@unpublished{WohlgemuthMiyazakiTsukadaetal.2017, author = {Wohlgemuth, Matthias and Miyazaki, Mitsuhiko and Tsukada, Kohei and Weiler, Martin and Dopfer, Otto and Fujii, Masaaki and Mitrić, Roland}, title = {Deciphering environment effects in peptide bond solvation dynamics by experiment and theory}, series = {Physical Chemistry Chemical Physics}, journal = {Physical Chemistry Chemical Physics}, doi = {10.1039/C7CP03992A}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159483}, year = {2017}, abstract = {Most proteins work in aqueous solution and the interaction with water strongly affects their structure and function. However, experimentally the motion of a specific single water molecule is difficult to trace by conventional methods, because they average over the heterogeneous solvation structure of bulk water surrounding the protein. Here, we provide a detailed atomistic picture of the water rearrangement dynamics around the -CONH- peptide linkage in the two model systems formanilide and acetanilide, which simply differ by the presence of a methyl group at the peptide linkage. The combination of picosecond pump-probe time-resolved infrared spectroscopy and molecular dynamics simulations demonstrates that the solvation dynamics at the molecular level is strongly influenced by this small structural difference. The effective timescales for solvent migration triggered by ionization are mainly controlled by the efficiency of the kinetic energy redistribution rather than the shape of the potential energy surface. This approach provides a fundamental understanding of protein hydration and may help to design functional molecules in solution with tailored properties.}, language = {en} } @article{WohllebenScherzadGuettleretal.2015, author = {Wohlleben, Gisela and Scherzad, Agmal and G{\"u}ttler, Antje and Vordermark, Dirk and Kuger, Sebastian and Flentje, Michael and Polat, Buelent}, title = {Influence of hypoxia and irradiation on osteopontin expression in head and neck cancer and glioblastoma cell lines}, series = {Radiation Oncology}, volume = {10}, journal = {Radiation Oncology}, number = {167}, doi = {10.1186/s13014-015-0473-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125746}, year = {2015}, abstract = {Background Tumor hypoxia is a known risk factor for reduced response to radiotherapy. The evaluation of noninvasive methods for the detection of hypoxia is therefore of interest. Osteopontin (OPN) has been discussed as an endogenous hypoxia biomarker. It is overexpressed in many cancers and is involved in tumor progression and metastasis. Methods To examine the influence of hypoxia and irradiation on osteopontin expression we used different cell lines (head and neck cancer (Cal27 and FaDu) and glioblastoma multiforme (U251 and U87)). Cells were treated with hypoxia for 24 h and were then irradiated with doses of 2 and 8 Gy. Osteopontin expression was analyzed on mRNA level by quantitative real-time RT-PCR (qPCR) and on protein level by western blot. Cell culture supernatants were evaluated for secreted OPN by ELISA. Results Hypoxia caused an increase in osteopontin protein expression in all cell lines. In Cal27 a corresponding increase in OPN mRNA expression was observed. In contrast the other cell lines showed a reduced mRNA expression under hypoxic conditions. After irradiation OPN mRNA expression raised slightly in FaDu and U87 cells while it was reduced in U251 and stable in Cal27 cells under normoxia. The combined treatment (hypoxia and irradiation) led to a slight increase of OPN mRNA after 2 Gy in U251 (24 h) and in U87 (24 and 48 h) cell lines falling back to base line after 8 Gy. This effect was not seen in Cal27 or in FaDu cells. Secreted OPN was detected only in the two glioblastoma cell lines with reduced protein levels under hypoxic conditions. Again the combined treatment resulted in a minor increase in OPN secretion 48 hours after irradiation with 8 Gy. Conclusion Osteopontin expression is strongly modulated by hypoxia and only to a minor extent by irradiation. Intracellular OPN homeostasis seems to vary considerably between cell lines. This may explain the partly conflicting results concerning response prediction and prognosis in the clinical setting.}, language = {en} } @article{WohlwendCravenWeigeltetal.2021, author = {Wohlwend, Michael R. and Craven, Dylan and Weigelt, Patrick and Seebens, Hanno and Winter, Marten and Kreft, Holger and Zurell, Damaris and Sarmento Cabral, Juliano and Essl, Franz and van Kleunen, Mark and Pergl, Jan and Pyšek, Petr and Knight, Tiffany M.}, title = {Anthropogenic and environmental drivers shape diversity of naturalized plants across the Pacific}, series = {Diversity and Distributions}, volume = {27}, journal = {Diversity and Distributions}, number = {6}, doi = {10.1111/ddi.13260}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239925}, pages = {1120 -- 1133}, year = {2021}, abstract = {Aim The Pacific exhibits an exceptional number of naturalized plant species, but the drivers of this high diversity and the associated compositional patterns remain largely unknown. Here, we aim to (a) improve our understanding of introduction and establishment processes and (b) evaluate whether this information is sufficient to create scientific conservation tools, such as watchlists. Location Islands in the Pacific Ocean, excluding larger islands such as New Zealand, Japan, the Philippines and Indonesia. Methods We combined information from the most up-to-date data sources to quantify naturalized plant species richness and turnover across island groups and investigate the effects of anthropogenic, biogeographic and climate drivers on these patterns. In total, we found 2,672 naturalized plant species across 481 islands and 50 island groups, with a total of 11,074 records. Results Most naturalized species were restricted to few island groups, and most island groups have a low number of naturalized species. Island groups with few naturalized species were characterized by a set of widespread naturalized species. Several plant families that contributed many naturalized species globally also did so in the Pacific, particularly Fabaceae and Poaceae. However, many families were significantly over- or under-represented in the Pacific naturalized flora compared to other regions of the world. Naturalized species richness increased primarily with increased human activity and island altitude/area, whereas similarity between island groups in temperature along with richness differences was most important for beta diversity. Main conclusions The distribution and richness of naturalized species can be explained by a small set of drivers. The Pacific region contains many naturalized plant species also naturalized in other regions in the world, but our results highlight key differences such as a stronger role of anthropogenic drivers in shaping diversity patterns. Our results establish a basis for predicting and preventing future naturalizations in a threatened biodiversity hotspot.}, language = {en} } @article{WohnradeVellingMixetal.2023, author = {Wohnrade, Camilla and Velling, Ann-Kathrin and Mix, Lucas and Wurster, Claudia D. and Cordts, Isabell and Stolte, Benjamin and Zeller, Daniel and Uzelac, Zeljko and Platen, Sophia and Hagenacker, Tim and Deschauer, Marcus and Lingor, Paul and Ludolph, Albert C. and Lul{\´e}, Doroth{\´e}e and Petri, Susanne and Osmanovic, Alma and Schreiber-Katz, Olivia}, title = {Health-related quality of life in spinal muscular atrophy patients and their caregivers — a prospective, cross-sectional, multi-center analysis}, series = {Brain Sciences}, volume = {13}, journal = {Brain Sciences}, number = {1}, issn = {2076-3425}, doi = {10.3390/brainsci13010110}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305048}, year = {2023}, abstract = {Spinal muscular atrophy (SMA) is a disabling disease that affects not only the patient's health-related quality of life (HRQoL), but also causes a high caregiver burden (CGB). The aim of this study was to evaluate HRQoL, CGB, and their predictors in SMA. In two prospective, cross-sectional, and multi-center studies, SMA patients (n = 39) and SMA patient/caregiver couples (n = 49) filled in the EuroQoL Five Dimension Five Level Scale (EQ-5D-5L) and the Short Form Health Survey 36 (SF-36). Caregivers (CGs) additionally answered the Zarit Burden Interview (ZBI) and the Hospital Anxiety and Depression Scale (HADS). Patients were clustered into two groups with either low or high HRQoL (EQ-5D-5L index value <0.259 or >0.679). The latter group was mostly composed of ambulatory type III patients with higher motor/functional scores. More severely affected patients reported low physical functioning but good mental health and vitality. The CGB (mean ZBI = 22/88) correlated negatively with patients' motor/functional scores and age. Higher CGB was associated with a lower HRQoL, higher depression and anxiety, and more health impairments of the CGs. We conclude that patient and CG well-being levels interact closely, which highlights the need to consider the health of both parties while evaluating novel treatments.}, language = {en} } @article{WolfAkrapMargetal.2013, author = {Wolf, Annette and Akrap, Nina and Marg, Berenice and Galliardt, Helena and Heiligentag, Martyna and Humpert, Fabian and Sauer, Markus and Kaltschmidt, Barbara and Kaltschmidt, Christian and Seidel, Thorsten}, title = {Elements of Transcriptional Machinery Are Compatible among Plants and Mammals}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0053737}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131203}, pages = {e53737}, year = {2013}, abstract = {In the present work, the objective has been to analyse the compatibility of plant and human transcriptional machinery. The experiments revealed that nuclear import and export are conserved among plants and mammals. Further it has been shown that transactivation of a human promoter occurs by human transcription factor NF-\(\kappa\) B in plant cells, demonstrating that the transcriptional machinery is highly conserved in both kingdoms. Functionality was also seen for regulatory elements of NF-\(\kappa\) B such as its inhibitor I\(\kappa\)B isoform \(\alpha\) that negatively regulated the transactivation activity of the p50/RelA heterodimer by interaction with NF-\(\kappa\)B in plant cells. Nuclear export of RelA could be demonstrated by FRAP-measurements so that RelA shows nucleo-cytoplasmic shuttling as reported for RelA in mammalian cells. The data reveals the high level of compatibility of human transcriptional elements with the plant transcriptional machinery. Thus, Arabidopsis thaliana mesophyll protoplasts might provide a new heterologous expression system for the investigation of the human NF-\(\kappa\)B signaling pathways. The system successfully enabled the controlled manipulation of NF-\(\kappa\)B activity. We suggest the plant protoplast system as a tool for reconstitution and analyses of mammalian pathways and for direct observation of responses to e. g. pharmaceuticals. The major advantage of the system is the absence of interference with endogenous factors that affect and crosstalk with the pathway.}, language = {en} } @phdthesis{Wolf2017, author = {Wolf, Beat}, title = {Reducing the complexity of OMICS data analysis}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153687}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {The field of genetics faces a lot of challenges and opportunities in both research and diagnostics due to the rise of next generation sequencing (NGS), a technology that allows to sequence DNA increasingly fast and cheap. NGS is not only used to analyze DNA, but also RNA, which is a very similar molecule also present in the cell, in both cases producing large amounts of data. The big amount of data raises both infrastructure and usability problems, as powerful computing infrastructures are required and there are many manual steps in the data analysis which are complicated to execute. Both of those problems limit the use of NGS in the clinic and research, by producing a bottleneck both computationally and in terms of manpower, as for many analyses geneticists lack the required computing skills. Over the course of this thesis we investigated how computer science can help to improve this situation to reduce the complexity of this type of analysis. We looked at how to make the analysis more accessible to increase the number of people that can perform OMICS data analysis (OMICS groups various genomics data-sources). To approach this problem, we developed a graphical NGS data analysis pipeline aimed at a diagnostics environment while still being useful in research in close collaboration with the Human Genetics Department at the University of W{\"u}rzburg. The pipeline has been used in various research papers on covering subjects, including works with direct author participation in genomics, transcriptomics as well as epigenomics. To further validate the graphical pipeline, a user survey was carried out which confirmed that it lowers the complexity of OMICS data analysis. We also studied how the data analysis can be improved in terms of computing infrastructure by improving the performance of certain analysis steps. We did this both in terms of speed improvements on a single computer (with notably variant calling being faster by up to 18 times), as well as with distributed computing to better use an existing infrastructure. The improvements were integrated into the previously described graphical pipeline, which itself also was focused on low resource usage. As a major contribution and to help with future development of parallel and distributed applications, for the usage in genetics or otherwise, we also looked at how to make it easier to develop such applications. Based on the parallel object programming model (POP), we created a Java language extension called POP-Java, which allows for easy and transparent distribution of objects. Through this development, we brought the POP model to the cloud, Hadoop clusters and present a new collaborative distributed computing model called FriendComputing. The advances made in the different domains of this thesis have been published in various works specified in this document.