that simulated a clinical interaction. In the paradigm, each participant watched two immersive 360° videos via a head-mounted display from a patient's perspective. The physicians in the videos behaved either empathic or not empathic towards a third person. Importantly, these physicians remained emotionally neutral in the subsequent virtual interaction with the participants. Finally, participants received a controlled, painful pressure stimulus within the narratives of the videos. Results The physicians in the high compared with the low empathy videos were rated as more empathic and more likable, indicating successful experimental manipulation. In spite of later neutral behaviour of physicians, this short observation of physicians' behaviour towards a third person was sufficient to modulate pain tolerance of the participants. Conclusions The finding of this study that the mere observation of physicians' behaviour towards a third person modulates pain, despite a neutral direct interaction with the participants, has important clinical implications. Further, the proposed paradigm enables investigating aspects of patient-physician communication that are difficult to examine in a clinical setting.}, language = {en} } @article{AchenbachLeHanneurCamenzindetal.2022, author = {Achenbach, Leonard and Le Hanneur, Malo and Camenzind, Roland S. and Bouyer, Michael and Pottecher, Pierre and Lafosse, Thibault}, title = {Systematic bifocal decompression for isolated long thoracic nerve paresis: A case series of 12 patients}, series = {Interdisciplinary Neurosurgery}, volume = {27}, journal = {Interdisciplinary Neurosurgery}, doi = {10.1016/j.inat.2021.101384}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265085}, year = {2022}, abstract = {To date, no consensus exists regarding the best surgical management of isolated, micro-traumatic long thoracic nerve (LTN) paresis. Our hypothesis was that a combined decompression of the LTN at two potential locations for entrapment would be effective in the management of dynamic LTN paresis. We report on twelve patients with isolated LTN parersis, with tenderness at two entrapment sites, who underwent bifocal LTN decompression after undergoing unsuccessful conservative treatment for at least 6 months; all patients had preoperative electrodiagnostic studies that confirmed the paresis and ruled out peripheral neuritis. Clinical and electrical improvements were observed in eight patients (67\%) regarding shoulder flexion, shoulder abduction, and Quick-DASH scores. Four patients (33\%) did not improve after surgery. The results corroborate our hypothesis that a bifocal LTN decompression can be an effective and reliable therapeutic option in more than half of a very selective patient population suffering from serratus anterior muscle deficiency.}, language = {en} } @techreport{VomhoffGeisslerHossfeld2022, type = {Working Paper}, author = {Vomhoff, Viktoria and Geißler, Stefan and Hoßfeld, Tobias}, title = {Identification of Signaling Patterns in Mobile IoT Signaling Traffic}, series = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, journal = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, doi = {10.25972/OPUS-28081}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280819}, pages = {4}, year = {2022}, abstract = {We attempt to identify sequences of signaling dialogs, to strengthen our understanding of the signaling behavior of IoT devices by examining a dataset containing over 270.000 distinct IoT devices whose signaling traffic has been observed over a 31-day period in a 2G network [4]. We propose a set of rules that allows the assembly of signaling dialogs into so-called sessions in order to identify common patterns and lay the foundation for future research in the areas of traffic modeling and anomaly detection.}, subject = {Datennetz}, language = {en} } @article{SpitzelWagnerBreyeretal.2022, author = {Spitzel, Marlene and Wagner, Elise and Breyer, Maximilian and Henniger, Dorothea and Bayin, Mehtap and Hofmann, Lukas and Mauceri, Daniela and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan}, title = {Dysregulation of immune response mediators and pain-related ion channels is associated with pain-like behavior in the GLA KO mouse model of Fabry disease}, series = {Cells}, volume = {11}, journal = {Cells}, number = {11}, issn = {2073-4409}, doi = {10.3390/cells11111730}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275186}, year = {2022}, abstract = {Fabry disease (FD) is a rare life-threatening disorder caused by deficiency of the alpha-galactosidase A (GLA) enzyme with a characteristic pain phenotype. Impaired GLA production or function leads to the accumulation of the cell membrane compound globotriaosylceramide (Gb3) in the neurons of the dorsal root ganglia (DRG) of FD patients. Applying immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT PCR) analysis on DRG tissue of the GLA knockout (KO) mouse model of FD, we address the question of how Gb3 accumulation may contribute to FD pain and focus on the immune system and pain-associated ion channel gene expression. We show a higher Gb3 load in the DRG of young (<6 months) (p < 0.01) and old (≥12 months) (p < 0.001) GLA KO mice compared to old wildtype (WT) littermates, and an overall suppressed immune response in the DRG of old GLA KO mice, represented by a reduced number of CD206\(^+\) macrophages (p < 0.01) and lower gene expression levels of the inflammation-associated targets interleukin(IL)1b (p < 0.05), IL10 (p < 0.001), glial fibrillary acidic protein (GFAP) (p < 0.05), and leucine rich alpha-2-glycoprotein 1 (LRG1) (p < 0.01) in the DRG of old GLA KO mice compared to old WT. Dysregulation of immune-related genes may be linked to lower gene expression levels of the pain-associated ion channels calcium-activated potassium channel 3.1 (KCa3.1) and transient receptor potential ankyrin 1 channel (TRPA1). Ion channel expression might further be disturbed by impaired sphingolipid recruitment mediated via the lipid raft marker flotillin-1 (FLOT1). This impairment is represented by an increased number of FLOT1\(^+\) DRG neurons with a membranous expression pattern in old GLA KO mice compared to young GLA KO, young WT, and old WT mice (p < 0.001 each). Further, we provide evidence for aberrant behavior of GLA KO mice, which might be linked to dysregulated ion channel gene expression levels and disturbed FLOT1 distribution patterns. Behavioral testing revealed mechanical hypersensitivity in young (p < 0.01) and old (p < 0.001) GLA KO mice compared to WT, heat hypersensitivity in young GLA KO mice (p < 0.001) compared to WT, age-dependent heat hyposensitivity in old GLA KO mice (p < 0.001) compared to young GLA KO mice, and cold hyposensitivity in young (p < 0.001) and old (p < 0.001) GLA KO mice compared to WT, which well reflects the clinical phenotype observed in FD patients.}, language = {en} } @article{DahlhoffManzSteinfattetal.2022, author = {Dahlhoff, Julia and Manz, Hannah and Steinfatt, Tim and Delgado-Tascon, Julia and Seebacher, Elena and Schneider, Theresa and Wilnit, Amy and Mokhtari, Zeinab and Tabares, Paula and B{\"o}ckle, David and Rasche, Leo and Martin Kort{\"u}m, K. and Lutz, Manfred B. and Einsele, Hermann and Brandl, Andreas and Beilhack, Andreas}, title = {Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression}, series = {Leukemia}, volume = {36}, journal = {Leukemia}, number = {3}, issn = {1476-5551}, doi = {10.1038/s41375-021-01422-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271787}, pages = {790-800}, year = {2022}, abstract = {Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to disease relapse in patients. In the bone marrow, CD4\(^{+}\)FoxP3\(^{+}\) regulatory T cells (Tregs) are highly abundant amongst CD4\(^{+}\) T cells providing an immune protective niche for different long-living cell populations, e.g., hematopoietic stem cells. Here, we addressed the functional role of Tregs in multiple myeloma dissemination to bone marrow compartments and disease progression. To investigate the immune regulation of multiple myeloma, we utilized syngeneic immunocompetent murine multiple myeloma models in two different genetic backgrounds. Analyzing the spatial immune architecture of multiple myeloma revealed that the bone marrow Tregs accumulated in the vicinity of malignant plasma cells and displayed an activated phenotype. In vivo Treg depletion prevented multiple myeloma dissemination in both models. Importantly, short-term in vivo depletion of Tregs in mice with established multiple myeloma evoked a potent CD8 T cell- and NK cell-mediated immune response resulting in complete and stable remission. Conclusively, this preclinical in-vivo study suggests that Tregs are an attractive target for the treatment of multiple myeloma.}, language = {en} } @article{ForsterDichtlWagener2022, author = {Forster, Johannes and Dichtl, Karl and Wagener, Johannes}, title = {Lower beta-1,3-D-glucan testing cut-offs increase sensitivity for non-albicans Candida species bloodstream infections}, series = {Mycoses}, volume = {65}, journal = {Mycoses}, number = {5}, doi = {10.1111/myc.13421}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276515}, pages = {500 -- 507}, year = {2022}, abstract = {Purpose Fungal biomarkers support early diagnosis of invasive fungal infections. In this study, we evaluated the impact of a recent update to the manufacturer-recommended cut-off for beta-1,3-D-glucan (BDG) testing (Fujifilm Wako BDG assay) on sensitivity and specificity for the detection of candidemia. Additionally, we compared the performance with tests for Candida antigen (Ag by Serion ELISA antigen Candida, Virion\Serion) and anti-mannan antibodies (Ab by Hemkit Candida IHA, Ravo Diagnostika). Methods Sera of 82 patients with candidemia, which were sampled with a maximum distance of ±14 days from the date of sampling of the corresponding positive blood cultures, were retrospectively analysed for BDG, Ag and Ab. Results of BDG testing were compared with results from sera of 129 patients with candidemia from a different hospital. Results Sensitivity of BDG testing (47\%) was higher than for Ag (17\%) or Ab (20\%). By combining Ag and Ab testing, sensitivity was raised to 32\%. Lowering the cut-off of BDG from 11 pg/ml to the newly recommended cut-off of 7 pg/ml resulted in a significant increase in sensitivity (47\% vs 58\%, p = .01 and 63\% vs 71\% p < .01). At both centres, the increase was significant in NAC but not in C. albicans candidemia. No significant effects on specificity were observed. Conclusion BDG testing outperformed Ag and Ab testing and its combination. Lowering the BDG cut-off had no significant impact on specificity. The increase in sensitivity can be mainly attributed to a gain in sensitivity for non-albicans Candida species bloodstream infections.}, language = {en} } @article{FengZhouQiuetal.2022, author = {Feng, Yi and Zhou, Jiadong and Qiu, Honglin and Schnitzlein, Matthias and Hu, Jingtao and Liu, Linlin and W{\"u}rthner, Frank and Xie, Zengqi}, title = {Boron-Locked Starazine - A Soluble and Fluorescent Analogue of Starphene}, series = {Chemistry - A European Journal}, volume = {28}, journal = {Chemistry - A European Journal}, number = {29}, doi = {10.1002/chem.202200770}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276423}, year = {2022}, abstract = {A starlike heterocyclic molecule containing an electron-deficient nonaaza-core structure and three peripheral isoquinolines locked by three tetracoordinate borons, namely isoquinoline-nona-starazine (QNSA), is synthesized by using readily available reactants through a rather straightforward approach. This new heteroatom-rich QNSA possesses a quasi-planar π-backbone structure, and bears phenyl substituents on borons which protrude on both sides of the π-backbones endowing it with good solubility in common organic solvents. Contrasting to its starphene analogue, QNSA shows intense fluorescence with a quantum yield (PLQY) of up to 62 \% in dilute solution.}, language = {en} } @article{KraemerSchuhmannVolkmannetal.2022, author = {Kr{\"a}mer, Stefanie D. and Schuhmann, Michael K. and Volkmann, Jens and Fluri, Felix}, title = {Deep brain stimulation in the subthalamic nucleus can improve skilled Forelimb movements and retune dynamics of striatal networks in a rat stroke model}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {24}, doi = {10.3390/ijms232415862}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312828}, year = {2022}, abstract = {Recovery of upper limb (UL) impairment after stroke is limited in stroke survivors. Since stroke can be considered as a network disorder, neuromodulation may be an approach to improve UL motor dysfunction. Here, we evaluated the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in rats on forelimb grasping using the single-pellet reaching (SPR) test after stroke and determined costimulated brain regions during STN-HFS using 2-[\(^{18}\)F]Fluoro-2-deoxyglucose-([\(^{18}\)F]FDG)-positron emission tomography (PET). After a 4-week training of SPR, photothrombotic stroke was induced in the sensorimotor cortex of the dominant hemisphere. Thereafter, an electrode was implanted in the STN ipsilateral to the infarction, followed by a continuous STN-HFS or sham stimulation for 7 days. On postinterventional day 2 and 7, an SPR test was performed during STN-HFS. Success rate of grasping was compared between these two time points. [\(^{18}\)F]FDG-PET was conducted on day 2 and 3 after stroke, without and with STN-HFS, respectively. STN-HFS resulted in a significant improvement of SPR compared to sham stimulation. During STN-HFS, a significantly higher [\(^{18}\)F]FDG-uptake was observed in the corticosubthalamic/pallidosubthalamic circuit, particularly ipsilateral to the stimulated side. Additionally, STN-HFS led to an increased glucose metabolism within the brainstem. These data demonstrate that STN-HFS supports rehabilitation of skilled forelimb movements, probably by retuning dysfunctional motor centers within the cerebral network.}, language = {en} } @article{Halbig Babu Gatter etal.2022, author = {Halbig , Andreas and Babu , Sooraj K. and Gatter , Shirin and Latoschik , Marc Erich and Brukamp, Kirsten and von Mammen , Sebastian}, title = {Opportunities and challenges of Virtual Reality in healthcare - a domain experts inquiry}, series = {Frontiers in Virtual Reality}, volume = {3}, journal = {Frontiers in Virtual Reality}, issn = {2673-4192}, doi = {10.3389/frvir.2022.837616}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284752}, year = {2022}, abstract = {In recent years, the applications and accessibility of Virtual Reality (VR) for the healthcare sector have continued to grow. However, so far, most VR applications are only relevant in research settings. Information about what healthcare professionals would need to independently integrate VR applications into their daily working routines is missing. The actual needs and concerns of the people who work in the healthcare sector are often disregarded in the development of VR applications, even though they are the ones who are supposed to use them in practice. By means of this study, we systematically involve health professionals in the development process of VR applications. In particular, we conducted an online survey with 102 healthcare professionals based on a video prototype which demonstrates a software platform that allows them to create and utilise VR experiences on their own. For this study, we adapted and extended the Technology Acceptance Model (TAM). The survey focused on the perceived usefulness and the ease of use of such a platform, as well as the attitude and ethical concerns the users might have. The results show a generally positive attitude toward such a software platform. The users can imagine various use cases in different health domains. However, the perceived usefulness is tied to the actual ease of use of the platform and sufficient support for learning and working with the platform. In the discussion, we explain how these results can be generalized to facilitate the integration of VR in healthcare practice.}, language = {en} } @incollection{Kushch2022, author = {Kushch, Elina}, title = {The aphoristic potential of presidential rhetoric of G. Bush Jr.}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-25}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296456}, publisher = {W{\"u}rzburg University Press}, pages = {25-39}, year = {2022}, abstract = {This research paper concentrates on the analysis of the aphoristic potential of G. W. Bush's presidential rhetoric. Aphorisms are the most ancient laconic forms of expressing original and completed thoughts which reveal the peculiarity of their authors' world perception and worldview. From this perspective, these units can serve as the means of values codification. Repeatability and widespread use of aphorisms in various communications contribute to transmitting the values and ideas between the generations. Political aphorisms, which are a combination of aphoristic expressions from political communication and discourse, play an important role in this process. The authors of these expressions are not only politicians, but also philosophers, historians, writers, celebrities of different nationalities and generations. Presidential rhetoric is an integral and significant part of political discourse. The use of aphorisms as the means of codification of national and common human values in President G. W. Bush's formal addresses and speeches is intentional. It makes them concise and original, influential and convincing. Aphoristic expressions denoting common human values show the ideas and beliefs of their authors, as well as the politician, about life, justice, equality, freedom, faith, family. Aphorisms defining national values become the means of updating concepts of democracy, unity and diversity, freedom and security, success, and opportunity to fulfill one's potential in American society. The distinctive feature of G.W. Bush's rhetoric is the frequent use of aphorisms whose authors are the Founding Fathers.}, language = {en} } @incollection{Shtaltovna2022, author = {Shtaltovna, Yuliya}, title = {Linguistic Democratization of the Modern English Language: Functional Parameters of English Youth Slang Neologisms}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-105}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296514}, publisher = {W{\"u}rzburg University Press}, pages = {105-115}, year = {2022}, abstract = {No abstract available.}, language = {en} } @incollection{Kumar2022, author = {Kumar, Dinesh}, title = {A Brief Historical and Present Perspective of ELT in India}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-11}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296434}, publisher = {W{\"u}rzburg University Press}, pages = {11-17}, year = {2022}, abstract = {English language is being taught as a second foreign language in India. For most of the learners in India, English still a foreign language or target language. The study of this language is important to fulfill different kinds of academic and professional requirements. Still, there is a big gulf between demand and supply for which the failure of the system is largely responsible as its main emphasis on to adherence to the foreign curriculum. The government tries to impose this curriculum on English teachers, but, in fact, the curriculum is outdated.}, language = {en} } @incollection{Ali2022, author = {Ali, Zuraina}, title = {A Case Study of the Basic Learners' Struggles in Guessing from Context to Retain Words Learned}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296529}, publisher = {W{\"u}rzburg University Press}, pages = {117-124}, year = {2022}, abstract = {Guessing meaning from context is a challenging strategy for Second Language Learners (SLLs). In using the strategy, research found that poor students or low proficiency learners struggled in their attempts to use it. Mainly, it was reported that it was due to their vocabulary knowledge was limited. In another aspect, retaining vocabulary learnt is also important. Such is essential since learning vocabulary does not mean knowing the definition only. Yet, learners must also be able to use the vocabulary as they engage in language skills such as reading, writing, speaking and listening. The study aims at finding the hindrances faced among poor students' using contextual clues in retaining vocabulary. The study employed a case study to collect data from two basic students studying at a tertiary level. The study found that their hindrances in guessing meaning contexts were due to their being confused in guessing meaning when reading a sentence. Also, it was found that they were not able to find clues since they lacked vocabulary to guess correctly. The study implied that guessing meaning from context required sizeable vocabulary knowledge. Therefore, more training is necessary to assist basic learners in being successful in guessing from contexts.