@article{AadAbbottAbdallahetal.2012, author = {Aad, G. and Abbott, B. and Abdallah, J. and Abdel Khalek, S. and Abdelalim, A. A.}, title = {Search for the Standard Model Higgs boson in the H→WW(⋆)→ℓνℓνH→WW(⋆)→ℓνℓν decay mode with 4.7 fb\(^{-1}\) of ATLAS data at \(\sqrt{s}\)=7 TeV}, series = {Physics Letters B}, volume = {761}, journal = {Physics Letters B}, number = {1}, organization = {ATLAS Collaboration}, doi = {10.1016/j.physletb.2012.08.010}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127307}, pages = {62-81}, year = {2012}, abstract = {A search for the Standard Model Higgs boson in the H→WW(⋆)→ℓνℓνH→WW(⋆)→ℓνℓν (ℓ=e,μℓ=e,μ) decay mode is presented. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 4.7 fb\(^{-1}\) at a centre-of-mass energy of 7 TeV collected during 2011 with the ATLAS detector at the Large Hadron Collider. No significant excess of events over the expected background is observed. An upper bound is placed on the Higgs boson production cross section as a function of its mass. A Standard Model Higgs boson with mass in the range between 133 GeV and 261 GeV is excluded at 95\% confidence level, while the expected exclusion range is from 127 GeV to 233 GeV.}, language = {en} } @article{AadAbbottAbdallahetal.2012, author = {Aad, G. and Abbott, B. and Abdallah, J. and Abdelalim, A. A. and Abdesselam, A.}, title = {Electron performance measurements with the ATLAS detector using the 2010 LHC proton-proton collision data}, series = {The European Physical Journal C}, volume = {72}, journal = {The European Physical Journal C}, number = {1909}, doi = {10.1140/epjc/s10052-012-1909-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127313}, year = {2012}, abstract = {Detailed measurements of the electron performance of the ATLAS detector at the LHC are reported, using decays of the Z, W and J/ψ particles. Data collected in 2010 at s√=7 TeV are used, corresponding to an integrated luminosity of almost 40 pb\(^{-1}\). The inter-alignment of the inner detector and the electromagnetic calorimeter, the determination of the electron energy scale and resolution, and the performance in terms of response uniformity and linearity are discussed. The electron identification, reconstruction and trigger efficiencies, as well as the charge misidentification probability, are also presented.}, language = {en} } @article{AadAbbottAbdallahetal.2012, author = {Aad, G. and Abbott, B. and Abdallah, J. and Abdelalim, A. A. and Abdesselam, A.}, title = {Performance of the ATLAS Trigger System in 2010}, series = {The European Physical Journal C}, volume = {72}, journal = {The European Physical Journal C}, number = {1849}, doi = {10.1140/epjc/s10052-011-1849-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127321}, year = {2012}, abstract = {Proton-proton collisions at √s=7 TeV and heavy ion collisions at \(\sqrt{sNN}\)=2.76 TeV were produced by the LHC and recorded using the ATLAS experiment's trigger system in 2010. The LHC is designed with a maximum bunch crossing rate of 40 MHz and the ATLAS trigger system is designed to record approximately 200 of these per second. The trigger system selects events by rapidly identifying signatures of muon, electron, photon, tau lepton, jet, and B meson candidates, as well as using global event signatures, such as missing transverse energy. An overview of the ATLAS trigger system, the evolution of the system during 2010 and the performance of the trigger system components and selections based on the 2010 collision data are shown. A brief outline of plans for the trigger system in 2011 is presented.}, language = {en} } @article{AadAbbottAbdallahetal.2012, author = {Aad, G. and Abbott, B. and Abdallah, J. and Abdelalim, A. A. and Abdesselam, A.}, title = {Forward-backward correlations and charged-particle azimuthal distributions in pp interactions using the ATLAS detector}, series = {Journal of High Energy Physics}, volume = {7}, journal = {Journal of High Energy Physics}, number = {19}, organization = {ATLAS Collaboration}, doi = {10.1007/JHEP07(2012)019}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127336}, year = {2012}, abstract = {Using inelastic proton-proton interactions at s√=900 GeV and 7 TeV, recorded by the ATLAS detector at the LHC, measurements have been made of the correlations between forward and backward charged-particle multiplicities and, for the first time, between forward and backward charged-particle summed transverse momentum. In addition, jet-like structure in the events is studied by means of azimuthal distributions of charged particles relative to the charged particle with highest transverse momentum in a selected kinematic region of the event. The results are compared with predictions from tunes of the pythia and herwig++ Monte Carlo generators, which in most cases are found to provide a reasonable description of the data.}, language = {en} } @phdthesis{Aaken2003, author = {Aaken, Claas van}, title = {Adjuvante Radiochemotherapie des Rektumkarzinoms - multizentrische retrospektive Analyse von 534 Patienten in Franken - Behandlungsergebnisse der Strahlentherapie und Evaluation (A) - eine retrospektive Analyse des Krankengutes 6 fr{\"a}nkischer Strahlenkliniken im Zeitraum 4/93 bis 3/98}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-7681}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2003}, abstract = {Die adjuvante Radiochemotherapie des Rektumkarzinoms im UICC-Stadium II/III wird seit 1991 vom National Cancer Institute (NCI) und in Deutschland seit 1994 als Standard empfohlen. Die Qualit{\"a}t und Ergebnisse der postoperativen Therapie in der t{\"a}glichen klinischen Praxis wurden fl{\"a}chendeckend retrospektiv untersucht. Insgesamt wurden 534 Patienten aus sechs Institutionen ausgewertet, die zwischen 1993 und 1998 behandelt wurden. Die beteiligten Kliniken versorgten strahlentherapeutisch fl{\"a}chendeckend große Teile des nordbayerischen Raumes. Die Stadienverteilung der Patienten war: UICC I 1\%, II 28\%, III 69\% und IV 2\%. 92\% erhielten eine RChT, 8\% eine alleinige RT. Die mediane Nachbeobachtungszeit der Patienten betrug 40 Monate. Ergebnisse (Teil A): Nur etwa 37\% der epidemiologisch erwarteten Patienten wurden entsprechend der Konsensusvereinbarung einer postoperativen Therapie zugewiesen. Nach 5 Jahren betrug die aktuarische lokale Kontrolle 75\%, die Freiheit von Fernmetastasen 56\%, das krankheitsfreie {\"U}berleben 53\% und das Gesamt{\"u}berleben 57\%. Weitere Ergebnisse siehe Teil B. Schlussfolgerung: Der niedrige Anteil von der adjuvanten Therapie zugewiesenen Patienten sowie die im Vergleich zu randomisierten Studien ung{\"u}nstigeren Ergebnisse weisen auf die Auswahl eines Risikokollektivs hin. Anstelle einer stadienbezogenen Zuweisung scheint eine Auswahl mit individueller Risikoabsch{\"a}tzung bevorzugt zu werden. Neben Therapieverbesserungen durch randomisierte Studien sollten ebenso Anstrengungen zur {\"U}bertragung dieser Ergebnisse in die fl{\"a}chendeckende Praxis {\"u}bernommen werden.}, language = {de} } @phdthesis{Abbas2024, author = {Abbas, Eid Nagy Eid}, title = {Demotic Texts from Medinet Habu (Philological, Paleographical, and Cultural Study)}, doi = {10.25972/OPUS-35265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-352653}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {The current study presents a new a group of Demotic ostraca in the belongings of the Cairo Museum. A large part of this group stem from Medinet Habu in the western bank of modern Luxor in Upper Egypt and was discovered in the beginning of the thirties of the last century by the Chicago Oriental Institute (recently renamed as Institute for the Study of Ancient Cultures 'ISAC'). A small portion of the collection under consideration come from other Upper Egyptian provenances including Gebelein, Edfu, Kom Ombo, and possibly elsewhere in Thebes. The main goal of the present dissertation is to decipher, translate, and provide a philological, paleographical, and cultural analysis of the group of texts in question. The results of this study are spread over two main parts, the first of which is dedicated to the main and largest part of the collection, i.e. ostraca from Medinet Habu, while the second is concerned with ostraca from other places. The first part comprises of five sections beginning with receipts of money and in-kind payments including some receipts for the payments of the different capitation charges in the Ptolemaic and Roman Periods, a few for land-related payments, as well as others related to different Ptolemaic monopolies or trades such as a receipt for the price of oil, one for the linen tax, in addition to a unique receipt for the rarely attested fish tax. The second section includes accounts and lists of different kinds be it monetary, in-kind, agriculture, or any other type of lists or accounts that record different everyday transactions. The following section presents a relatively different type of lists, namely lists of personal names. The fourth section incorporates a variety of texts of different concerns, e.g. texts of religious nature, letters, temples oaths, or other private documents. Unidentified texts occupy the fifth and final section of the first part. The second part of the study, which comprises texts that originate from different Upper Egyptian localities, includes three sections, i.e. receipts, accounts, and lists of names.}, language = {en} } @article{AbboudAsendorfHeinrichetal.2021, author = {Abboud, Tammam and Asendorf, Thomas and Heinrich, Jutta and Faust, Katharina and Krieg, Sandro M. and Seidel, Kathleen and Mielke, Dorothee and Matthies, Cordola and Ringel, Florian and Rohde, Veit and Szel{\´e}nyi, Andrea}, title = {Transcranial versus direct cortical stimulation for motor-evoked potentials during resection of supratentorial tumors under general anesthesia (the TRANSEKT-trial): study protocol for a randomized controlled trial}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {10}, issn = {2227-9059}, doi = {10.3390/biomedicines9101490}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248513}, year = {2021}, abstract = {Background: Monitoring of motor function during surgery for supratentorial tumors under general anesthesia applies either transcranial electrical stimulation (TES) or direct cortical stimulation (DCS) to elicit motor-evoked potentials. To date, there is no guideline that favor one method over the other. Therefore, we designed this randomized study to compare between both methods regarding the prediction of postoperative motor deficits and extent of tumor resection. Methods: This is a multicenter (six centers in Germany and one in Switzerland), double blind, parallel group, exploratory, randomized controlled clinical trial. Patients without or with mild paresis, who are scheduled for surgical resection of motor-eloquent brain tumors under general anesthesia will be randomized to surgical resection under TES or surgical resection under DCS. The primary endpoint is sensitivity and specificity in prognosis of motor function 7 days after surgery. The main secondary endpoint is the extent of tumor resection. The study is planned to include 120 patients within 2 years. Discussion: The present exploratory study should compare TES and DCS regarding sensitivity and specificity in predicting postoperative motor deficit and extent of tumor resection to calculate the required number of patients in a confirmatory trial to test the superiority of one method over the other.}, language = {en} } @article{AbdElAzizElMaghrabyEwaldetal.2021, author = {Abd El-Aziz, Asmaa M. and El-Maghraby, Azza and Ewald, Andrea and Kandil, Sherif H.}, title = {In-vitro cytotoxicity study: cell viability and cell morphology of carbon nanofibrous scaffold/hydroxyapatite nanocomposites}, series = {Molecules}, volume = {26}, journal = {Molecules}, number = {6}, issn = {1420-3049}, doi = {10.3390/molecules26061552}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234037}, year = {2021}, abstract = {Electrospun carbon nanofibers (CNFs), which were modified with hydroxyapatite, were fabricated to be used as a substrate for bone cell proliferation. The CNFs were derived from electrospun polyacrylonitrile (PAN) nanofibers after two steps of heat treatment: stabilization and carbonization. Carbon nanofibrous (CNF)/hydroxyapatite (HA) nanocomposites were prepared by two different methods; one of them being modification during electrospinning (CNF-8HA) and the second method being hydrothermal modification after carbonization (CNF-8HA; hydrothermally) to be used as a platform for bone tissue engineering. The biological investigations were performed using in-vitro cell counting, WST cell viability and cell morphology after three and seven days. L929 mouse fibroblasts were found to be more viable on the hydrothermally-modified CNF scaffolds than on the unmodified CNF scaffolds. The biological characterizations of the synthesized CNF/HA nanofibrous composites indicated higher capability of bone regeneration.