}, subject = {Bioinformatik}, language = {en} } @article{WolfKuonenDandekaretal.2015, author = {Wolf, Beat and Kuonen, Pierre and Dandekar, Thomas and Atlan, David}, title = {DNAseq workflow in a diagnostic context and an example of a user friendly implementation}, series = {BioMed Research International}, journal = {BioMed Research International}, number = {403497}, doi = {10.1155/2015/403497}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144527}, year = {2015}, abstract = {Over recent years next generation sequencing (NGS) technologies evolved from costly tools used by very few, to a much more accessible and economically viable technology. Through this recently gained popularity, its use-cases expanded from research environments into clinical settings. But the technical know-how and infrastructure required to analyze the data remain an obstacle for a wider adoption of this technology, especially in smaller laboratories. We present GensearchNGS, a commercial DNAseq software suite distributed by Phenosystems SA. The focus of GensearchNGS is the optimal usage of already existing infrastructure, while keeping its use simple. This is achieved through the integration of existing tools in a comprehensive software environment, as well as custom algorithms developed with the restrictions of limited infrastructures in mind. This includes the possibility to connect multiple computers to speed up computing intensive parts of the analysis such as sequence alignments. We present a typical DNAseq workflow for NGS data analysis and the approach GensearchNGS takes to implement it. The presented workflow goes from raw data quality control to the final variant report. This includes features such as gene panels and the integration of online databases, like Ensembl for annotations or Cafe Variome for variant sharing.}, 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{WolfBraunHainingetal.2016, author = {Wolf, Karen and Braun, Attila and Haining, Elizabeth J. and Tseng, Yu-Lun and Kraft, Peter and Schuhmann, Michael K. and Gotru, Sanjeev K. and Chen, Wenchun and Hermanns, Heike M. and Stoll, Guido and Lesch, Klaus-Peter and Nieswandt, Bernhard}, title = {Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice}, series = {PLoS One}, volume = {11}, journal = {PLoS One}, number = {1}, doi = {10.1371/journal.pone.0147664}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146399}, pages = {e0147664}, year = {2016}, abstract = {Background Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation. Objective To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke. Methods: 5-HT transporter knockout mice (5Htt\(^{-/-}\)) were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke. Results In 5Htt\(^{-/-}\) platelets, 5-HT uptake from the blood was completely abolished and agonist-induced Ca2+ influx through store operated Ca\(^{2+}\) entry (SOCE), integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) were reduced. These observed in vitro defects in 5Htt\(^{-/-}\) platelets could be normalized by the addition of exogenous 5-HT. Moreover, reduced 5-HT levels in the plasma, an increased bleeding time and the formation of unstable thrombi were observed ex vivo under flow and in vivo in the abdominal aorta and carotid artery of 5Htt\(^{-/-}\) mice. Surprisingly, in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke 5Htt\(^{-/-}\) mice showed nearly normal infarct volume and the neurological outcome was comparable to control mice. Conclusion Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization.}, language = {en} } @phdthesis{Wolf2002, author = {Wolf, Katarina}, title = {Migration of tumor cells and leukocytes in extracellular matrix : proteolytic and nonproteolytic strategies for overcoming tissue barriers}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-5670}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2002}, abstract = {The extracellular matrix within connective tissues represents a structural scaffold as well as a barrier for motile cells, such as invading tumor cells or passenger leukocytes. It remains unclear how different cell types utilize matrix-degrading enzymes for proteolytic migration strategies and, on the other hand, non-proteolytic strategies to overcome 3D fibrillar matrix networks. To monitor cell migration, a 3D collagen model in vitro or the mouse dermis in vivo were used, in combination with time-lapse video-, confocal- or intravital multiphoton-microscopy, and computer-assisted cell tracking. Expression of proteases, including several MMPs, ADAMs, serine proteases and cathepsins, was shown by flow cytometry, Western blot, zymography, and RT-PCR. Protease activity by migrating HT-1080 fibrosarcoma cells resulting in collagenolysis in situ and generation of tube-like matrix defects was detected by three newly developed techniques:(i) quantitative FITC-release from FITC-labelled collagen, (ii) structural alteration of the pyhsical matrix structure (macroscopically and microscopically), and (iii) the visualization of focal in situ cleavage of individual collagen fibers. The results show that highly invasive ollagenolytic cells utilized a spindle-shaped "mesenchymal" migration strategy, which involved beta1 integrindependent interaction with fibers, coclustering of beta1 integrins and matrix metalloproteinases (MMPs) at fiber bundling sites, and the proteolytic generation of a tube-like matrix-defect by MMPs and additional proteases. In contrast to tumor cells, activated T cells migrated through the collagen fiber network by flexible "amoeboid" crawling including a roundish, elliptoid shape and morphological adaptation along collagen fibers, which was independent of collagenase function and fiber degradation. Abrogation of collagenolysis in tumor cells was achieved by a cocktail of broad-spectrum protease inhibitors at non-toxic conditions blocking collagenolysis by up to 95\%. While in T cells protease inhibition induced neither morphodynamic changes nor reduced migration rates, in tumor cells a time-dependent conversion was obtained from proteolytic mesenchymal to non-proteolytic amoeboid migration in collagen lattices in vitro as well as the mouse dermis in vivo monitored by intravital microscopy. Tumor cells vigorously squeezed through matrix gaps and formed constriction rings in regions of narrow space, while the matrix structure remained intact. MMPs were excluded from fiber binding sites and beta1 integrin distribution was non-clustered linear. Besides for fibrosarcoma cells, this mesenchymal-toameboid transition (MAT) was confirmed for epithelial MDA-MB-231 breast carcinoma cells. In conclusion, cells of different origin exhibit significant diversity as well as plasticity of protease function in migration. In tumor cells, MAT could respresent a functionally important cellular and molecular escape pathway in tumor invasion and migration.}, subject = {Zellmigration}, language = {en} } @article{WolfKlugHackenbergetal.1992, author = {Wolf, Markus and Klug, J{\"o}rg and Hackenberg, Reinhard and Gessler, Manfred and Grzeschik, Karl-Heinz and Beato, Miguel and Suske, Guntram}, title = {Human CC10, the homologue of rabbit uteroglobin: genomic cloning, chromosomal localization and expression in endometrial cell lines}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59206}, year = {1992}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{Wolf2021, author = {Wolf, Matthias}, title = {How to teach about what is a species}, series = {Biology}, volume = {10}, journal = {Biology}, number = {6}, issn = {2079-7737}, doi = {10.3390/biology10060523}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241052}, year = {2021}, abstract = {To ask students what a species is always has something rhetorical about it. Too quickly comes the rote answer, often learned by heart without ever thinking about it: "A species is a reproductive community of populations (reproductively isolated from others), which occupies a specific niche in nature" (Mayr 1982). However, do two people look alike because they are twins or are they twins because they look alike? "Two organisms do not belong to the same species because they mate and reproduce, but they only are able to do so because they belong to the same species" (Mahner and Bunge 1997). Unfortunately, most biology (pre-university) teachers have no opinion on whether species are real or conceptual, simply because they have never been taught the question themselves, but rather one answer they still pass on to their students today, learned by heart without ever thinking about it. Species are either real or conceptual and, in my opinion, it is this "or" that we should teach about. Only then can we discuss those fundamental questions such as who or what is selected, who or what evolves and, finally, what is biodiversity and phylogenetics all about? Individuals related to each other by the tree of life.}, language = {en} } @article{WolfChenSongetal.2013, author = {Wolf, Matthias and Chen, Shilin and Song, Jingyuan and Ankenbrand, Markus and M{\"u}ller, Tobias}, title = {Compensatory Base Changes in ITS2 Secondary Structures Correlate with the Biological Species Concept Despite Intragenomic Variability in ITS2 Sequences - A Proof of Concept}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0066726}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96450}, year = {2013}, abstract = {Compensatory base changes (CBCs) in internal transcribed spacer 2 (ITS2) rDNA secondary structures correlate with Ernst Mayr's biological species concept. This hypothesis also referred to as the CBC species concept recently was subjected to large-scale testing, indicating two distinct probabilities. (1) If there is a CBC then there are two different species with a probability of ~0.93. (2) If there is no CBC then there is the same species with a probability of ~0.76. In ITS2 research, however, the main problem is the multicopy nature of ITS2 sequences. Most recently, 454 pyrosequencing data have been used to characterize more than 5000 intragenomic variations of ITS2 regions from 178 plant species, demonstrating that mutation of ITS2 is frequent, with a mean of 35 variants per species, respectively per individual organism. In this study, using those 454 data, the CBC criterion is reconsidered in the light of intragenomic variability, a proof of concept, a necessary criterion, expecting no intragenomic CBCs in variant ITS2 copies. In accordance with the CBC species concept, we could demonstrate that the probability that there is no intragenomic CBC is ~0.99.}, language = {en} } @article{WolfBrandstetterBeutnerHessetal.2020, author = {Wolf-Brandstetter, C and Beutner, R and Hess, R and Bierbaum, S and Wagner, K and Scharnweber, D and Gbureck, U and Moseke, C}, title = {Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements}, series = {Biomedical Materials}, volume = {15}, journal = {Biomedical Materials}, number = {2}, doi = {10.1088/1748-605X/ab5d7b}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254085}, year = {2020}, abstract = {For decades, the main focus of titanium implants developed to restore bone functionality was on improved osseointegration. Additional antimicrobial properties have now become desirable, due to the risk that rising antibiotic resistance poses for implant-associated infections. To this end, the trace elements of copper and zinc were integrated into calcium phosphate based coatings by electrochemically assisted deposition. In addition to their antimicrobial activity, zinc is reported to attract bone progenitor cells through chemotaxis and thus increase osteogenic differentiation, and copper to stimulate angiogenesis. Quantities of up to 68.9 ± 0.1 μg cm\(^{-2}\) of copper and 56.6 ± 0.4 μg cm\(^{-2}\) of zinc were deposited; co-deposition of both ions did not influence the amount of zinc but slightly increased the amount of copper in the coatings. The release of deposited copper and zinc species was negligible in serum-free simulated body fluid. In protein-containing solutions, a burst release of up to 10 μg ml\(^{-1}\) was observed for copper, while zinc was released continuously for up to 14 days. The presence of zinc was beneficial for adhesion and growth of human mesenchymal stromal cells in a concentration-dependent manner, but cytotoxic effects were already visible for coatings with an intermediate copper content. However, co-deposited zinc could somewhat alleviate the adverse effects of copper. Antimicrobial tests with E. coli revealed a decrease in adherent bacteria on brushite without copper or zinc of 60\%, but if the coating contained both ions there was almost no bacterial adhesion after 12 h. Coatings with high zinc content and intermediate copper content had the overall best multifunctional properties.}, language = {en} } @article{WolfahrtHermanScholzetal.2013, author = {Wolfahrt, Sonja and Herman, Sandra and Scholz, Claus-J{\"u}rgen and Sauer, Georg and Deissler, Helmut}, title = {Identification of alternative transcripts of rat CD9 expressed by tumorigenic neural cell lines and in normal tissues}, series = {Genetics and Molecular Biology}, volume = {36}, journal = {Genetics and Molecular Biology}, number = {2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131801}, pages = {276-281}, year = {2013}, abstract = {CD9 is the best-studied member of the tetraspanin family of transmembrane proteins. It is involved in various fundamental cellular processes and its altered expression is a characteristic of malignant cells of different origins. Despite numerous investigations confirming its fundamental role, the heterogeneity of CD9 or other tetraspanin proteins was considered only to be caused by posttranslational modification, rather than alternative splicing. Here we describe the first identification of CD9 transcript variants expressed by cell lines derived from fetal rat brain cells. Variant mRNA-B lacks a potential translation initiation codon in the alternative exon 1 and seems to be characteristic of the tumorigenic BT cell lines. In contrast, variant mRNA-C can be translated from a functional initiation codon located in its extended exon 2, and substantial amounts of this form detected in various tissues suggest a contribution to CD9 functions. From the alternative sequence of variant C, a different membrane topology ( 5 transmembrane domains) and a deviating spectrum of functions can be expected.