}, language = {en} } @incollection{KellenRibeiroWengDeToni2022, author = {Kellen Ribeiro Weng, Ana and De Toni, Plinio Marco}, title = {Differences and Similarities between the Fields of Bilingualism and Second Language Acquisition}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-19}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296447}, publisher = {W{\"u}rzburg University Press}, pages = {19-24}, year = {2022}, abstract = {No abstract available.}, language = {en} } @article{EnglmeiervonHoermannRiekeretal.2022, author = {Englmeier, Jana and von Hoermann, Christian and Rieker, Daniel and Benbow, Marc Eric and Benjamin, Caryl and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Lackner, Tom{\´a}š and Mitesser, Oliver and Redlich, Sarah and Riebl, Rebekka and Rojas-Botero, Sandra and Rummler, Thomas and Salamon, J{\"o}rg-Alfred and Sommer, David and Steffan-Dewenter, Ingolf and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Zhang, Jie and M{\"u}ller, J{\"o}rg}, title = {Dung-visiting beetle diversity is mainly affected by land use, while community specialization is driven by climate}, series = {Ecology and Evolution}, volume = {12}, journal = {Ecology and Evolution}, number = {10}, issn = {2045-7758}, doi = {10.1002/ece3.9386}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312846}, year = {2022}, abstract = {Dung beetles are important actors in the self-regulation of ecosystems by driving nutrient cycling, bioturbation, and pest suppression. Urbanization and the sprawl of agricultural areas, however, destroy natural habitats and may threaten dung beetle diversity. In addition, climate change may cause shifts in geographical distribution and community composition. We used a space-for-time approach to test the effects of land use and climate on α-diversity, local community specialization (H\(_2\)′) on dung resources, and γ-diversity of dung-visiting beetles. For this, we used pitfall traps baited with four different dung types at 115 study sites, distributed over a spatial extent of 300 km × 300 km and 1000 m in elevation. Study sites were established in four local land-use types: forests, grasslands, arable sites, and settlements, embedded in near-natural, agricultural, or urban landscapes. Our results show that abundance and species density of dung-visiting beetles were negatively affected by agricultural land use at both spatial scales, whereas γ-diversity at the local scale was negatively affected by settlements and on a landscape scale equally by agricultural and urban land use. Increasing precipitation diminished dung-visiting beetle abundance, and higher temperatures reduced community specialization on dung types and γ-diversity. These results indicate that intensive land use and high temperatures may cause a loss in dung-visiting beetle diversity and alter community networks. A decrease in dung-visiting beetle diversity may disturb decomposition processes at both local and landscape scales and alter ecosystem functioning, which may lead to drastic ecological and economic damage.}, language = {en} } @article{HolzmannLittigFrankSchmadereretal.2022, author = {Holzmann-Littig, Christopher and Frank, Tamara and Schmaderer, Christoph and Braunisch, Matthias C. and Renders, Lutz and Kranke, Peter and Popp, Maria and Seeber, Christian and Fichtner, Falk and Littig, Bianca and Carbajo-Lozoya, Javier and Meerpohl, Joerg J. and Haller, Bernhard and Allwang, Christine}, title = {COVID-19 Vaccines: Fear of side effects among German health care workers}, series = {Vaccines}, volume = {10}, journal = {Vaccines}, number = {5}, issn = {2076-393X}, doi = {10.3390/vaccines10050689}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270561}, year = {2022}, abstract = {(1) Background: Health care workers (HCWs) play a key role in increasing anti-COVID vaccination rates. Fear of potential side effects is one of the main reasons for vaccine hesitancy. We investigated which side effects are of concern to HCWs and how these are associated with vaccine hesitancy. (2) Methods: Data were collected in an online survey in February 2021 among HCWs from across Germany with 4500 included participants. Free-text comments on previously experienced vaccination side effects, and fear of short- and long-term side effects of the COVID-19 vaccination were categorized and analyzed. (3) Results: Most feared short-term side effects were vaccination reactions, allergic reactions, and limitations in daily life. Most feared long-term side effects were (auto-) immune reactions, neurological side effects, and currently unknown long-term consequences. Concerns about serious vaccination side effects were associated with vaccination refusal. There was a clear association between refusal of COVID-19 vaccination in one's personal environment and fear of side effects. (4) Conclusions: Transparent information about vaccine side effects is needed, especially for HCW. Especially when the participants' acquaintances advised against vaccination, they were significantly more likely to fear side effects. Thus, further education of HCW is necessary to achieve good information transfer in clusters as well.}, language = {en} } @article{KochPetzoldWesselyetal.2022, author = {Koch, Elias A. T. and Petzold, Anne and Wessely, Anja and Dippel, Edgar and Gesierich, Anja and Gutzmer, Ralf and Hassel, Jessica C. and Haferkamp, Sebastian and K{\"a}hler, Katharina C. and Knorr, Harald and Kreuzberg, Nicole and Leiter, Ulrike and Loquai, Carmen and Meier, Friedegund and Meissner, Markus and Mohr, Peter and Pf{\"o}hler, Claudia and Rahimi, Farnaz and Schadendorf, Dirk and Schell, Beatrice and Schlaak, Max and Terheyden, Patrick and Thoms, Kai-Martin and Schuler-Thurner, Beatrice and Ugurel, Selma and Ulrich, Jens and Utikal, Jochen and Weichenthal, Michael and Ziller, Fabian and Berking, Carola and Heppt, Markus V.}, title = {Immune checkpoint blockade for metastatic uveal melanoma: re-induction following resistance or toxicity}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {3}, issn = {2072-6694}, doi = {10.3390/cancers14030518}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254814}, year = {2022}, abstract = {Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95\% CI: 11.1-23.8) versus 9.4 months (cohort B, 95\% CI: 6.1-14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities.}, language = {en} } @article{NoyaletIlgenBuerkleinetal.2022, author = {Noyalet, Laurent and Ilgen, Lukas and B{\"u}rklein, Miriam and Shehata-Dieler, Wafaa and Taeger, Johannes and Hagen, Rudolf and Neun, Tilmann and Zabler, Simon and Althoff, Daniel and Rak, Kristen}, title = {Vestibular aqueduct morphology and Meniere's disease - development of the vestibular aqueduct score by 3D analysis}, series = {Frontiers in Surgery}, volume = {9}, journal = {Frontiers in Surgery}, issn = {2296-875X}, doi = {10.3389/fsurg.2022.747517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312893}, year = {2022}, abstract = {Improved radiological examinations with newly developed 3D models may increase understanding of Meniere's disease (MD). The morphology and course of the vestibular aqueduct (VA) in the temporal bone might be related to the severity of MD. The presented study explored, if the VA of MD and non-MD patients can be grouped relative to its angle to the semicircular canals (SCC) and length using a 3D model. Scans of temporal bone specimens (TBS) were performed using micro-CT and micro flat panel volume computed tomography (mfpVCT). Furthermore, scans were carried out in patients and TBS by computed tomography (CT). The angle between the VA and the three SCC, as well as the length of the VA were measured. From these data, a 3D model was constructed to develop the vestibular aqueduct score (VAS). Using different imaging modalities it was demonstrated that angle measurements of the VA are reliable and can be effectively used for detailed diagnostic investigation. To test the clinical relevance, the VAS was applied on MD and on non-MD patients. Length and angle values from MD patients differed from non-MD patients. In MD patients, significantly higher numbers of VAs could be assigned to a distinct group of the VAS. In addition, it was tested, whether the outcome of a treatment option for MD can be correlated to the VAS.}, language = {en} } @article{GehrkeScherzadHagenetal.2022, author = {Gehrke, Thomas and Scherzad, Agmal and Hagen, Rudolf and Hackenberg, Stephan}, title = {Deep neck infections with and without mediastinal involvement: treatment and outcome in 218 patients}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {3}, issn = {1434-4726}, doi = {10.1007/s00405-021-06945-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266814}, pages = {1585-1592}, year = {2022}, abstract = {Purpose Infections of the deep neck, although becoming scarcer due to the widespread use of antibiotics, still represent a dangerous and possibly deadly disease, especially when descending into the mediastinum. Due to the different specialities involved in the treatment and the heterogenous presentation of the disease, therapeutic standard is still controversial. This study analyzes treatment and outcome in these patients based on a large retrospective review and proposes a therapeutic algorithm. Methods The cases of 218 adult patients treated with deep neck abscesses over a 10-year period at a tertiary university hospital were analyzed retrospectively. Clinical, radiological, microbiological and laboratory findings were compared between patients with and without mediastinal involvement. Results Forty-five patients (20.64\%) presented with abscess formation descending into the mediastinum. Those patients had significantly (all items p < 0.0001) higher rates of surgical interventions (4.27 vs. 1.11) and tracheotomies (82\% vs. 3.4\%), higher markers of inflammation (CRP 26.09 vs. 10.41 mg/dl), required more CT-scans (3.58 vs. 0.85), longer hospitalization (39.78 vs 9.79 days) and more frequently needed a change in antibiotic therapy (44.44\% vs. 6.40\%). Multi-resistant pathogens were found in 6.67\% vs. 1.16\%. Overall mortality rate was low with 1.83\%. Conclusion Despite of the high percentage of mediastinal involvement in the present patient collective, the proposed therapeutic algorithm resulted in a low mortality rate. Frequent CT-scans, regular planned surgical revisions with local drainage and lavage, as well as an early tracheotomy seem to be most beneficial regarding the outcome.}, language = {en} } @article{KrausHackenbergShehataDieleretal.2022, author = {Kraus, Fabian and Hackenberg, Stephan and Shehata-Dieler, Wafaa and Hagen, Rudolf}, title = {High-sensitivity FEES\(^{®}\) with the professional image enhancement technology "PIET"}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {1}, issn = {1434-4726}, doi = {10.1007/s00405-021-07067-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266822}, pages = {293-298}, year = {2022}, abstract = {Purpose Flexible endoscopic evaluation of swallowing (FEES\(^{®}\)) is a standard diagnostic tool in dysphagia. The combination of FEES® and narrow band light (narrow band imaging; NBI) provides a more precise and detailed investigation method. So far, this technique could only be performed with the NBI illumination. The new version of the "professional image enhancement technique" (PIET) provides another image enhancing system. This study investigates the eligibility of PIET in the FEES\(^{®}\) procedure. Methods Both techniques, NBI and PIET, were compared using a target system. Furthermore, the image enhancement during FEES\(^{®}\) was performed and recorded with the two systems during daily routine. Results Performing an image enhancement during FEES\(^{®}\) is possible with both systems PIET and NBI. On the target system, the contrast of the PIET showed a brighter and a more detailed picture. In dysphagia patients, no difference between PIET and NBI was detected. Conclusion PIET proved to be non-inferior to NBI during image enhancement FEES\(^{®}\). So far, image enhancement FEES\(^{®}\) was exclusively connected to NBI. With the PIET system, an alternative endoscopy technology is available for certain indications.}, language = {en} } @article{WunderPempCeciletal.2022, author = {Wunder, Juliane and Pemp, Daniela and Cecil, Alexander and Mahdiani, Maryam and Hauptstein, Ren{\´e} and Schmalbach, Katja and Geppert, Leo N. and Ickstadt, Katja and Esch, Harald L. and Dankekar, Thomas and Lehmann, Leane}, title = {Influence of breast cancer risk factors on proliferation and DNA damage in human breast glandular tissues: role of intracellular estrogen levels, oxidative stress and estrogen biotransformation}, series = {Archives of Toxicology}, volume = {96}, journal = {Archives of Toxicology}, number = {2}, issn = {1432-0738}, doi = {10.1007/s00204-021-03198-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265343}, pages = {673-687}, year = {2022}, abstract = {Breast cancer etiology is associated with both proliferation and DNA damage induced by estrogens. Breast cancer risk factors (BCRF) such as body mass index (BMI), smoking, and intake of estrogen-active drugs were recently shown to influence intratissue estrogen levels. Thus, the aim of the present study was to investigate the influence of BCRF on estrogen-induced proliferation and DNA damage in 41 well-characterized breast glandular tissues derived from women without breast cancer. Influence of intramammary estrogen levels and BCRF on estrogen receptor (ESR) activation, ESR-related proliferation (indicated by levels of marker transcripts), oxidative stress (indicated by levels of GCLC transcript and oxidative derivatives of cholesterol), and levels of transcripts encoding enzymes involved in estrogen biotransformation was identified by multiple linear regression models. Metabolic fluxes to adducts of estrogens with DNA (E-DNA) were assessed by a metabolic network model (MNM) which was validated by comparison of calculated fluxes with data on methoxylated and glucuronidated estrogens determined by GC- and UHPLC-MS/MS. Intratissue estrogen levels significantly influenced ESR activation and fluxes to E-DNA within the MNM. Likewise, all BCRF directly and/or indirectly influenced ESR activation, proliferation, and key flux constraints influencing E-DNA (i.e., levels of estrogens, CYP1B1, SULT1A1, SULT1A2, and GSTP1). However, no unambiguous total effect of BCRF on proliferation became apparent. Furthermore, BMI was the only BCRF to indeed influence fluxes to E-DNA (via congruent adverse influence on levels of estrogens, CYP1B1 and SULT1A2).}, language = {en} } @incollection{LazebnaPrykhodko2022, author = {Lazebna, Nataliia and Prykhodko, Anatoliy}, title = {English-language Digital Discourse of Human-Machine Communication}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-41}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296468}, publisher = {W{\"u}rzburg University Press}, pages = {41-51}, year = {2022}, abstract = {The paper focuses on digital discourse. This is a speech-intellectual product of innovative information technologies, a phenomenon, which needs further interdisciplinary and linguistic interpretation. The English-language digital discourse shows how linguistic verbal communication is mediated by digits and to what extent these Signum and Verbum unity reigns over the world. The paper analyzes the ways and methods of integrated and differential use of verbal and non-verbal sign systems in the English language as compared to programming languages, considering the types of synchronous changes in the socio-cultural dimension of the sign. This research describes the processes of signs transformation during their functioning in programming languages and in the English language, common and distinctive features in the arrangement of grammatical, lexical-semantic, and graphic means of (natural) English and (artificial) programming languages in their projection on different modes of communication in the system Human ↔ Machine. Programming languages are constituted by verbal means of the English language with additional use of its own semiotic resources, which testifies to their integrative linguistic and mathematical nature. The specific representation of ElDD conveys its reciprocal nature when the English language using its own tools combines them with the elements of the programming languages thus creating an effective toolkit for self-process}, language = {en} } @incollection{LutStarenkova2022, author = {Lut, Kateryna and Starenkova, Hanna}, title = {The Relationship between Language, Culture, and Development of Society}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-63}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296484}, publisher = {W{\"u}rzburg University Press}, pages = {63-72}, year = {2022}, abstract = {The paper analyses specific characteristics of language that influence the development of culture and societies. The problem of the connection between language and culture has occupied the minds of many famous scientists: some believe that language is a part of the culture as a whole; others think that language is only a form of cultural expression. Undoubtedly, language constitutes a vital component of the cultural background underlying social development. Language is an essential means of communication and interaction. However, language is at the same time sovereign about culture as a whole and can be separate from culture or compared to culture as an equal element (i.e., that language is neither a form nor a component of culture).}, language = {en} } @incollection{LubbunguMoongaMuyunietal.2022, author = {Lubbungu, Jive and Moonga, Ireen and Muyuni, Audrey and Zimba, Samson}, title = {English Language Variation: Creation of Zambian English (ZamEnglish)}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-53}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296477}, publisher = {W{\"u}rzburg University Press}, pages = {53-61}, year = {2022}, abstract = {In the present chapter, an attempt has been made to discuss the need to create Zambian English to address English language variations in Zambia. No language in the world can remain the same after interacting with other languages. The present chapter intends to propose and support the idea of using 'Zambian English' for both formal and informal business. Such a measure would create the communicative competence that the majority of the Zambians have always longed for. In Zambia, the purpose of using English language office is to deliberate day to day's business. On the contrary, this has been found to be an obstacle to those who lack principles of command in the language usage, but are able to construct sentences for communicative purposes yet are deprived in international interactions. The views expressed in this chapter are those of the language experts who were engaged in a conver� sation with regard to the possibility of creating what would be known as Zambian English (ZamEnglish).}, language = {en} } @article{HennegesMorbachSahitietal.2022, author = {Henneges, Carsten and Morbach, Caroline and Sahiti, Floran and Scholz, Nina and Frantz, Stefan and Ertl, Georg and Angermann, Christiane E. and St{\"o}rk, Stefan}, title = {Sex-specific bimodal clustering of left ventricular ejection fraction in patients with acute heart failure}, series = {ESH Heart Failure}, volume = {9}, journal = {ESH Heart Failure}, number = {1}, doi = {10.1002/ehf2.13618}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265839}, pages = {786-790}, year = {2022}, abstract = {Aims There is an ongoing discussion whether the categorization of patients with heart failure according to left ventricular ejection fraction (LVEF) is scientifically justified and clinically relevant. Major efforts are directed towards the identification of appropriate cut-off values to correctly allocate heart failure-specific pharmacotherapy. Alternatively, an LVEF continuum without definite subgroups is discussed. This study aimed to evaluate the natural distribution of LVEF in patients presenting with acutely decompensated heart failure and to identify potential subgroups of LVEF in male and female patients. Methods and results We identified 470 patients (mean age 75 ± 11 years, n = 137 female) hospitalized for acute heart failure in whom LVEF could be quantified by Simpson's method in an in-hospital echocardiogram. Non-parametric modelling revealed a bimodal shape of the LVEF distribution. Parametric modelling identified two clusters suggesting two LVEF peaks with mean (variance) of 61\% (9\%) and 31\% (10\%), respectively. Sub-differentiation by sex revealed a sex-specific bimodal clustering of LVEF. The respective threshold differentiating between 'high' and 'low' LVEF was 45\% in men and 52\% in women. Conclusions In patients presenting with acute heart failure, LVEF clustered in two subgroups and exhibited profound sex-specific distributional differences. These findings might enrich the scientific process to identify distinct subgroups of heart failure patients, which might each benefit from respectively tailored (pharmaco)therapies.