}, language = {en} } @article{AbdaKrysciakKrohnMoltetal.2015, author = {Abda, Ebrahim M. and Krysciak, Dagmar and Krohn-Molt, Ines and Mamat, Uwe and Schmeisser, Christel and F{\"o}rstner, Konrad U. and Schaible, Ulrich E. and Kohi, Thomas A. and Nieman, Stefan and Streit, Wolfgang R.}, title = {Phenotypic Heterogeneity Affects Stenotrophomonas maltophilia K279a Colony Morphotypes and \(\beta\)-Lactamase Expression}, series = {Frontiers in Microbiology}, volume = {6}, journal = {Frontiers in Microbiology}, number = {1373}, doi = {10.3389/fmicb.2015.01373}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136446}, year = {2015}, abstract = {Phenotypic heterogeneity at the cellular level in response to various stresses, e.g., antibiotic treatment has been reported for a number of bacteria. In a clonal population, cell-to-cell variation may result in phenotypic heterogeneity that is a mechanism to survive changing environments including antibiotic therapy. Stenotrophomonas rnaltophilia has been frequently isolated from cystic fibrosis patients, can cause numerous infections in other organs and tissues, and is difficult to treat due to antibiotic resistances. S. maltophilia K279a produces the Li and L2 beta-lactamases in response to beta-lactam treatment. Here we report that the patient isolate S. rnaltophilia K279a diverges into cellular subpopulations with distinct but reversible morphotypes of small and big colonies when challenged with ampicillin. This observation is consistent with the formation of elongated chains of bacteria during exponential growth phase and the occurrence of mainly rod-shaped cells in liquid media. RNA-seq analysis of small versus big colonies revealed differential regulation of at least seven genes among the colony morphotypes. Among those, bleu and bla(L2) were transcriptionally the most strongly upregulated genes. Promoter fusions of b/a(L1) and b/a(L2) genes indicated that expression of both genes is also subject to high levels of phenotypic heterogeneous expression on a single cell level. Additionally, the comE homolog was found to be differentially expressed in homogenously versus heterogeneously bla(L2) expressing cells as identified by RNA(seq) analysis. Overexpression of cornE in S. maltophilia K279a reduced the level of cells that were in a bla(L2)-ON mode to 1\% or lower. Taken together, our data provide strong evidence that S. maltophilia K279a populations develop phenotypic heterogeneity in an ampicillin challenged model. This cellular variability is triggered by regulation networks including b/a(L1), b/a(L2), and comE.}, language = {en} } @article{AbdaliBarthNorouzyetal.2013, author = {Abdali, Narges and Barth, Enrico and Norouzy, Amir and Schulz, Robert and Nau, Werner M. and Kleinekathofer, Ulrich and Tauch, Andreas and Benz, Roland}, title = {Corynebacterium jeikeium jk0268 Constitutes for the 40 Amino Acid Long PorACj, Which Forms a Homooligomeric and Anion- Selective Cell Wall Channel}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {10}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129989}, pages = {e75651}, year = {2013}, abstract = {Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed.}, language = {en} } @article{AbdaliYounasMafakherietal.2018, author = {Abdali, Narges and Younas, Farhan and Mafakheri, Samaneh and Pothula, Karunakar R. and Kleinekath{\"o}fer, Ulrich and Tauch, Andreas and Benz, Roland}, title = {Identification and characterization of smallest pore-forming protein in the cell wall of pathogenic Corynebacterium urealyticum DSM 7109}, series = {BMC Biochemistry}, volume = {19}, journal = {BMC Biochemistry}, doi = {10.1186/s12858-018-0093-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226959}, year = {2018}, abstract = {Background: Corynebacterium urealyticum, a pathogenic, multidrug resistant member of the mycolata, is known as causative agent of urinary tract infections although it is a bacterium of the skin flora. This pathogenic bacterium shares with the mycolata the property of having an unusual cell envelope composition and architecture, typical for the genus Corynebacterium. The cell wall of members of the mycolata contains channel-forming proteins for the uptake of solutes. Results: In this study, we provide novel information on the identification and characterization of a pore-forming protein in the cell wall of C. urealyticum DSM 7109. Detergent extracts of whole C. urealyticum cultures formed in lipid bilayer membranes slightly cation-selective pores with a single-channel conductance of 1.75 nS in 1 M KCl. Experiments with different salts and non-electrolytes suggested that the cell wall pore of C. urealyticum is wide and water-filled and has a diameter of about 1.8 nm. Molecular modelling and dynamics has been performed to obtain a model of the pore. For the search of the gene coding for the cell wall pore of C. urealyticum we looked in the known genome of C. urealyticum for a similar chromosomal localization of the porin gene to known porH and porA genes of other Corynebacterium strains. Three genes are located between the genes coding for GroEL2 and polyphosphate kinase (PKK2). Two of the genes (cur_1714 and cur_1715) were expressed in different constructs in C. glutamicum Delta porA Delta porH and in porin-deficient BL21 DE3 Omp8 E. coli strains. The results suggested that the gene cur_1714 codes alone for the cell wall channel. The cell wall porin of C. urealyticum termed PorACur was purified to homogeneity using different biochemical methods and had an apparent molecular mass of about 4 kDa on tricine-containing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Conclusions: Biophysical characterization of the purified protein (PorACur) suggested indeed that cur_1714 is the gene coding for the pore-forming protein in C. urealyticum because the protein formed in lipid bilayer experiments the same pores as the detergent extract of whole cells. The study is the first report of a cell wall channel in the pathogenic C. urealyticum.}, language = {en} } @phdthesis{AbdelRahman2003, author = {Abdel Rahman, Faisal Mirghani}, title = {Systematic analysis of genes expressed in the retinal pigment epithelium (RPE) and identification of candidates for genetic susceptibility to age-related macular degeneration (AMD)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-7053}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2003}, abstract = {Age related macular degeneration (AMD) is the leading cause of visual impairment in the elderly and the major cause of blindness in the developed world. To date, the molecular mechanisms underlying the disease are not well understood although in recent years a primary involvement of the retinal pigment epithelium (RPE) has become evident. The aim of the present study is to systematically analyse genes which are differentially expressed in the RPE, and to assess their possible association with mechanisms and pathways likely to be related to retinal disease, in particular AMD. Towards this goal, 2379 expressed sequence tags (ESTs) were established from an inhouse generated RPE cDNA library. This library was constructed by using the suppression subtraction hybridization (SSH) technique which normalises redundant sequences and ensures enrichment of rare transcripts. In a first phase, 1002 ESTs were sequenced and subjected to comprehensive alignment with public nucleotide and protein databases. A search of the 1002 ESTs against the human genome draft sequence yielded 168 known genes, 51 predicted genes, 15 unknown transcripts and 41 clones with no significant similarity. Reverse Northern blot hybridization was performed for 318 EST clusters to identify abundantly expressed genes in the RPE and to prioritize subsequent analyses. Representative clones were spotted onto a nylon membrane and hybridized with cDNA probes of driver (heart and liver) and tester (RPE) used in the cDNA library construction. Subsequently, 107 EST clusters were subjected to Northern blot hybridizations. These analyses identified 7 RPE-specific, 3 retina-specific, 7 RPE/retina-specific, and 7 tissue restricted transcripts, while 29 EST clusters were ubiquitously expressed, and evaluation was not possible for another 54 EST clusters. Of the 24 transcripts with specific or restricted expression, 16 clones were selected for further characterization. The predicted gene MGC2477 and 2 novel isoforms of the human transient receptor potential cation channel, subfamily M, member 3 (TRPM3) were cloned and further described in detail. In addition, polymorphic variations for these 2 genes as well as for the human MT-Protocadherin gene were determined. For MGC2477, 15 single nucleotide polymorphisms (SNPs) were identified, with 13 having a frequency of the minor allele greater than 20\%. 10 of the 15 SNPs have not been reported in so far in public SNP repertoires. Partial assessment of the TRPM3 gene yielded 35 SNPs. Of these, 30 (85.7\%) were highly frequent (0.17-0.5\%), and 14 (40\%) were novel. The MT-Protocadherin gene revealed 35 SNPs, including 28 (80\%) with high frequency of the minor allele. 23 (65.7\%) were novel SNPs. These SNPs will be used to construct the most common haplotypes. These will be used in case/control association studies in 400 AMD patients and 200 ethnically and aged matched controls to assess a possible contribution of these genes in the etiology of AMD.}, subject = {Senile Makuladegeneration / Pigmentepithel / Genexpression}, language = {en} } @article{AbdelLatifFathyAnwaretal.2022, author = {Abdel-Latif, Rania and Fathy, Moustafa and Anwar, Hend Ali and Naseem, Muhammad and Dandekar, Thomas and Othman, Eman M.}, title = {Cisplatin-induced reproductive toxicity and oxidative stress: ameliorative effect of kinetin}, series = {Antioxidants}, volume = {11}, journal = {Antioxidants}, number = {5}, issn = {2076-3921}, doi = {10.3390/antiox11050863}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271223}, year = {2022}, abstract = {Cisplatin is a commonly used chemotherapeutic agent; however, its potential side effects, including gonadotoxicity and infertility, are a critical problem. Oxidative stress has been implicated in the pathogenesis of cisplatin-induced testicular dysfunction. We investigated whether kinetin use at different concentrations could alleviate gonadal injury associated with cisplatin treatment, with an exploration of the involvement of its antioxidant capacity. Kinetin was administered in different doses of 0.25, 0.5, and 1 mg/kg, alone or along with cisplatin for 10 days. Cisplatin toxicity was induced via a single IP dose of 7 mg/kg on day four. In a dose-dependent manner, concomitant administration of kinetin with cisplatin significantly restored testicular oxidative stress parameters, corrected the distorted sperm quality parameters and histopathological changes, enhanced levels of serum testosterone and testicular StAR protein expression, as well as reduced the up-regulation of testicular TNF-α, IL-1β, Il-6, and caspase-3, caused by cisplatin. It is worth noting that the testicular protective effect of the highest kinetin dose was comparable/more potent and significantly higher than the effects of vitamin C and the lowest kinetin dose, respectively. Overall, these data indicate that kinetin may offer a promising approach for alleviating cisplatin-induced reproductive toxicity and organ damage, via ameliorating oxidative stress and reducing inflammation and apoptosis.}, language = {en} } @article{AbdelhafezFawzyFahimetal.2018, author = {Abdelhafez, Omnia Hesham and Fawzy, Michael Atef and Fahim, John Refaat and Desoukey, Samar Yehia and Krischke, Markus and Mueller, Martin J. and Abdelmohsen, Usama Ramadan}, title = {Hepatoprotective potential of Malvaviscus arboreus against carbon tetrachloride-induced liver injury in rats}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0202362}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177243}, pages = {e0202362}, year = {2018}, abstract = {Malvaviscus arboreus Cav. is a medicinal plant belonging to family Malvaceae with both ethnomedical and culinary value; however, its phytochemical and biological profiles have been scarcely studied. Accordingly, this work was designed to explore the chemical composition and the hepatoprotective potential of M. arboreus against carbon tetrachloride (CCl\(_4\))-induced hepatotoxicity. The total extract of the aerial parts and its derived fractions (petroleum ether, dichloromethane, ethyl acetate, and aqueous) were orally administered to rats for six consecutive days, followed by injection of CCl\(_4\) (1:1 v/v, in olive oil, 1.5 ml/kg, i.p.) on the next day. Results showed that the ethyl acetate and dichloromethane fractions significantly alleviated liver injury in rats as indicated by the reduced levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (TB), and malondialdehyde (MDA), along with enhancement of the total antioxidant capacities of their livers, with the maximum effects were recorded by the ethyl acetate fraction. Moreover, the protective actions of both fractions were comparable to those of silymarin (100 mg/kg), and have been also substantiated by histopathological evaluations. On the other hand, liquid chromatography-high resolution electrospray ionization mass spectrometry (LC‒HR‒ESI‒MS) metabolomic profiling of the crude extract of M. arboreus aerial parts showed the presence of a variety of phytochemicals, mostly phenolics, whereas the detailed chemical analysis of the most active fraction (i.e. ethyl acetate) resulted in the isolation and identification of six compounds for the first time in the genus, comprising four phenolic acids; β-resorcylic, caffeic, protocatechuic, and 4-hydroxyphenylacetic acids, in addition to two flavonoids; trifolin and astragalin. Such phenolic principles, together with their probable synergistic antioxidant and liver-protecting properties, seem to contribute to the observed hepatoprotective potential of M. arboreus.