}, language = {en} } @article{WolffRutter2012, author = {Wolff, Alexander and Rutter, Iganz}, title = {Augmenting the Connectivity of Planar and Geometric Graphs}, series = {Journal of Graph Algorithms and Applications}, journal = {Journal of Graph Algorithms and Applications}, doi = {10.7155/jgaa.00275}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97587}, year = {2012}, abstract = {In this paper we study connectivity augmentation problems. Given a connected graph G with some desirable property, we want to make G 2-vertex connected (or 2-edge connected) by adding edges such that the resulting graph keeps the property. The aim is to add as few edges as possible. The property that we consider is planarity, both in an abstract graph-theoretic and in a geometric setting, where vertices correspond to points in the plane and edges to straight-line segments. We show that it is NP-hard to � nd a minimum-cardinality augmentation that makes a planar graph 2-edge connected. For making a planar graph 2-vertex connected this was known. We further show that both problems are hard in the geometric setting, even when restricted to trees. The problems remain hard for higher degrees of connectivity. On the other hand we give polynomial-time algorithms for the special case of convex geometric graphs. We also study the following related problem. Given a planar (plane geometric) graph G, two vertices s and t of G, and an integer c, how many edges have to be added to G such that G is still planar (plane geometric) and contains c edge- (or vertex-) disjoint s{t paths? For the planar case we give a linear-time algorithm for c = 2. For the plane geometric case we give optimal worst-case bounds for c = 2; for c = 3 we characterize the cases that have a solution.}, language = {en} } @article{WolffWeikampBatinic2018, author = {Wolff, Hans-Georg and Weikamp, Julia G. and Batinic, Bernad}, title = {Implicit Motives as Determinants of Networking Behaviors}, series = {Frontiers in Psychology}, volume = {9}, journal = {Frontiers in Psychology}, number = {411}, issn = {1664-1078}, doi = {10.3389/fpsyg.2018.00411}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189954}, year = {2018}, abstract = {In today's world of work, networking behaviors are an important and viable strategy to enhance success in work and career domains. Concerning personality as an antecedent of networking behaviors, prior studies have exclusively relied on trait perspectives that focus on how people feel, think, and act. Adopting a motivational perspective on personality, we enlarge this focus and argue that beyond traits predominantly tapping social content, motives shed further light on instrumental aspects of networking - or why people network. We use McClelland's implicit motives framework of need for power (nPow), need for achievement (nAch), and need for affiliation (nAff) to examine instrumental determinants of networking. Using a facet theoretical approach to networking behaviors, we predict differential relations of these three motives with facets of (1) internal vs. external networking and (2) building, maintaining, and using contacts. We conducted an online study, in which we temporally separate measures (N = 539 employed individuals) to examine our hypotheses. Using multivariate latent regression, we show that nAch is related to networking in general. In line with theoretical differences between networking facets, we find that nAff is positively related to building contacts, whereas nPow is positively related to using internal contacts. In sum, this study shows that networking is not only driven by social factors (i.e., nAff), but instead the achievement motive is the most important driver of networking behaviors.}, language = {en} } @phdthesis{Wolfrom2002, author = {Wolfrom, Martin}, title = {Isoparametric hypersurfaces with a homogeneous focal manifold}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-3505}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2002}, abstract = {The classification of isoparametric hypersurfaces in spheres with a homogeneous focal manifold is a project that has been started by Linus Kramer. It extends results by E. Cartan and Hsiang and Lawson. Kramer does most part of this classification in his Habilitationsschrift. In particular he obtains a classification for the cases where the homogeneous focal manifold is at least 2-connected. Results of E. Cartan, Dorfmeister and Neher, and Takagi also solve parts of the classification problem. This thesis completes the classification. We classify all closed isoparametric hypersurfaces in spheres with g>2 distinct principal curvatures one of whose multiplicities is 2 such that the lower dimensional focal manifold is homogeneous. The methods are essentially the same as in Kramer's 'Habilitationsschrift'. The cohomology of the focal manifolds in question is known. This leads to two topological classification problems, which are also solved in this thesis. We classify simply connected homogeneous spaces of compact Lie groups with the same integral cohomology ring as a product of spheres S^2 x S^m and m odd on the one hand and a truncated polynomial ring Q[a]/(a^m) with one generator of even degree and m > 1 as its rational cohomology ring on the other hand.}, subject = {Isoparametrische Hyperfl{\"a}che}, language = {en} } @article{WollbornWunderStixetal.2015, author = {Wollborn, Jakob and Wunder, Christian and Stix, Jana and Neuhaus, Winfried and Bruno, Rapahel R. and Baar, Wolfgang and Flemming, Sven and Roewer, Norbert and Schlegel, Nicolas and Schick, Martin A.}, title = {Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression}, series = {Journal of Pharmacology and Pharmacotherapeutics}, volume = {6}, journal = {Journal of Pharmacology and Pharmacotherapeutics}, number = {1}, doi = {10.4103/0976-500X.149138}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149336}, pages = {13-23}, year = {2015}, abstract = {Objective: To investigate the impact of the phophodiesterase-4 inhibition (PD-4-I) with rolipram on hepatic integrity in lipopolysaccharide (LPS) induced hyperinflammation. Materials and Methods: Liver microcirculation in rats was obtained using intravital microscopy. Macrohemodynamic parameters, blood assays, and organs were harvested to determine organ function and injury. Hyperinflammation was induced by LPS and PD-4-I rolipram was administered intravenously one hour after LPS application. Cell viability of HepG2 cells was measured by EZ4U-kit based on the dye XTT. Experiments were carried out assessing the influence of different concentrations of tumor necrosis factor alpha (TNF-α) and LPS with or without PD-4-I. Results: Untreated LPS-induced rats showed significantly decreased liver microcirculation and increased hepatic cell death, whereas LPS + PD-4-I treatment could improve hepatic volumetric flow and cell death to control level whithout influencing the inflammatory impact. In HepG2 cells TNF-α and LPS significantly reduced cell viability. Coincubation with PD-4-I increased HepG2 viability to control levels. The heme oxygenase 1 (HO-1) pathway did not induce the protective effect of PD-4-I. Conclusion: Intravenous PD-4-I treatment was effective in improving hepatic microcirculation and hepatic integrity, while it had a direct protective effect on HepG2 viability during inflammation.}, language = {en} } @phdthesis{Wollmershaeuser2003, author = {Wollmersh{\"a}user, Timo}, title = {A theory of managed floating}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-8676}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2003}, abstract = {After the experience with the currency crises of the 1990s, a broad consensus has emerged among economists that such shocks can only be avoided if countries that decided to maintain unrestricted capital mobility adopt either independently floating exchange rates or very hard pegs (currency boards, dollarisation). As a consequence of this view which has been enshrined in the so-called impossible trinity all intermediate currency regimes are regarded as inherently unstable. As far as the economic theory is concerned, this view has the attractive feature that it not only fits with the logic of traditional open economy macro models, but also that for both corner solutions (independently floating exchange rates with a domestically oriented interest rate policy; hard pegs with a completely exchange rate oriented monetary policy) solid theoretical frameworks have been developed. Above all the IMF statistics seem to confirm that intermediate regimes are indeed less and less fashionable by both industrial countries and emerging market economies. However, in the last few years an anomaly has been detected which seriously challenges this paradigm on exchange rate regimes. In their influential cross-country study, Calvo and Reinhart (2000) have shown that many of those countries which had declared themselves as 'independent floaters' in the IMF statistics were charaterised by a pronounced 'fear of floating' and were actually heavily reacting to exchange rate movements, either in the form of an interest rate response, or by intervening in foreign exchange markets. The present analysis can be understood as an approach to develop a theoretical framework for this managed floating behaviour that - even though it is widely used in practice - has not attracted very much attention in monetary economics. In particular we would like to fill the gap that has recently been criticised by one of the few 'middle-ground' economists, John Williamson, who argued that "managed floating is not a regime with well-defined rules" (Williamson, 2000, p. 47). Our approach is based on a standard open economy macro model typically employed for the analysis of monetary policy strategies. The consequences of independently floating and market determined exchange rates are evaluated in terms of a social welfare function, or, to be more precise, in terms of an intertemporal loss function containing a central bank's final targets output and inflation. We explicitly model the source of the observable fear of floating by questioning the basic assumption underlying most open economy macro models that the foreign exchange market is an efficient asset market with rational agents. We will show that both policy reactions to the fear of floating (an interest rate response to exchange rate movements which we call indirect managed floating, and sterilised interventions in the foreign exchange markets which we call direct managed floating) can be rationalised if we allow for deviations from the assumption of perfectly functioning foreign exchange markets and if we assume a central bank that takes these deviations into account and behaves so as to reach its final targets. In such a scenario with a high degree of uncertainty about the true model determining the exchange rate, the rationale for indirect managed floating is the monetary policy maker's quest for a robust interest rate policy rule that performs comparatively well across a range of alternative exchange rate models. We will show, however, that the strategy of indirect managed floating still bears the risk that the central bank's final targets might be negatively affected by the unpredictability of the true exchange rate behaviour. This is where the second policy measure comes into play. The use of sterilised foreign exchange market interventions to counter movements of market determined exchange rates can be rationalised by a central bank's effort to lower the risk of missing its final targets if it only has a single instrument at its disposal. We provide a theoretical model-based foundation of a strategy of direct managed floating in which the central bank targets, in addition to a short-term interest rate, the nominal exchange rate. In particular, we develop a rule for the instrument of intervening in the foreign exchange market that is based on the failure of foreign exchange market to guarantee a reliable relationship between the exchange rate and other fundamental variables.}, language = {en} } @article{WoloshynPressleySchneider1992, author = {Woloshyn, Vera E. and Pressley, Michael and Schneider, Wolfgang}, title = {Elaborative interrogation as a function of prior knowledge}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62187}, year = {1992}, abstract = {No abstract available}, subject = {Psychologie}, language = {en} } @phdthesis{Wolpert2008, author = {Wolpert, Daniel}, title = {Quantum Control of Photoinduced Chemical Reactions}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-27171}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {The control of quantum mechanical processes, especially the selective manipulation of photochemical reactions by shaped fs laser pulses was successfully demonstrated in many experiments in the fields of physics, chemistry and biology. In this work, attention is directed to the control of two systems that mark a bridge to real synthetic chemistry. In a liquid phase environment the outcome of the photo-induced Wolff rearrangement of an industrially relevant diazonaphthoquinone compound, normally used in photoresists (e.g. Novolak) was optimized using shaped fs laser pulses. In the second series of experiments chemical reactions on a catalyst metal surface which comprise laser induced molecular bond formation channels were selectively manipulated for the first time. The control of liquid phase reactions necessitates adequate spectroscopic signals that are characteristic for the formed product species. Therefore, a pump-probe setup for transient absorption spectroscopy in the mid-infrared for the purpose of investigating ultrafast structural changes of molecules during photoreactions was constructed. This versatile setup enables to monitor structural changes of molecules in the liquid phase and to find appropriate feedback signals for the control of these processes. Prior to quantum control experiments, the photoinduced Wolff-rearrangement reaction of 2-diazo-1-naphthoquinone (DNQ) dissolved in water and methanol was thoroughly investigated. Steady state absorption measurements in the mid-infrared in combination with quantum chemical density functional theory (DFT) calculations revealed the characteristic vibrational bands of DNQ and of possible products. A mid-infrared transient absorption study was performed, to illuminate the structural dynamics of the ultrafast rearrangement reaction of DNQ. The experimental observations indicate, that the Wolff rearrangement reaction of DNQ proceeds within 300 fs. A model for the relaxation dynamics of the ketene photoproduct and DNQ after photoexcitation can be deduced that fits the measured data very