}, language = {en} } @article{MuellerGraffIlgenSchendzielorzetal.2022, author = {M{\"u}ller-Graff, Franz-Tassilo and Ilgen, Lukas and Schendzielorz, Philipp and Voelker, Johannes and Taeger, Johannes and Kurz, Anja and Hagen, Rudolf and Neun, Tilmann and Rak, Kristen}, title = {Implementation of secondary reconstructions of flat-panel volume computed tomography (fpVCT) and otological planning software for anatomically based cochlear implantation}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {5}, issn = {1434-4726}, doi = {10.1007/s00405-021-06924-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266798}, pages = {2309-2319}, year = {2022}, abstract = {Purpose For further improvements in cochlear implantation, the measurement of the cochlear duct length (CDL) and the determination of the electrode contact position (ECP) are increasingly in the focus of clinical research. Usually, these items were investigated by multislice computed tomography (MSCT). The determination of ECP was only possible by research programs so far. Flat-panel volume computed tomography (fpVCT) and its secondary reconstructions (fpVCT\(_{SECO}\)) allow for high spatial resolution for the visualization of the temporal bone structures. Using a newly developed surgical planning software that enables the evaluation of CDL and the determination of postoperative ECP, this study aimed to investigate the combination of fpVCT and otological planning software to improve the implementation of an anatomically based cochlear implantation. Methods Cochlear measurements were performed utilizing surgical planning software in imaging data (MSCT, fpVCT and fpVCT\(_{SECO}\)) of patients with and without implanted electrodes. Results Measurement of the CDL by the use of an otological planning software was highly reliable using fpVCT\(_{SECO}\) with a lower variance between the respective measurements compared to MSCT. The determination of the inter-electrode-distance (IED) between the ECP was improved in fpVCT\(_{SECO}\) compared to MSCT. Conclusion The combination of fpVCT\(_{SECO}\) and otological planning software permits a simplified and more reliable analysis of the cochlea in the pre- and postoperative setting. The combination of both systems will enable further progress in the development of an anatomically based cochlear implantation.}, language = {en} } @article{RajeswaranTavoraVieiraMertensetal.2022, author = {Rajeswaran, Ranjith and Tavora-Vieira, Dayse and Mertens, Griet and Dillon, Margaret and Narayan, Saranya and Kameswaran, Mohan and Kurz, Anja}, title = {Audiological practice and COVID-19: recommendations that audiological centers can use to maintain the safety and quality of service-expert opinion}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {3}, issn = {1434-4726}, doi = {10.1007/s00405-021-06766-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266774}, pages = {1251-1256}, year = {2022}, abstract = {Purpose Audiology is an essential service for some patient groups and some interventions. This article sets forth experience-based recommendations for how audiological centers can continue to safely and effectively function during COVID-19. Methods The recommendations are the result of panel discussion and are based on the clinical experience of the panelists/authors. Results The recommendations cover which patient groups and which interventions should be treated when and whether this can be performed in the clinic or remotely; how to maintain the safety of workplace via optimizing patient flow within the clinic and the sanitation of rooms and equipment; and overcoming communication challenges that COVID-19 intensifies. Conclusion For essential audiological services to continue under COVID-19, safety measures must be implemented and maintained, and treatment and communication strategies must be adapted to offset communication difficulties due to personal protective equipment (PPE) and social distancing and to bolster patient confidence. In short, it is vital that staff feel safe, that patients either feel the clinic is safe enough to visit or that remote treatment may be an option, and that clinics and patients have a broad agreement on the urgency of any needed service. We hope that these recommendations help clinics effectively accomplish these goals.}, language = {en} } @article{BraeuerBurchardtMunkeltBleieretal.2022, author = {Br{\"a}uer-Burchardt, Christian and Munkelt, Christoph and Bleier, Michael and Heinze, Matthias and Gebhart, Ingo and K{\"u}hmstedt, Peter and Notni, Gunther}, title = {A new sensor system for accurate 3D surface measurements and modeling of underwater objects}, series = {Applied Sciences}, volume = {12}, journal = {Applied Sciences}, number = {9}, issn = {2076-3417}, doi = {10.3390/app12094139}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270792}, year = {2022}, abstract = {A new underwater 3D scanning device based on structured illumination and designed for continuous capture of object data in motion for deep sea inspection applications is introduced. The sensor permanently captures 3D data of the inspected surface and generates a 3D surface model in real time. Sensor velocities up to 0.7 m/s are directly compensated while capturing camera images for the 3D reconstruction pipeline. The accuracy results of static measurements of special specimens in a water basin with clear water show the high accuracy potential of the scanner in the sub-millimeter range. Measurement examples with a moving sensor show the significance of the proposed motion compensation and the ability to generate a 3D model by merging individual scans. Future application tests in offshore environments will show the practical potential of the sensor for the desired inspection tasks.}, language = {en} } @article{MuthHeiligMarquardtetal.2022, author = {Muth, Felicitas V. and Heilig, Michael and Marquardt, Dorothea and Mittelberg, Linda and Sebald, Albrecht and Kunde, Wilfried}, title = {Lightness perception of structured surfaces}, series = {Color Research and Application}, volume = {47}, journal = {Color Research and Application}, number = {2}, doi = {10.1002/col.22740}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257314}, pages = {377-387}, year = {2022}, abstract = {Visual perception of surfaces is of utmost importance in everyday life. Therefore, it comes naturally, that different surface structures evoke different visual impressions in the viewer even if the material underlying these surface structures is the same. This topic is especially virulent for manufacturing processes in which more than one stakeholder is involved, but where the final product needs to meet certain criteria. A common practice to address such slight but perceivable differences in the visual appearance of structured surfaces is that trained evaluators assess the samples and assign a pass or fail. However, this process is both time consuming and cost intensive. Thus, we conducted two studies to analyze the relationship between physical surface structure parameters and participants visual assessment of the samples. With the first experiment, we aimed at uncovering a relationship between physical roughness parameters and visual lightness perception while the second experiment was designed to test participants' discrimination sensitivity across the range of stimuli. Perceived lightness and the measured surface roughness were nonlinearly related to the surface structure. Additionally, we found a linear relationship between the engraving parameter and physical brightness. Surface structure was an ideal predictor for perceived lightness and participants discriminated equally well across the entire range of surface structures.}, language = {en} } @article{GuptaOsmanogluMinochaetal.2022, author = {Gupta, Shishir K. and Osmanoglu, {\"O}zge and Minocha, Rashmi and Bandi, Sourish Reddy and Bencurova, Elena and Srivastava, Mugdha and Dandekar, Thomas}, title = {Genome-wide scan for potential CD4+ T-cell vaccine candidates in Candida auris by exploiting reverse vaccinology and evolutionary information}, series = {Frontiers in Medicine}, volume = {9}, journal = {Frontiers in Medicine}, issn = {2296-858X}, doi = {10.3389/fmed.2022.1008527}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293953}, year = {2022}, abstract = {Candida auris is a globally emerging fungal pathogen responsible for causing nosocomial outbreaks in healthcare associated settings. It is known to cause infection in all age groups and exhibits multi-drug resistance with high potential for horizontal transmission. Because of this reason combined with limited therapeutic choices available, C. auris infection has been acknowledged as a potential risk for causing a future pandemic, and thus seeking a promising strategy for its treatment is imperative. Here, we combined evolutionary information with reverse vaccinology approach to identify novel epitopes for vaccine design that could elicit CD4+ T-cell responses against C. auris. To this end, we extensively scanned the family of proteins encoded by C. auris genome. In addition, a pathogen may acquire substitutions in epitopes over a period of time which could cause its escape from the immune response thus rendering the vaccine ineffective. To lower this possibility in our design, we eliminated all rapidly evolving genes of C. auris with positive selection. We further employed highly conserved regions of multiple C. auris strains and identified two immunogenic and antigenic T-cell epitopes that could generate the most effective immune response against C. auris. The antigenicity scores of our predicted vaccine candidates were calculated as 0.85 and 1.88 where 0.5 is the threshold for prediction of fungal antigenic sequences. Based on our results, we conclude that our vaccine candidates have the potential to be successfully employed for the treatment of C. auris infection. However, in vivo experiments are imperative to further demonstrate the efficacy of our design.}, language = {en} } @article{WeigelMalkmusWeigeletal.2022, author = {Weigel, Tobias and Malkmus, Christoph and Weigel, Verena and Wußmann, Maximiliane and Berger, Constantin and Brennecke, Julian and Groeber-Becker, Florian and Hansmann, Jan}, title = {Fully Synthetic 3D Fibrous Scaffolds for Stromal Tissues—Replacement of Animal-Derived Scaffold Materials Demonstrated by Multilayered Skin}, series = {Advanced Materials}, volume = {34}, journal = {Advanced Materials}, number = {10}, doi = {10.1002/adma.202106780}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276403}, year = {2022}, abstract = {The extracellular matrix (ECM) of soft tissues in vivo has remarkable biological and structural properties. Thereby, the ECM provides mechanical stability while it still can be rearranged via cellular remodeling during tissue maturation or healing processes. However, modern synthetic alternatives fail to provide these key features among basic properties. Synthetic matrices are usually completely degraded or are inert regarding cellular remodeling. Based on a refined electrospinning process, a method is developed to generate synthetic scaffolds with highly porous fibrous structures and enhanced fiber-to-fiber distances. Since this approach allows for cell migration, matrix remodeling, and ECM synthesis, the scaffold provides an ideal platform for the generation of soft tissue equivalents. Using this matrix, an electrospun-based multilayered skin equivalent composed of a stratified epidermis, a dermal compartment, and a subcutis is able to be generated without the use of animal matrix components. The extension of classical dense electrospun scaffolds with high porosities and motile fibers generates a fully synthetic and defined alternative to collagen-gel-based tissue models and is a promising system for the construction of tissue equivalents as in vitro models or in vivo implants.}, language = {en} } @article{BoschetScherbaumPittig2022, author = {Boschet, Juliane M. and Scherbaum, Stefan and Pittig, Andre}, title = {Costly avoidance of Pavlovian fear stimuli and the temporal dynamics of its decision process}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-09931-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301041}, year = {2022}, abstract = {Conflicts between avoiding feared stimuli versus approaching them for competing rewards are essential for functional behavior and anxious psychopathology. Yet, little is known about the underlying decision process. We examined approach-avoidance decisions and their temporal dynamics when avoiding Pavlovian fear stimuli conflicted with gaining rewards. First, a formerly neutral stimulus (CS+) was repeatedly paired with an aversive stimulus (US) to establish Pavlovian fear. Another stimulus (CS-) was never paired with the US. A control group received neutral tones instead of aversive USs. Next, in each of 324 trials, participants chose between a CS-/low reward and a CS+/high reward option. For the latter, probability of CS+ presentation (Pavlovian fear information) and reward magnitude (reward information) varied. Computer mouse movements were tracked to capture the decision dynamics. Although no more USs occurred, pronounced and persistent costly avoidance of the Pavlovian fear CS+ was found. Time-continuous multiple regression of movement trajectories revealed a stronger and faster impact of Pavlovian fear compared to reward information during decision-making. The impact of fear information, but not reward information, modestly decreased across trials. These findings suggest a persistently stronger weighting of fear compared to reward information during approach-avoidance decisions, which may facilitate the development of pathological avoidance.}, language = {en} } @article{EderMaasSchubmannetal.2022, author = {Eder, Andreas B. and Maas, Franzisca and Schubmann, Alexander and Krishna, Anand and Erle, Thorsten M.}, title = {Motivations underlying self-infliction of pain during thinking for pleasure}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-14775-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301059}, year = {2022}, abstract = {Previous research suggested that people prefer to administer unpleasant electric shocks to themselves rather than being left alone with their thoughts because engagement in thinking is an unpleasant activity. The present research examined this negative reinforcement hypothesis by giving participants a choice of distracting themselves with the generation of electric shock causing no to intense pain. Four experiments (N = 254) replicated the result that a large proportion of participants opted to administer painful shocks to themselves during the thinking period. However, they administered strong electric shocks to themselves even when an innocuous response option generating no or a mild shock was available. Furthermore, participants inflicted pain to themselves when they were assisted in the generation of pleasant thoughts during the waiting period, with no difference between pleasant versus unpleasant thought conditions. Overall, these results question that the primary motivation for the self-administration of painful shocks is avoidance of thinking. Instead, it seems that the self-infliction of pain was attractive for many participants, because they were curious about the shocks, their intensities, and the effects they would have on them.}, language = {en} } @article{GanuzaRedlichUhleretal.2022, author = {Ganuza, Cristina and Redlich, Sarah and Uhler, Johannes and Tobisch, Cynthia and Rojas-Botero, Sandra and Peters, Marcell K. and Zhang, Jie and Benjamin, Caryl S. and Englmeier, Jana and Ewald, J{\"o}rg and Fricke, Ute and Haensel, Maria and Kollmann, Johannes and Riebl, Rebekka and Uphus, Lars and M{\"u}ller, J{\"o}rg and Steffan-Dewenter, Ingolf}, title = {Interactive effects of climate and land use on pollinator diversity differ among taxa and scales}, series = {Science Advances}, volume = {8}, journal = {Science Advances}, number = {18}, doi = {10.1126/sciadv.abm9359}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301303}, year = {2022}, abstract = {Changes in climate and land use are major threats to pollinating insects, an essential functional group. Here, we unravel the largely unknown interactive effects of both threats on seven pollinator taxa using a multiscale space-for-time approach across large climate and land-use gradients in a temperate region. Pollinator community composition, regional gamma diversity, and community dissimilarity (beta diversity) of pollinator taxa were shaped by climate-land-use interactions, while local alpha diversity was solely explained by their additive effects. Pollinator diversity increased with reduced land-use intensity (forest < grassland < arable land < urban) and high flowering-plant diversity at different spatial scales, and higher temperatures homogenized pollinator communities across regions. Our study reveals declines in pollinator diversity with land-use intensity at multiple spatial scales and regional community homogenization in warmer and drier climates. Management options at several scales are highlighted to mitigate impacts of climate change on pollinators and their ecosystem services.}, language = {en} } @article{KooMatthewsHarrisonetal.2022, author = {Koo, Chek Ziu and Matthews, Alexandra L. and Harrison, Neale and Szyroka, Justyna and Nieswandt, Bernhard and Gardiner, Elizabeth E. and Poulter, Natalie S. and Tomlinson, Michael G.}, title = {The platelet collagen receptor GPVI is cleaved by Tspan15/ADAM10 and Tspan33/ADAM10 molecular scissors}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {5}, issn = {1422-0067}, doi = {10.3390/ijms23052440}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284468}, year = {2022}, abstract = {The platelet-activating collagen receptor GPVI represents the focus of clinical trials as an antiplatelet target for arterial thrombosis, and soluble GPVI is a plasma biomarker for several human diseases. A disintegrin and metalloproteinase 10 (ADAM10) acts as a 'molecular scissor' that cleaves the extracellular region from GPVI and many other substrates. ADAM10 interacts with six regulatory tetraspanin membrane proteins, Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 and Tspan33, which are collectively termed the TspanC8s. These are emerging as regulators of ADAM10 substrate specificity. Human platelets express Tspan14, Tspan15 and Tspan33, but which of these regulates GPVI cleavage remains unknown. To address this, CRISPR/Cas9 knockout human cell lines were generated to show that Tspan15 and Tspan33 enact compensatory roles in GPVI cleavage, with Tspan15 bearing the more important role. To investigate this mechanism, a series of Tspan15 and GPVI mutant expression constructs were designed. The Tspan15 extracellular region was found to be critical in promoting GPVI cleavage, and appeared to achieve this by enabling ADAM10 to access the cleavage site at a particular distance above the membrane. These findings bear implications for the regulation of cleavage of other ADAM10 substrates, and provide new insights into post-translational regulation of the clinically relevant GPVI protein.}, language = {en} } @article{PradaMaagSiegmundetal.2022, author = {Prada, Juan Pablo and Maag, Luca Estelle and Siegmund, Laura and Bencurova, Elena and Liang, Chunguang and Koutsilieri, Eleni and Dandekar, Thomas and Scheller, Carsten}, title = {Estimation of R0 for the spread of SARS-CoV-2 in Germany from excess mortality}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-22101-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301415}, year = {2022}, abstract = {For SARS-CoV-2, R0 calculations in the range of 2-3 dominate the literature, but much higher estimates have also been published. Because capacity for RT-PCR testing increased greatly in the early phase of the Covid-19 pandemic, R0 determinations based on these incidence values are subject to strong bias. We propose to use Covid-19-induced excess mortality to determine R0 regardless of RT-PCR testing capacity. We used data from the Robert Koch Institute (RKI) on the incidence of Covid cases, Covid-related deaths, number of RT-PCR tests performed, and excess mortality calculated from data from the Federal Statistical Office in Germany. We determined R0 using exponential growth estimates with a serial interval of 4.7 days. We used only datasets that were not yet under the influence of policy measures (e.g., lockdowns or school closures). The uncorrected R0 value for the spread of SARS-CoV-2 based on RT-PCR incidence data was 2.56 (95\% CI 2.52-2.60) for Covid-19 cases and 2.03 (95\% CI 1.96-2.10) for Covid-19-related deaths. However, because the number of RT-PCR tests increased by a growth factor of 1.381 during the same period, these R0 values must be corrected accordingly (R0corrected = R0uncorrected/1.381), yielding 1.86 for Covid-19 cases and 1.47 for Covid-19 deaths. The R0 value based on excess deaths was calculated to be 1.34 (95\% CI 1.32-1.37). A sine-function-based adjustment for seasonal effects of 40\% corresponds to a maximum value of R0January = 1.68 and a minimum value of R0July = 1.01. Our calculations show an R0 that is much lower than previously thought. This relatively low range of R0 fits very well with the observed seasonal pattern of infection across Europe in 2020 and 2021, including the emergence of more contagious escape variants such as delta or omicron. In general, our study shows that excess mortality can be used as a reliable surrogate to determine the R0 in pandemic situations.