}, language = {en} } @article{AbdelhameedEltamanyHaletal.2020, author = {Abdelhameed, Reda F. A. and Eltamany, Enas E. and Hal, Dina M. and Ibrahim, Amany K. and AboulMagd, Asmaa M. and Al-Warhi, Tarfah and Youssif, Khayrya A. and Abd El-kader, Adel M. and Hassanean, Hashim A. and Fayez, Shaimaa and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan}, title = {New cytotoxic cerebrosides from the Red Sea cucumber Holothuria spinifera supported by in-silico studies}, series = {Marine Drugs}, volume = {18}, journal = {Marine Drugs}, number = {8}, issn = {1660-3397}, doi = {10.3390/md18080405}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211089}, year = {2020}, abstract = {Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC\(_{50}\) values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC\(_{50}\) 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.}, language = {en} } @article{AbdelhameedHabibEltahawyetal.2020, author = {Abdelhameed, Reda F. A. and Habib, Eman S. and Eltahawy, Nermeen A. and Hassanean, Hashim A. and Ibrahim, Amany K. and Mohammed, Anber F. and Fayez, Shaimaa and Hayallah, Alaa M. and Yamada, Koji and Behery, Fathy A. and Al-Sanea, Mohammad M. and Alzarea, Sami I. and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan}, title = {New cytotoxic natural products from the Red Sea sponge Stylissa carteri}, series = {Marine Drugs}, volume = {18}, journal = {Marine Drugs}, number = {5}, issn = {1660-3397}, doi = {10.3390/md18050241}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205795}, year = {2020}, abstract = {Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract's metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC\(_{50}\) values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC\(_{50}\) at 36.8 ± 0.16 µM for 1 and IC\(_{50}\) 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.}, language = {en} } @article{AbdelhameedHabibGodaetal.2020, author = {Abdelhameed, Reda F. A. and Habib, Eman S. and Goda, Marwa S. and Fahim, John Refaat and Hassanean, Hashem A. and Eltamany, Enas E. and Ibrahim, Amany K. and AboulMagd, Asmaa M. and Fayez, Shaimaa and Abd El-kader, Adel M. and Al-Warhi, Tarfah and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan}, title = {Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass Thalassodendron ciliatum}, series = {Marine Drugs}, volume = {18}, journal = {Marine Drugs}, number = {7}, doi = {10.3390/md18070354}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236085}, year = {2020}, abstract = {Thalassodendron ciliatum (Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol (1) was isolated from the methanolic extract of T. ciliatum growing in the Red Sea, along with two known first-reported sterols, namely ergosterol (2) and stigmasterol (3), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC\(_{50}\) values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol 1 explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of T. ciliatum using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides.}, language = {en} } @phdthesis{Abdelmohsen2010, author = {Abdelmohsen, Usama Ramadan}, title = {Antimicrobial Activities from Plant Cell Cultures and Marine Sponge-Associated Actinomycetes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51483}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {This thesis is divided into three parts with the main goal allocating novel antimicrobial compounds that could be used as future antibiotics. The first part aimed to evaluate the potential of plant suspension cultures for the production of antimicrobial proteins. The extracellular, intracellular and cell wall bound fractions of seven heterotrophic and photomixotrophic plant cell suspension cultures treated with nine different elicitors were tested for the elicitor dependent production of antimicrobial proteins. Bioactivities were tested against a selected panel of human isolates including Gram-positive and Gram-negative bacteria as well as fungi using the disc diffusion assay. The intracellular fractions of elicited cell cultures were more active than extracellular fractions while the cell wall bound fractions showed lowest activities. Among the 21 fractions tested, the intracellular fraction of Lavendula angustifolia elicited with DC3000 was most active against Candida maltosa. The second most active fraction was the intracellular fraction of Arabidopsis thaliana elicited with salicylic acid which was moreover active against all test strains. The antimicrobial activity of elicited Arabidopsis thaliana cell cultures was tested by bioautography to locate the antimicrobial proteins in the crude extract. The intracellular fraction of photomixotrophic Arabidopsis thaliana cells elicited with salicylic acid was selected for further gel filtration chromatography on S-200 column leading to the purification of one 19 kDa antimicrobially active protein, designated, AtAMP. Our findings suggest that elicited plant cell cultures may present a new promising alternative source of antimicrobial proteins. The second part comprises the isolation of actinomycetes associated with marine sponges and testing the bioactivities of new species for further investigations. Actinobacterial communities of eleven taxonomically different sponges that had been collected from offshore Ras Mohamed (Egypt) and from Rovinj (Croatia) were investigated by a culture-based approach using different standard media for isolation of actinomycetes and media enriched with aqueous sponge extract to target rare and new actinomycete species. Phylogenetic characterization of 52 representative isolates out of 90 based on almost complete sequences of genes encoding 16S rRNA supported their assignment to 18 different actinomycete genera. Altogether 14 putatively new species were identified based on sequence similarity values below 98.2\% to other strains in the NCBI database. The use of M1 agar amended with aqueous sponge extract yielded a putative new genus related to Rubrobacter which highlighting the need for innovative cultivation protocols. Biological activity testing showed that five isolates were active against Gram-positives only, one isolate was active against Candida albicans only and one isolate showed activity against both groups of pathogens. Moreover, the antiparasistic activity was documented for four isolates. These results showed a high diversity of actinomycetes associated with marine sponges as well as highlighted their potential to produce anti-infective agents. The third part of the thesis focused on the isolation and structure elucidation of new bioactive compounds. Streptomyces strain RV15 recovered from sponge Dysidea tupha, was selected for further chemical analysis by virtue of the fact that it exhibited the greatest antimicrobial potential against Staphylococcus aureus as well as Candida albicans among the all tested strains. Moreover, members of the genus Streptomyces are well known as prolific producers of interesting pharmacologically active metabolites. Chemical analysis of the methanolic crude extract using different chromatographic tools yielded four new compounds. The structures of the new compounds were spectroscopically elucidated to be four new cyclic peptides, namely, cyclodysidins A-D. Their bioactivity was tested against different proteases, bacteria and Candida as well as tumor cell lines. The compounds did not show any significant activities at this point.}, subject = {Antimikrobieller Wirkstoff}, language = {en} } @article{AbdelmohsenChengViegelmannetal.2014, author = {Abdelmohsen, Usama Ramadan and Cheng, Cheng and Viegelmann, Christina and Zhang, Tong and Grkovic, Tanja and Ahmed, Safwat and Quinn, Ronald J. and Hentschel, Ute and Edrada-Ebel, RuAngelie}, title = {Dereplication Strategies for Targeted Isolation of New Antitrypanosomal Actinosporins A and B from a Marine Sponge Associated-Actinokineospora sp EG49}, series = {Marine Drugs}, volume = {12}, journal = {Marine Drugs}, number = {3}, issn = {1660-3397}, doi = {10.3390/md12031220}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119876}, pages = {1220-44}, year = {2014}, abstract = {High resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy were employed as complementary metabolomic tools to dereplicate the chemical profile of the new and antitrypanosomally active sponge-associated bacterium Actinokineospora sp. EG49 extract. Principal Component (PCA), hierarchical clustering (HCA), and orthogonal partial least square-discriminant analysis (OPLS-DA) were used to evaluate the HRFTMS and NMR data of crude extracts from four different fermentation approaches. Statistical analysis identified the best culture one-strain-many-compounds (OSMAC) condition and extraction procedure, which was used for the isolation of novel bioactive metabolites. As a result, two new O-glycosylated angucyclines, named actinosporins A (1) and B (2), were isolated from the broth culture of Actinokineospora sp. strain EG49, which was cultivated from the Red Sea sponge Spheciospongia vagabunda. The structures of actinosporins A and B were determined by 1D- and 2D-NMR techniques, as well as high resolution tandem mass spectrometry. Testing for antiparasitic properties showed that actinosporin A exhibited activity against Trypanosoma brucei brucei with an IC₅₀ value of 15 µM; however no activity was detected against Leishmania major and Plasmodium falciparum, therefore suggesting its selectivity against the parasite Trypanosoma brucei brucei; the causative agent of sleeping sickness.}, language = {en} } @article{AbdelmohsenPimentelElardoHanoraetal.2010, author = {Abdelmohsen, Usama Ramadan and Pimentel-Elardo, Sheila M. and Hanora, Amro and Radwan, Mona and Abou-El-Ela, Soad H. and Ahmed, Safwat and Hentschel, Ute}, title = {Isolation, Phylogenetic Analysis and Anti-infective Activity Screening of Marine Sponge-Associated Actinomycetes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68307}, year = {2010}, abstract = {Terrestrial actinomycetes are noteworthy producers of a multitude of antibiotics, however the marine representatives are much less studied in this regard. In this study, 90 actinomycetes were isolated from 11 different species of marine sponges that had been collected from offshore Ras Mohamed (Egypt) and from Rovinj (Croatia). Phylogenetic characterization of the isolates based on 16S rRNA gene sequencing supported their assignment to 18 different actinomycete genera representing seven different suborders. Fourteen putatively novel species were identified based on sequence similarity values below 98.2\% to other strains in the NCBI database. A putative new genus related to Rubrobacter was isolated on M1 agar that had been amended with sponge extract, thus highlighting the need for innovative cultivation protocols. Testing for anti-infective activities was performed against clinically relevant, Gram-positive (Enterococcus faecalis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria, fungi (Candida albicans) and human parasites (Leishmania major, Trypanosoma brucei). Bioactivities against these pathogens were documented for 10 actinomycete isolates. These results show a high diversity of actinomycetes associated with marine sponges as well as highlight their potential to produce anti-infective agents.