well. The object of the quantum control experiments on DNQ was the improvement of the ketene yield. It was shown that the ketene formation after Wolff rearrangement of DNQ is very sensitive to the shape of the applied excitation laser pulses. The variation of single parameters, like the linear chirp as well as the pulse separation of colored double pulses lead to the conclusion that the well known intrapulse dumping mechanism is responsible for the impact of the frequency ordering within the excitation pulse on the photoproduct yield. Adaptive optimizations using a closed learning loop basically lead to the same result. Adaptive fs quantum control was also applied to surface reactions on a catalyst metal surface for the first time. Therefore, the laser-induced catalytic reactions of carbon monoxide (CO) and hydrogen (H2) on a Pd(100) single crystal surface were studied. This photochemical reaction initiated with fs laser pulses has not been observed before. Several product molecules could be synthesized, among them also species (e.g. CH^3+) for whose formation three particles are involved. The systematic variation of different parameters showed that the reactions are sensitive to the catalyst surface, the composition of the adsorbate and to the laser properties. A pump-probe study revealed that they occur on an ultrafast time scale. These catalytic surface reactions were then investigated and improved with phaseshaped fs laser pulses. By applying a feedback optimal control scheme, the reaction outcome could be successfully manipulated and the ratio of different reaction channels could be selectively controlled. Evidence has been found that the underlying control mechanism is nontrivial and sensitive to the specific conditions on the surface. The experiments shown here represent the first successful experiment on adaptive fs quantum control of a chemical reaction between adsorbate molecules on a surface. In contrast to previous quantum control experiments, reaction channels comprising the formation of new molecular bonds rather than the cleavage of already existing bonds are controlled. This work successfully showed that quantum control can be extended to systems closer to situations encountered in synthetic chemistry as was demonstrated in the two examples of the optimization of a complicated rearrangement reaction and the selective formation of chemical bonds with shaped fs laser pulses.}, subject = {Nichtlineare Spektroskopie}, language = {en} } @phdthesis{Wolski2011, author = {Wolski, Stefanie Carola}, title = {Structural and functional characterization of nucleotide excision repair proteins}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67183}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {XPD is a 5'-3' helicase of the superfamily 2. As part of the transcription factor IIH it functions in transcription initiation and nucleotide excision repair. This work focus on the role of XPD in nucleotide excision repair. NER is a DNA repair pathway unique for its broad substrate range. In placental mammals NER is the only repair mechanism able to remove lesions induced by UV-light. NER can be divided into four different steps that are conserved between pro- and eukaryotes. Step 1 consists of the initial damage recognition, during step 2 the putative damage is verified, in step 3 the verified damage is excised and in the 4th and final step the resulting gap in the DNA is refilled. XPD was shown to be involved in the damage verification step. It was possible to solve the first apo XPD structure by a MAD approach using only the endogenous iron from the iron sulfur cluster. Based on the apo XPD structure several questions arise: where is DNA bound? Where is DNA separated? How is damage verification achieved? What is the role of the FeS cluster? These questions were addressed in this work. Hypothesis driven structure based functional mutagenesis was employed and combined with detailed biochemical characterization of the variants. The variants were analyzed by thermal unfolding studies to exclude the possibility that the overall stability could be affected by the point mutation. DNA binding assays, ATPase assays and helicase assays were performed to delineate amino acid residues important for DNA binding, helicase activity and damage recognition. A structure of XPD containing a four base pair DNA fragment was solved by molecular replacement. This structure displays the polarity of the translocated strand with respect to the helicase framework. Moreover the properties of the FeS cluster were studied by electron paramagnetic resonance to get insights into the role of the FeS cluster. Furthermore XPD from Ferroplasma acidarmanus was investigated since it was shown that it is stalled at CPD containing lesions. The data provide the first detailed insight into the translocation mechanism of a SF2B helicase and reveal how polarity is achieved. This provides a basis for further anlayses understanding the combined action of the helicase and the 4Fe4S cluster to accomplish damage verification within the NER cascade.}, subject = {DNS-Reparatur}, language = {en} } @phdthesis{Wolter2015, author = {Wolter, Patrick}, title = {Characterization of the mitotic localization and function of the novel DREAM target GAS2L3 and Mitotic kinesins are regulated by the DREAM complex, often up-regulated in cancer cells, and are potential targets for anti-cancer therapy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122531}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {The recently discovered human DREAM complex (for DP, RB-like, E2F and MuvB complex) is a chromatin-associated pocket protein complex involved in cell cycle- dependent gene expression. DREAM consists of five core subunits and forms a complex either with the pocket protein p130 and the transcription factor E2F4 to repress gene expression or with the transcription factors B-MYB and FOXM1 to promote gene expression. Gas2l3 was recently identified by our group as a novel DREAM target gene. Subsequent characterization in human cell lines revealed that GAS2L3 is a microtubule and F-actin cross-linking protein, expressed in G2/M, plays a role in cytokinesis, and is important for chromosomal stability. The aim of the first part of the study was to analyze how expression of GAS2L3 is regulated by DREAM and to provide a better understanding of the function of GAS2L3 in mitosis and cytokinesis. ChIP assays revealed that the repressive and the activating form of DREAM bind to the GAS2L3 promoter. RNA interference (RNAi) mediated GAS2L3 depletion demonstrated the requirement of GAS2L3 for proper cleavage furrow ingression in cytokinesis. Immunofluorescence-based localization studies showed a localization of GAS2L3 at the mitotic spindle in mitosis and at the midbody in cytokinesis. Additional experiments demonstrated that the GAS2L3 GAR domain, a putative microtubule- binding domain, is responsible for GAS2L3 localization to the constriction zones in cytokinesis suggesting a function for GAS2L3 in the abscission process. DREAM is known to promote G2/M gene expression. DREAM target genes include several mitotic kinesins and mitotic microtubule-associated proteins (mitotic MAPs). However, it is not clear to what extent DREAM regulates mitotic kinesins and MAPs, so far. Furthermore, a comprehensive study of mitotic kinesin expression in cancer cell lines is still missing. Therefore, the second major aim of the thesis was to characterize the regulation of mitotic kinesins and MAPs by DREAM, to investigate the expression of mitotic kinesins in cancer cell line panels and to evaluate them as possible anti-cancer targets. ChIP assays together with RNAi mediated DREAM subunit depletion experiments demonstrated that DREAM is a master regulator of mitotic kinesins. Furthermore, expression analyses in a panel of breast and lung cancer cell lines revealed that mitotic kinesins are up-regulated in the majority of cancer cell lines in contrast to non-transformed controls. Finally, an inducible lentiviral-based shRNA system was developed to effectively deplete mitotic kinesins. Depletion of selected mitotic kinesins resulted in cytokinesis failures and strong anti-proliferative effects in several human cancer cell lines. Thus, this system will provide a robust tool for future investigation of mitotic kinesin function in cancer cells.}, subject = {Zellzyklus}, language = {en} } @article{WolterHanselmannPattschulletal.2017, author = {Wolter, Patrick and Hanselmann, Steffen and Pattschull, Grit and Schruf, Eva and Gaubatz, Stefan}, title = {Central spindle proteins and mitotic kinesins are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cell lines and are potential targets for therapy}, series = {Oncotarget}, volume = {8}, journal = {Oncotarget}, number = {7}, doi = {10.18632/oncotarget.14466}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171851}, pages = {11160-11172}, year = {2017}, abstract = {The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1. We demonstrate that six mitotic kinesins and two microtubule-associated non-motor proteins (MAPs) CEP55 and PRC1 are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cells. Suppression of KIF23 and PRC1 strongly suppressed proliferation of MDA-MB-231 cells. The set of MMB-FOXM1 regulated kinesins genes and 4 additional kinesins which we referred to as the mitotic kinesin signature (MKS) is linked to poor outcome in breast cancer patients. Thus, mitotic kinesins could be used as prognostic biomarker and could be potential therapeutic targets for the treatment of breast cancer.}, language = {en} } @article{WolterAizezersFenneletal.2012, author = {Wolter, Steffen and Aizezers, Janis and Fennel, Franziska and Seidel, Marcus and W{\"u}rthner, Frank and K{\"u}hn, Oliver and Lochbrunner, Stefan}, title = {Size-dependent exciton dynamics in one-dimensional perylene bisimide aggregates}, series = {New Journal of Physics}, volume = {14}, journal = {New Journal of Physics}, number = {105027}, doi = {10.1088/1367-2630/14/10/105027}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135190}, year = {2012}, abstract = {The size-dependent exciton dynamics of one-dimensional aggregates of substituted perylene bisimides are studied by ultrafast transient absorption spectroscopy and kinetic Monte-Carlo simulations as a function of the excitation density and the temperature in the range of 25-90 degrees C. For low temperatures, the aggregates can be treated as infinite chains and the dynamics is dominated by diffusion-driven exciton-exciton annihilation. With increasing temperature the aggregates dissociate into small fragments consisting of very few monomers. This scenario is also supported by the time-dependent anisotropy deduced from polarization-dependent experiments.}, language = {en} } @phdthesis{Wolter2014, author = {Wolter, Steve}, title = {Single-molecule localization algorithms in super-resolution microscopy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-109370}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2014}, abstract = {Lokalisationsmikroskopie ist eine Methodenklasse der superaufl{\"o}senden Fluoreszenzmikroskopie, deren Methoden sich durch stochastische zeitliche Isolation der Fluoreszenzemission auszeichnen. Das Blinkverhalten von Fluorophoren wird so ver{\"a}ndert, dass gleichzeitige Aktivierung von einander nahen Fluorophoren unwahrscheinlich ist. Bekannte okalisationsmikroskopische Methoden umfassen dSTORM, STORM, PALM, FPALM, oder GSDIM. Lokalisationsmikroskopie ist von hohem biologischem Interesse, weil sie die Aufl{\"o}sung des Fluoreszenzmikroskops bei minimalem technischem Aufwand um eine Gr{\"o}ßenordnung verbessert. Der verbundene Rechenaufwand ist allerdings erheblich, da Millionen von Fluoreszenzemissionen einzeln mit Nanometergenauigkeit lokalisiert werden m{\"u}ssen. Der Rechen- und Implementationsaufwand dieser Auswertung hat die Verbreitung der superaufl{\"o}senden Mikroskopie lange verz{\"o}gert. Diese Arbeit beschreibt meine algorithmische Grundstruktur f{\"u}r die Auswertung lokalisationsmikroskopischer Daten. Die Echtzeitf{\"a}higkeit, d.h. eine Auswertegeschwindigkeit oberhalb der Datenaufnahmegeschwindigkeit an normalen Messaufbauten, meines neuartigen und quelloffenen Programms wird demonstriert. Die Geschwindigkeit wird auf verbrauchermarktg{\"a}ngigen Prozessoren erreicht und dadurch spezialisierte Rechenzentren oder der Einsatz von Grafikkarten vermieden. Die Berechnung wird mit dem allgemein anerkannten Gaussschen Punktantwortmodell und einem Rauschmodell auf Basis der gr{\"o}ßten Poissonschen Wahrscheinlichkeit durchgef{\"u}hrt. Die algorithmische Grundstruktur wird erweitert, um robuste und optimale Zweifarbenauswertung zu realisieren und damit korrelative Mikroskopie zwischen verschiedenen Proteinen und Strukturen zu erm{\"o}glichen. Durch den Einsatz von kubischen Basissplines wird die Auswertung von dreidimensionalen Proben vereinfacht und stabilisiert, um pr{\"a}zisem Abbilden von mikrometerdicken Proben n{\"a}her zu kommen. Das Grenzverhalten von Lokalisationsalgorithmen bei hohen Emissionsdichten wird untersucht. Abschließend werden Algorithmen f{\"u}r die Anwendung der Lokalisationsmikroskopie auf verbreitete Probleme der Biologie aufgezeigt. Zellul{\"a}re Bewegung und Motilit{\"a}t werden anhand der in vitro Bewegung von Myosin-Aktin-Filamenten studiert. Lebendzellbildgebung mit hellen und stabilen organischen Fluorophoren wird mittels SNAP-tag-Fusionsproteinen realisiert. Die Analyse des Aufbaus von Proteinklumpen zeigt, wie Lokalisationsmikroskopie neue quantitative Ans{\"a}tze jenseits reiner Bildgebung bietet.}, subject = {Fluoreszenzmikroskopie}, language = {en} } @article{WolterEndesfelderLindeetal.2011, author = {Wolter, Steve and Endesfelder, Ulrike and Linde, Sebastian van de and Heilemann, Mike and Sauer, Markus}, title = {Measuring localization performance of super-resolution algorithms on very active samples}, series = {Optics Express}, journal = {Optics Express}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85936}, year = {2011}, abstract = {Super-resolution fluorescence imaging based on inglemolecule localization relies critically on the availability of efficient processing algorithms to distinguish, identify, and localize emissions of single fluorophores. In multiple current applications, such as threedimensional, time-resolved or cluster imaging, high densities of fluorophore emissions are common. Here, we provide an analytic tool to test the performance and quality of localization microscopy algorithms and demonstrate that common algorithms encounter difficulties for samples with high fluorophore density. We demonstrate that, for typical single-molecule localization microscopy methods such as dSTORM and the commonly used rapidSTORM scheme, computational precision limits the acceptable density of concurrently active fluorophores to 0.6 per square micrometer and that the number of successfully localized fluorophores per frame is limited to 0.2 per square micrometer.