}, language = {en} } @article{ChristHaertlKlosteretal.2022, author = {Christ, Andreas and H{\"a}rtl, Patrick and Kloster, Patrick and Bode, Matthias and Leisegang, Markus}, title = {Influence of band structure on ballistic transport revealed by molecular nanoprobe}, series = {Physical Review Research}, volume = {4}, journal = {Physical Review Research}, number = {4}, doi = {10.1103/PhysRevResearch.4.043016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300855}, year = {2022}, abstract = {In this study we characterize the tautomerization of HPc on Cu(111) as a charge-carrier-induced reversible one-electron process. An analysis of the bias-dependent tautomerization rate finds an energy threshold that corresponds to the energy of the N-H stretching mode. By using the tautomerization of the molecule as a detector for charge carrier transport in the so-called molecular nanoprobe (MONA) technique, we provide evidence for an inhomogeneous coupling between the fourfold-symmetric molecule and sixfold-symmetric surface. We conclude the study by comparing the energy dependence of charge carrier transport on the Cu(111) to the Ag(111) surface. While the MONA technique is limited to the detection of hot-electron transport for Ag(111), our data reveal that the lower onset energy of the Cu surface state also allows for the detection of hot-hole transport. The influence of surface and bulk transport on the MONA technique is discussed.}, language = {en} } @phdthesis{Kneer2022, author = {Kneer, Katharina Johanna}, title = {The association of three anxiety dimensions in children and adolescents: their influence on the brain and malleability by a prevention program}, doi = {10.25972/OPUS-25746}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257468}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Anxiety disorders are the most prevalent group of neuropsychiatric disorders and go along with high personal suffering. They often arise during childhood and show a progression across the life span, thus making this age a specific vulnerable period during development. Still most research about these disorders is done in adults. In light of this, it seems of utmost importance to identify predictive factors of anxiety disorders in children and adolescents. Temperament or personality traits have been proclaimed as risk markers for the development of subsequent anxiety disorders, but their exact interplay is not clear. In this dissertation an effort is made to contribute to the understanding of how risk markers of early temperamental traits, in this case Trait Anxiety, Anxiety Sensitivity and Separation Anxiety are interplaying. While Trait Anxiety is regarded as a more general tendency to react anxiously to threatening situations or stimuli (Unnewehr, Joormann, Schneider, \& Margraf, 1992), Anxiety Sensitivity is the tendency to react with fear to one's own anxious sensations (Allan et al., 2014; S. Reiss, Peterson, Gursky, \& McNally, 1986), and Separation Anxiety is referring to the extent to which the child is avoiding certain situations because of the fear of being separated from primary care givers (In-Albon \& Schneider, 2011). In addition, it will be addressed how these measurements are associated with negative life events, as well as brain functioning and if they are malleable by a prevention program in children and adolescents. In study 1 the aim was to extend the knowledge about the interrelations of this anxiety dimensions and negative life events. Results indicated positive correlations of all three anxiety traits as well as with negative life events. Thus, a close connection of all three anxiety measures as well as with negative life events could be indicated. The closest association was found between Anxiety Sensitivity and Trait Anxiety and between Separation Anxiety and Anxiety Sensitivity. Furthermore, negative life events functioned as mediator between Anxiety Sensitivity and Trait Anxiety, indicating that a part of the association was explained by negative life events. In study 2 we extended the findings from study 1 with neurobiological parameters and examined the influence of anxiety traits on emotional brain activation by administering the "emotional face matching task". This task activated bilateral prefrontal regions as well as both hippocampi and the right amygdala. Further analyses indicated dimension-specific brain activations: Trait Anxiety was associated with a hyperactivation of the left inferior frontal gyrus (IFG) and Separation Anxiety with a lower activation bilaterally in the IFG and the right middle frontal gyrus (MFG). Furthermore, the association between Separation Anxiety and Anxiety Sensitivity was moderated by bi-hemispheric Separation-Anxiety-related IFG activation. Thus, we could identify distinct brain activation patterns for the anxiety dimensions (Trait Anxiety and Separation Anxiety) and their associations (Separation Anxiety and Anxiety Sensitivity). The aim of study 3 was to probe the selective malleability of the anxiety dimensions via a prevention program in an at-risk population. We could identify a reduction of all three anxiety traits from pre- to post-prevention-assessment and that this effect was significant in Anxiety Sensitivity and Trait Anxiety scores. Furthermore, we found that pre-intervention Separation Anxiety and Anxiety Sensitivity post-intervention were associated. In addition, pre-interventive scores were correlated with the intervention-induced change within the measure (i.e., the higher the score before the intervention the higher the prevention-induced change) and pre-intervention Anxiety Sensitivity correlated with the change in Separation Anxiety scores. All relations, seemed to be direct, as mediation/moderation analyses with negative life events did not reveal any significant effect. These results are very promising, because research about anxiety prevention in children and adolescents is still rare and our results are indicating that cognitive-behavioural-therapy based prevention is gilding significant results in an indicated sample even when samples sizes are small like in our study. In sum the present findings hint towards distinct mechanisms underlying the three different anxiety dimensions on a phenomenological and neurobiological level, though they are highly overlapping (Higa-McMillan, Francis, Rith-Najarian, \& Chorpita, 2016; Taylor, 1998). Furthermore, the closest associations were found between Anxiety Sensitivity and Trait Anxiety, as well as between Separation Anxiety and Anxiety Sensitivity. Specifically, we were able to find a neuronal manifestation of the association between Separation Anxiety and Anxiety Sensitivity (Separation Anxiety-specific IFG activation) and a predictive potential on prevention influence. The results of these studies lead to a better understanding of the etiology of anxiety disorders and the interplay between different anxiety-related temperamental traits and could lead to further valuable knowledge about the intervention as well as further prevention strategies.}, subject = {Pr{\"a}vention}, language = {en} } @phdthesis{Upcin2022, author = {Upcin, Berin}, title = {Contribution of vascular adventitia-resident progenitor cells to new vessel formation in \(ex\) \(vivo\) 3D models}, doi = {10.25972/OPUS-25507}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255070}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Ongoing research to fight cancer, one of the dominant diseases of the 21st century has led to big progress especially when it comes to understanding the tumor growth and metastasis. This includes the discovery of the molecular mechanisms of tumor vascularization, which is critically required for establishment of tumor metastasis. Formation of new blood vessels is the first step in tumor vascularization. Therefore, understanding the molecular and cellular basis of tumor vascularization attracted a significant effort studying in biomedical research. The blood vessels for supplying tumor can be formed by sprouting from pre-existing vessels, a process called angiogenesis, or by vasculogenesis, that is de novo formation of blood vessels from not fully differentiated progenitor cell populations. Vasculogenic endothelial progenitor cells (EPCs) can either be activated from populations in the bone marrow reaching the pathological region via the circulation or they can be recruited from local reservoirs. Neovessel formation influences tumor progression, hence therapeutic response model systems of angiogenesis/vasculogenesis are necessary to study the underlying mechanisms. Although, initially the research in this area focused more on angiogenesis, it is now well understood that both angiogenesis and postnatal vasculogenesis contribute to neovessel formation in adult under both most pathological as well as physiological conditions. Studies in the last two decades demonstrate that in addition to the intimal layer of fully differentiated mature endothelial cells (ECs) and various smaller supplying vessels (vasa vasorum) that can serve as a source for new vessels by angiogenesis, especially the adventitia of large and medium size blood vessels harbors various vascular wall-resident stem and progenitor cells (VW-SPCs) populations that serve as a source for new vessels by postnatal vasculogenesis. However, little is known about the potential role of VW-SPCs in tumor vascularization. To this end, the present work started first to establish a modified aortic ring assay (ARA) using mouse aorta in order to study the contribution of vascular adventitia-resident VW-SPCs to neovascularization in general and in presence of tumor cells. ARA is already established an ex vivo model for neovascularization allows to study the morphogenetic events of complex new vessel formation that includes all layers of mature blood vessels, a significant advantage over the assays that employ monolayer endothelial cell cultures. Moreover, in contrast to assays employing endothelial cells monocultures, both angiogenic and vasculogenic events take place during new vessel formation in ARA although the exact contribution of these two processes to new vessel formation cannot be easily distinguished in conventional ARA. Thus, in this study, a modified protocol for the ARA (mdARA) was established by either removing or keeping the aortic adventitia in place. The mdARA allows to distinguish the role of VW-SPCs from those of other aortic layers. The present data show that angiogenic sprouting from mature aortic endothelium was markedly delayed when the adventitial layer was removed. Furthermore, the network between the capillary-like sprouts was significantly reduced in absence of aortic adventitia. Moreover, the stabilization of new sprouts by assembling the NG2+ pericyte-like cells that enwrapped the endothelial sprouts from the outside was improved when the adventitial layer remained in place. Next, mimicking the tumor-vessel adventitia-interaction, multicellular tumor spheroids (MCTS) and aortic rings (ARs) with or without adventitia of C57BL/6-Tg (UBC-GFP) mice were confronted within the collagen gel and cultured ex vivo. This 3D model enabled analysis of the mobilization, migration and capillary-like sprouts formation by VW-SPCs within tumor-vessel wall-interface in comparison to tumor-free side of the ARs. Interestingly, while MCTS preferred the uptake of single vascular adventitia-derived cells, neural spheroids were directly penetrated by capillary-like structures that were sprouted from the aortic adventitia. In summary, the model established in this work allows to study new vessel formation by both postnatal vasculogenesis and angiogenesis under same conditions. It can be applied in various mouse models including reporter mouse models, e.g. Cxcr1 CreER+/mTmG+/- mice, in which GFP-marked macrophages of the vessel wall were directly observed as they mobilized from their niche and migrated into collagen gel. Another benefit of the model is that it can be used for testing different factors such as small molecules, growth factors, cytokines, and drugs with both pro- and anti-angiogenic/vasculogenic effects.}, language = {en} } @phdthesis{Greving2022, author = {Greving, Carla Elisabeth}, title = {Improving Learning from Texts: Distributed Practice and Distributed Learning as Desirable Difficulty in Reading Single and Multiple Texts}, doi = {10.25972/OPUS-29685}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296859}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Distributed practice is a well-known learning strategy whose beneficial effects on long-term learning are well proven by various experiments. In learning from texts, the benefits of distribution might even go beyond distributed practice, i.e. distribution of repeated materials. In realistic learning scenarios as for example school or university learning, the reader might read multiple texts that not repeat but complement each other. Therefore, distribution might also be implemented between multiple texts and benefit long-term learning in analogy to distributed practice. The assumption of beneficial effects of this distributed learning can be deduced from theories about text comprehension as the landscape model of reading (van den Broek et al., 1996) in combination with theories of desirable difficulties in general (R. A. Bjork \& Bjork, 1992) and distributed practice in particular (Benjamin \& Tullis, 2010). This dissertation aims to investigate (1) whether distributed learning benefits learning; (2) whether the amount of domain-specific prior knowledge moderates the effects of distribution, (3) whether distributed learning affects the learner's meta-cognitive judgments in analogy to distributed practice and (4) whether distributed practice is beneficial for seventh graders in learning from single text. In Experiment 1, seventh graders read two complementary texts either massed or distributed by a lag of one week between the texts. Learning outcomes were measured immediately after reading the second text and one week later. Judgements of learning were assessed immediately after each text. Experiment 2 replicated the paradigm of Experiment 1 while shortening the lag between the texts in the distributed condition to 15 min. In both experiments, an interaction effect between learning condition (distributed vs. massed) and retention interval (immediate vs. delayed) was found. In the distributed condition, the participants showed no decrease in performance between the two tests, whereas participants in the massed condition did. However, no beneficial effects were found in the delayed test for the distributed condition but even detrimental effects for the distributed condition in the immediate test. In Experiment 1, participants in the distributed condition perceived learning as less difficult but predicted lower success than the participants in the massed condition. Experiment 3 replicated the paradigm of Experiment 1 with university students in the laboratory. In the preregistered Experiment 4, an additional retention interval of two weeks was realized. In both experiments, the same interaction between learning condition and retention interval was found. In Experiment 3, the participants in the distributed condition again showed no decrease in performance between the two tests, whereas participants in the massed condition did. However, even at the longer retention interval in Experiment 4, no beneficial effects were found for the distributed condition. Domain-specific prior knowledge was positively associated with test performance in both experiments. In Experiment 4, the participants with low prior knowledge seemed to be impaired by distributed learning, whereas no difference was found for participants with medium or high prior knowledge. In the preregistered Experiment 5, seventh graders read a single text twice. The rereading took place either massed or distributed with one week. Immediately after rereading, judgements of learning were assessed. Learning outcomes were assessed four min after second reading or one week later. Participants in the distributed condition predicted lower learning success than participants in the massed condition. An interaction effect between learning condition and retention interval was found, but no advantage for the distributed condition. Participants with low domain-specific prior knowledge showed lower performance in short-answer questions in the distributed condition than in the massed condition. Overall, the results seem less encouraging regarding the effectiveness of distribution on learning from single and multiple texts. However, the experiments reported here can be perceived as first step in the realistic investigation of distribution in learning from texts.}, subject = {Textverstehen}, language = {en} } @phdthesis{Zoran2022, author = {Zoran, Tamara}, title = {Multilevel analysis of the human immune response to \(Aspergillus\) \(fumigatus\) infection: Characteristic molecular signatures and individual risk factors}, doi = {10.25972/OPUS-29851}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-298512}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Although the field of fungal infections advanced tremendously, diagnosis of invasive pulmonary aspergillosis (IPA) in immunocompromised patients continues to be a challenge. Since IPA is a multifactorial disease, investigation from different aspects may provide new insights, helpful for improving IPA diagnosis. This work aimed to characterize the human immune response to Aspergillus fumigatus in a multilevel manner to identify characteristic molecular candidates and risk factors indicating IPA, which may in the future support already established diagnostic assays. We combined in vitro studies using myeloid cells infected with A. fumigatus and longitudinal case-control studies investigating patients post allogeneic stem cell transplantation (alloSCT) suffering from IPA and their match controls. Characteristic miRNA and mRNA signatures indicating A. fumigatus-infected monocyte-derived dendritic cells (moDCs) demonstrated the potential to differentiate between A. fumigatus and Escherichia coli infection. Transcriptome and protein profiling of alloSCT patients suffering from IPA and their matched controls revealed a distinctive IPA signature consisting of MMP1 induction and LGAL2 repression in combination with elevated IL-8 and caspase-3 levels. Both, in vitro and case-control studies, suggested cytokines, matrix-metallopeptidases and galectins are important in the immune response to A. fumigatus. Identified IPA characteristic molecular candidates are involved in numerous processes, thus a combination of these in a distinctive signature may increase the specificity. Finally, low monocyte counts, severe GvHD of the gut (grade ≥ 2) and etanercept administration were significantly associated with IPA diagnosis post alloSCT. Etanercept in monocyte-derived macrophages (MDM) infected with A. fumigatus downregulates genes involved in the NF-κB and TNF-α pathway and affects the secretion of CXCL10. Taken together, identified characteristic molecular signatures and risk factors indicating IPA may in the future in combination with established fungal biomarkers overcome current diagnostic challenges and help to establish tailored antifungal therapy. Therefore, further multicentre studies are encouraged to evaluate reported findings.