}, subject = {Biologie}, language = {en} } @article{AbdelmohsenSzesnyOthmanetal.2012, author = {Abdelmohsen, Usama Ramadan and Szesny, Matthias and Othman, Eman Maher and Schirmeister, Tanja and Grond, Stepanie and Stopper, Helga and Hentschel, Ute}, title = {Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76279}, year = {2012}, abstract = {Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the known microbial metabolites discovered so far. Diazepinomicin was isolated from the marine sponge-associated strain Micromonospora sp. RV115 and was identified by spectroscopic analysis and by comparison to literature data. In addition to its interesting preclinical broad-spectrum antitumor potential, we report here new antioxidant and anti-protease activities for this compound. Using the ferric reducing antioxidant power (FRAP) assay, a strong antioxidant potential of diazepinomicin was demonstrated. Moreover, diazepinomicin showed a significant antioxidant and protective capacity from genomic damage induced by the reactive oxygen species hydrogen peroxide in human kidney (HK-2) and human promyelocytic (HL-60) cell lines. Additionally, diazepinomicin inhibited the proteases rhodesain and cathepsin L at an IC50 of 70-90 μM. It also showed antiparasitic activity against trypomastigote forms of Trypanosoma brucei with an IC50 of 13.5 μM. These results showed unprecedented antioxidant and anti-protease activities of diazepinomicin, thus further highlighting its potential as a future drug candidate.}, subject = {Biologie}, language = {en} } @article{AbdelmohsenYangHornetal.2014, author = {Abdelmohsen, Usama Ramadan and Yang, Chen and Horn, Hannes and Hajjar, Dina and Ravasi, Timothy and Hentschel, Ute}, title = {Actinomycetes from Red Sea Sponges: Sources for Chemical and Phylogenetic Diversity}, doi = {10.3390/md12052771}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112882}, year = {2014}, abstract = {The diversity of actinomycetes associated with marine sponges collected off Fsar Reef (Saudi Arabia) was investigated in the present study. Forty-seven actinomycetes were cultivated and phylogenetically identified based on 16S rRNA gene sequencing and were assigned to 10 different actinomycete genera. Eight putatively novel species belonging to genera Kocuria, Mycobacterium, Nocardia, and Rhodococcus were identified based on sequence similarity values below 98.2\% to other 16S rRNA gene sequences available in the NCBI database. PCR-based screening for biosynthetic genes including type I and type II polyketide synthases (PKS-I, PKS-II) as well as nonribosomal peptide synthetases (NRPS) showed that 20 actinomycete isolates encoded each at least one type of biosynthetic gene. The organic extracts of nine isolates displayed bioactivity against at least one of the test pathogens, which were Gram-positive and Gram-negative bacteria, fungi, human parasites, as well as in a West Nile Virus protease enzymatic assay. These results emphasize that marine sponges are a prolific resource for novel bioactive actinomycetes with potential for drug discovery.}, subject = {Meeresschw{\"a}mme}, language = {en} } @article{AbdullahiWesselHuberetal.2019, author = {Abdullahi, Sahra and Wessel, Birgit and Huber, Martin and Wendleder, Anna and Roth, Achim and Kuenzer, Claudia}, title = {Estimating penetration-related X-band InSAR elevation bias: a study over the Greenland ice sheet}, series = {Remote Sensing}, volume = {11}, journal = {Remote Sensing}, number = {24}, issn = {2072-4292}, doi = {10.3390/rs11242903}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193902}, year = {2019}, abstract = {Accelerating melt on the Greenland ice sheet leads to dramatic changes at a global scale. Especially in the last decades, not only the monitoring, but also the quantification of these changes has gained considerably in importance. In this context, Interferometric Synthetic Aperture Radar (InSAR) systems complement existing data sources by their capability to acquire 3D information at high spatial resolution over large areas independent of weather conditions and illumination. However, penetration of the SAR signals into the snow and ice surface leads to a bias in measured height, which has to be corrected to obtain accurate elevation data. Therefore, this study purposes an easy transferable pixel-based approach for X-band penetration-related elevation bias estimation based on single-pass interferometric coherence and backscatter intensity which was performed at two test sites on the Northern Greenland ice sheet. In particular, the penetration bias was estimated using a multiple linear regression model based on TanDEM-X InSAR data and IceBridge laser-altimeter measurements to correct TanDEM-X Digital Elevation Model (DEM) scenes. Validation efforts yielded good agreement between observations and estimations with a coefficient of determination of R\(^2\) = 68\% and an RMSE of 0.68 m. Furthermore, the study demonstrates the benefits of X-band penetration bias estimation within the application context of ice sheet elevation change detection.}, language = {en} } @phdthesis{Abel2023, author = {Abel, Daniel Karl-Joseph}, title = {Weiterentwicklung der Bodenhydrologie des regionalen Klimamodells REMO}, doi = {10.25972/OPUS-31146}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311468}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die Bodenfeuchte stellt eine essenzielle Variable f{\"u}r den Energie-, Feuchte- und Stoffaustausch zwischen Landoberfl{\"a}che und Atmosph{\"a}re dar. Ihre Auswirkungen auf Temperatur und Niederschlag sind vielf{\"a}ltig und komplex. Die in Klimamodellen verwendeten Schemata zur Simulation der Bodenfeuchte, auch bodenhydrologische Schemata genannt, sind aufgrund des Ursprungs der Klimamodelle aus Wettermodellen jedoch h{\"a}ufig sehr stark vereinfacht dargestellt. Bei Klimamodellen, die Simulationen mit einer groben Aufl{\"o}sung von mehreren Zehner- oder Hunderterkilometern rechnen, k{\"o}nnen viele Prozesse vernachl{\"a}ssigt werden. Da die Aufl{\"o}sung der Klimamodelle jedoch stetig steigt und mittlerweile beim koordinierten Projekt regionaler Klimamodelle CORDEX-CORE standardm{\"a}ßig bei 0.22° Kantenl{\"a}nge liegt, m{\"u}ssen auch h{\"o}her aufgel{\"o}ste Daten und mehr Prozesse simuliert werden. Dies gilt erst recht mit Blick auf konvektionsaufl{\"o}sende Simulationen mit wenigen Kilometern Kantenl{\"a}nge. Mit steigenden Modellaufl{\"o}sungen steigt zugleich die Komplexit{\"a}t und Differenziertheit der Fragestellungen, die mit Hilfe von Klimamodellen beantwortet werden sollen. An diesem Punkt setzt auch das Projekt BigData@Geo an, in dessen Rahmen die vorliegende Arbeit entstand. Ziel dieses Projektes ist es, hochaufgel{\"o}ste Klimainformationen f{\"u}r den bayerischen Regierungsbezirk Unterfranken f{\"u}r Akteure aus der Land- und Forstwirtschaft sowie dem Weinbau zur Verf{\"u}gung zu stellen. Auf diesen angewandten und grundlegenden Anforderungen und Zielsetzungen basierend, bedarf auch das in dieser Arbeit verwendete regionale Klimamodell REMO (Version 2015) der weiteren Entwicklung. So ist das Hauptziel der Arbeit das bestehende einschichtige bodenhydrologische Schema durch ein mehrschichtiges zu ersetzen. Der Vorteil mehrerer simulierter Bodenschichten besteht darin, dass nun die vertikale Bewegung des Wassers in Form von Versickerung und kapillarem Aufstieg simuliert werden kann. Dies geschieht auf der Basis bodenhydrologischer Parameter, deren Wert in Abh{\"a}ngigkeit vom Boden und der Bodenfeuchte {\"u}ber die Wasserr{\"u}ckhaltekurve bestimmt wird. F{\"u}r diese Kurve existieren verschiedene Parametrisierungen, von denen die Ans{\"a}tze von Clapp-Hornberger und van Genuchten verwendet wurden. Außerdem kann die Bodenfeuchte nun bis zu einer Tiefe von circa 10 m beziehungsweise der Tiefe des anstehenden Gesteins simuliert werden. Damit besteht im Gegensatz zum vorherigen Schema, dessen Tiefe auf die Wurzeltiefe beschr{\"a}nkt ist, die M{\"o}glichkeit, dass Wasser auch unterhalb der Wurzeln zur Verf{\"u}gung stehen kann und somit die absolute im Boden verf{\"u}gbare Wassermenge zunimmt. Die Schichtung erlaubt dar{\"u}ber hinaus die Verdunstung aus unbewachsenem Boden lediglich auf Basis des in der obersten Schicht verf{\"u}gbaren Wassers. Ein weiterer Prozess, der dank der Schichtung und der weiter unten erl{\"a}uterten Datens{\"a}tze neu parametrisiert werden kann, ist die Infiltration. F{\"u}r die Verwendung des Schemas sind Informationen {\"u}ber bodenhydrologische Parameter, die Wurzeltiefe und die Tiefe bis zum anstehenden Gestein erforderlich. Entsprechende Datens{\"a}tze m{\"u}ssen hierf{\"u}r aufbereitet und in das Modell eingebaut werden. Bez{\"u}glich der Wurzeltiefe wurden drei sich bez{\"u}glich der Tiefe, der Definition und der verf{\"u}gbaren Aufl{\"o}sung stark voneinander unterscheidende Datens{\"a}tze verglichen. Letztendlich wird die Wurzeltiefe aus dem mit einer anderen REMO-Version gekoppelten Vegetationsmodul iMOVE verwendet, da zuk{\"u}nftig eine Kopplung dieses Moduls mit dem mehrschichtigen Boden geplant ist und die Wurzeltiefen damit konsistent sind. Zudem ist die zugrundeliegende Aufl{\"o}sung der Daten hoch und es werden maximale Wurzeltiefen ber{\"u}cksichtigt, die besonders wichtig f{\"u}r die Simulation von Landoberfl{\"a}che-Atmosph{\"a}re-Interaktionen sind. Diese Vorteile brachten die anderen Datens{\"a}tze nicht mit. In der finalen Modellversion werden f{\"u}r die Tiefe bis zum anstehenden Gestein und die Korngr{\"o}ßenverteilungen die Daten von SoilGrids verwendet. Ein Vergleich mit anderen Bodendatens{\"a}tzen fand in einer parallel laufenden Dissertation statt (Ziegler 2022). Bei SoilGrids ist hervorzuheben, dass die Korngr{\"o}ßenverteilungen in einer hohen r{\"a}umlichen Aufl{\"o}sung (1 km^2 oder h{\"o}her) und mit mehreren vertikalen Schichten vorliegen. Gegen{\"u}ber dem urspr{\"u}nglich in REMO verwendeten Datensatz mit einer Kantenl{\"a}nge von 0.5° und ohne vertikale Differenzierung ist dies eine starke Verbesserung der Eingangsdaten. Dazu kommt, dass die Korngr{\"o}ßenverteilungen die Verwendung kontinuierlicher Pedotransferfunktionen statt f{\"u}nf diskreter Texturklassen, denen f{\"u}r die bodenhydrologischen Parameter fixe Tabellenwerte zugewiesen werden, erm{\"o}glichen. Dies f{\"u}hrt zu einer deutlich besseren Differenzierung des heterogenen Bodens. Im Rahmen der Arbeit wurden insgesamt 19 Simulationen f{\"u}r Europa und ein erweitertes Deutschlandgebiet mit Aufl{\"o}sungen von 0.44° beziehungsweise 0.11° f{\"u}r den Zeitraum 2000 bis 2018 gerechnet. Dabei zeigte sich, dass die Einf{\"u}hrung des mehrschichtigen Bodenschemas gegen{\"u}ber dem einschichtigen Schema zu einer Verringerung der Bodenfeuchte in der Wurzeltiefe f{\"u}hrt. Nichtsdestotrotz nimmt die absolute Wassermenge des Bodens durch die Ber{\"u}cksichtigung des Bodens unterhalb der Wurzelzone zu. Bezogen auf die einzelnen Schichten wird die Bodenfeuchte damit zwar untersch{\"a}tzt, im Laufe der Modellentwicklung kann jedoch eine Verbesserung im Vergleich zu ERA5 erzielt werden. Das neue Schema f{\"u}hrt zu einer Verringerung der Evapotranspiration, die {\"u}ber alle Schritte der Modellentwicklung und besonders w{\"a}hrend der Sommermonate auftritt. Im Vergleich zu Validationsdaten von ERA5 und GLEAM zeigt sich, dass dies eine Verbesserung dieser Gr{\"o}ße bedeutet, die sowohl in der Fl{\"a}che als auch beim Fehler und in der Verteilung auftritt. Gleiches l{\"a}sst sich f{\"u}r den Oberfl{\"a}chenabfluss sagen. Hierf{\"u}r implementierte Schemata (Philip, Green-Ampt), die anders als das standardm{\"a}ßig verwendete Improved-Arno-Schema bodenhydrologische Parameter ber{\"u}cksichtigen, konnten eine weitere Verbesserung im Flachland zeigen. In Gebirgsregionen nahm der Fehler durch die nicht enthaltene Ber{\"u}cksichtigung der Hangneigung jedoch zu, sodass in der finalen Modellversion auf das Improved-Arno-Schema zur{\"u}ckgegriffen wurde. Die Temperatur steigt durch die urspr{\"u}ngliche Version des mehrschichtigen Schemas zun{\"a}chst an, was zu einer {\"U}ber- statt der vorherigen Untersch{\"a}tzung gegen{\"u}ber E-OBS f{\"u}hrt. Die Modellentwicklung resultiert zwar in einer Reduzierung der Temperatur, jedoch f{\"a}llt diese zu stark aus, sodass der Temperaturfehler letztendlich gr{\"o}ßer als in der einschichtigen Modellversion ist. Da die Evapotranspiration jedoch maßgeblich verbessert wurde, kann dieser Fehler eventuell auf ein {\"u}berm{\"a}ßiges Tuning der Temperatur zur{\"u}ckgef{\"u}hrt werden. Die Betrachtung von Hitzeereignissen am Beispiel der Sommer 2003 und 2018 hat gezeigt, dass die Modellentwicklung dazu beitr{\"a}gt, diese Ereignisse besser als das einschichtige Schema zu simulieren. Zwar trifft dies nicht auf das r{\"a}umliche Verhalten der mittleren Temperatur zu, jedoch auf deren zeitlichen Verlauf. Hinzu kommt die bessere Simulation der t{\"a}glichen Extrem- und besonders der Minimaltemperatur, was zu einer Erh{\"o}hung der t{\"a}glichen Temperaturspanne f{\"u}hrt. Diese wird von Klimamodellen in der Regel zu stark untersch{\"a}tzt. Durch die Ber{\"u}cksichtigung der vertikalen Wasserfl{\"u}sse hat sich jedoch auch gezeigt, dass noch enormes Entwicklungspotenzial mit Blick auf (boden)hydrologische Prozesse besteht. Dies gilt in besonderem Maße f{\"u}r zuk{\"u}nftige Simulationen mit konvektionserlaubender Aufl{\"o}sung. So sollten subskalige Informationen des Bodens und der Orographie ber{\"u}cksichtigt werden. Dies dient einerseits der Repr{\"a}sentation vorliegender Heterogenit{\"a}ten und kann andererseits, wie am Beispiel der Infiltrationsschemata dargelegt, zur Verbesserung bestehender Prozesse beitragen. Da die simulierte Drainage durch das mehrschichtige Bodenschema im gleichen Maße zu- wie der Oberfl{\"a}chenabfluss abnimmt und das Wasser dem Modell in der Folge nicht weiter zur Verf{\"u}gung steht, sollte zuk{\"u}nftig auch Grundwasser im Modell ber{\"u}cksichtigt werden. Eine Vielzahl von Studien konnte einen Mehrwert durch die Implementierung dieser Variable und damit verbundener Prozesse feststellen. Mittelfristig ist jedoch insgesamt die Kopplung an ein hydrologisches Modell zu empfehlen, um die bei hochaufl{\"o}senden Simulationen relevanten Prozesse angemessen repr{\"a}sentieren zu k{\"o}nnen. Hierf{\"u}r bieten sich beispielsweise ParFlow oder mHM an. Insgesamt ist festzuhalten, dass das mehrschichtige Bodenschema einen Mehrwert liefert, da schwer zu simulierende und in der Postprozessierung zu korrigierende Variablen wie die Evapotranspiration und der Oberfl{\"a}chenabfluss deutlich besser modelliert werden k{\"o}nnen als mit dem einschichtigen Schema. Dies gilt auch f{\"u}r die Extremtemperaturen. Beides ist klar auf die Schichtung des Bodens und damit einhergehender Prozesse zur{\"u}ckzuf{\"u}hren. Bez{\"u}glich der Daten zeigt sich, dass die Wurzeltiefe, die Ber{\"u}cksichtigung von SoilGrids und die vertikale Bodeninformation f{\"u}r die weitere Optimierung verantwortlich sind. Dar{\"u}ber hinaus ist der h{\"o}here Informationsgehalt, der anhand der geschichteten Bodenfeuchte zur Verf{\"u}gung steht, ebenfalls als Mehrwert einzustufen.