}, language = {en} } @article{WondergemHerrmannSyrbuetal.2014, author = {Wondergem, Marielle J. and Herrmann, Ken and Syrbu, Sergei and Zijlstra, Jos{\´e}e M. and Hoetjes, Nikie and Hoekstra, Otto S. and Cillessen, Saskia A. G. M. and Moesbergen, Laura M. and Buck, Andreas K. and Vose, Julie M. and Juweid, Malik E.}, title = {18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair}, series = {EJNMMI Research}, volume = {4}, journal = {EJNMMI Research}, doi = {10.1186/2191-219x-4-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121233}, pages = {3}, year = {2014}, abstract = {BACKGROUND: We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL). METHODS: We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed. RESULTS: 18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10\% (range, 10\% to 20\%) in FL and 70\% (40\% to 80\%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90\% (range, 80 to 100), 90\% (80 to 100) and 100\% (80 to 100) in FL versus 90\% (60 to 100), 90\% (60 to 100) and 100\% (80 to 100) in DLBCL, respectively. CONCLUSIONS: This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma.}, language = {en} } @article{WongPittig2022, author = {Wong, Alex H. K. and Pittig, Andre}, title = {A dimensional measure of safety behavior: A non-dichotomous assessment of costly avoidance in human fear conditioning}, series = {Psychological Research}, volume = {86}, journal = {Psychological Research}, number = {1}, issn = {1430-2772}, doi = {10.1007/s00426-021-01490-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267688}, pages = {312-330}, year = {2022}, abstract = {Safety behavior prevents the occurrence of threat, thus it is typically considered adaptive. However, safety behavior in anxiety-related disorders is often costly, and persists even the situation does not entail realistic threat. Individuals can engage in safety behavior to varying extents, however, these behaviors are typically measured dichotomously (i.e., to execute or not). To better understand the nuances of safety behavior, this study developed a dimensional measure of safety behavior that had a negative linear relationship with the admission of an aversive outcome. In two experiments, a Reward group receiving fixed or individually calibrated incentives competing with safety behavior showed reduced safety behavior than a Control group receiving no incentives. This allowed extinction learning to a previously learnt warning signal in the Reward group (i.e., updating the belief that this stimulus no longer signals threat). Despite the Reward group exhibited extinction learning, both groups showed a similar increase in fear to the warning signal once safety behavior was no longer available. This null group difference was due to some participants in the Reward group not incentivized enough to disengage from safety behavior. Dimensional assessment revealed a dissociation between low fear but substantial safety behavior to a safety signal in the Control group. This suggests that low-cost safety behavior does not accurately reflect the fear-driven processes, but also other non-fear-driven processes, such as cost (i.e., engage in safety behavior merely because it bears little to no cost). Pinpointing both processes is important for furthering the understanding of safety behavior.}, language = {en} } @phdthesis{Wong2001, author = {Wong, Amanda}, title = {Implications of Advanced Glycation Endproducts in Oxidative Stress and Neurodegenerative Disorders}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-2537}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2001}, abstract = {The reactions of reducing sugars with primary amino groups are the most common nonenzymatic modifications of proteins. Subsequent rearrangements, oxidations, and dehydrations yield a heterogeneous group of mostly colored and fluorescent compounds, termed "Maillard products" or advanced glycation end products (AGEs). AGE formation has been observed on long-lived proteins such as collagen, eye lens crystalline, and in pathological protein deposits in Alzheimer's (AD) and Parkinson's disease (PD) and dialysis-related amyloidosis. AGE-modified proteins are also involved in the complications of diabetes. AGEs accumulate in the the ß-amyloid plaques and neurofibrillary tangles (NFT) associated with AD and in the Lewy bodies characteristic of PD. Increasing evidence supports a role for oxidative stress in neurodegenerative disorders such as AD and PD. AGEs have been shown to contribute towards oxidative damage and chronic inflammation, whereby activated microglia secrete cytokines and free radicals, including nitric oxide (NO). Roles proposed for NO in the pathophysiology of the central nervous system are increasingly diverse and range from intercellular signaling, through necrosis of cells and invading pathogens, to the involvement of NO in apoptosis. Using in vitro experiments, it was shown that AGE-modified bovine serum albumin (BSA-AGE) and AGE-modified ß-amyloid, but not their unmodified proteins, induce NO production in N-11 murine microglia cells. This was mediated by the receptor for AGEs (RAGE) and upregulation of the inducible nitric oxide synthase (iNOS). AGE-induced enzyme activation and NO production could be blocked by intracellular-acting antioxidants: Ginkgo biloba special extract EGb 761, the estrogen derivative, 17ß-estradiol, R-(+)-thioctic acid, and a nitrone-based free radical trap, N-tert.-butyl-*-phenylnitrone (PBN). Methylglyoxal (MG) and 3-deoxyglucosone (3-DG), common precursors in the Maillard reaction, were also tested for their ability to induce the production of NO in N-11 microglia. However, no significant changes in nitrite levels were detected in the cell culture medium. The significance of these findings was supported by in vivo immunostaining of AD brains. Single and double immunostaining of cryostat sections of normal aged and AD brains was performed with polyclonal antibodies to AGEs and iNOS and monoclonal antibodies to Aß and PHF-1 (marker for NFT) and reactive microglia. In aged normal individuals as well as early stage AD brains (i.e. no pathological findings in isocortical areas), a few astrocytes showed co-localisation of AGE and iNOS in the upper neuronal layers of the temporal (Area 22) and entorhinal (Area 28, 34) cortices compared with no astrocytes detected in young controls. In late AD brains, there was a much denser accumulation of astrocytes co-localised with AGE and iNOS in the deeper and particularly upper neuronal layers. Also, numerous neurons with diffuse AGE but not iNOS reactivity and some AGE and iNOS-positive microglia were demonstrated, compared with only a few AGE-reactive neurons and no microglia in controls. Finally, astrocytes co-localised with AGE and iNOS as well as AGE and ß-amyloid were found surrounding mature but not diffuse ß-amyloid plaques in the AD brain. Parts of NFT were AGE-immunoreactive. Immunohistochemical staining of cryostat sections of normal aged and PD brains was performed with polyclonal antibodies to AGEs. The sections were counterstained with monoclonal antibodies to neurofilament components and a-synuclein. AGEs and a-synuclein were colocalized in very early Lewy bodies in the substantia nigra of cases with incidental Lewy body disease. These results support an AGE-induced oxidative damage due to the action of free radicals, such as NO, occurring in the AD and PD brains. Furthermore, the involvement of astrocytes and microglia in this pathological process was confirmed immunohistochemically in the AD brain. It is suggested that oxidative stress and AGEs participate in the very early steps of Lewy body formation and resulting cell death in PD. Since the iNOS gene can be regulated by redox-sensitive transcription factors, the use of membrane permeable antioxidants could be a promising strategy for the treatment and prevention of chronic inflammation in neurodegenerative disorders.}, subject = {Maillard-Reaktion}, language = {en} } @article{WongWinterHartigetal.2014, author = {Wong, David and Winter, Oliver and Hartig, Christina and Siebels, Svenja and Szyska, Martin and Tiburzy, Benjamin and Meng, Lingzhang and Kulkarni, Upasana and F{\"a}hnrich, Anke and Bommert, Kurt and Bargou, Ralf and Berek, Claudia and Van, Trung Chu and Bogen, Bjarne and Jundt, Franziska and Manz, Rudolf Armin}, title = {Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {10}, doi = {10.1371/journal.pone.0109018}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115269}, pages = {e109018}, year = {2014}, abstract = {Multiple myeloma is a bone marrow plasma cell tumor which is supported by the external growth factors APRIL and IL-6, among others. Recently, we identified eosinophils and megakaryocytes to be functional components of the micro-environmental niches of benign bone marrow plasma cells and to be important local sources of these cytokines. Here, we investigated whether eosinophils and megakaryocytes also support the growth of tumor plasma cells in the MOPC315. BM model for multiple myeloma. As it was shown for benign plasma cells and multiple myeloma cells, IL-6 and APRIL also supported MOPC315. BM cell growth in vitro, IL-5 had no effect. Depletion of eosinophils in vivo by IL-5 blockade led to a reduction of the early myeloma load. Consistent with this, myeloma growth in early stages was retarded in eosinophil-deficient Delta dblGATA-1 mice. Late myeloma stages were unaffected, possibly due to megakaryocytes compensating for the loss of eosinophils, since megakaryocytes were found to be in contact with myeloma cells in vivo and supported myeloma growth in vitro. We conclude that eosinophils and megakaryocytes in the niches for benign bone marrow plasma cells support the growth of malignant plasma cells. Further investigations are required to test whether perturbation of these niches represents a potential strategy for the treatment of multiple myeloma.}, language = {en} } @phdthesis{Wongkaew2015, author = {Wongkaew, Suttida}, title = {On the control through leadership of multi-agent systems}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120914}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {The investigation of interacting multi-agent models is a new field of mathematical research with application to the study of behavior in groups of animals or community of people. One interesting feature of multi-agent systems is collective behavior. From the mathematical point of view, one of the challenging issues considering with these dynamical models is development of control mechanisms that are able to influence the time evolution of these systems. In this thesis, we focus on the study of controllability, stabilization and optimal control problems for multi-agent systems considering three models as follows: The first one is the Hegselmann Krause opinion formation (HK) model. The HK dynamics describes how individuals' opinions are changed by the interaction with others taking place in a bounded domain of confidence. The study of this model focuses on determining feedback controls in order to drive the agents' opinions to reach a desired agreement. The second model is the Heider social balance (HB) model. The HB dynamics explains the evolution of relationships in a social network. One purpose of studying this system is the construction of control function in oder to steer the relationship to reach a friendship state. The third model that we discuss is a flocking model describing collective motion observed in biological systems. The flocking model under consideration includes self-propelling, friction, attraction, repulsion, and alignment features. We investigate a control for steering the flocking system to track a desired trajectory. Common to all these systems is our strategy to add a leader agent that interacts with all other members of the system and includes the control mechanism. Our control through leadership approach is developed using classical theoretical control methods and a model predictive control (MPC) scheme. To apply the former method, for each model the stability of the corresponding linearized system near consensus is investigated. Further, local controllability is examined. However, only in the Hegselmann-Krause opinion formation model, the feedback control is determined in order to steer agents' opinions to globally converge to a desired agreement. The MPC approach is an optimal control strategy based on numerical optimization. To apply the MPC scheme, optimal control problems for each model are formulated where the objective functions are different depending on the desired objective of the problem. The first-oder necessary optimality conditions for each problem are presented. Moreover for the numerical treatment, a sequence of open-loop discrete optimality systems is solved by accurate Runge-Kutta schemes, and in the optimization procedure, a nonlinear conjugate gradient solver is implemented. Finally, numerical experiments are performed to investigate the properties of the multi-agent models and demonstrate the ability of the proposed control strategies to drive multi-agent systems to attain a desired consensus and to track a given trajectory.}, subject = {Mehragentensystem}, language = {en} } @article{WoodcockGarrattPowneyetal.2019, author = {Woodcock, B. A. and Garratt, M. P. D. and Powney, G. D. and Shaw, R. F. and Osborne, J. L. and Soroka, J. and Lindstr{\"o}m, S. A. M. and Stanley, D. and Ouvrard, P. and Edwards, M. E. and Jauker, F. and McCracken, M. E. and Zou, Y. and Potts, S. G. and Rundl{\"o}f, M. and Noriega, J. A. and Greenop, A. and Smith, H. G. and Bommarco, R. and van der Werf, W. and Stout, J. C. and Steffan-Dewenter, I. and Morandin, L. and Bullock, J. M. and Pywell, R. F.}, title = {Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, doi = {10.1038/s41467-019-09393-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233787}, year = {2019}, abstract = {How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture.}, language = {en} } @article{WorkuStichDaugschiesetal.2015, author = {Worku, Netsanet and Stich, August and Daugschies, Arwid and Wenzel, Iris and Kurz, Randy and Thieme, Rene and Kurz, Susanne and Birkenmeier, Gerd}, title = {Ethyl Pyruvate Emerges as a Safe and Fast Acting Agent against Trypanosoma brucei by Targeting Pyruvate Kinase Activity}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0137353}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150002}, pages = {e0137353}, year = {2015}, abstract = {Background Human African Trypanosomiasis (HAT) also called sleeping sickness is an infectious disease in humans caused by an extracellular protozoan parasite. The disease, if left untreated, results in 100\% mortality. Currently available drugs are full of severe drawbacks and fail to escape the fast development of trypanosoma resistance. Due to similarities in cell metabolism between cancerous tumors and trypanosoma cells, some of the current registered drugs against HAT have also been tested in cancer chemotherapy. Here we demonstrate for the first time that the simple ester, ethyl pyruvate, comprises such properties. Results The current study covers the efficacy and corresponding target evaluation of ethyl pyruvate on T. brucei cell lines using a combination of biochemical techniques including cell proliferation assays, enzyme kinetics, phasecontrast microscopic video imaging and ex vivo toxicity tests. We have shown that ethyl pyruvate effectively kills trypanosomes most probably by net ATP depletion through inhibition of pyruvate kinase (Ki = 3.0\(\pm\)0.29 mM). The potential of ethyl pyruvate as a trypanocidal compound is also strengthened by its fast acting property, killing cells within three hours post exposure. This has been demonstrated using video imaging of live cells as well as concentration and time dependency experiments. Most importantly, ethyl pyruvate produces minimal side effects in human red cells and is known to easily cross the blood-brain-barrier. This makes it a promising candidate for effective treatment of the two clinical stages of sleeping sickness. Trypanosome drug-resistance tests indicate irreversible cell death and a low incidence of resistance development under experimental conditions. Conclusion Our results present ethyl pyruvate as a safe and fast acting trypanocidal compound and show that it inhibits the enzyme pyruvate kinase. Competitive inhibition of this enzyme was found to cause ATP depletion and cell death. Due to its ability to easily cross the blood-brain-barrier, ethyl pyruvate could be considered as new candidate agent to treat the hemo-lymphatic as well as neurological stages of sleeping sickness.}, language = {en} } @phdthesis{Worschech2010, author = {Worschech, Andrea}, title = {Oncolytic Therapy with Vaccinia Virus GLV-1h68 - Comparative Microarray Analysis of Infected Xenografts and Human Tumor Cell Lines -}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45338}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {Aim of this thesis was to study the contribution of the hosts immune system during tumor regression. A wild-type rejection model was studied in which tumor regression is mediated through an adaptive, T cell host response (Research article 1). Additionally, the relationship between VACV infection and cancer rejection was assessed by applying organism-specific microarray platforms to infected and non-infected xenografts. It could be shown that tumor rejection in this nude mouse model was orchestrated solely by the hosts innate immune system without help of the adaptive immunity. In a third study the inflammatory baseline status of 75 human cancer cell lines was tested in vitro which was correlated with the susceptibility to VACV and Adenovirus 5 (Ad5) replication of the respective cell line (Manuscript for Research article 3). Although xenografts by themselves lack the ability to signal danger and do not provide sufficient proinflammatory signals to induce acute inflammation, the presence of viral replication in the oncolytic xenograft model provides the "tissue-specific trigger" that activates the immune response and in concordance with the hypothesis, the ICR is activated when chronic inflammation is switched into an acute one. Thus, in conditions in which a switch from a chronic to an acute inflammatory process can be induced by other factors like the immune-stimulation induced by the presence of a virus in the target tissue, adaptive immune responses may not be necessary and immune-mediated rejection can occur without the assistance of T or B cells. However, in the regression study using neu expressing MMC in absence of a stimulus such as a virus and infected cancer cells thereafter, adaptive immunity is needed to provoke the switch into an acute inflammation and initiate tissue rejection. Taken together, this work is supportive of the hypothesis that the mechanisms prompting TSD differ among immune pathologies but the effect phase converges and central molecules can be detected over and over every time TSD occurs. It could be shown that in presence of a trigger such as infection with VACV and functional danger signaling pathways of the infected tumor cells, innate immunity is sufficient to orchestrate rejection of manifested tumors.}, subject = {Tumorimmunologie}, language = {en} } @article{WortmannSalehEngelsPeyerimhoff1994, author = {Wortmann-Saleh, D. and Engels, Bernd and Peyerimhoff, S. D.}, title = {Theoretical Study of the Reaction O(\(^3\)P) + C\(_2\)H\(_4\) and comparison with the \(^3\)CH\(_3\) + C\(_2\)H\(_4\) Reaction}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59076}, year = {1994}, abstract = {The minimum energy path for the reaction O(\(^3\)P\(_g\)) + C\(_2\)H\(_4\)(\(^1\)A\(_g\)) has been calculated by optimizing all relevant geometrical parameters along the approach of oxygen to ethene. A barrier of 4.7 kcal/mol in the \(^3\)A"( ... 9a'\(^2\)- 10a'3a") potential energy surface and an energy difference of 14.4 kcal/mol between the product and the fragments is found at the multireference-configuration interaction level. The corresponding values at the lower-level treatment CASSCF are 9 kcal/mol for the barrier and 9 kcal/mol for the depth of the potential; this shows the importance of inclusion of electron correlation. The barrier for CH\(_2\) rotation for the lowestenergy structure (asymmetric OC\(_2\)H\(_4\)) is around 5 kcal/mol. The energy gap to the first excited state \(^3\)A'( ... 9a'l0a'3a'12) is found tobe 3.6 kcal/mol in MRD-CI calculations at the ground-state minimum. Comparison with \(^3\)CH\(_2\) + C\(_2\)H\(_4\) shows that in this system the lowest-energy surface is \(^3\)A', i.e., the state which is the excited state in 0 + C\(_2\)H\(_4\). This difference in energy ordering of \(^3\)A' and \(^3\)A" states results from the fact that the p\(_x\), p\(_y\), p\(_z\) degeneracy of oxygen orbitals is lifted in \(^3\)CH\(_2\)leading to b\(_1\), b\(_2\). and a\(_1\) MOs whereby the lowest b\(_2\) (a") remains doubly occupied; as a consequence, the reaction pattem between the oxygen and \(^3\)CH\(_2\) approach is different, which is also quite apparent in the calculated charge transfer.}, subject = {Organische Chemie}, language = {en} } @article{WoznickiLaquaBleyetal.2022, author = {Woznicki, Piotr and Laqua, Fabian and Bley, Thorsten and Baeßler, Bettina}, title = {AutoRadiomics: a framework for reproducible radiomics research}, series = {Frontiers in Radiology}, volume = {2}, journal = {Frontiers in Radiology}, issn = {2673-8740}, doi = {10.3389/fradi.2022.919133}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284813}, year = {2022}, abstract = {Purpose Machine learning based on radiomics features has seen huge success in a variety of clinical applications. However, the need for standardization and reproducibility has been increasingly recognized as a necessary step for future clinical translation. We developed a novel, intuitive open-source framework to facilitate all data analysis steps of a radiomics workflow in an easy and reproducible manner and evaluated it by reproducing classification results in eight available open-source datasets from different clinical entities. Methods The framework performs image preprocessing, feature extraction, feature selection, modeling, and model evaluation, and can automatically choose the optimal parameters for a given task. All analysis steps can be reproduced with a web application, which offers an interactive user interface and does not require programming skills. We evaluated our method in seven different clinical applications using eight public datasets: six datasets from the recently published WORC database, and two prostate MRI datasets—Prostate MRI and Ultrasound With Pathology and Coordinates of Tracked Biopsy (Prostate-UCLA) and PROSTATEx. Results In the analyzed datasets, AutoRadiomics successfully created and optimized models using radiomics features. For WORC datasets, we achieved AUCs ranging from 0.56 for lung melanoma metastases detection to 0.93 for liposarcoma detection and thereby managed to replicate the previously reported results. No significant overfitting between training and test sets was observed. For the prostate cancer detection task, results were better in the PROSTATEx dataset (AUC = 0.73 for prostate and 0.72 for lesion mask) than in the Prostate-UCLA dataset (AUC 0.61 for prostate and 0.65 for lesion mask), with external validation results varying from AUC = 0.51 to AUC = 0.77. Conclusion AutoRadiomics is a robust tool for radiomic studies, which can be used as a comprehensive solution, one of the analysis steps, or an exploratory tool. Its wide applicability was confirmed by the results obtained in the diverse analyzed datasets. The framework, as well as code for this analysis, are publicly available under https://github.com/pwoznicki/AutoRadiomics.}, language = {en} } @article{WoznickiLaquaAlHajetal.2023, author = {Woznicki, Piotr and Laqua, Fabian Christopher and Al-Haj, Adam and Bley, Thorsten and Baeßler, Bettina}, title = {Addressing challenges in radiomics research: systematic review and repository of open-access cancer imaging datasets}, series = {Insights into Imaging}, volume = {14}, journal = {Insights into Imaging}, issn = {1869-4101}, doi = {10.1186/s13244-023-01556-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357936}, year = {2023}, abstract = {Objectives Open-access cancer imaging datasets have become integral for evaluating novel AI approaches in radiology. However, their use in quantitative analysis with radiomics features presents unique challenges, such as incomplete documentation, low visibility, non-uniform data formats, data inhomogeneity, and complex preprocessing. These issues may cause problems with reproducibility and standardization in radiomics studies. Methods We systematically reviewed imaging datasets with public copyright licenses, published up to March 2023 across four large online cancer imaging archives. We included only datasets with tomographic images (CT, MRI, or PET), segmentations, and clinical annotations, specifically identifying those suitable for radiomics research. Reproducible preprocessing and feature extraction were performed for each dataset to enable their easy reuse. Results We discovered 29 datasets with corresponding segmentations and labels in the form of health outcomes, tumor pathology, staging, imaging-based scores, genetic markers, or repeated imaging. We compiled a repository encompassing 10,354 patients and 49,515 scans. Of the 29 datasets, 15 were licensed under Creative Commons licenses, allowing both non-commercial and commercial usage and redistribution, while others featured custom or restricted licenses. Studies spanned from the early 1990s to 2021, with the majority concluding after 2013. Seven different formats were used for the imaging data. Preprocessing and feature extraction were successfully performed for each dataset. Conclusion RadiomicsHub is a comprehensive public repository with radiomics features derived from a systematic review of public cancer imaging datasets. By converting all datasets to a standardized format and ensuring reproducible and traceable processing, RadiomicsHub addresses key reproducibility and standardization challenges in radiomics. Critical relevance statement This study critically addresses the challenges associated with locating, preprocessing, and extracting quantitative features from open-access datasets, to facilitate more robust and reliable evaluations of radiomics models. Key points - Through a systematic review, we identified 29 cancer imaging datasets suitable for radiomics research. - A public repository with collection overview and radiomics features, encompassing 10,354 patients and 49,515 scans, was compiled. - Most datasets can be shared, used, and built upon freely under a Creative Commons license. - All 29 identified datasets have been converted into a common format to enable reproducible radiomics feature extraction.}, language = {en} } @article{WoźnickiLaquaMessmeretal.2022, author = {Wo{\'{z}}nicki, Piotr and Laqua, Fabian Christopher and Messmer, Katharina and Kunz, Wolfgang Gerhard and Stief, Christian and N{\"o}renberg, Dominik and Schreier, Andrea and W{\´o}jcik, Jan and Ruebenthaler, Johannes and Ingrisch, Michael and Ricke, Jens and Buchner, Alexander and Schulz, Gerald Bastian and Gresser, Eva}, title = {Radiomics for the prediction of overall survival in patients with bladder cancer prior to radical cystectomy}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {18}, issn = {2072-6694}, doi = {10.3390/cancers14184449}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288098}, year = {2022}, abstract = {(1) Background: To evaluate radiomics features as well as a combined model with clinical parameters for predicting overall survival in patients with bladder cancer (BCa). (2) Methods: This retrospective study included 301 BCa patients who received radical cystectomy (RC) and pelvic lymphadenectomy. Radiomics features were extracted from the regions of the primary tumor and pelvic lymph nodes as well as the peritumoral regions in preoperative CT scans. Cross-validation was performed in the training cohort, and a Cox regression model with an elastic net penalty was trained using radiomics features and clinical parameters. The models were evaluated with the time-dependent area under the ROC curve (AUC), Brier score and calibration curves. (3) Results: The median follow-up time was 56 months (95\% CI: 48-74 months). In the follow-up period from 1 to 7 years after RC, radiomics models achieved comparable predictive performance to validated clinical parameters with an integrated AUC of 0.771 (95\% CI: 0.657-0.869) compared to an integrated AUC of 0.761 (95\% CI: 0.617-0.874) for the prediction of overall survival (p = 0.98). A combined clinical and radiomics model stratified patients into high-risk and low-risk groups with significantly different overall survival (p < 0.001). (4) Conclusions: Radiomics features based on preoperative CT scans have prognostic value in predicting overall survival before RC. Therefore, radiomics may guide early clinical decision-making.