}, subject = {Aspergillus fumigatus}, language = {en} } @phdthesis{Knoepper2022, author = {Kn{\"o}pper, Konrad}, title = {Lymph node heterogeneity is imprinted by unconventional T cells that are organized in functional units}, doi = {10.25972/OPUS-29694}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296949}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {The immune system has the function to defend organisms against a variety of pathogens and malignancies. To perform this task, different parts of the immune system work in concert and influence each other to balance and optimize its functional output upon activation. One aspect that determines this output and ultimately the outcome of the infection is the tissue context in which the activation takes place. As such, it has been shown that dendritic cells can relay information from the infection sites to draining lymph nodes. This way, the ensuing adaptive immune response that is initiated by dendritic cells, is optimized to the tissue context in which the infection needs to be cleared. Here, we set out to investigate whether unconventional T cells (UTC) could have a similar function in directing a site-specific immune response. Using flow cytometry, scRNA-sequencing and functional assays we demonstrated that UTC indeed drive a characteristic immune response in lymph nodes depending on the drained tissues. This function of UTC was directly connected to their lymphatic migration from tissues to draining lymph nodes reminiscent of dendritic cells. Besides these tissue-derived UTC that migrated via the lymph, we further identified circulatory UTC that migrated between lymph nodes via the blood. Functional characterization of UTC following bacterial infection in wt and single TCR-based lineage deficient mice that lacked subgroups of UTC further revealed that both tissue-derived and circulatory UTC were organized in functional units independent of their TCR-based lineage-affiliation (MAIT, NKT, gd T cells). Specific reporter mouse models revealed that UTC within the same functional unit were also located in the same microanatomical areas of lymph nodes, further supporting their shared function. Our data show that the numbers and function of UTC were compensated in single TCR-based lineage deficient mice that lacked subgroups of UTC. Taken together, our results characterize the transcriptional landscape and migrational behavior of UTC in different lymph nodes. UTC contribute to a functional heterogeneity of lymph nodes, which in turn guides optimized, site-specific immune responses. Additionally, we propose the classification of UTC within functional units independent of their TCR-based lineage. These results add significantly to our understanding of UTC biology and have direct clinical implications. We hope that our data will guide targeted vaccination approaches and cell-based therapies to optimize immune responses against pathogens and cancer.}, language = {en} } @phdthesis{Hausoel2022, author = {Hausoel, Andreas}, title = {Electronic magnetism in correlated systems: from quantum materials down to Earth's core}, doi = {10.25972/OPUS-25444}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254444}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {In the last decade continuous-time quantum Monte Carlo in the hybridization expansion (CTHYB) was one of the most successful Monte Carlo techniques to describe correlated quantum phenomena in conjunction with dynamical mean field theory (DMFT). The first part of the thesis consists of algorithmical developments regarding CTHYB and DMFT. I provide a complete derivation and an extensive discussion of the expansion formula. We generalized it to treat spin-orbit coupling, and invented the superstate sampling algorithm to make it efficient enough for describing systems with general interactions, crystal fields and spin-orbit coupling at low temperatures. But CTHYB is known to fail in the standard implementation for equal-time correlators, certain higher-order Green's functions and the atomic limit; we discovered that its estimator for the Greens function is also inconsistent for Anderson impurities with finite, discrete baths. I focus then on further improvements of CTHYB that we have conceived and worked on, in particular for f-orbitals and for taking physical symmetries into account in the calculation of the Monte Carlo observables. The second part of the thesis presents selected physical applications of these methods. I show DMFT calculations of highest accuracy for elemental iron and nickel and discover a new mechanism of magnetic ordering in nickel: the ordering of band structure-induced local moments. Then we analyze the stability of this phenomenon under pressure and temperatures, that characterize in the Earth's core. We find, that the mechanism survives these conditions and may give a significant contribution to the generation of the Earth's magnetic field. The next topic is the stability of double Dirac fermions against electronic correlations. We find, that the Coulomb interaction in the corresponding material Bi2 CuO4 are strong enough to destroy the double Dirac cone, and substantial uniform pressure is necessary to restore them. In the last chapter I derive the properties of Higgs and Goldstone bosons from Ginzburg-Landau theory, and identify these excitations in a model of an excitonic magnet.}, subject = {Monte-Carlo-Simulation}, language = {en} } @phdthesis{Weissenseel2022, author = {Weißenseel, Sebastian G{\"u}nter}, title = {Spin-Spin Interactions and their Impact on Organic Light-Emitting Devices}, doi = {10.25972/OPUS-25745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257458}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {This work investigates the correlations between spin states and the light emission properties of organic light-emitting diodes (OLEDs), which are based on the principle of thermally activated delayed fluorescence. The spin-spin interactions responsible for this mechanism are investigated in this work using methods based on spin-sensitive electron paramagnetic resonance (EPR). In particular, this method has been applied to electrically driven OLEDs. The magnetic resonance has been detected by electroluminescence, giving this method its name: electroluminescence detected magnetic resonance (ELDMR). Initial investigations on a novel deep blue TADF emitter were performed. Furthermore, the ELDMR method was used in this work to directly detect the spin states in the OLED. These measurements were further underlined by time-resolved experiments such as transient electro- and photoluminescence.}, subject = {Elektronenspinresonanz}, language = {en} } @phdthesis{Brych2022, author = {Brych, Mareike Kimberly}, title = {How movements and cognition interact: An investigation of spontaneous blinks}, doi = {10.25972/OPUS-26737}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267376}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {During natural behavior, cognitive processes constantly coincide with body movements such as head or eye movements or blinks. However, during experimental investigations of cognitive processes, movements are often highly restricted which is rather unnatural. In order to improve our understanding of natural behavior, this thesis investigates the interaction between cognition and movements by focusing on spontaneous blinks, which naturally interact with other body movements. Spontaneous blinks are inevitably connected to vision as they shut out incoming visual information. Both sensory-based and cognitive factors, for example, stimulus occurrence and evaluation, were reported to influence blink behavior. Our first study investigated if such influences are comparable for visual and non-visual input. The chosen experimental design allowed dissociating sensory-driven and cognitive influences, which then could be compared between the visual and auditory domain. Our results show that blinks are more strongly modulated during passive observation of visual input compared to auditory input. This modulation is however enhanced for both input modalities by an increased attentional demand. In addition, the cognitively defined meaning of a stimulus changes blink latency independent of the sensory domain. Overall, our findings show that spontaneous blinks and cognitive processes are linked beyond vision. Moreover, the underlying cognitive processes that influence blinks are largely the same across different sensory input indicating that blinks are profoundly integrated into our system. When investigating natural behavior, it is important to consider that movements rarely occur in isolation, but are executed side by side. As these movements interact and have a link to cognitive processes, the complexity of our system increases. In order to take this complexity into account, the second part of the experimental research focused on movement interactions, more specifically on the interactions between blinks, pupil size and speaking. Our results reveal that speech-related motor activity increases blink rate and pupil size as well as modulates blink timing. This is in line with previous research that described a relation between different body and eye movements. Importantly, each bodily-induced change in eye movements affects visual information intake. Therefore, different movements can be tightly linked to perceptual processes through complex interactions. Altogether, the work of this thesis provides rich evidence that movements and cognitive processes are deeply intertwined. Therefore, movements should be seen as an integral part of our system. Taking the relevance of movements and their interactions into account during experimental investigations is necessary in order to reveal a more realistic and complete picture of human natural behavior.}, subject = {Kognition}, language = {en} } @article{KarakayaBiderFranketal.2022, author = {Karakaya, Emine and Bider, Faina and Frank, Andreas and Teßmar, J{\"o}rg and Sch{\"o}bel, Lisa and Forster, Leonard and Schr{\"u}fer, Stefan and Schmidt, Hans-Werner and Schubert, Dirk Wolfram and Blaeser, Andreas and Boccaccini, Aldo R. and Detsch, Rainer}, title = {Targeted printing of cells: evaluation of ADA-PEG bioinks for drop on demand approaches}, series = {Gels}, volume = {8}, journal = {Gels}, number = {4}, issn = {2310-2861}, doi = {10.3390/gels8040206}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267317}, year = {2022}, abstract = {A novel approach, in the context of bioprinting, is the targeted printing of a defined number of cells at desired positions in predefined locations, which thereby opens up new perspectives for life science engineering. One major challenge in this application is to realize the targeted printing of cells onto a gel substrate with high cell survival rates in advanced bioinks. For this purpose, different alginate-dialdehyde—polyethylene glycol (ADA-PEG) inks with different PEG modifications and chain lengths (1-8 kDa) were characterized to evaluate their application as bioinks for drop on demand (DoD) printing. The biochemical properties of the inks, printing process, NIH/3T3 fibroblast cell distribution within a droplet and shear forces during printing were analyzed. Finally, different hydrogels were evaluated as a printing substrate. By analysing different PEG chain lengths with covalently crosslinked and non-crosslinked ADA-PEG inks, it was shown that the influence of Schiff's bases on the viscosity of the corresponding materials is very low. Furthermore, it was shown that longer polymer chains resulted in less stable hydrogels, leading to fast degradation rates. Several bioinks highly exhibit biocompatibility, while the calculated nozzle shear stress increased from approx. 1.3 and 2.3 kPa. Moreover, we determined the number of cells for printed droplets depending on the initial cell concentration, which is crucially needed for targeted cell printing approaches.}, language = {en} } @article{HellmuthKlingenberg2022, author = {Hellmuth, Kathrin and Klingenberg, Christian}, title = {Computing Black Scholes with uncertain volatility — a machine learning approach}, series = {Mathematics}, volume = {10}, journal = {Mathematics}, number = {3}, issn = {2227-7390}, doi = {10.3390/math10030489}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262280}, year = {2022}, abstract = {In financial mathematics, it is a typical approach to approximate financial markets operating in discrete time by continuous-time models such as the Black Scholes model. Fitting this model gives rise to difficulties due to the discrete nature of market data. We thus model the pricing process of financial derivatives by the Black Scholes equation, where the volatility is a function of a finite number of random variables. This reflects an influence of uncertain factors when determining volatility. The aim is to quantify the effect of this uncertainty when computing the price of derivatives. Our underlying method is the generalized Polynomial Chaos (gPC) method in order to numerically compute the uncertainty of the solution by the stochastic Galerkin approach and a finite difference method. We present an efficient numerical variation of this method, which is based on a machine learning technique, the so-called Bi-Fidelity approach. This is illustrated with numerical examples.}, language = {en} } @phdthesis{Heinrich2022, author = {Heinrich, Robert}, title = {Multi-species gas detection based on an external-cavity quantum cascade laser spectrometer in the mid-infrared fingerprint region}, doi = {10.25972/OPUS-26864}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268640}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Laser spectroscopic gas sensing has been applied for decades for several applications as atmospheric monitoring, industrial combustion gas analysis or fundamental research. The availability of new laser sources in the mid-infrared opens the spectral fingerprint range to the technology where multiple molecules possess their fundamental ro-vibrational absorption features that allow very sensitive detection and accurate discrimination of the species. The increasing maturity of quantum cascade lasers that cover this highly interesting spectral range motivated this research to gain fundamental knowledge about the spectra of hydrocarbon gases in pure composition and in complex mixtures as they occur in the petro-chemical industry. The long-term target of developing accurate and fast hydrocarbon gas analyzers, capable of real-time operation while enabling feedback-loops, would lead to a paradigm change in this industry. This thesis aims to contribute to a higher accuracy and more comprehensive understanding of the sensing of hydrocarbon gas mixtures. This includes the acquisition of yet unavailable high resolution and high accuracy reference spectra of the respective gases, the investigation of their spectral behavior in mixtures due to collisional broadening of their transitions and the verification of the feasibility to quantitatively discriminate the spectra when several overlapping species are simultaneously measured in gas mixtures. To achieve this knowledge a new laboratory environment was planned and built up to allow for the supply of the individual gases and their arbitrary mixing. The main element was the development of a broadly tunable external-cavity quantum cascade laser based spectrometer to record the required spectra. This also included the development of a new measurement method to obtain highly resolved and nearly gap-less spectral coverage as well as a sophisticated signal post-processing that was crucial to achieve the high accuracy of the measurements. The spectroscopic setup was used for a thorough investigation of the spectra of the first seven alkanes as of their mixtures. Measurements were realized that achieved a spectral resolution of 0.001 cm-1 in the range of 6-11 µm while ensuring an accuracy of 0.001 cm-1 of the spectra and attaining a transmission sensitivity of 2.5 x 10-4 for long-time averaging of the acquired spectra. These spectral measurements accomplish a quality that compares to state-of-the art spectral databases and revealed so far undocumented details of several of the investigated gases that have not been measured with this high resolution before at the chosen measurement conditions. The results demonstrate the first laser spectroscopic discrimination of a seven component gas mixture with absolute accuracies below 0.5 vol.\% in the mid-infrared provided that a sufficiently broad spectral range is covered in the measurements. Remaining challenges for obtaining improved spectral models of the gases and limitations of the measurement accuracy and technology are discussed.}, subject = {Quantenkaskadenlaser}, language = {en} } @phdthesis{Hajer2022, author = {Hajer, Jan}, title = {Mercury Telluride Nanowires for Topological Quantum Transport}, doi = {10.25972/OPUS-29322}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293222}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Novel appraches to the molecular beam epitaxy of core-shell nanowires in the group II telluride material system were explored in this work. Significant advances in growth spurred the development of a flexible and reliable platform for a charge transport characterization of the topological insulator HgTe in a tubular nanowire geometry. The transport results presented provide an important basis for the design of future studies that strive for the experimental realization of topological charge transport in the quantum wire limit.}, subject = {Quecksilbertellurid}, language = {en} } @phdthesis{Huang2022, author = {Huang, Mingming}, title = {C-S Bond Borylation and Diborylation of Alkyl Halides, Tosylates, and Alcohols}, doi = {10.25972/OPUS-25718}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257186}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Alkylboronates play an important role in synthetic chemistry, materials science and drug discovery. They are easy to handle due to their good air and moisture stability, and can be readily employed to form carbon-carbon and carbon-heteroatom bonds and can be converted to various functional groups under mild reaction conditions. Compared with conventional groups, such as aryl (pseudo)halides or alcohols, organosulfur compounds represent an alternative and complimentary substitute in coupling reactions. The construction of C-B bond from C-SO bond of aryl sulfoxide is presented in Chapter 2. The selective cleavage of either alkyl(C)-sulfonyl or aryl(C)-sulfonyl bonds of an aryl alkyl sulfone via Cu-free or Cu-mediated processes generates the corresponding boronate esters, which are presented in Chapter 3 and Chapter 4. 1,2-Bis(boronate esters) are emerging as important synthetic intermediates for preparing 1,2-difunctional compounds. In addition, the boryl moieties in different environments in a 1,2-bis(boronate ester) can be differentiated and converted selectively, allowing the synthesis of a wide variety of complex molecules. A direct and selective diboration of C-X and C-O bonds for the preparation of 1,2-bis(boronate esters) is presented in Chapter 5.}, language = {en} } @phdthesis{Selby2022, author = {Selby, Joshua}, title = {Design and Chiroptical Properties of Chirally Substituted Indolenine Squaraine Mono-, Oligo-, and Polymers}, doi = {10.25972/OPUS-28206}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282067}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {A series of monomeric chirally substituted indolenine squaraine monomers were successfully synthesized and utilized for the construction of various oligo- and polymers, in order to study their chiroptical properties in terms of exciton chirality. The quaternary carbon atom at the 3-position of the indolenine subunit, as well as the alkyl side chain attached to the indolenine nitrogen were selected as the most suitable site for chiral functionalization. For the C(3)-chiral derivatives, two synthetic routes depending on the desired substitution at the stereogenic center were established. The chiral side chains were prepared via Evans asymmetric alkylation where the resulting branching point at the 2 position constituted the chiral center. While the chiral substitution only had minor effects on the linear optical properties and geometric structure of the chromophore, all compounds exhibited a distinct and measurable CD signal that correlated with the distance of the chiral center to the central chromophore. Polymers bearing chiral side chains exhibited a solvent- and temperature-dependent helix-coil equilibrium, which was influenced by the type of side chain used. CD spectroscopy revealed the helical conformation to possess a preferred twist sense, and temperature-dependent measurements showed the degree of homohelicity to be nearly complete in certain cases. Furthermore, a CPL signal was able to be obtained for the helical conformer of one polymer. Various (co)oligo- and polymers comprising the C(3)-chiral monomers only displayed a solvent-independent J-type absorption behavior and thus did not form helical conformations in solution. CD spectroscopy revealed a solvent-dependent adoption of quasi-enantiomeric conformers, which was elucidated by quantum chemical TDDFT calculations.