}, subject = {Klima}, language = {de} } @phdthesis{Abele2009, author = {Abele, Marion}, title = {Die Bedeutung des Zwei-Partner-Sekretionssystems f{\"u}r die Adh{\"a}renz von Meningokokken an Epithelzellen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45369}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2009}, abstract = {Das two-partner secretion-system (TPS-System) ist ein unter Gram-negativen Bakterien weit verbreiteter Weg der Proteinsekretion. Die als TpsA bezeichneten Exoproteine des TPS Systems ben{\"o}tigen ein spezifisches Partnerprotein (genannt TpsB) in Form eines kanalbildenden Transporters. Im sequenzierten Genom des Meningokokkenstammes MC58 finden sich f{\"u}nf putative tpsA Gene, die als hemagglutinin/hemolysin-related protein (hrps) bezeichnete werden. Neben MC58 finden sich auch in den anderen sequenzierten Meningokokkenst{\"a}mmen (FAM18, Z2491, alpha14) hrps. Diese weisen N-terminal Homologien zum filament{\"o}sen H{\"a}magglutinin (FHA) von B. pertussis auf, das als TpsA-Protein des two-partner-secretion-system (TPS) aus der Zelle transportiert wird. In dieser Arbeit werden die hrps als hrpA Gene bzw. HrpA-Proteine bezeichnet. Alle sequenzierten Meningokokkenst{\"a}mme verf{\"u}gen {\"u}ber tpsB homologe Gene (hrpB), die jeweils in enger Nachbarschaft zu den hrpA Genen zu finden sind. Das Vorhandensein von hrpA und hrpB Genen deutet darauf hin, dass auch Meningokokken {\"u}ber ein funktionales TPS-System verf{\"u}gen. Bei einer Dot-Blot-Analyse von 830 Meningokokkenst{\"a}mmen aus einer bayerischen Tr{\"a}gerstudie mit Sonden spezifisch f{\"u}r die C-terminalen Bereiche der im Stamm MC58 gefundenen hrpA Gene hybridisierten 80\% der ausgewerteten St{\"a}mme mit mindestens einer der Sonden. St{\"a}mme der hypervirulenten klonalen Komplexen (ST-8, ST-11, ST32, ST-44) zeigten sogar in {\"u}ber 99\% eine positive Reaktion. Dagegen wiesen die nicht-hypervirulenten klonalen Komplexe zu 29\% im Dot Blot kein hrpA auf, das homolog zu den hrpA Genen von Stamm MC58 ist, wobei es sich hierbei mehrheitlich (82\%) um cnl St{\"a}mme handelte, so dass sich nur in 10\% der untersuchten Kapsel-null-locus-St{\"a}mme (cnl) ein zu den hrpA Genen von MC58 homologes Gen nachweisen ließ. Mit der Hypothese, dass auch diese St{\"a}mme ein hrpA besitzen, welches sich im C-terimalen Anteil von denen des MC58 unterscheidet wurden in dieser Arbeit Dot Blots durchgef{\"u}hrt, deren Sonde spezifisch f{\"u}r das hrpB NMC0443 war. 97,6\% der mit dieser Sonde untersuchten St{\"a}mme zeigten die Anwesenheit eines hrpB Homologs. Um die Vermutung zu best{\"a}tigen, dass allen hrpB Genen ein zugeh{\"o}riges hrpA Gen benachbart liegt, wurden repr{\"a}sentativ PCRs von h{\"a}ufigen klonalen Komplexen durchgef{\"u}hrt. Dabei konnte gezeigt werden, dass ein TPS-System sowohl in den hypervirulenten als auch den nicht-hypervirulenten klonalen Komplexen der Meningokokken vorkommt. Die vielf{\"a}ltigen Funktionen von bereits untersuchten TpsA Proteinen sind zumeist mit der Pathogenit{\"a}t der Bakterien assoziiert. In dieser Arbeit wurde ein m{\"o}glicher Einfluss der HrpA Proteine auf die Adh{\"a}sion der Bakterien an humane Zellen untersucht. Es konnte gezeigt werden, dass sowohl eine kapsellose, als auch eine kapsellose, LPS-trunkierte hrpA Deletionsmutante signifikant schlechter an Epithelzellen adh{\"a}riert als die parentalen Vergleichsst{\"a}mme. Ebenso zeigten die analog durchgef{\"u}hrten Infektionsversuche mit der hrpB Deletionsmutante einen Adh{\"a}renzverlust, der jedoch nur f{\"u}r die unbekapselte und LPS trunkierte hrpB Deletionsmutante signifikant war. In dieser Arbeit ist es gelungen das HrpB Protein des Stammes 2120 in E. coli zu exprimieren und aufzureinigen, sodass die Entwicklung eines gegen HrpB gerichteten Antik{\"o}rpers in Auftrag gegeben werden konnte. Mit Hilfe dieses Antik{\"o}rpers sollen noch offene Fragen zur Synthese und dem Transport des HrpB Transportproteins beantwortet werden. Außerdem k{\"o}nnen weitere Untersuchungen zur Lage und Verteilung der HrpBs in der Meningokokkenmembran dazu beitragen, weiteren Aufschluss {\"u}ber die Komplexit{\"a}t von Pathogenit{\"a}t und Virulenz von N. meningitidis zu geben.}, subject = {W{\"u}rzburg / Institut f{\"u}r Hygiene und Mikrobiologie}, language = {de} } @phdthesis{Abele2002, author = {Abele, Tobias}, title = {Invasion, Replikation und Stadienkonversion von Toxoplasma gondii in permanenten ZNS-Zelllinien der Ratte}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-4521}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2002}, abstract = {Permanente ZNS-Zelllinien der Ratte wurden mit Toxoplasma gondii unter Betrachtung der Invasions-, Replikations- und Stadienkonversionf{\"a}higeit des Parasiten infiziert. Additiv zu bekannten Tiermodellen konnte so ein Zellkulturmodell zur Erforschung der zerebralen Persistenz des Protozoons etabliert werden.}, language = {de} } @phdthesis{Abelein2024, author = {Abelein, Christian Karl}, title = {„Ich habe mich so daran gew{\"o}hnt, daß ich beinahe nie dichte ohne zugleich zu singen!" - Der Briefwechsel zwischen August Heinrich Hoffmann von Fallersleben (1798-1874) und Hans Michael Schletterer (1824-1893) als Dokument einer konstruktiven Zusammenarbeit zwischen Dichter und Komponist im 19. Jahrhundert.}, doi = {10.25972/OPUS-36386}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363862}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Die von Friedhelm Brusniak und Ulrich Konrad betreute und angenommene Dissertation nimmt den Briefwechsel zwischen August Heinrich Hoffmann von Fallersleben und dem j{\"u}ngeren Augsburger Kapellmeister und Komponisten Hans Michael Schletterer in den Jahren 1862 bis 1873 in den Blick und dokumentiert dabei Hoffmanns Einfluss auf den Entstehungsprozess der Vertonungen seiner Lieder, besonders seiner Kinderlieder. Die Arbeit beleuchtet zudem den Erfahrungsschatz, den sich der ‚Dichter-S{\"a}nger' Hoffmann von Fallersleben auch durch die Zusammenarbeit mit anderen Musikern seiner Zeit, vorrangig Ludwig Christian Erk (1807-1883) und Ernst Heinrich Leopold Richter (1805-1876), erworben hatte. Dar{\"u}ber hinaus werden in der Korrespondenz Themen des gesellschaftlichen und politischen Lebens, der privaten und beruflichen Situation beider wie auch Hoffmanns Rolle als v{\"a}terlicher Berater Schletterers ber{\"u}hrt. Die Arbeit darf als neuer substantieller Beitrag der Hoffmann-Forschung und der interdisziplin{\"a}ren Liedforschung angesehen werden, der insbesondere der Kinderliedforschung neue Impulse verleiht.}, subject = {Hoffmann von Fallersleben, August Heinrich}, language = {de} } @phdthesis{Abels2014, author = {Abels, Henrike}, title = {Sprachkompetenz und motorische F{\"a}higkeiten von S{\"a}uglingen mit lagerungsbedingtem Plagiozephalus und Helmtherapie im Alter von sechs und zw{\"o}lf Monaten im Vergleich zu gleichaltrigen unauff{\"a}lligen S{\"a}uglingen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-102084}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2014}, abstract = {Die vorliegende Arbeit wurde im Rahmen eines interdisziplin{\"a}ren Forschungsprojektes der Universit{\"a}tsklinik W{\"u}rzburg verfasst (IZKF-Studiennr. F-164, CFCW-Projekt). Ziel dieser Arbeit war es, explorativ zu untersuchen, inwieweit ein Lagerungsplagiozephalus (LP) die sprachlich-kognitive und motorische Entwicklung eines S{\"a}uglings/ Kindes beeinflusst und ob es Hinweise auf eine Auswirkung der Dauer der Therapie mittels Kopforthese auf die fr{\"u}hkindliche Entwicklung gibt. Sie liefert erstmalig Untersuchungsdaten zur vorsprachlichen und fr{\"u}hen sprachlichen Entwicklung von S{\"a}uglingen mit LP. Das Probandenkollektiv bestand aus 71 Probanden (Plagiozephalus mit Helmtherapie (PMH)-Gruppe: N=36, Kontrollgruppe (KG): N=35). Im Alter von zw{\"o}lf Monaten wurde die Sprachleistung aller Probanden mithilfe des ELFRA-1 eingesch{\"a}tzt. Zudem wurden die Ergebnisse der deutschen Fassung der BSID II vom sechsten und zw{\"o}lften Lebensmonat herangezogen. Um den Effekt der Helmtherapie auf die Entwicklung der Kinder mit LP zu ber{\"u}cksichtigen, fand eine Korrelation zwischen der Tragedauer und sprachproduktiven, sprachperzeptiven, gestischen, (fein-)motorischen und kognitiven Leistungen der Probanden statt. Ein maskierender Einfluss des Co-Faktors SLI-Risiko auf die Befunde konnte ausgeschlossen werden. Zusammengefasst zeigen die hier untersuchten S{\"a}uglinge mit LP im Alter von sechs Monaten statistisch gerade signifikant schlechtere motorische F{\"a}higkeiten als S{\"a}uglinge mit normaler Kopfform. Im Alter von zw{\"o}lf Monaten holen sie diese Defizite jedoch auf und sind teilweise sogar motorisch geschickter als die Vergleichsgruppe. Die kognitive Entwicklung von Kindern mit LP scheint nicht verz{\"o}gert zu sein, wie in der Fachliteratur postuliert. In den Analysen zeigte sich kein signifikanter Zusammenhang zwischen der Helmtragedauer und den sprachlichen (ELFRA-1) und kognitiven (BSID: MDI 12 Monate) F{\"a}higkeiten der Probanden mit LP. Die motorischen F{\"a}higkeiten (BSID: PDI 12 Monate) zeigten einen statistisch signifikanten Zusammenhang zur Tragedauer der Kopforthese. Je l{\"a}nger der Helm getragen wurde, desto besser fielen die motorischen Leistungen der Probanden im Alter von zw{\"o}lf Monaten aus. Zus{\"a}tzlich wurden Vokalisationen einer Untergruppe (High-Contrast-Gruppe (HC), N=20) im Hinblick auf melodische Variationsf{\"a}higkeiten im sechsten Lebensmonat untersucht. Dazu wurden die digitalen Lautaufnahmen im S{\"a}uglingslabor des ZVES an der Poliklinik f{\"u}r Kieferorthop{\"a}die editiert und mithilfe spezifischer Analyseprogramme quantitativ analysiert. Die S{\"a}uglinge mit LP wiesen genauso variantenreiche Melodien in ihren Vokalisationen auf wie die S{\"a}uglinge der Kontrollgruppe. Sp{\"a}tere Sprachauff{\"a}lligkeiten w{\"u}rden sich bereits in diesen vorsprachlichen F{\"a}higkeiten manifestieren. Auch wenn zuk{\"u}nftige Studien best{\"a}tigen, dass ein LP - entgegen den Erkenntnissen anderer Autoren (Korpilahti et al. 2012, Speltz et al. 2010 u.a.) - keine kognitiven Beeintr{\"a}chtigungen zur Folge hat, ist die Therapie dieser Sch{\"a}delasymmetrie auf psychosozialer Ebene und wegen m{\"o}glicher Auswirkungen auf das maxillomandibul{\"a}re System zu bef{\"u}rworten (Meyer-Marcotty et al. 2012).}, subject = {Lagerungsplagiozephalus}, language = {de} } @article{AbendrothNaurothRichteretal.2022, author = {Abendroth, Johanna and Nauroth, Peter and Richter, Tobias and Gollwitzer, Mario}, title = {Non-strategic detection of identity-threatening information: Epistemic validation and identity defense may share a common cognitive basis}, series = {PLoS ONE}, volume = {17}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0261535}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301019}, year = {2022}, abstract = {Readers use prior knowledge to evaluate the validity of statements and detect false information without effort and strategic control. The present study expands this research by exploring whether people also non-strategically detect information that threatens their social identity. Participants (N = 77) completed a task in which they had to respond to a "True" or "False" probe after reading true, false, identity-threatening, or non-threatening sentences. Replicating previous studies, participants reacted more slowly to a positive probe ("True") after reading false (vs. true) sentences. Notably, participants also reacted more slowly to a positive probe after reading identity-threatening (vs. non-threatening) sentences. These results provide first evidence that identity-threatening information, just as false information, is detected at a very early stage of information processing and lends support to the notion of a routine, non-strategic identity-defense mechanism.