}, language = {en} } @article{WrońskiWyborskiMusiałetal.2021, author = {Wroński, Piotr Andrzej and Wyborski, Paweł and Musiał, Anna and Podemski, Paweł and Sęk, Grzegorz and H{\"o}fling, Sven and Jabeen, Fauzia}, title = {Metamorphic Buffer Layer Platform for 1550 nm Single-Photon Sources Grown by MBE on (100) GaAs Substrate}, series = {Materials}, volume = {14}, journal = {Materials}, number = {18}, issn = {1996-1944}, doi = {10.3390/ma14185221}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246145}, year = {2021}, abstract = {We demonstrate single-photon emission with a low probability of multiphoton events of 5\% in the C-band of telecommunication spectral range of standard silica fibers from molecular beam epitaxy grown (100)-GaAs-based structure with InAs quantum dots (QDs) on a metamorphic buffer layer. For this purpose, we propose and implement graded In content digitally alloyed InGaAs metamorphic buffer layer with maximal In content of 42\% and GaAs/AlAs distributed Bragg reflector underneath to enhance the extraction efficiency of QD emission. The fundamental limit of the emission rate for the investigated structures is 0.5 GHz based on an emission lifetime of 1.95 ns determined from time-resolved photoluminescence. We prove the relevance of a proposed technology platform for the realization of non-classical light sources in the context of fiber-based quantum communication applications.}, language = {en} } @misc{Wu2021, type = {Master Thesis}, author = {Wu, Dong}, title = {Aspects of Gender in The Unofficial History of the Scholars}, doi = {10.25972/OPUS-21920}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219202}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {The present study focuses on Rulin waishi 儒林外史 (The Unofficial History of the Scholars), a well-known Qing novel, from the perspective of gender. It attempts to contribute to the discussion about Chinese masculinity by identifying the representation of the scholars' masculinity in Rulin waishi and offer a better understanding of the novel's position regarding femininity and women. This project shows that the novel nevertheless reflects rather than challenges gender ideologies of its time. The ideal manhood showed in the novel comprises real virtues and authentic learning. It goes against the traditional, orthodox Confucian masculinity which advocates that officialdom is the glorious path to fulfill a learned man's masculinity. It is mainly due to Wu Jingzi's own failure in the civil service examinations and official careers. Regarding the relation of masculinity and sexuality, the novel reveals that a masculine man is not tempted by female charm but can enjoy a harmonious and companionate marriage. Besides, scholars show great anxiety about their masculinity since they are in a marginal position in society. Their manliness is challenged by officials, merchants, and even commoners, as well as their colleagues. Through a careful examination of stories of Pinniang, Miss Lu, and Mrs. Wang, it reveals that the novel holds a conventional opinion on women although it criticizes widow suicide and shows an egalitarian husband-wife relationship. It praises Confucian womanly virtues, such as following and serving the husband, managing the household, and keeping chastity. Female sexuality is blamed as an evil temptation to lead men to go astray. Women's learning gains legitimacy when serving to fulfill domestic responsibilities. It carries the Confucian message that men should take the lead and maintain order in the household and reinforces the rightful patriarchy. In a word, rather than go ahead of its time, Rulin waishi holds a conservative attitude towards gender issues.}, language = {en} } @phdthesis{Wu2019, author = {Wu, Fang}, title = {Adding new functions to insulin-like growth factor-I (IGF-I) via genetic codon expansion}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175330}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Insulin-like growth factor-I (IGF-I) is a 70-amino acid polypeptide with a molecular weight of approximately 7.6 kDa acting as an anabolic effector. It is essential for tissue growth and remodeling. Clinically, it is used for the treatment of growth disorders and has been proposed for various other applications including musculoskeletal diseases. Unlike insulin, IGF-I is complexed to at least six high-affinity binding proteins (IGFBPs) exerting homeostatic effects by modulating IGF-I availability to its receptor (IGF-IR) on most cells in the body as well as changing the distribution of the growth factor within the organism.1-3 Short half-lived IGF-I have been the driving forces for the design of localized IGF-I depot systems or protein modification with enhanced pharmacokinetic properties. In this thesis, we endeavor to present a versatile biologic into which galenical properties were engineered through chemical synthesis, e.g., by site-specific coupling of biomaterials or complex composites to IGF-I. For that, we redesigned the therapeutic via genetic codon expansion resulting in an alkyne introduced IGF-I, thereby becoming a substrate for biorthogonal click chemistries yielding a site-specific decoration. In this approach, an orthogonal pyrrolysine tRNA synthetase (PylRS)/tRNAPyl CUA pair was employed to direct the co-translational incorporation of an unnatural amino acid—¬propargyl-L-lysine (plk)—bearing a clickable alkyne functional handle into IGF-I in response to the amber stop codon (UAG) introduced into the defined position in the gene of interest. We summarized the systematic optimization of upstream and downstream process alike with the ultimate goal to increase the yield of plk modified IGF-I therapeutic, from the construction of gene fusions resulting in (i) Trx-plk-IGF-I fusion variants, (ii) naturally occurring pro-IGF-I protein (IGF-I + Ea peptide) (plk-IGF-I Ea), over the subsequent bacterial cultivation and protein extraction to the final chromatographic purification. The opportunities and hurdles of all of the above strategies were discussed. Evidence was provided that the wild-type IGF-I yields were pure by exploiting the advantages of the pHisTrx expression vector system in concert with a thrombin enzyme with its highly specific proteolytic digestion site and multiple-chromatography steps. The alkyne functionality was successfully introduced into IGF-I by amber codon suppression. The proper folding of plk-IGF-I Ea was assessed by WST-1 proliferation assay and the detection of phosphorylated AKT in MG-63 cell lysate. The purity of plk-IGF-I Ea was monitored with RP-HPLC and SDS-PAGE analysis. This work also showed site-specific coupling an alkyne in plk-IGF-I Ea by copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) with potent activities in vitro. The site-specific immobilization of plk-IGF-I Ea to the model carrier (i.e., agarose beads) resulted in enhanced cell proliferation and adhesion surrounding the IGF-I-presenting particles. Cell proliferation and differentiation were enhanced in the accessibility of IGF-I decorated beads, reflecting the multivalence on cellular performance. Next, we aimed at effectively showing the disease environment by co-delivery of fibroblast growth factor 2 (FGF2) and IGF-I, deploying localized matrix metalloproteinases (MMPs) upregulation as a surrogate marker driving the response of the drug delivery system. For this purpose, we genetically engineered FGF2 variant containing an (S)-2-amino-6-(((2-azidoethoxy)carbonyl)amino)hexanoic acid incorporated at its N-terminus, followed by an MMPs-cleavable linker (PCL) and FGF2 sequence, thereby allowing site-directed, specific decoration of the resultant azide-PCL-FGF2 with the previously mentioned plk-IGF-I Ea to generate defined protein-protein conjugates with a PCL in between. The click reaction between plk-IGF-I Ea and azide-PCL-FGF2 was systematically optimized to increase the yield of IGF-FGF conjugates, including reaction temperature, incubation duration, the addition of anionic detergent, and different ratios of the participating biopharmaceutics. The challenge here was that CuAAC reaction components or conditions might oxidize free cysteines of azide-PCL-FGF2 and future work needs to present the extent of activity retention after conjugation. Furthermore, our study provides potential options for dual-labeling of IGF-I either by the introduction of unnatural amino acids within two distinct positions of the protein of interest for parallel "double-click" labeling of the resultant plk-IGF-I Ea-plk or by using a combination of enzymatic-catalyzed and CuAAC bioorthogonal coupling strategies for sequentially dual-labeling of plk-IGF-I Ea. In conclusion, genetic code expansion in combination with click-chemistry provides the fundament for novel IGF-I analogs allowing unprecedented site specificity for decoration. Considerable progress towards IGF-I based therapies with enhanced pharmacological properties was made by demonstrating the feasibility of the expression of plk incorporated IGF-I using E. coli and retained activity of unconjugated and conjugated IGF-I variant. Dual-labeling of IGF-I provides further insights into the functional requirements of IGF-I. Still, further investigation warrants to develop precise IGF-I therapy through unmatched temporal and spatial regulation of the pleiotropic IGF-I.}, subject = {Insulin-like Growth Factor I}, language = {en} } @article{WuReimannSiddiquietal.2019, author = {Wu, Hao and Reimann, Sabine and Siddiqui, Sophiya and Haag, Rainer and Siegmund, Britta and Dernedde, Jens and Glauben, Rainer}, title = {dPGS Regulates the Phenotype of Macrophages via Metabolic Switching}, series = {Macromolecular Bioscience}, volume = {19}, journal = {Macromolecular Bioscience}, number = {12}, doi = {10.1002/mabi.201900184}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212711}, year = {2019}, abstract = {The synthetic compound dendritic polyglycerol sulfate (dPGS) is a pleiotropic acting molecule but shows a high binding affinity to immunological active molecules as L-/P-selectin or complement proteins leading to well described anti-inflammatory properties in various mouse models. In order to make a comprehensive evaluation of the direct effect on the innate immune system, macrophage polarization is analyzed in the presence of dPGS on a phenotypic but also metabolic level. dPGS administered macrophages show a significant increase of MCP1 production paralleled by a reduction of IL-10 secretion. Metabolic analysis reveals that dPGS could potently enhance the glycolysis and mitochondrial respiration in M0 macrophages as well as decrease the mitochondrial respiration of M2 macrophages. In summary the data indicate that dPGS polarizes macrophages into a pro-inflammatory phenotype in a metabolic pathway-dependent manner.}, language = {en} } @article{WuZhaoHochreinetal.2023, author = {Wu, Hao and Zhao, Xiufeng and Hochrein, Sophia M. and Eckstein, Miriam and Gubert, Gabriela F. and Kn{\"o}pper, Konrad and Mansilla, Ana Maria and {\"O}ner, Arman and Doucet-Ladev{\`e}ze, Remi and Schmitz, Werner and Ghesqui{\`e}re, Bart and Theurich, Sebastian and Dudek, Jan and Gasteiger, Georg and Zernecke, Alma and Kobold, Sebastian and Kastenm{\"u}ller, Wolfgang and Vaeth, Martin}, title = {Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-42634-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358052}, year = {2023}, abstract = {T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity. Terminally exhausted T cells are steadily replenished by a precursor population (Tpex), but the metabolic principles governing Tpex maintenance and the regulatory circuits that control their exhaustion remain incompletely understood. Using a combination of gene-deficient mice, single-cell transcriptomics, and metabolomic analyses, we show that mitochondrial insufficiency is a cell-intrinsic trigger that initiates the functional exhaustion of T cells. At the molecular level, we find that mitochondrial dysfunction causes redox stress, which inhibits the proteasomal degradation of hypoxia-inducible factor 1α (HIF-1α) and promotes the transcriptional and metabolic reprogramming of Tpex cells into terminally exhausted T cells. Our findings also bear clinical significance, as metabolic engineering of chimeric antigen receptor (CAR) T cells is a promising strategy to enhance the stemness and functionality of Tpex cells for cancer immunotherapy.}, language = {en} } @phdthesis{Wu2013, author = {Wu, Lingdan}, title = {Emotion Regulation in Addicted Smokers}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85471}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Background: Nicotine addiction is the most prevalent type of drug addiction that has been described as a cycle of spiraling dysregulation of the brain reward systems. Imaging studies have shown that nicotine addiction is associated with abnormal function in prefrontal brain regions that are important for cognitive emotion regulation. It was assumed that addicts may perform less well than healthy nonsmokers in cognitive emotion regulation tasks. The primary aims of this thesis were to investigate emotional responses to natural rewards among smokers and nonsmokers and to determine whether smokers differ from nonsmokers in cognitive regulation of positive and negative emotions. To address these aims, two forms of appraisal paradigms (i.e., appraisal frame and reappraisal) were applied to compare changes in emotional responses of smokers with that of nonsmokers as a function of appraisal strategies. Experiment 1: The aim of the first experiment was to evaluate whether and how appraisal frames preceding positive and negative picture stimuli affect emotional experience and facial expression of individuals. Twenty participants were exposed to 125 pairs of auditory appraisal frames (either neutral or emotional) followed by picture stimuli reflecting five conditions: unpleasant-negative, unpleasant-neutral, pleasant-positive, pleasant-neutral and neutral-neutral. Ratings of valence and arousal as well as facial EMG activity over the corrugator supercilii and the zygomaticus major were measured simultaneously. The results indicated that appraisal frames could alter both subjective emotional experience and facial expressions, irrespective of the valence of the pictorial stimuli. These results suggest and support that appraisal frame is an efficient paradigm in regulation of multi-level emotional responses. 