}, subject = {Squaraine}, language = {en} } @phdthesis{Dirscherl2022, author = {Dirscherl, Mariel Christina}, title = {Remote Sensing of Supraglacial Lake Dynamics in Antarctica - Exploiting Methods from Artificial Intelligence for Derivation of Antarctic Supraglacial Lake Extents in Multi-Sensor Remote Sensing Data}, doi = {10.25972/OPUS-27950}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279505}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {With accelerating global climate change, the Antarctic Ice Sheet is exposed to increasing ice dynamic change. During 1992 and 2017, Antarctica contributed ~7.6 mm to global sea-level-rise mainly due to ocean thermal forcing along West Antarctica and atmospheric warming along the Antarctic Peninsula (API). Together, these processes caused the progressive retreat of glaciers and ice shelves and weakened their efficient buttressing force causing widespread ice flow accelerations. Holding ~91\% of the global ice mass and 57.3 m of sea-level-equivalent, the Antarctic Ice Sheet is by far the largest potential contributor to future sea-level-rise. Despite the improved understanding of Antarctic ice dynamics, the future of Antarctica remains difficult to predict with its contribution to global sea-level-rise representing the largest uncertainty in current projections. Given that recent studies point towards atmospheric warming and melt intensification to become a dominant driver for future Antarctic ice mass loss, the monitoring of supraglacial lakes and their impacts on ice dynamics is of utmost importance. In this regard, recent progress in Earth Observation provides an abundance of high-resolution optical and Synthetic Aperture Radar (SAR) satellite data at unprecedented spatial and temporal coverage and greatly supports the monitoring of the Antarctic continent where ground-based mapping efforts are difficult to perform. As an automated mapping technique for supraglacial lake extent delineation in optical and SAR satellite imagery as well as a pan-Antarctic inventory of Antarctic supraglacial lakes at high spatial and temporal resolution is entirely missing, this thesis aims to advance the understanding of Antarctic surface hydrology through exploitation of spaceborne remote sensing. In particular, a detailed literature review on spaceborne remote sensing of Antarctic supraglacial lakes identified several research gaps including the lack of (1) an automated mapping technique for optical or SAR satellite data that is transferable in space and time, (2) high-resolution supraglacial lake extent mappings at intra-annual and inter-annual temporal resolution and (3) large-scale mapping efforts across the entire Antarctic continent. In addition, past method developments were found to be restricted to purely visual, manual or semi-automated mapping techniques hindering their application to multi-temporal satellite imagery at large-scale. In this context, the development of automated mapping techniques was mainly limited by sensor-specific characteristics including the similar appearance of supraglacial lakes and other ice sheet surface features in optical or SAR data, the varying temporal signature of supraglacial lakes throughout the year as well as effects such as speckle noise and wind roughening in SAR data or cloud coverage in optical data. To overcome these limitations, this thesis exploits methods from artificial intelligence and big data processing for development of an automated processing chain for supraglacial lake extent delineation in Sentinel-1 SAR and optical Sentinel-2 satellite imagery. The combination of both sensor types enabled to capture both surface and subsurface lakes as well as to acquire data during cloud cover or wind roughening of lakes. For Sentinel-1, a deep convolutional neural network based on residual U-Net was trained on the basis of 21,200 labeled Sentinel-1 SAR image patches covering 13 Antarctic regions. Similarly, optical Sentinel-2 data were collected over 14 Antarctic regions and used for training of a Random Forest classifier. Optical and SAR classification products were combined through decision-level fusion at bi-weekly temporal scale and unprecedented 10 m spatial resolution. Finally, the method was implemented as part of DLR's High-Performance Computing infrastructure allowing for an automated processing of large amounts of data including all required pre- and postprocessing steps. The results of an accuracy assessment over independent test scenes highlighted the functionality of the classifiers returning accuracies of 93\% and 95\% for supraglacial lakes in Sentinel-1 and Sentinel-2 satellite imagery, respectively. Exploiting the full archive of Sentinel-1 and Sentinel-2, the developed framework for the first time enabled the monitoring of seasonal characteristics of Antarctic supraglacial lakes over six major ice shelves in 2015-2021. In particular, the results for API ice shelves revealed low lake coverage during 2015-2018 and particularly high lake coverage during the 2019-2020 and 2020-2021 melting seasons. On the contrary, East Antarctic ice shelves were characterized by high lake coverage during 2016-2019 and extremely low lake coverage during the 2020-2021 melting season. Over all six investigated ice shelves, the development of drainage systems was revealed highlighting an increased risk for ice shelf instability. Through statistical correlation analysis with climate data at varying time lags as well as annual data on Southern Hemisphere atmospheric modes, environmental drivers for meltwater ponding were revealed. In addition, the influence of the local glaciological setting was investigated through computation of annual recurrence times of lakes. Over both ice sheet regions, the complex interplay between local, regional and large-scale environmental drivers was found to control supraglacial lake formation despite local to regional discrepancies, as revealed through pixel-based correlation analysis. Local control factors included the ice surface topography, the ice shelf geometry, the presence of low-albedo features as well as a reduced firn air content and were found to exert strong control on lake distribution. On the other hand, regional controls on lake evolution were revealed to be the amount of incoming solar radiation, air temperature and wind occurrence. While foehn winds were found to dictate lake evolution over the API, katabatic winds influenced lake ponding in East Antarctica. Furthermore, the regional near-surface climate was shown to be driven by large-scale atmospheric modes and teleconnections with the tropics. Overall, the results highlight that similar driving factors control supraglacial lake formation on the API and EAIS pointing towards their transferability to other Antarctic regions.}, subject = {Optische Fernerkundung}, language = {en} } @phdthesis{Haider2022, author = {Haider, Malik Salman}, title = {Structure Property Relationship and Therapeutic Potential of Poly(2-oxazoline)s and Poly(2-oxazines)s based Amphiphiles}, doi = {10.25972/OPUS-28903}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-289036}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {In the past decade, poly(2-oxazoline)s (POx) and very recently poly(2-oxazine)s (POzi) based amphiphiles have shown great potential for medical applications. Therefore, the major aim of this thesis was to further explore the pharmaceutical and biomedical applications of POx/POzi based ABA triblock and AB diblock copolymers, respectively with the special emphasis on structure property relationship (SPR). ABA triblock copolymers (with shorter side chain length in the hydrophobic block) have shown high solubilizing capacity for hydrophobic drugs. The issue of poor aqueous solubility was initially addressed by developing a (micellar) formulation library of 21 highly diverse, hydrophobic drugs with POx/POzi based ABA triblock copolymers. Theoretically, the extent of compatibility between polymers and drug was determined by calculating solubility parameters (SPs). The SPs were thoroughly investigated to check their applicability in present systems. The selected formulations were further characterized by various physico-chemical techniques. For the biomedical applications, a novel thermoresposive diblock copolymer was synthesized which has shown promising properties to be used as hydrogel bioink or can potentially be used as fugitive support material. The most important aspect i.e. SPR, was studied with respect to hydrophilic block in either tri- or di-block copolymers. In triblock copolymer, the hydrophilic block played an important role for ultra high drug loading, while in case of diblock, it has improved the printability of the hydrogels. Apart from the basic research, the therapeutic applications of two formulations i.e. mitotane (commercially available as tablet dosage form for adrenocortical carcinoma) and BT-44 (lead compound for nerve regeneration) were studied in more detail.}, language = {en} } @phdthesis{Lewerentz2022, author = {Lewerentz, Anne F.}, title = {Spatiotemporal dynamics of freshwater macrophytes in Bavarian lakes under environmental change}, doi = {10.25972/OPUS-28770}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287700}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Macrophytes are key components of freshwater ecosystems because they provide habitat, food, and improve the water quality. Macrophyte are vulnerable to environmental change as their physiological processes depend on changing environmental factors, which themselves vary within a geographical region and along lake depth. Their spatial distribution is not well understood and their importance is publicly little-known. In this thesis, I have investigated the spatiotemporal dynamics of freshwater macrophytes in Bavarian lakes to understand their diversity pattern along different scales and to predict and communicate potential consequences of global change on their richness. In the introduction (Chapter 1), I provide an overview of the current scientific knowledge of the species richness patterns of macrophytes in freshwater lakes, the influences of climate and land-use change on macrophyte growth, and different modelling approaches of macrophytes. The main part of the thesis starts with a study about submerged and emergent macrophyte species richness in natural and artificial lakes of Bavaria (Chapter 2). By analysing publicly available monitoring data, I have found a higher species richness of submerged macrophytes in natural lakes than in artificial lakes. Furthermore, I showed that the richness of submerged species is better explained by physio-chemical lake parameters than the richness of emergent species. In Chapter 3, I considered that submerged macrophytes grow along a depth gradient that provides a sharp environmental gradient on a short spatial scale. This study is the first comparative assessment of the depth diversity gradient (DDG) of macrophytes. I have found a hump-shaped pattern of different diversity components. Generalised additive mixed-effect models indicate that the shape of the DDG is influenced mainly by light quality, light quantity, layering depth, and lake area. I could not identify a general trend of the DDG within recent years, but single lakes show trends leading into different directions. In Chapter 4, I used a mechanistic eco-physiological model to explore changes in the distribution of macrophyte species richness under different scenarios of environmental conditions across lakes and with depths. I could replicate the hump-shaped pattern of potential species richness along depth. Rising temperature leads to increased species richness in all lake types, and depths. The effect of turbidity and nutrient change depends on depth and lake type. Traits that characterise "loser species" under increased turbidity and nutrients are a high light consumption and a high sensibility to disturbances. "Winner species" can be identified by a high biomass production. In Chapter 5, I discuss the image problem of macrophytes. Unawareness, ignorance, and the poor accessibility of macrophytes can lead to conflicts of use. I assumed that an increased engagement and education could counteract this. Because computer games can transfer knowledge interactively while creating an immersive experience, I present in the chapter an interactive single-player game for children. Finally, I discuss the findings of this thesis in the light of their implications for ecological theory, their implications for conservation, and future research ideas (Chapter 6). The findings help to understand the regional distribution and the drivers of macrophyte species richness. By applying eco-physiological models, multiple environmental shaping factors for species richness were tested and scenarios of climate and land-use change were explored.}, subject = {{\"O}kologie}, language = {en} } @phdthesis{Greving2022, author = {Greving, Sven}, title = {Desirable Difficulties in Applied Learning Settings: Mechanisms and Effects}, doi = {10.25972/OPUS-28884}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288848}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Improving retention of learned content by means of a practice test is a learning strategy that has been researched since a century and has been consistently found to be more effective than comparable learning strategies such as restudy (i.e., the testing effect). Most importantly, practicing test questions has been found to outperform restudy even when no additional information about the correct answers was provided to practice test takers, rendering practice tests effective and efficient in fostering retention of learning content. Since 15 years, additional scientific attention is devoted to this memory phenomenon and additional research investigated to what extend practicing test questions is relevant in real-world educational settings. This dissertation first presents the evidence for testing effects in applied educational settings by presenting key publications and presenting findings from a methodological review conducted for this purpose. Within this dissertation, theories are presented why practicing test questions should benefit learning in real-world educational settings even without the provision of additional information and key variables for the effectiveness of practicing test questions are presented. Four studies presented in this dissertation aimed at exploring these assumptions in actual university classrooms while also trying to implement new methods of practicing learning content and thus augment course procedures. Findings from these studies—although not often consistent—will be incorporated and interpreted in the light of the theoretical accounts on the testing effect. The main conclusion that can be drawn from this dissertation is that, given the right circumstances, practicing test questions can elicit beneficial effects on the retention of learning content that are independent of additional information and thus taking a practice test per se, can foster retention of real-world learning content.}, subject = {Unterrichtspsychologie}, language = {en} } @phdthesis{Elsner2022, author = {Elsner, Clara Dorothea}, title = {Ultrastructural analysis of biogenesis and release of endothelial extracellular vesicles}, doi = {10.25972/OPUS-28852}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288526}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Extracellular vesicle (EV)-mediated intercellular communication through exosomes, microvesicles (MVs) and apoptotic bodies has been shown to be implicated in various physiological as well as pathological processes such as the development and progression of atherosclerosis. While the cellular machinery controlling EV formation and composition has been studied extensively, little is known about the underlying morphological processes. This study focuses on a detailed ultrastructural analysis of the different steps of EV formation and release in Myocardial Endothelial (MyEnd) and Aortic Endothelial (AoEnd) cells cultured under serum starvation and inflammatory stimulation with TNF-α. Detailed morphological analyses were conducted applying and comparing different high- resolution light and electron microscopic methods. In this study, we could depict all steps of MV biogenesis named in literature. However, during the study of exosome biogenesis, we discovered a yet undescribed process: Instead of a direct fusion with the plasma membrane, multivesicular bodies were incorporated into a new distinct cellular compartment bound by fenestrated endothelium first. This may present a novel step in exosome biogenesis and warrants further study. Regarding the conditions of cell cultivation, we observed that the commonly used serum starvation causes MyEnd cells, but not AoEnd cells, to enter apoptosis after 48 hours. When preparing functional EV studies, we therefore recommend assessing the morphological condition of the serum-starved cells at different cultivation points first. When evaluating MV production, a statistical analysis showed that the more time AoEnd cells spent in cultivation under serum starvation, the higher the percentage of MV producing cells. However, additional TNF-α stimulation induced a significantly higher MV production than serum starvation alone. Lastly, our results show that TNF-α stimulation of AoEnd cells in vitro leads to the upregulation of CD44, an adhesion molecule critical in the early stages of atherosclerosis. CD44 was then depicted on the surface of generated MVs and exosomes. We conclude that under inflammatory conditions, EVs can mediate the transfer of CD44 from endothelial cells to target cells. This could be a novel mechanism by which MVs contribute to the development and progression of atherosclerotic disease and should be clarified by further studies.}, subject = {Vesikel}, language = {en} } @phdthesis{Wu2022, author = {Wu, Zhu}, title = {Room Temperature Phosphorescence (RTP): Experimental And Theoretical Studies on Boron-Containing Materials}, doi = {10.25972/OPUS-26084}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260844}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Persistent room temperature phosphorescent (RTP) luminophores have gained remarkable interest recently for a number of applications in security printing, OLEDs, optical storage, time-gated biological imaging and oxygen sensors. We report the first persistent RTP with lifetimes up to 0.5 s from simple triarylboranes which have no lone pairs. We also have prepared 3 isomeric (o, m, p-bromophenyl)-bis(2,6-dimethylphenyl)boranes. Among the 3 isomers (o-, m- and p-BrTAB) synthesized, the ortho-one is the only one which shows dual phosphorescence, with a short lifetime of 0.8 ms and a long lifetime of 234 ms in the crystalline state at room temperature. At last, we checked the RTP properties from the boric acid. We found that the pure boric acid does not show RTP in the solid state.}, language = {en} } @phdthesis{Panzer2022, author = {Panzer, Sabine}, title = {Spotlight on Fungal Rhodopsins: A Microscopic and Electrophysiological Study}, doi = {10.25972/OPUS-27185}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271859}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Microbial rhodopsins are abundant membrane proteins often capable of ion transport and are found in all three domains of life. Thus, many fungi, especially phyto-associated or phyto-pathogenic ones, contain these green-light-sensing photoreceptors. Proteins that perceive other wavelengths are often well characterized in terms of their impact on fungal biology whereas little is known about the function of fungal rhodopsins. In this work, five fungal rhodopsins, UmOps1 and UmOps2 from the corn smut Ustilago maydis as well as ApOps1, ApOps2 and ApOps3 from the black yeast Aureobasidium pullulans, were characterized electrophysiologically using mammalian expression systems and the patch-clamp technique to explore their ion transport properties. The latter three were modified using a membrane trafficking cassette, termed "2.0" that consists of the lucy rho motif, two Kir2.1 Golgi apparatus trafficking signals and a Kir2.1 endoplasmic reticulum export signal, what resulted in better plasma membrane localization. Rhodopsin mutants were created to identify amino acid residues that are key players in the ion transport process. Current enhancement in the presence of weak organic acids, that was already described before for the fungal rhodopsin CarO from Fusarium fujikuroi (Garc{\´i}a-Mart{\´i}nez et al., 2015; Adam et al., 2018), was investigated for the U. maydis rhodopsins as well as for ApOps2 by supplementing acetate in the patch-clamp electrolyte solutions. All five rhodopsins were found to be proton pumps unidirectionally transporting protons out of the cytosol upon green-light exposure with every rhodopsin exhibiting special features or unique characteristics in terms of the photocurrents. To name just a few, UmOps1, for example, showed a striking pH-dependency with massive enhancement of pump currents in the presence of extracellular acidic pH. Moreover, especially ApOps2 and ApOps3 showed very high current densities, however, the ones of ApOps3 were impaired when exchanging intracellular sodium to cesium. Concerning the mutations, it was found, that the electron releasing group in UmOps1 seems to be involved in the striking pH effect and that the mutation of the proton donor site resulted in almost unfunctional proteins. Moreover, a conserved arginine inside ApOps2 was mutated to turn the proton pump into a channel. Regarding the effect of weak organic acids, acetate was able to induce enhanced pump currents in UmOps1 and ApOps2, but not in UmOps2. Due to the capability of current production upon light illumination, microbial rhodopsins are used in the research field of optogenetics that aims to control neuronal activity by light. ApOps2 was used to test its functionality in differentiated NG108-15 cells addressing the question whether it is a promising candidate that can be used as an optogenetic tool. Indeed, this rhodopsin could be functionally expressed in this experimental system. Furthermore, microscopic studies were done to elucidate the localization of selected rhodopsins in fungal cells. Therefore, conventional (confocal laser scanning or structured illumination microscopy) as well as novel super-resolution techniques (expansion or correlated light and electron microscopy) were used. This was done on U. maydis sporidia, the yeast-like form of this fungus, via eGFP-tagged UmOps1 or UmOps2 expressing strains. Moreover, CarO-eYFP expressing F. fujikuroi was imaged microscopically to confirm the plasma membrane and tonoplast localization (Garc{\´i}a-Mart{\´i}nez et al., 2015) with the help of counterstaining experiments. UmOps1 was found to reside in the plasma membrane, UmOps2 localized to the tonoplast and CarO was indeed found in both of these localizations. This work gains further insight into rhodopsin functions and paves the way for further research in terms of the biological role of rhodopsins in fungal life cycles.