}, language = {en} } @inproceedings{AbendscheinDesaiAstell2023, author = {Abendschein, Robin and Desai, Shital and Astell, Arlene J.}, title = {Towards Accessibility Guidelines for the Metaverse : A Synthesis of Recommendations for People Living With Dementia}, series = {Conference on Human Factors in Computing Systems (CHI'23) : Workshop "Towards an Inclusive and Accessible Metaverse"}, booktitle = {Conference on Human Factors in Computing Systems (CHI'23) : Workshop "Towards an Inclusive and Accessible Metaverse"}, doi = {10.25972/OPUS-32019}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320199}, pages = {6}, year = {2023}, abstract = {Given the growing interest of corporate stakeholders in Metaverse applications, there is a need to understand accessibility of these technologies for marginalized populations such as people living with dementia to ensure inclusive design of Metaverse applications. We assessed the accessibility of extended reality technology for people living with mild cognitive impairment and dementia to develop accessibility guidelines for these technologies. We used four strategies to synthesize evidence for barriers and facilitators of accessibility: (1) Findings from a non-systematic literature review, (2) guidelines from well-researched technology, (3) exploration of selected mixed reality technologies, and (4) observations from four sessions and video data of people living with dementia using mixed reality technologies. We utilized template analysis to develop codes and themes towards accessibility guidelines. Future work can validate our preliminary findings by applying them on video recordings or testing them in experiments.}, subject = {CHI Conference}, language = {en} } @article{AbimannanSumathiKrishnarajasekharetal.2019, author = {Abimannan, Nagarajan and Sumathi, G. and Krishnarajasekhar, O. R. and Sinha, Bhanu and Krishnan, Padma}, title = {Clonal Clusters and Virulence Factors of Methicillin-Resistant \(Staphylococcus\) \(Aureus\): Evidence for Community-Acquired Methicillin-Resistant \(Staphylococcus\) \(Aureus\) Infiltration into Hospital Settings in Chennai, South India}, series = {Indian Journal of Medical Microbiology}, volume = {37}, journal = {Indian Journal of Medical Microbiology}, number = {3}, doi = {10.4103/ijmm.IJMM_18_271}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226963}, pages = {326-336}, year = {2019}, abstract = {Background and Objective: Staphylococcus aureus is one of the major pathogens of nosocomial infections as wells as community-acquired (CA) infections worldwide. So far, large-scale comprehensive molecular and epidemiological characterisation of S. aureus from very diverse settings has not been carried out in India. The objective of this study is to evaluate the molecular, epidemiological and virulence characteristics of S. aureus in both community and hospital settings in Chennai, southern India. Methods: S. aureus isolates were obtained from four different groups (a) healthy individuals from closed community settings, (b) inpatients from hospitals, (c) outpatients from hospitals, representing isolates of hospital-community interface and (d) HIV-infected patients to define isolates associated with the immunocompromised. Antibiotic susceptibility testing, multiplex polymerase chain reactions for detection of virulence and resistance determinants, molecular typing including Staphylococcal cassette chromosome mec (SCCmec) and agr typing, were carried out. Sequencing-based typing was done using spa and multilocus sequence typing (MLST) methods. Clonal complexes (CC) of hospital and CA methicillin-resistant S. aureus (MRSA) were identified and compared for virulence and resistance. Results and Conclusion: A total of 769 isolates of S. aureus isolates were studied. The prevalence of MRSA was found to be 7.17\%, 81.67\%, 58.33\% and 22.85\% for groups a, b, c and d, respectively. Of the four SCCmec types (I, III, IV and V) detected, SCCmec V was found to be predominant. Panton-Valentine leucocidin toxin genes were detected among MRSA isolates harbouring SCCmec IV and V. A total of 78 spa types were detected, t657 being the most prevalent. 13 MLST types belonging to 9 CC were detected. CC1 (ST-772, ST-1) and CC8 (ST238, ST368 and ST1208) were found to be predominant among MRSA. CA-MRSA isolates with SCCmec IV and V were isolated from all study groups including hospitalised patients and were found to be similar by molecular tools. This shows that CA MRSA has probably infiltrated into the hospital settings.}, language = {en} } @article{AblinFitzcharlesBuskilaetal.2013, author = {Ablin, Jacob and Fitzcharles, Mary-Ann and Buskila, Dan and Shir, Yoram and Sommer, Claudia and H{\"a}user, Winfried}, title = {Treatment of Fibromyalgia Syndrome: Recommendations of Recent Evidence-Based Interdisciplinary Guidelines with Special Emphasis on Complementary and Alternative Therapies}, series = {Evidence-Bayed Complementary and Alternative Medicine}, journal = {Evidence-Bayed Complementary and Alternative Medicine}, issn = {1741-427X}, doi = {10.1155/2013/485272}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122235}, pages = {485272}, year = {2013}, abstract = {Objective. Current evidence indicates that there is no single ideal treatment for fibromyalgia syndrome (FMS). First choice treatment options remain debatable, especially concerning the importance of complementary and alternative medicine (CAM) treatments. Methods. Three evidence-based interdisciplinary guidelines on FMS in Canada, Germany, and Israel were compared for their first choice and CAM-recommendations. Results. All three guidelines emphasized a patient-tailored approach according to the key symptoms. Aerobic exercise, cognitive behavioral therapy, and multicomponent therapy were first choice treatments. The guidelines differed in the grade of recommendation for drug treatment. Anticonvulsants (gabapentin, pregabalin) and serotonin noradrenaline reuptake inhibitors (duloxetine, milnacipran) were strongly recommended by the Canadian and the Israeli guidelines. These drugs received only a weak recommendation by the German guideline. In consideration of CAM-treatments, acupuncture, hypnosis/guided imagery, and Tai Chi were recommended by the German and Israeli guidelines. The Canadian guidelines did not recommend any CAM therapy. Discussion. Recent evidence-based interdisciplinary guidelines concur on the importance of treatment tailored to the individual patient and further emphasize the need of self-management strategies (exercise, and psychological techniques).}, language = {en} } @article{AboagyeWeberMerdianetal.2021, author = {Aboagye, B. and Weber, T. and Merdian, H. L. and Bartsch, D. and Lesch, K. P. and Waider, J.}, title = {Serotonin deficiency induced after brain maturation rescues consequences of early life adversity}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, issn = {2045-2322}, doi = {10.1038/s41598-021-83592-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258626}, year = {2021}, abstract = {Brain serotonin (5-HT) system dysfunction is implicated in depressive disorders and acute depletion of 5-HT precursor tryptophan has frequently been used to model the influence of 5-HT deficiency on emotion regulation. Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the tryptophan hydroxylase-2 gene (Tph2) was used to investigate the effects of provoked 5-HT deficiency in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). The efficiency of Tph2 inactivation was validated by immunohistochemistry and HPLC. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKOxMS) on physiological parameters, emotional behavior and expression of 5-HT system-related marker genes were assessed. Tph2 icKO mice displayed a significant reduction in 5-HT immunoreactive cells and 5-HT concentrations in the rostral raphe region within four weeks following TAM treatment. Tph2 icKO and MS differentially affected food and water intake, locomotor activity as well as panic-like escape behavior. Tph2 icKO prevented the adverse effects of MS stress and altered the expression of the genes previously linked to stress and emotionality. In conclusion, an experimental model was established to study the behavioral and neurobiological consequences of 5-HT deficiency in adulthood in interaction with early-life adversity potentially affecting brain development and the pathogenesis of depressive disorders.}, language = {en} } @phdthesis{Aboagye2019, author = {Aboagye, Benjamin}, title = {Behavioral and physiologic consequences of inducible inactivation of the \(Tryptophan\) \(hydroxylase\) 2 gene in interaction with early-life adversity}, doi = {10.25972/OPUS-17358}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173581}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Disruptions in brain serotonin (5-hydroxytryptamine, 5-HT) signaling pathways have been associated with etiology and pathogenesis of various neuropsychiatric disorders, but specific neural mechanisms of 5-HT function are yet to be fully elucidated. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme for brain 5-HT synthesis. Therefore, in this study a tamoxifen (Tam)-inducible cre-mediated conditional gene (Tph2) knockout in adult mouse brain (Tph2icKO) has been established to decipher the specific role of brain 5-HT in the regulation of behavior in adulthood. Immunohistochemistry and high-performance liquid chromatography (HPLC) were used first to test the efficacy of Tam-inducible inactivation of Tph2 and consequential reduction of 5-HT in adult mouse brain. Tam treatment resulted in ≥90\% reduction in the number of 5-HT immuno-reactive cells in the anterior raphe nuclei. HPLC revealed a significant reduction in concentration of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) in selected brain regions of Tph2icKO, indicating the effectiveness of the protocol used. Second, standard behavioral tests were used to assess whether reduced brain 5-HT concentrations could alter anxiety-, fear- and depressive-like behavior in mice. No altered anxiety- and depressive-like behaviors were observed in Tph2icKO compared to control mice (Tph2CON) in all indices measured, but Tph2icKO mice exhibited intense and sustained freezing during context-dependent fear memory retrieval. Tph2icKO mice also exhibited locomotor hyperactivity in the aversive environments, such as the open field, and consumed more food and fluid than Tph2CON mice. Lastly, the combined effect of maternal separation (MS) stress and adult brain 5-HT depletion on behavior was assessed in male and female mice. Here, MS stress, 5-HT depletion and their interaction elicited anxiety-like behavior in a sex-dependent manner. MS reduced exploratory behavior in both male and female mice. Reduced 5-HT enhanced anxiety in female, but not in male mice. Furthermore, expression of genes related to the 5-HT system and emotionality (Tph2, Htr1a, Htr2a, Maoa and Avpr1a) was assessed by performing a quantitative real-time PCR. In Tph2icKO mice there was a reduction in expression of Tph2 in the raphe nuclei of both male and female mice. Interaction between MS stress and 5-HT deficiency was detected showing increased Htr2a and Maoa expression in raphe and hippocampus respectively of female mice. In male mice, MS stress and 5-HT depletion interaction effects reduced Avpr1a expression in raphe, while the expression of Htr1a, Htr2a and Maoa was differentially altered by 5-HT depletion and MS in various brain regions.