8 Experiment 2: The second experiment applied the appraisal frame paradigm to investigate how smokers differ from nonsmokers on cognitive emotion regulation. Sixty participants (22 nonsmokers, 19 nondeprived smokers and 19 12-h deprived smokers) completed emotion regulation tasks as described in Experiment 1 while emotional responses were concurrently recorded as reflected by self-ratings and psychophysiological measures (i.e., facial EMG and EEG). The results indicated that there was no group difference on emotional responses to natural rewards. Moreover, nondeprived smokers and deprived smokers performed as well as nonsmokers on the emotion regulation task. The lack of group differences in multiple emotional responses (i.e., self-reports, facial EMG activity and brain EEG activity) suggests that nicotine addicts have no deficit in cognitive emotion regulation of natural rewards via appraisal frames. Experiment 3: The third experiment aimed to further evaluate smokers' emotion regulation ability by comparing performances of smokers and nonsmokers in a more challenging cognitive task (i.e., reappraisal task). Sixty-five participants (23 nonsmokers, 22 nondeprived smokers and 20 12-h deprived smokers) were instructed to regulate emotions by imagining that the depicted negative or positive scenario would become less negative or less positive over time, respectively. The results showed that nondeprived smokers and deprived smokers responded similarly to emotional pictures and performed as well as nonsmokers in down-regulating positive and negative emotions via the reappraisal strategy. These results indicated that nicotine addicts do not have deficit in emotion regulation using cognitive appraisal strategies. In sum, the three studies consistently revealed that addicted smokers were capable to regulate emotions via appraisal strategies. This thesis establishes the groundwork for therapeutic use of appraisal instructions to cope with potential self-regulation failures in nicotine addicts.}, subject = {Gef{\"u}hl}, language = {en} } @article{WuPuAllenetal.2012, author = {Wu, Lingdan and Pu, Jie and Allen, John J. B. and Pauli, Paul}, title = {Recognition of facial expressions in individuals with elevated levels of depressive symptoms: an eye-movement study}, series = {Depression Research and Treatment}, volume = {2012}, journal = {Depression Research and Treatment}, number = {249030}, doi = {10.1155/2012/249030}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123153}, year = {2012}, abstract = {Previous studies consistently reported abnormal recognition of facial expressions in depression. However, it is still not clear whether this abnormality is due to an enhanced or impaired ability to recognize facial expressions, and what underlying cognitive systems are involved. The present study aimed to examine how individuals with elevated levels of depressive symptoms differ from controls on facial expression recognition and to assess attention and information processing using eye tracking. Forty participants (18 with elevated depressive symptoms) were instructed to label facial expressions depicting one of seven emotions. Results showed that the high-depression group, in comparison with the low-depression group, recognized facial expressions faster and with comparable accuracy. Furthermore, the high-depression group demonstrated greater leftwards attention bias which has been argued to be an indicator of hyperactivation of right hemisphere during facial expression recognition.}, language = {en} } @article{WuWinklerWieseretal.2015, author = {Wu, Lingdan and Winkler, Markus H. and Wieser, Matthias J. and Andreatta, Marta and Li, Yonghui and Pauli, Paul}, title = {Emotion regulation in heavy smokers: experiential, expressive and physiological consequences of cognitive reappraisal}, series = {Frontiers in Psychology}, volume = {6}, journal = {Frontiers in Psychology}, number = {1555}, doi = {10.3389/fpsyg.2015.01555}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145225}, year = {2015}, abstract = {Emotion regulation dysfunctions are assumed to contribute to the development of tobacco addiction and relapses among smokers attempting to quit. To further examine this hypothesis, the present study compared heavy smokers with non-smokers (NS) in a reappraisal task. Specifically, we investigated whether non-deprived smokers (NDS) and deprived smokers (DS) differ from non-smokers in cognitive emotion regulation and whether there is an association between the outcome of emotion regulation and the cigarette craving. Sixty-five participants (23 non-smokers, 22 NDS, and 20 DS) were instructed to down-regulate emotions by reappraising negative or positive pictorial scenarios. Self-ratings of valence, arousal, and cigarette craving as well as facial electromyography and electroencephalograph activities were measured. Ratings, facial electromyography, and electroencephalograph data indicated that both NDS and DS performed comparably to nonsmokers in regulating emotional responses via reappraisal, irrespective of the valence of pictorial stimuli. Interestingly, changes in cigarette craving were positively associated with regulation of emotional arousal irrespective of emotional valence. These results suggest that heavy smokers are capable to regulate emotion via deliberate reappraisal and smokers' cigarette craving is associated with emotional arousal rather than emotional valence. This study provides preliminary support for the therapeutic use of reappraisal to replace maladaptive emotion-regulation strategies in nicotine addicts.}, language = {en} } @phdthesis{Wu2006, author = {Wu, Rongxue}, title = {Integrins and SPARC : potential implications for cardiac remodeling}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-17531}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2006}, abstract = {Der enorme Umbau des Herzgewebes, wie man ihn nach Druck{\"u}berlastung des Ventrikels oder MyokardInfarkt beobachten kann, gilt als eine der kausalen Ursachen des Herzversagens. Die Ver{\"a}nderungen in der Architektur des Herzens beeinflussen die mechanischen Eigenschaften des Herzmuskels, begr{\"u}ndet sind sie jedoch in Anpassungsprozessen auf der zellul{\"a}ren Ebene vor allem in einer Modulation der Expression bestimmter Gene. Gemeinsam mit Integrinen, den Transmembran-Rezeptoren, welche die extrazellul{\"a}re Umgebung mit dem intrazellul{\"a}ren Zytoskelett verbinden, geh{\"o}ren Proteine der extrazellul{\"a}ren Matrix (ECM) und matrizellul{\"a}re Proteine zu den Schl{\"u}sselkomponenten, die den Umbauprozess im Herzen steuern. Aus diesen Gr{\"u}nden hatte diese Doktorarbeit zum Ziel, die Rolle der Integrine f{\"u}r die Regulation der Genexpression und die Leistungsf{\"a}higkeit des Herzmuskels w{\"a}hrend der durch Druck{\"u}berlastung oder myokardialen Infarkt (MI) hervorgerufenen Wundheilungsprozesse zu analysieren. Um die Beteiligung von Integrin Beta 1 zu untersuchen, wurde ein experimentelles Modell der Druck{\"u}berlastung im Mausherzen (aortic banding; Konstriktion der Aorta; AB) eingesetzt, wobei M{\"a}use mit einer konditionalen, Herz-spezifischen Deletion des Integrin Beta 1 Gens untersucht wurden. Ein besonderes Augenmerk wurde dabei auf die physiologischen Unterschiede und eine ver{\"a}nderte Genexpression im gestressten Herzen in An- oder Abwesenheit von Integrin Beta 1 gelegt. Interessanterweise wurden die M{\"a}use, welche eine Kombination aus Integrin knock-out Allel und dem Kardiomyozyten-spezifischen konditionalen knock-out Allel von Integrin Beta 1 aufwiesen im normalen Mendelschen Verh{\"a}ltnis geboren und wuchsen normal auf. Obwohl diese Tiere immer noch geringe Mengen von Integrin Beta 1 in ihrem Herzen aufwiesen (exprimiert von nicht-Myozyten), besaßen diese M{\"a}use eine ver{\"a}nderte Herzfunktion und waren sehr sensitiv gegen{\"u}ber AB. Im Gegensatz zu der kompensatorischen hypertrophischen Reaktion, die in Wildtyp M{\"a}usen zu beobachten war, zeigte sich in den Integrin Beta 1-defizienten Mausherzen kein Gewebeumbau. Auch die erh{\"o}hte Expression von verschiedenen ECM Proteinen, insbesondere die verst{\"a}rkte Expression des matrizellul{\"a}ren Proteins SPARC, unterblieb nach AB in den Integrin Beta 1-defizienten Tieren. Interessanterweise konnte auch eine transiente Erh{\"o}hung der SPARC mRNA w{\"a}hrend der Umbauprozesse im Herzen in Folge von myokardialem Infarkt (MI) mittels cDNA Makroarrays festgestellt werden. In der Tat fanden sich gr{\"o}ßere Mengen von SPARC bereits 2 Tage (~2,5-fach erh{\"o}ht), 7 Tage (~4-fach erh{\"o}ht) und 1 Monat (~2-fach erh{\"o}ht) nach MI, w{\"a}hrend ein spezifischer Inhibitor der Integrin alpha v Untereinheit diese Hochregulation von SPARC in vivo verhinderte. Immunfluoreszenz Untersuchungen von Herzgewebe verdeutlichten, dass sich die erh{\"o}hte Expression von SPARC auf das Infarktareal beschr{\"a}nkte, dass die Expression von SPARC nach einer anf{\"a}nglichen Erh{\"o}hung im Verlauf von 1 Monaten wieder auf das Anfangsniveau zur{\"u}ckging und dass die verst{\"a}rkte Expression von der Einwanderung von Fibroblasten in das isch{\"a}mische Herzgewebe begleitet war. In vitro stimulierten die Wachstumsfaktoren TGF-Beta 1 und PDGF-BB die Expression von SPARC durch Fibroblasten. Wie sich an Hand von ELISA und Western Blot Untersuchungen feststellen ließ, war die Inhibition von Integrin Beta v nicht in der Lage, die durch TGF-Beta 1 oder PDGF induzierte Sekretion von SPARC zu beeinflussen. Jedoch zeigte sich, dass Vitronektin, ein Ligand von Integrin alpha v, sowohl die Sekretion von TGF-Beta 1 als auch von PDGF-BB durch Kardiomyozyten induzierte und diese Reaktion wurde durch den Integrin alpha v Inhibitor komplett unterdr{\"u}ckt. In funktioneller Hinsicht wirkte SPARC auf die durch ECM Proteine induzierte Migration von Fibroblasten ein, so dass man davon ausgehen kann, dass die lokale Freisetzung von SPARC nach myokardialem Infarkt zur Wundheilung im Herzen beitr{\"a}gt. Zusammenfassend l{\"a}ßt die Kombination der in vivo und in vitro erhobenen experimentellen Daten den Schluss zu, dass mehrere Integrin Untereinheiten eine entscheidende Rolle w{\"a}hrend der Gewebeumbildung im Herzen spielen. Integrin-abh{\"a}ngige Genexpressionsereignisse wie beispielsweise die erh{\"o}hte Expression von SPARC nach MI sind entscheidend an der Koordination der Wundheilung beteiligt. Diese Prozesse scheinen auf einer komplexen Wechselwirkung und Kommunikation zwischen verschiedenen Zelltypen wie Kardiomyozyten und Fibroblasten zu beruhen, um lokal begrenzt eine Heilung und Vernarbung des verletzten Gewebes zu regulieren. Die Aufkl{\"a}rung des fein abgestimmten Wechselspiels zwischen Integrinen matrizellul{\"a}ren Proteinen wie SPARC und Wachstumsfaktoren wird sicherlich zu einem besseren und klinisch nutzbarem Verst{\"a}ndnis der molekularen Mechanismen des Gewebeumbaus im Herzen beitragen.}, subject = {Integrine}, language = {en} } @phdthesis{Wu2007, author = {Wu, Rongxue}, title = {Treatment with integrin alpha v inhibitor abolishes compensatory cardiac hypertrophy due to altered signal transduction and ECM gene expression}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-21339}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {Integrine sind Transmembranrezeptoren, welche mechanische Signale von der extrazellul{\"a}ren Matrix (ECM) zum Zytoskelett {\"u}bermitteln ("outside-in-signaling"). Viele molekulare Defekte in der Verbindung zwischen Zytoskelett und ECM erzeugen bekanntermaßen Kardiomyopathien. alpha v Integrin scheint eine Hauptrolle in verschiedenen Prozessen der kardialen Reorganisation zu spielen, wie z.B. Regulation der Zellproliferation, -migration und -differenzierung. Unsere Hypothese war, dass alpha v -Integrin-vermittelte Signale notwendig f{\"u}r die kompensatorische Hypertrophie nach Aortenkonstriktion sind und assoziiert mit der Modulation der Expression von ECM-Proteinen. Dazu wurden M{\"a}use mit einem spezifischen alpha v Integrin-Inhibitor behandelt und einer Aortenkonstriktion (AB) unterzogen. Nach zwei Tagen und nach sieben Tagen wurden die M{\"a}use echokardiographisch untersucht und eingehende h{\"a}modynamische Untersuchungen wurden durchgef{\"u}hrt. Die Behandlung mit dem alpha v -Integrin-Inhibitor f{\"u}hrte zu einer dilatativen Kardiomyopathie und Herzinsuffizienz in den AB-M{\"a}usen, gekennzeichnet durch einen dilatierten linken Ventrikel, schlechte linksventrikul{\"a}re Funktion und einer Lungenstauung, wohingegen die scheinbehandelten Tiere eine kompensatorische Hypertrophie des linken Ventrikels zeigten. Untersuchungen der beteiligten Signalwege zeigten eine Aktivierung des p38 MAP-Kinase-Signalwegs, von ERK 1 und -2, der Focal Adhesion Kinase FAK und Tyrosin-Phosphorylierung von c-Src in den Kontrollherzen, was in den Inhibitor-behandelten Herzen fehlte. mRNA-Expressionsanalysen f{\"u}r 96 Gene mittels "Micro-Arrays" ermittelten verschiedene genomische Ziele des alpha v -Integrin-aktivierten Signalwegs. 18 f{\"u}r ECM-Proteine codierende Gene wurden mehr als 2-fach hochreguliert, z.B. Kollagen (8,11-fach ± 2,2), Fibronectin (2,32 ± 094), SPARC (3,78 ± 0,12), ADAMTS-1 (3,51 ± 0,81) und TIMP2 (2,23 ± 0,98), wohingegen die Aktivierung dieser Gene in Inhibitor-behandelten Tieren aufgehoben war. Wir folgern daraus, dass Signalwege unterhalb von alpha v -Integrin, mediiert durch MAP-Kinasen, FAK und c-Src, zu einer verst{\"a}rkten Expression von ECM-Komponenten f{\"u}hrt, welche f{\"u}r die kompensatorische Antwort auf Druckbelastung n{\"o}tig sind.}, subject = {Antigen}, language = {en} }