}, subject = {Opsin}, language = {en} } @phdthesis{Matera2022, author = {Matera, Gianluca}, title = {Global mapping of RNA-RNA interactions in \(Salmonella\) via RIL-seq}, doi = {10.25972/OPUS-26877}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268776}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {RNA represents one of the most abundant macromolecules in both eukaryotic and prokaryotic cells. Since the discovery that RNA could play important gene regulatory functions in the physiology of a cell, small regulatory RNAs (sRNAs) have been at the center of molecular biology studies. Functional sRNAs can be independently transcribed or derived from processing of mRNAs and other non-coding regions and they often associate with RNA-binding proteins (RBPs). Ever since the two major bacterial RBPs, Hfq and ProQ, were identified, the way we approach the identification and characterization of sRNAs has drastically changed. Initially, a single sRNA was annotated and its function studied with the use of low-throughput biochemical techniques. However, the development of RNA-seq techniques over the last decades allowed for a broader identification of sRNAs and their functions. The process of studying a sRNA mainly focuses on the characterization of its interacting RNA partner(s) and the consequences of this binding. By using RNA interaction by ligation and sequencing (RIL-seq), the present thesis aimed at a high-throughput mapping of the Hfq-mediated RNA-RNA network in the major human pathogen Salmonella enterica. RIL-seq was at first performed in early stationary phase growing bacteria, which enabled the identification of ~1,800 unique interactions. In- depth analysis of such complex network was performed with the aid of a newly implemented RIL-seq browser. The interactome revealed known and new interactions involving sRNAs and genes part of the envelope regulon. A deeper investigation led to the identification of a new RNA sponge of the MicF sRNA, namely OppX, involved in establishing a cross-talk between the permeability at the outer membrane and the transport capacity at the periplasm and the inner membrane. Additionally, RIL-seq was applied to Salmonella enterica grown in SPI-2 medium, a condition that mimicks the intracellular lifestyle of this pathogen, and finally extended to in vivo conditions during macrophage infection. Collectively, the results obtained in the present thesis helped unveiling the complexity of such RNA networks. This work set the basis for the discovery of new mechanisms of RNA-based regulation, for the identification of a new physiological role of RNA sponges and finally provided the first resource of RNA interactions during infection conditions in a major human pathogen.}, subject = {Small RNA}, language = {en} } @phdthesis{Hofmann2022, author = {Hofmann, Michael}, title = {Overcoming Obstacles in the Aqueous Processing of Nickel-rich Layered Oxide Cathode Materials}, doi = {10.25972/OPUS-27378}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-273787}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {The implementation of a water-based cathode manufacturing process is attractive, given the prospect of improved sustainability of future lithium-ion batteries. However, the sensitivity of many cathode materials to water poses a huge challenge. Within the scope of this work, a correlation between the water sensitivity of cathode materials from the class of layered oxides and their elemental composition was identified. In particular for the cathode material LiNi0.8Co0.15Al0.05O2 (NCA), the processes taking place in aqueous medium were clarified in detail. Based on this knowledge, the surface of NCA particles could be specifically modified, which led to a reduced water sensitivity. As a result, the electrochemical performance of cells with water-based NCA cathodes was significantly improved and a remarkable long-term cycling performance was achieved. The present work contributes to a deeper understanding of the water sensitivity of cathode materials and at the same time presents a promising approach to overcome this obstacle. Consequently, this work advances the successful widespread realization of water-based cathode manufacturing.}, subject = {Elektrochemie}, language = {en} } @phdthesis{vonRueden2022, author = {von R{\"u}den, Martin Frederik}, title = {The Venus flytrap - Role of oxylipins in trap performance of Dionaea muscipula}, doi = {10.25972/OPUS-27385}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-273854}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {A part of the plant kingdom consists of a variety of carnivorous plants. Some trap their prey using sticky leaves, others have pitfall traps where prey cannot escape once it has fallen inside. A rare trap type is the snap-trap: it appears only twice in the plant kingdom, in the genera Aldrovanda and Dionaea. Even Charles Darwin himself described Dionaea muscipula, the Venus flytrap, with the following words "This plant, commonly called Venus' fly-trap, from the rapidity and force of its movements, is one of the most wonderful in the world". For a long time now, the mechanisms of Dionaea's prey recognition, capture and utilization are of interest for scientists and have been studied intensively. Dionaea presents itself with traps wide-open, ready to catch insects upon contact. For this, the insect has to touch the trigger hairs of the opened trap twice within about 20-30 seconds. Once the prey is trapped, the trap lobes close tight, forming a hermetically sealed "green stomach". Until lately, there was only limited knowledge about the molecular and hormonal mechanisms which lead to prey capture and excretion of digestive fluids. It is known that the digestion process is very water-consuming; therefore, the interplay of digestion-inducing and digestion inhibiting substances was to be analyzed in this work, to elucidate the fine-tuning of the digestive pathway. Special attention was given to the impact of phytohormones on mRNA transcript levels of digestion-related proteins after various stimuli as well as their effect on Dionaea's physiological responses. Jasmonic acid (JA) and its isoleucine-conjugated form, JA-Ile, are an important signal in the jasmonate pathway. In the majority of non-carnivorous plants, jasmonates are critical for the defense against herbivory and pathogens. In Dionaea, this defense mechanism has been restructured towards offensive prey catching. One question in this work was how the frequency of trigger hair bendings is related to the formation of jasmonates and the induction of the digestion process. Upon contact of a prey with the trigger hairs in the inside of the trap, the trap closes and jasmonates are produced biosynthetically. JA-Ile interacts with the COI1- receptor, thereby activating the digestion pathway which leads to the secretion of digestive fluid and production of transporters needed to take up prey-derived nutrients. In this work it could be shown that the number of trigger hair bendings is positively correlated with the level and duration of transcriptional induction of several digestive enzymes/hydrolases. Abscisic acid (ABA) acts, along with many other functions, as the plant "drought stress hormone". It is synthesized either by roots as the primary sensor for water shortage or by guard cells in the leaves. ABA affects a network of several thousand genes whose regulation prepares the plant for drought and initiates protective measurements. It was known from previous work that the application of ABA for 48 hours increased the required amount of trigger hair bendings to achieve trap closure. As the digestion process is very water-intensive, the question arose how exactly the interplay between the jasmonate- and the ABA-pathway is organized, and if ABA could stop the running digestion process once it had been activated. In the present work it could be shown that the application of ABA on intact traps prior to mechanically stimulating the trigger hairs (mechanostimulation) already significantly reduced the transcription of digestive enzymes for an incubation time as short as 4 h, showing that already short-term exposure to ABA counteracts the effects of jasmonates when it comes to initiating the digestion process, but does not inhibit trap closure. Incubation for 24 and 48 hours with 100 μM active ABA had no effect on trap reopening, only very high levels of 200 μM of active ABA inhibited trap reopening but also led to tissue necrosis. As the application of ABA could reduce the transcription of digestive hydrolases, it is likely that Dionaea can stop the digestion process, if corresponding external stimuli are received. Another factor, which only emerged later, was the effect of the wounding-induced systemic jasmonate burst. As efficient as ABA was in inhibiting marker hydrolase expression after mechanostimulation in intact plants, the application of ABA on truncated traps was not able to inhibit mechanostimulation-induced marker hydrolase expression. One reason might be that the ABA-signal is perceived in the roots, and therefore truncated traps were not able to react to it. Another reason might be that the wounding desensitized the tissue for the ABAsignal. Further research is required at this point. Inhibitors of the jasmonate pathway were also used to assess their effect on the regulation of Dionaea´s hunting cycle. Coronatine-O-methyloxime proved to be a potent inhibitor of mechanostimulation-induced expression of digestive enzymes, thus confirming the key regulatory role of jasmonates for Dionaea´s prey consumption mechanism. In a parallel project, the generation of in vitro cultures from sterilized seeds and single plant parts proved successful, which may be important for stock-keeping of future transgenic lines. Protoplasts were generated from leaf blade tissue and transiently transformed, expressing the reporter protein YFP after 24 h of incubation. In the future this might be the starting point for the generation of transgenic lines or the functional testing of DNA constructs.}, subject = {Venusfliegenfalle}, language = {en} } @phdthesis{Duque2022, author = {Duque, Laura Maria Ribeiro}, title = {Effects of ozone on plants and plant-insect interactions}, doi = {10.25972/OPUS-27798}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277983}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Anthropogenic activities are causing air pollution. Amongst air pollutants, tropospheric ozone is a major threat to human health and ecosystem functioning. In this dissertation, I present three studies that aimed at increasing our knowledge on how plant exposure to ozone affects its reproduction and its interactions with insect herbivores and pollinators. For this purpose, a new fumigation system was built and placed in a greenhouse. The annual plant Sinapis arvensis (wild mustard) was used as the model plant. Plants were exposed to either 0 ppb (control) or 120 ppb of ozone, for variable amounts of time and at different points of their life cycle. After fumigation, plants were exposed to herbivores or pollinators in the greenhouse, or to both groups of insects in the field. My research shows that ozone affected reproductive performance differently, depending on the timing of exposure: plants exposed at earlier ages had their reproductive fitness increased, while plants exposed later in their life cycle showed a tendency for reduced reproductive fitness. Plant phenology was a key factor influencing reproductive fitness: ozone accelerated flowering and increased the number of flowers produced by plants exposed at early ages, while plants exposed to ozone at later ages tended to have fewer flowers. On the other hand, the ozone-mediated changes in plant-insect interactions had little impact on plant reproductive success. The strongest effect of ozone on plant-pollinator interactions was the change in the number of flower visits received per plant, which was strongly linked to the number of open flowers. This means that, as a rule, exposure of plants to ozone early in the life cycle resulted in a higher number of pollinator visits, while exposure later in the life cycle resulted in fewer flower visits by potential pollinators. An exception was observed: the higher number of visits performed by large syrphid flies to young ozone-exposed plants than to the respective control plants went beyond the increase in the number of open flowers in those plants. Also, honeybees spent more time per flower in plants exposed to ozone than on control plants, while other pollinators spent similar amounts of time in control and ozone-exposed plants. This guild-dependent preference for ozone-exposed plants may be due to species-specific preferences related to changes in the quality and quantity of floral rewards. In the field, ozone-exposed plants showed only a tendency for increased colonization by sucking herbivores and slightly more damage by chewing herbivores than control plants. On the other hand, in the greenhouse experiment, Pieris brassicae butterflies preferred control plants over ozone-exposed plants as oviposition sites. Eggs laid on ozone-exposed plants took longer to hatch, but the chances of survival were higher. Caterpillars performed better in control plants than in ozone-exposed plants, particularly when the temperature was high. Most of the described effects were dependent on the duration and timing of the ozone exposure and the observed temperature, with the strongest effects being observed for longer exposures and higher temperatures. Furthermore, the timing of exposure altered the direction of the effects. The expected climate change provides ideal conditions for further increases in tropospheric ozone concentrations, therefore for stronger effects on plants and plant-insect interactions. Acceleration of flowering caused by plant exposure to ozone may put plant-pollinator interactions at risk by promoting desynchronization between plant and pollinator activities. Reduced performance of caterpillars feeding on ozone-exposed plants may weaken herbivore populations. On the other hand, the increased plant reproduction that results from exposing young plants to ozone may be a source of good news in the field of horticulture, when similar results would be achieved in high-value crops. However, plant response to ozone is highly species-specific. In fact, Sinapis arvensis is considered a weed and the advantage conferred by ozone exposure may increase its competitiveness, with negative consequences for crops or plant communities in general. Overall, plant exposure to ozone might constitute a threat for the balance of natural and agro-ecosystems.}, subject = {Plant}, language = {en} } @phdthesis{Ghanawi2022, author = {Ghanawi, Hanaa}, title = {Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to Chromatin}, doi = {10.25972/OPUS-25849}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258492}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Motoneurons are highly compartmentalized cells with very long extensions that separate their nerve terminals from cell bodies. To maintain their extensive morphological complexity and protect their cellular integrity from neurotoxic stresses, neurons rely on the functions of RNA-binding proteins. One such protein is hnRNP R, a multifunctional protein with a plethora of roles related to RNA metabolism that comes into play in the nervous system. hnRNP R is localized mainly in the nucleus but also exists in the cytoplasm and axons of motoneurons. Increasing in vitro evidence indicates a potential function of hnRNP R in the development and maintenance of motoneurons by regulating axon growth and axonal RNA transport. Additionally, hnRNP R interacts with several proteins involved in motoneuron diseases. Hnrnpr pre-mRNA undergoes alternative splicing to produce transcripts encoding two protein isoforms: a full-length protein (hnRNP R-FL) and a shorter form lacking the N-terminal acidic domain (hnRNP R-ΔN). While the neuronal defects produced by total hnRNP R depletion have been investigated before, the contribution of individual isoforms towards such functions has remained mostly unknown. In this study, we showed that while both isoforms are expressed across multiple tissues, the full-length isoform is particularly abundant in the nervous system. We generated a mouse model for selective knockout of the full-length hnRNP R isoform (Hnrnprtm1a/tm1a) and found that the hnRNP R-∆N isoform remains expressed in these mice and is upregulated in a compensatory post-transcriptional process. We found that the truncated isoform is sufficient to support subcellular RNA transport related to axon growth in primary motoneurons. However, Hnrnprtm1a/tm1a mice show defects in DNA damage repair after exposure to γ-irradiation and etoposide. Knock down of both hnRNP R isoforms showed a similar extent of DNA damage as for motoneurons depleted of just full-length hnRNP R. Rescue experiments showed that expression of full-length hnRNP R but not of hnRNP R-ΔN can restore DNA damage repair when endogenous hnRNP R is depleted. By performing subcellular fractionation, we found that hnRNP R associates with chromatin independently from its association with pre-mRNA. Interestingly, we show that hnRNP R interacts with phosphorylated histone H2AX (γ-H2AX), following DNA damage. Proteomics analysis identifies the multifunctional protein Y-box binding protein 1 (Yb1) as one of the top interacting partners of hnRNP R. Similar to loss of full-length hnRNP R, DNA damage repair was impaired upon knockdown of Yb1 in motoneurons. Finally, we show that following exposure to γ-irradiation, Yb1 is recruited to the chromatin where it interacts with γ-H2AX, a mechanism that is dependent on the full-length hnRNP R. Taken together, this study describes a novel function of the full-length isoform of hnRNP R in maintaining the genomic integrity of motoneurons and provides new mechanistic insights into its function in DNA damage response.}, language = {en} } @phdthesis{Grossekathoefer2022, author = {Großekath{\"o}fer, Jonas David}, title = {Virtually Valid? On the Importance of Ecological Validity and Virtual Reality for Social Attention Research}, doi = {10.25972/OPUS-26041}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260417}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Gazes are of central relevance for people. They are crucial for navigating the world and communicating with others. Nevertheless, research in recent years shows that many findings from experimental research on gaze behavior cannot be transferred from the laboratory to everyday behavior. For example, the frequency with which conspecifics are looked at is considerably higher in experimental contexts than what can be observed in daily behavior. In short: findings from laboratories cannot be generalized into general statements. This thesis is dedicated to this matter. The dissertation describes and documents the current state of research on social attention through a literature review, including a meta-analysis on the /gaze cueing/ paradigm and an empirical study on the robustness of gaze following behavior. In addition, virtual reality was used in one of the first studies in this research field. Virtual reality has the potential to significantly improve the transferability of experimental laboratory studies to everyday behavior. This is because the technology enables a high degree of experimental control in naturalistic research designs. As such, it has the potential to transform empirical research in the same way that the introduction of computers to psychological research did some 50 years ago. The general literature review on social attention is extended to the classic /gaze cueing/ paradigm through a systematic review of publications and a meta-analytic evaluation (Study 1). The cumulative evidence supported the findings of primary studies: Covert spatial attention is directed by faces. However, the experimental factors included do not explain the surprisingly large variance in the published results. Thus, there seem to be further, not well-understood variables influencing these social processes. Moreover, classic /gaze cueing/ studies have limited ecological validity. This is discussed as a central reason for the lack of generalisability. Ecological validity describes the correspondence between experimental factors and realistic situations. A stimulus or an experimental design can have high and low ecological validity on different dimensions and have different influences on behavior. Empirical research on gaze following behavior showed that the /gaze cueing/ effect also occurs with contextually embedded stimuli (Study 2). The contextual integration of the directional cue contrasted classical /gaze cueing/ studies, which usually show heads in isolation. The research results can thus be transferred /within/ laboratory studies to higher ecologically valid research paradigms. However, research shows that the lack of ecological validity in experimental designs significantly limits the transferability of experimental findings to complex situations /outside/ the laboratory. This seems to be particularly the case when social interactions and norms are investigated. However, ecological validity is also often limited in these studies for other factors, such as contextual embedding /of participants/, free exploration behavior (and, thus, attentional control), or multimodality. In a first study, such high ecological validity was achieved for these factors with virtual reality, which could not be achieved in the laboratory so far (Study 3). Notably, the observed fixation patterns showed differences even under /most similar/ conditions in the laboratory and natural environments. Interestingly, these were similar to findings also derived from comparisons of eye movement in the laboratory and field investigations. These findings, which previously came from hardly comparable groups, were thus confirmed by the present Study 3 (which did not have this limitation). Overall, /virtual reality/ is a new technical approach to contemporary social attention research that pushes the boundaries of previous experimental research. The traditional trade-off between ecological validity and experimental control thus becomes obsolete, and laboratory studies can closely inherit an excellent approximation of reality. Finally, the present work describes and discusses the possibilities of this technology and its practical implementation. Within this context, the extent to which this development can still guarantee a constructive classification of different laboratory tests in the future is examined.