}, subject = {Anxiety}, language = {en} } @phdthesis{Abraham2018, author = {Abraham, Carolin}, title = {Vergleich der Sensitivit{\"a}t pr{\"a}- und intraoperativer bildgebender Verfahren bei der Detektion von Lebertumoren unter besonderer Ber{\"u}cksichtigung der MRT-Diffusionswichtung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167960}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {In dieser Studie wurden 280 Patienten, die im Zeitraum vom 01.01.2008 bis 30.06.2012 am Universit{\"a}tsklinikum W{\"u}rzburg aufgrund einer Raumforderung der Leber operiert wurden, analysiert. Davon konnten 150 Patienten mit insgesamt 385 Tumoren bewertet werden. Die zentrale Fragestellung der Arbeit besch{\"a}ftigte sich damit, die Sensitivit{\"a}t der MR-DWI mit anderen pr{\"a}operativen bildgebenden Untersuchungsmethoden zu bewerten. Bisherige Studien besch{\"a}ftigten sich bereits mit dem Vergleich der MR-DWI mit anderen diagnostischen Verfahren. Jedoch wurden dabei nicht konkret die aus Sicht eines Chirurgen wichtigen Punkte detailliert beleuchtet. In dieser Arbeit wurden daher die Ergebnisse der Befunde der MR-DWI, CT und konventionellem MRT dem intraoperativen und histopathologisch gesichertem Endbefund gegen{\"u}bergestellt und bez{\"u}glich der Parameter: Tumordignit{\"a}t, Tumoranzahl, Tumorgr{\"o}ße und Tumorlokalisation verglichen. W{\"a}hrend die Sensitivit{\"a}t der MR-DWI zur Tumorlokalisation etwas unter der Sensitivit{\"a}t der CT und MRT lag, konnten f{\"u}r die Parameter Tumoranzahl und Tumordignit{\"a}t bessere Ergebnisse der MR-DWI als f{\"u}r die CT herausgestellt werden. Die Genauigkeit der DWI f{\"u}r diese beiden Punkte liegt nah bei der hohen Sensitivit{\"a}t der MRT. Jedoch m{\"u}ssen die sehr guten Ergebnisse der MRT in dieser Arbeit durch die geringe Anzahl der MRT Untersuchungen relativiert werden. Bez{\"u}glich der Tumoranzahl ergibt sich bei der MR-DWI die h{\"o}chste Sensitivit{\"a}t, gefolgt von MRT und CT. Zusammenfassend kann gesagt werden, dass die MR-DWI wie auch die CT und MRT ein sehr sensitives Verfahren zur Detektion von Leberl{\"a}sionen darstellt. Dabei m{\"u}ssen gewisse Vor- und Nachteile gegen{\"u}ber den anderen Methoden abgewogen werden. Eine als ung{\"u}nstig zu wertende Strahlenexposition besteht nicht, ebenso kein zus{\"a}tzlicher zeitlicher Aufwand. In nahezu allen hier untersuchten Bereichen zeigte die MR-DWI vorrangig bessere Resultate als die CT. Im Vergleich mit der MRT konnten geringf{\"u}gig niedrigere oder {\"a}hnlich gute Werte ermittelt werden. In Bezug auf die Tumoranzahl war die MR-DWI das sensitivste Verfahren. Um die hier erbrachten Ergebnisse zu sichern, sollten zuk{\"u}nftige Studien die Homogenit{\"a}t der Patienten sowie die Anzahl der CT, MRT und MR-DWI Untersuchungen erh{\"o}hen. Weiterhin k{\"o}nnten die Ger{\"a}teeinstellungen bei der MRDWI an bestimmte Fragestellungen angepasst und so genauere Ergebnisse erzielt werden. Bruegel et al konnte f{\"u}r unterschiedliche Leberl{\"a}sionen bereits die charakteristischen ADC-Werte ermitteln. In einer weiteren Studie von Kilickesmez wurden ebenfalls maligne und benigne Leberl{\"a}sionen {\"u}ber die entsprechenden ADC-Werte voneinander abgegrenzt. Daraus ergab sich die Empfehlung, zur Diagnostik von Leberl{\"a}sionen die konventionelle MRT mit der MRDWI zu erg{\"a}nzen. Ein weiterer Ansatzpunkt ist die Reduktion von St{\"o}rfaktoren f{\"u}r die MR-DWI und damit die Verbesserung der Bildbeurteilung. In einer Arbeit von Yu-Chun wurde beispielsweise die optimale Temperatur f{\"u}r die MR-DWI Schnittbildgebung am Tiermodell angewandt und so auf molekularer Ebene die Artefaktbildung reduziert. Eine Verbesserung konnte auch durch Erg{\"a}nzung der MR-DWI mit anderen Verfahren nachgewiesen werden. MR-DWI in Verbindung mit Kontrastmittel ergab eine erh{\"o}hte Sensitivit{\"a}t f{\"u}r kleine HCC bis 2cm als Kontrastmittel-MRT ohne DWI. Es ist zu erwarten, dass die MR-DWI in Zukunft durch exaktere Einstellungen der b- Werte und ADC-Messungen in Abh{\"a}ngigkeit der zu untersuchenden Organregion, durch Reduktion st{\"o}render Faktoren oder durch Kombination mit anderen bildgebenden Verfahren zur Optimierung der pr{\"a}operativen Diagnostik bei Lebertumoren beitr{\"a}gt.}, subject = {Diffusionsgewichtete Magnetresonanztomographie}, language = {de} } @phdthesis{Abt2020, author = {Abt, Alexander}, title = {Einfluss von HGF und Foretinib auf den Glukosestoffwechsel bei Zelllinien des oralen Plattenepithelkarzinoms}, doi = {10.25972/OPUS-20728}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207286}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Die Aktivierung des HGF/c-Met-Signalweges wird unter anderem seit l{\"a}ngerer Zeit als verantwortlicher Mechanismus f{\"u}r die Entwicklung von Resistenzen gegen den EGF-Rezeptor gerichteter Medikamente diskutiert. In verschiedenen Studien konnte die klinische Bedeutung des HGF/c-Met-Signalwegs belegt werden. In der j{\"u}ngeren Vergangenheit konzentriert sich die Forschung immer mehr auf das Tumormikromilieu und dessen Einfluss auf die Tumorprogression. So konnte gezeigt werden, dass erh{\"o}hte Laktatwerte, resultierend aus einer gesteigerten Glykolyse, zytotoxische T-Zellen inhibieren. Es wurden vier etablierte Zelllinien des oralen Plattenepithelkarzinoms sowie eine Zelllinie eines Mukoepidermoidkarzinom verwendet, um den Einfluss von HGF und des Tyrosinkinaseinhibitors Foretinib auf den Glukosemetabolismus zu pr{\"u}fen. Bei allen Zelllinien konnte der c-Met-Rezeptor nachgewiesen werden. Ebenso konnte in einem ELISA belegt werden, dass die Zelllinien selbst kein HFG produzieren. Es wurden proliferationsf{\"o}rdernde Effekte f{\"u}r HGF sowie zytotoxische Effekte durch Foretinib aufgezeigt. Ferner konnte der proliferationsf{\"o}rdernde Effekt durch HGF durch die Behandlung mit Foretinib aufgehoben werden. Im RT-PCR-Verfahren wurden die Auswirkungen auf die Transkription verschiedener Gene, die f{\"u}r wichtige Enzyme des Glukosemetabolismus kodieren, nach der Stimulation mit HGF sowie der Inhibition mit Foretinib untersucht. Es konnten substanzielle Ver{\"a}nderungen in der Expression einzelner Gene nachgewiesen werden. Zelllinien{\"u}bergreifend konnte allerdings keine verst{\"a}rkte bzw. verminderte Transkription durch die Behandlung mit HGF bzw. Foretinib nachgewiesen werden. Die Ergebnisse lassen auf die Komplexit{\"a}t der Regulierung des Glukosemetabolismus schließen. In der Durchflusszytometrie konnte gezeigt werden, dass eine Behandlung mit HGF nicht zu einer Zunahme des GLUT1 in der Zellmembran f{\"u}hrt, wohingegen eine Behandlung mit Foretinib mit einer gesteigerten Menge von GLUT1 einhergeht. Die Ergebnisse der vorliegenden Arbeit belegen einen Einfluss des HGF/c-Met-Signalwegs auf den Glukosemetabolismus bei Zelllinien des oralen Plattenepithelkarzinoms.}, subject = {Hepatozyten-Wachstumsfaktor}, language = {de} } @phdthesis{Abt2006, author = {Abt, Marion}, title = {Interaktion von Masernviren mit Dendritischen Zellen : Untersuchungen zur Rezeptorbenutzung, Regulation der Chemotaxis und T-Zellkommunikation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-19706}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2006}, abstract = {Im Rahmen der vorliegenden Arbeit wurde der Einfluss von MV auf die Expression und Nutzung verschiedener Rezeptoren auf Dendritischen Zellen (DC) untersucht. Dazu wurden DC in vitro aus Monozyten gewonnen und mit IL- 4 und GM-CSF ausdifferenziert. In der Arbeit wurden das Wildtypvirus WTF und der Vakzinestamm ED eingesetzt. Im ersten Teil der Arbeit wurde die Expression der Chemokinrezeptoren 5 (CCR5) und 7 (CCR7) auf MV-infizierten DC-Kulturen sowie das Migrationsverhalten der DC untersucht. Die Expression von CCR5 ist abh{\"a}ngig vom Reifungszustand der DC. W{\"a}hrend unreife DC CCR5 exprimieren, verringert sich die Expression im Zuge der Ausreifung, w{\"a}hrend die Expression von CCR7 induziert wird. In der vorliegenden Arbeit konnte gezeigt werden, dass die MV-Infektion einer DC-Kultur die Expression von CCR5 nicht beeinflusst, obwohl die Expression anderer charakteristischer Reifungsmarker erh{\"o}ht wird. Weiterhin konnte die Expression von CCR7 durch eine Infektion der DC-Kulturen mit MV nicht induziert werden. Die Ergebnisse der durchgef{\"u}hrten durchflusszytometrischen Analysen zur Rezeptorexpression wurden in Chemotaxis-Assays eingehender untersucht. DC aus MV-infizierten Kulturen zeigten trotz anhaltender CCR5-Expression nur eine geringe Migration in Richtung des CCR5-Liganden CCL-3. Aufgrund der fehlenden CCR7- Expression konnte erwartungsgem{\"a}ß keine Migration der eingesetzten DC gegen{\"u}ber dem CCR7-Liganden CCL-19 beobachtet werden. Weiterhin konnten Unterschiede im induzierten Chemokinmuster in MV-infizierten DCKulturen im Vergleich zu LPS-ausgereiften oder mit einer Mockpr{\"a}paration behandelten DC nachgewiesen werden. Kurz nach der Infektion konnte in MVinfizierten DC-Kulturen eine reduzierte Menge CXCL-8 und CCL-20 sowohl auf mRNA Ebene als auch auf Proteinebene detektiert werden. In weiteren Experimenten konnte eine verminderte Migration von T-Zellen auf Zusammenfassung 152 Zellkultur{\"u}berst{\"a}nde aus infizierten DC-Kulturen im Vergleich zu {\"U}berst{\"a}nden aus LPS-behandelten DC-Kulturen festgestellt werden. Im zweiten Teil der vorgelegten Arbeit konnte MV als Ligand f{\"u}r das DCspezifische Oberfl{\"a}chenmolek{\"u}l DC-SIGN (dendritic cell-specific intercellular adhesion molecule (ICAM)-3 grabbing non-integrin) identifiziert werden. Dabei konnte gezeigt werden, dass beide verwendeten Virusst{\"a}mme an DC-SIGN binden k{\"o}nnen, DC-SIGN jedoch keinen Eintrittsrezeptor f{\"u}r MV darstellt. Weitere Analysen zeigten, dass DC-SIGN die Infektion, besonders bei geringen Viruskonzentrationen, verst{\"a}rkt. In erster Linie zeigt die MV-Infektion unreifer DC die Bedeutung von DC-SIGN als Bindungsrezeptor f{\"u}r MV. Die hohe Expression von DC-SIGN auf unreifen DC erm{\"o}glicht eine effiziente effektive Infektion dieser Zellen. Auf reifen DC ist der Einfluss von DC-SIGN auf die Effektivit{\"a}t der Infektion der DC deutlich verringert. Im dritten Teil dieser Arbeit wurden die Kontaktzeiten zwischen DC und TZellen in dreidimensionalen Kollagenmatrices untersucht. Dabei wurde eine in etwa doppelt so lange Kontaktzeit zwischen MV-infizierten DC und durch Oxidative Mitogenese ver{\"a}nderten T-Zellen gegen{\"u}ber LPS-behandelten DC bzw. MV-infizierten und nicht-modifizierten T-Zellen festgestellt. In den parallel durchgef{\"u}hrten Proliferationstests wurde eine reduzierte Proliferation der TZellen beobachtet, die mit MV-infizierten DC kokultiviert wurden. Im Gegensatz zu den k{\"u}rzeren Kontakten zwischen LPS-behandelten DC und modifizierten TZellen waren die Kontakte zwischen MV-infizierten DC und modifizierten TZellen nicht-stimulatorisch.}, subject = {Dendritische Zelle}, language = {de} } @phdthesis{Abt2019, author = {Abt, Raimond}, title = {Implementing Aspects of Quantum Information into the AdS/CFT Correspondence}, doi = {10.25972/OPUS-18801}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188012}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {In recent years many discoveries have been made that reveal a close relation between quantum information and geometry in the context of the AdS/CFT correspondence. In this duality between a conformal quantum field theory (CFT) and a theory of gravity on Anti-de Sitter spaces (AdS) quantum information quantities in CFT are associated with geometric objects in AdS. Subject of this thesis is the examination of this intriguing property of AdS/CFT. We study two central elements of quantum information: subregion complexity -- which is a measure for the effort required to construct a given reduced state -- and the modular Hamiltonian -- which is given by the logarithm of a considered reduced state. While a clear definition for subregion complexity in terms of unitary gates exists for discrete systems, a rigorous formulation for quantum field theories is not known. In AdS/CFT, subregion complexity is proposed to be related to certain codimension one regions on the AdS side. The main focus of this thesis lies on the examination of such candidates for gravitational duals of subregion complexity. We introduce the concept of \textit{topological complexity}, which considers subregion complexity to be given by the integral over the Ricci scalar of codimension one regions in AdS. The Gauss-Bonnet theorem provides very general expressions for the topological complexity of CFT\(_2\) states dual to global AdS\(_3\), BTZ black holes and conical defects. In particular, our calculations show that the topology of the considered codimension one bulk region plays an essential role for topological complexity. Moreover, we study holographic subregion complexity (HSRC), which associates the volume of a particular codimension one bulk region with subregion complexity. We derive an explicit field theory expression for the HSRC of vacuum states. The formulation of HSRC in terms of field theory quantities may allow to investigate whether this bulk object indeed provides a concept of subregion complexity on the CFT side. In particular, if this turns out to be the case, our expression for HSRC may be seen as a field theory definition of subregion complexity. We extend our expression to states dual to BTZ black holes and conical defects. A further focus of this thesis is the modular Hamiltonian of a family of states \(\rho_\lambda\) depending on a continuous parameter \(\lambda\). Here \(\lambda\) may be associated with the energy density or the temperature, for instance. The importance of the modular Hamiltonian for quantum information is due to its contribution to relative entropy -- one of the very few objects in quantum information with a rigorous definition for quantum field theories. The first order contribution in \(\tilde{\lambda}=\lambda-\lambda_0\) of the modular Hamiltonian to the relative entropy between \(\rho_\lambda\) and a reference state \(\rho_{\lambda_0}\) is provided by the first law of entanglement. We study under which circumstances higher order contributions in \(\tilde{\lambda}\) are to be expected. We show that for states reduced to two entangling regions \(A\), \(B\) the modular Hamiltonian of at least one of these regions is expected to provide higher order contributions in \(\tilde{\lambda}\) to the relative entropy if \(A\) and \(B\) saturate the Araki-Lieb inequality. The statement of the Araki-Lieb inequality is that the difference between the entanglement entropies of \(A\) and \(B\) is always smaller or equal to the entanglement entropy of the union of \(A\) and \(B\). Regions for which this inequality is saturated are referred to as entanglement plateaux. In AdS/CFT the relation between geometry and quantum information provides many examples for entanglement plateaux. We apply our result to several of them, including large intervals for states dual to BTZ black holes and annuli for states dual to black brane geometries.