}, subject = {Aufmerksamkeit}, language = {en} } @phdthesis{Hauser2022, author = {Hauser, Tobias Gregor}, title = {Mineralocorticoid-receptor antagonism and its metabolic consequences in haemodialysis patients}, doi = {10.25972/OPUS-25938}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259382}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Patients on haemodialysis are highly susceptible to different forms of heart failure. To date, the benefit of Mineralocorticoid-receptor antagonist (MRA) administration in haemodialysis patients remains subject to discussion. Biomarkers play an important role in therapy guidance and pose a promising tool to detect pathological processes of heart failure in an earlier stage. The randomised-controlled Mineralocorticoid-Receptor Antagonists in End-Stage Renal Disease (MiREnDa) trial was set up to investigate the effect of 50 mg of spironolactone once daily on left ventricular mass index in haemodialysis patients and several secondary endpoints. This dissertation reports findings from the MiREnDa trial on (a) the efficacy of spironolactone to influence serum levels of biomarkers of heart failure, fibrosis and inflammation and electrolytes and (b) the ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP), Galectin-3 and soluble source of tumorigenicity 2 (sST2) to reflect left ventricular hypertrophy and diastolic dysfunction assessed by imaging characteristics. Treatment of spironolactone over a 40-week period did not alter serum levels of biomarkers of heart failure, fibrosis and inflammation including NT-proBNP, Galectin-3 and sST2. A small but significant effect on serum sodium but not potassium was observed. NT-proBNP was significantly different in the presence or absence of left ventricular hypertrophy (LVH) (normal vs. LVH (median [IQR]): 2,120 [810; 5,040] vs. 6,340 [2,410; 15,360] pg/ml, p<0.01) or moderate and severe diastolic dysfunction (DD) (normal diastolic function and DD grade I vs. DD grade II and DD grade III: 2,300 [850; 6,050] vs. 12,260 [3,340; 34,830] pg/ml, p=0.02). NT-proBNP further showed a significant correlation at baseline with LVMi (Spearman's rho=0.41, p<0.001), LAVi (Spearman's rho=0.55, p<0.001) and septal E/e' (Spearman's rho=0.45, p<0.001). No correlation was observed between Galectin-3 and the investigated functional and morphological parameters. sST2 was mildly correlated to LVMi at baseline (Spearman's rho=0.21, p=0.05) and NT-proBNP at baseline (Spearman's rho=0.37, p<0.001). In conclusion, spironolactone did not affect the investigated parameters but NT-proBNP proved to be significantly correlated to cardiac imaging measurements.}, subject = {Dialyse}, language = {en} } @article{KusanSuratKelmetal.2022, author = {Kusan, Simon and Surat, G{\"u}zin and Kelm, Matthias and Anger, Friedrich and Kim, Mia and Germer, Christoph-Thomas and Schlegel, Nicolas and Flemming, Sven}, title = {Microbial spectrum and antibiotic resistance in patients suffering from penetrating Crohn's disease}, series = {Journal of Clinical Medicine}, volume = {11}, journal = {Journal of Clinical Medicine}, number = {15}, issn = {2077-0383}, doi = {10.3390/jcm11154343}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281835}, year = {2022}, abstract = {Intraabdominal abscess formation occurs in up to 30\% of patients suffering from Crohn's disease (CD). While international guidelines recommend a step-up approach with a combination of empiric antibiotic therapy and percutaneous drainage to delay or even avoid surgery, evidence about microbial spectrum in penetrating ileitis is sparse. We retrospectively assessed outcomes of 46 patients with terminal penetrating Ileitis where microbial diagnostics have been performed and compared microbial spectrum and antibiotic resistance profile of CD patients with patients suffering from diverticulitis with intraabdominal abscess formation. In both groups, the most frequently isolated pathogen was the gram-negative bacterium E. coli belonging to the family of Enterobacterales. However, overall Enterobacterales were significantly more often verifiable in the control group than in CD patients. Furthermore, microbial analysis showed significant differences regarding isolation of anaerobic pathogens with decreased frequency in patients with CD. Subgroup analysis of CD patients to evaluate a potential influence of immunosuppressive therapy on microbial spectrum only revealed that Enterobacterales was less frequently detected in patients treated with steroids. Immunosuppressive therapy did not show any impact on all other groups of pathogens and did not change antibiotic resistance profile of CD patients. In conclusion, we were able to demonstrate that the microbial spectrum of CD patients does differ only for some pathogen species without increased rate of antibiotic resistance. However, the empiric antibiotic therapy for CD-associated intra-abdominal abscess remains challenging since different points such as local epidemiological and microbiological data, individual patient risk factors, severity of infection, and therapy algorithm including non-surgical and surgical therapy options should be considered before therapeutical decisions are made.}, language = {en} } @article{OttoKastnerSchmidtetal.2022, author = {Otto, Christoph and Kastner, Carolin and Schmidt, Stefanie and Uttinger, Konstantin and Baluapuri, Apoorva and Denk, Sarah and Rosenfeldt, Mathias T. and Rosenwald, Andreas and Roehrig, Florian and Ade, Carsten P. and Schuelein-Voelk, Christina and Diefenbacher, Markus E. and Germer, Christoph-Thomas and Wolf, Elmar and Eilers, Martin and Wiegering, Armin}, title = {RNA polymerase I inhibition induces terminal differentiation, growth arrest, and vulnerability to senolytics in colorectal cancer cells}, series = {Molecular Oncology}, volume = {16}, journal = {Molecular Oncology}, number = {15}, doi = {10.1002/1878-0261.13265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312806}, pages = {2788-2809}, year = {2022}, abstract = {Ribosomal biogenesis and protein synthesis are deregulated in most cancers, suggesting that interfering with translation machinery may hold significant therapeutic potential. Here, we show that loss of the tumor suppressor adenomatous polyposis coli (APC), which constitutes the initiating event in the adenoma carcinoma sequence for colorectal cancer (CRC), induces the expression of RNA polymerase I (RNAPOL1) transcription machinery, and subsequently upregulates ribosomal DNA (rDNA) transcription. Targeting RNAPOL1 with a specific inhibitor, CX5461, disrupts nucleolar integrity, and induces a disbalance of ribosomal proteins. Surprisingly, CX5461-induced growth arrest is irreversible and exhibits features of senescence and terminal differentiation. Mechanistically, CX5461 promotes differentiation in an MYC-interacting zinc-finger protein 1 (MIZ1)- and retinoblastoma protein (Rb)-dependent manner. In addition, the inhibition of RNAPOL1 renders CRC cells vulnerable towards senolytic agents. We validated this therapeutic effect of CX5461 in murine- and patient-derived organoids, and in a xenograft mouse model. These results show that targeting ribosomal biogenesis together with targeting the consecutive, senescent phenotype using approved drugs is a new therapeutic approach, which can rapidly be transferred from bench to bedside.}, language = {en} } @article{HeydarianRuehlRawaletal.2022, author = {Heydarian, Motaharehsadat and R{\"u}hl, Eva and Rawal, Ravisha and Kozjak-Pavlovic, Vera}, title = {Tissue models for Neisseria gonorrhoeae research — from 2D to 3D}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {12}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2022.840122}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-263046}, year = {2022}, abstract = {Neisseria gonorrhoeae is a human-specific pathogen that causes gonorrhea, the second most common sexually transmitted infection worldwide. Disease progression, drug discovery, and basic host-pathogen interactions are studied using different approaches, which rely on models ranging from 2D cell culture to complex 3D tissues and animals. In this review, we discuss the models used in N. gonorrhoeae research. We address both in vivo (animal) and in vitro cell culture models, discussing the pros and cons of each and outlining the recent advancements in the field of three-dimensional tissue models. From simple 2D monoculture to complex advanced 3D tissue models, we provide an overview of the relevant methodology and its application. Finally, we discuss future directions in the exciting field of 3D tissue models and how they can be applied for studying the interaction of N. gonorrhoeae with host cells under conditions closely resembling those found at the native sites of infection.}, language = {en} } @article{KoehlerReeseKastneretal.2022, author = {K{\"o}hler, Franziska and Reese, Lena and Kastner, Carolin and Hendricks, Anne and M{\"u}ller, Sophie and Lock, Johan F. and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Surgical site infection following single-port appendectomy: a systematic review of the literature and meta-analysis}, series = {Frontiers in Surgery}, volume = {9}, journal = {Frontiers in Surgery}, issn = {2296-875X}, doi = {10.3389/fsurg.2022.919744}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276943}, year = {2022}, abstract = {Introduction Surgical site infections (SSIs) are one of the most common postoperative complications after appendectomy leading to recurrent surgery, prolonged hospital stay, and the use of antibiotics. Numerous studies and meta-analyses have been published on the effect of open versus conventional laparoscopic appendectomy (CLA) reporting faster postoperative recovery and less postoperative pain for CLA. A development from CLA has been the single-port appendectomy (SPA), associated with a better cosmesis but seemingly having a higher risk of wound infections. The aim of this systematic literature review and meta-analysis is to investigate whether reduced port or SPA alters the ratio of SSIs. Methods Pubmed, Embase, and Cochrane databases were screened for suitable articles. All articles published between January 1, 2002, and March 23, 2022, were included. Articles regarding children below the age of 18 were excluded as well as manuscripts that investigated solemnly open appendectomies. Articles were screened for inclusion criteria by two independent authors. Incidence of SSI was the primary outcome. Duration of operation and length of hospital stay were defined as secondary outcomes. Results A total of 25 studies were found through a database search describing 5484 patients. A total of 2749 patients received SPA and 2735 received CLA. There was no statistical difference in the rate of SSI (P = 0.98). A total of 22 studies including 4699 patients reported the duration of operation (2223 SPA and 2476 CLA). There was a significantly shorter operation time seen in CLA. The length of hospital stay was reported in 23 studies (4735 patients: 2235 SPA and 2500 CLA). A shorter hospital stay was seen in the SPA group (P < 0.00001). Separately performed analysis of randomized controlled trials could not confirm this effect (P = 0.29). Discussion SPA is an equally safe procedure considering SSI compared to CLA and does not lead to an increased risk of SSI. A longer operation time for SPA and a minor difference in the length of stay does lead to the use of SPA in selected patients only.}, language = {en} } @article{HendricksMeirHankiretal.2022, author = {Hendricks, Anne and Meir, Michael and Hankir, Mohammed and Lenschow, Christina and Germer, Christoph-Thomas and Schneider, Michael and Wiegering, Armin and Schlegel, Nicolas}, title = {Suppurative thyroiditis caused by ingested fish bone in the thyroid gland: a case report on its diagnostics and surgical therapy}, series = {BMC Surgery}, volume = {22}, journal = {BMC Surgery}, number = {1}, doi = {10.1186/s12893-022-01542-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299775}, year = {2022}, abstract = {Background Accidental ingestion of fish bone is a common cause of otolaryngological emergency. Migration of the ingested bone into the thyroid gland, however, occurs very rarely. The associated clinical presentation, symptoms and duration of discomfort are also highly variable between patients and can be diagnostically challenging. Case presentation Here, we report the case of a 71-year-old female patient presenting with an ingested fish bone that migrated into the right thyroid lobe as a rare cause of suppurative thyroiditis with the clinical features of sepsis. We outline the diagnostic approach, peri- and intraoperative management as well as complications. It is proposed that besides endoscopy, imaging methods such as ultrasound or computed tomography may be necessary to verify the diagnosis and location of an ingested fish bone. Prompt surgical removal of the foreign body and resection of the infectious focus is recommended to minimize the risk of local inflammation, recurrent nerve lesions and septic complications arising from the spread of infection. Conclusion Fish bone migration into the thyroid gland is an extremely rare event, the successful detection and surgical management of which can be achieved through a careful interdisciplinary approach.}, language = {en} } @techreport{LohGeisslerHossfeld2022, type = {Working Paper}, author = {Loh, Frank and Geißler, Stefan and Hoßfeld, Tobias}, title = {LoRaWAN Network Planning in Smart Environments: Towards Reliability, Scalability, and Cost Reduction}, series = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, journal = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, doi = {10.25972/OPUS-28082}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280829}, pages = {4}, year = {2022}, abstract = {The goal in this work is to present a guidance for LoRaWAN planning to improve overall reliability for message transmissions and scalability. At the end, the cost component is discussed. Therefore, a five step approach is presented that helps to plan a LoRaWAN deployment step by step: Based on the device locations, an initial gateway placement is suggested followed by in-depth frequency and channel access planning. After an initial planning phase, updates for channel access and the initial gateway planning is suggested that should also be done periodically during network operation. Since current gateway placement approaches are only studied with random channel access, there is a lot of potential in the cell planning phase. Furthermore, the performance of different channel access approaches is highly related on network load, and thus cell size and sensor density. Last, the influence of different cell planning ideas on expected costs are discussed.}, subject = {Datennetz}, language = {en} } @phdthesis{Klinke2022, author = {Klinke, Christopher Matthias}, title = {Experimental investigation of the effect of distal stress induction on threat conditioning in humans}, doi = {10.25972/OPUS-22556}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225562}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Stress constitutes a major risk factor for the development of psychiatric disorders, such as PTSD and anxiety disorders, by shifting the brain into a state of sensitization and makes it more vulnerable when being exposed to further aversive events. This was experimentally in-vestigated in rodents by examining the effect of a distal stress induction on threat conditioning, where stress impaired extinction learning and caused spontaneous recovery. However, this effect has never been experimentally investigated in humans, so far. Thus, the aim of this dissertation was to investigate the effect of distal stress on threat conditioning in humans. Therefore, two subsequent studies were conducted. For both studies, the threat conditioning paradigm comprised threat acquisition, extinction learning, and re-extinction. In the threat acquisition phase, two geometrical shapes were used as conditioned stimulus (CS), from which one (CS+) was paired with a painful electric stimulus (unconditioned stimulus, US), but not the other one (CS-). During extinction learning 24 h later and re-extinction seventeen days later, CSs were again presented but without any US delivery. In Study 1, 69 participants underwent either a stress (socially evaluated cold pressor test; SECPT) or sham protocol 10 days prior to threat conditioning. Furthermore, context effects were examined by placing the stress protocol in the same context (context-A stress, and sham group) or a different context (context-B stress group) than conditioning. Results revealed that the context-A, but not context-B, stress group displayed impaired safety learning (i.e. potenti-ation towards CS-) for startle response during threat acquisition. Moreover, the same stress group showed impaired threat extinction, evident in sustained CS discrimination in valence and arousal ratings during extinction learning, and memory recall. In sum, distal stress on the one hand impaired safety learning during threat conditioning on a level of startle response. On the other hand, stress impaired threat extinction on a level of ratings. Noteworthy, the effect of distal stress was only found when the stressor was placed in the same context as later threat learning. Hence, suggesting that the combination of stressor and stressor-associated context exerted the effect on threat extinction. In Study 2, it was examined if distal stress induction could also have an impact on threat and extinction processes without the necessity of context association. Therefore, the same stress (n = 45) or sham protocol (n = 44) as in Study 1 was conducted in a different context than and 24 h prior to a threat conditioning paradigm. Similar to Study 1, weakened extinction learning was found in fear ratings for the stress (vs. sham) group, which was indicated by persistent CS+/CS- differentiation after the first block of extinction trials. Alterations in safety learning towards the CS- during threat acquisition were only supported by significant correlations between stress measures on the stress day and conditioned startle response of the CS- during acquisition. Taken together, in two subsequent studies this dissertation provided first evidence of impaired threat extinction after distal stress induction in humans. Furthermore, impairments in safety learning, as can be observed in PTSD, were additionally demonstrated. Interestingly, the effects were boosted and more profound when associating the stressor to the later learning context. These results have clinical implications as they can be translated to the notion that prior stress exposure makes an individual more vulnerable for later aversive events.}, subject = {Stress}, language = {en} }