}, subject = {AdS-CFT-Korrespondenz}, language = {en} } @article{AbtErdmenger2018, author = {Abt, Raimond and Erdmenger, Johanna}, title = {Properties of modular Hamiltonians on entanglement plateaux}, series = {Journal of High Energy Physics}, volume = {11}, journal = {Journal of High Energy Physics}, number = {2}, doi = {10.1007/JHEP11(2018)002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227693}, pages = {1-22}, year = {2018}, abstract = {The modular Hamiltonian of reduced states, given essentially by the logarithm of the reduced density matrix, plays an important role within the AdS/CFT correspondence in view of its relation to quantum information. In particular, it is an essential ingredient for quantum information measures of distances between states, such as the relative entropy and the Fisher information metric. However, the modular Hamiltonian is known explicitly only for a few examples. For a family of states rho(lambda) that is parametrized by a scalar lambda, the first order contribution in (lambda) over tilde = lambda-lambda(0) of the modular Hamiltonian to the relative entropy between rho(lambda) and a reference state rho(lambda 0) is completely determined by the entanglement entropy, via the first law of entanglement. For several examples, e.g. for ball-shaped regions in the ground state of CFTs, higher order contributions are known to vanish. In these cases the modular Hamiltonian contributes to the Fisher information metric in a trivial way. We investigate under which conditions the modular Hamiltonian provides a non-trivial contribution to the Fisher information metric, i.e. when the contribution of the modular Hamiltonian to the relative entropy is of higher order in (lambda) over tilde. We consider one-parameter families of reduced states on two entangling regions that form an entanglement plateau, i.e. the entanglement entropies of the two regions saturate the Araki-Lieb inequality. We show that in general, at least one of the relative entropies of the two entangling regions is expected to involve (lambda) over tilde contributions of higher order from the modular Hamiltonian. Furthermore, we consider the implications of this observation for prominent AdS/CFT examples that form entanglement plateaux in the large N limit.}, language = {en} } @article{AbtErdmengerGerbershagenetal.2019, author = {Abt, Raimond and Erdmenger, Johanna and Gerbershagen, Marius and Melby-Thompson, Charles M. and Northe, Christian}, title = {Holographic subregion complexity from kinematic space}, series = {Journal of High Energy Physics}, volume = {1}, journal = {Journal of High Energy Physics}, number = {12}, doi = {10.1007/JHEP01(2019)012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227711}, pages = {1-35}, year = {2019}, abstract = {We consider the computation of volumes contained in a spatial slice of AdS(3) in terms of observables in a dual CFT. Our main tool is kinematic space, defined either from the bulk perspective as the space of oriented bulk geodesics, or from the CFT perspective as the space of entangling intervals. We give an explicit formula for the volume of a general region in a spatial slice of AdS(3) as an integral over kinematic space. For the region lying below a geodesic, we show how to write this volume purely in terms of entangling entropies in the dual CFT. This expression is perhaps most interesting in light of the complexity = volume proposal, which posits that complexity of holographic quantum states is computed by bulk volumes. An extension of this idea proposes that the holographic subregion complexity of an interval, defined as the volume under its Ryu-Takayanagi surface, is a measure of the complexity of the corresponding reduced density matrix. If this is true, our results give an explicit relationship between entanglement and subregion complexity in CFT, at least in the vacuum. We further extend many of our results to conical defect and BTZ black hole geometries.}, language = {en} } @article{AbuHalimaHaeuslerBackesetal.2017, author = {Abu-Halima, Masood and H{\"a}usler, Sebastian and Backes, Christina and Fehlmann, Tobias and Staib, Claudia and Nestel, Sigrun and Nazarenko, Irina and Meese, Eckart and Keller, Andreas}, title = {Micro-ribonucleic acids and extracellular vesicles repertoire in the spent culture media is altered in women undergoing \(In\) \(Vitro\) Fertilization}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-13683-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173632}, year = {2017}, abstract = {MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71\% and a sensitivity of 85\%. Among the 621 miRNAs, 102 (16.4\%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 10\(^9\)/mL EVs), as compared to a negative outcome (7.35 × 10\(^9\)/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM.}, language = {en} } @phdthesis{Acar2014, author = {Acar, Selva}, title = {Die Entnahmemorbidit{\"a}t und Resensibilisierung des Acromiopectorallappens im Vergleich zum Pectoralis-Major-Lappen in der rekonstruktiven Mund-, Kiefer-, Gesichtschirurgie: Retrospektive Studie 2000-2010}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-108497}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2014}, abstract = {Die vorliegende Arbeit besch{\"a}ftigt sich mit der Rolle der gestielten Lappen, am Beispiel des Acromiopectoral- und Pectoralis-Major-Lappens, in der modernen Mund-, Kiefer-, Gesichtschirurgie in einer {\"A}ra, in der mikrochirurgisch revaskularisierten, freien Transplantaten meist der Vorzug gegeben wird. Insbesondere wird auf die Einheilung und Resensibilisierung des Acromiopectoral- und Pectoralis-Major-Lappens in der Empf{\"a}ngerregion des Kopf-/Halsbereiches eingegangen. Es wurde die Lebensqualit{\"a}t der Patienten anhand von verschiedenen Parametern wie Nahrungsaufnahme, Sprachverm{\"o}gen, Beschwerden und {\"A}sthetik beurteilt. Des Weiteren wurde die objektive und subjektive Morbidit{\"a}t der Spenderregion untersucht. Es wurde gepr{\"u}ft, inwieweit die Entnahme der Lappen die Funktion, die Sensibilit{\"a}t und die {\"A}sthetik des Schulter- und Brustbereiches beeinflussen. Anhand einer retrospektiven Datenauswertung von 30 Patienten werden die Unterschiede in den Indikationsbereichen, Komplikationsraten und Einheilraten der beiden Lappen im Zeitraum von 2000 bis 2010 aufgezeigt.}, subject = {gestielte Lappen}, language = {de} } @article{AchenbachHuppertzZemanetal.2022, author = {Achenbach, Leonard and Huppertz, Gunnar and Zeman, Florian and Weber, Johannes and Luig, Patrick and Rudert, Maximilian and Krutsch, Werner}, title = {Multicomponent stretching and rubber band strengthening exercises do not reduce overuse shoulder injuries: a cluster randomised controlled trial with 579 handball athletes}, series = {BMJ Open Sport \& Exercise Medicine}, volume = {8}, journal = {BMJ Open Sport \& Exercise Medicine}, number = {1}, issn = {2055-7647}, doi = {10.1136/bmjsem-2021-001270}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300770}, year = {2022}, abstract = {Objectives Handball is associated with a high risk of overuse shoulder injury. This study investigated if an injury prevention programme effectively reduces overuse injury to the throwing shoulder of handball athletes. Methods 61 men's and women's handball teams (u-19 and senior athletes) were cluster-randomised into an intervention and a control group in the 2019-2020 season. Players of the intervention group regularly carried out an injury prevention programme. Both groups documented overuse shoulder injuries via an online questionnaire every second week. The primary endpoint was the prevalence of overuse injury to the throwing shoulder. Secondary endpoints were the influence of compliance on the primary endpoint and intensity of overuse shoulder symptoms measured by a shortened, handball-specific Western Ontario Shoulder Index (WOSI). Results 31 teams (295 players) in the intervention group and 30 teams (284 players) in the control group were included for analyses. The overall questionnaire response rate was 61\%. The average prevalence of overuse shoulder injury did not significantly differ between the intervention group (n=109, 38.4\% (95\% CI 32.9\% to 44.2\%)) and the control group (n=106, 35.9\% (95\% CI 30.7\% to 41.6\%), p=0.542). Compliance with the intervention programme did not significantly affect overuse shoulder injury (p=0.893). Using generalised estimating equations for WOSI, the estimated mean for the intervention group was 44.6 points (95\% CI 42.0 to 47.1) and 47.6 points for the control group (95\% CI 44.9 to 50.3, p=0.111). Conclusions A multicomponent exercise programme using rubber bands and stretching did not significantly reduce the prevalence or symptoms of overuse throwing shoulder injury in handball athletes of both sexes. Randomised controlled study; level of evidence I.}, language = {en} } @article{AchenbachKleinLuigetal.2021, author = {Achenbach, Leonard and Klein, Christian and Luig, Patrick and Bloch, Hendrik and Schneider, Dominik and Fehske, Kai}, title = {Collision with opponents - but not foul play - dominates injury mechanism in professional men's basketball}, series = {BMC Sports Science Medicine and Rehabilitation}, volume = {13}, journal = {BMC Sports Science Medicine and Rehabilitation}, doi = {10.1186/s13102-021-00322-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261765}, year = {2021}, abstract = {Background To identify injury patterns and mechanisms in professional men's basketball by means of video match analysis. Methods In Germany, injuries are registered with the statutory accident insurance for professional athletes (VBG) by clubs or club physicians as part of occupational accident reporting. Moderate and severe injuries (absence of > 7 days) sustained during basketball competition in one of four seasons (2014-2017 and 2018-2019) in the first or second national men's league in Germany were prospectively analyzed using a newly developed standardized observation form. Season 2017-2018 was excluded because of missing video material. Results Video analysis included 175 (53\%) of 329 moderate and severe match injuries. Contact patterns categorized according to the different body sites yielded eight groups of typical injury patterns: one each for the head, shoulders, and ankles, two for the thighs, and three for the knees. Injuries to the head (92\%), ankles (76\%), shoulders (70\%), knees (47\%), and thighs (32\%) were mainly caused by direct contact. The injury proportion of foul play was 19\%. Most injuries (61\%) occurred in the central zone below the basket. More injuries occurred during the second (OR 1.8, p = 0.018) and fourth quarter (OR 1.8, p = 0.022) than during the first and third quarter of the match. Conclusion The eight identified injury patterns differed substantially in their mechanisms. Moderate and severe match injuries to the head, shoulders, knees, and ankles were mainly caused by collision with opponents and teammates. Thus, stricter rule enforcement is unlikely to facilitate safer match play.}, language = {en} } @article{AchenbachLeHanneurCamenzindetal.2022, author = {Achenbach, Leonard and Le Hanneur, Malo and Camenzind, Roland S. and Bouyer, Michael and Pottecher, Pierre and Lafosse, Thibault}, title = {Systematic bifocal decompression for isolated long thoracic nerve paresis: A case series of 12 patients}, series = {Interdisciplinary Neurosurgery}, volume = {27}, journal = {Interdisciplinary Neurosurgery}, doi = {10.1016/j.inat.2021.101384}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265085}, year = {2022}, abstract = {To date, no consensus exists regarding the best surgical management of isolated, micro-traumatic long thoracic nerve (LTN) paresis. Our hypothesis was that a combined decompression of the LTN at two potential locations for entrapment would be effective in the management of dynamic LTN paresis. We report on twelve patients with isolated LTN parersis, with tenderness at two entrapment sites, who underwent bifocal LTN decompression after undergoing unsuccessful conservative treatment for at least 6 months; all patients had preoperative electrodiagnostic studies that confirmed the paresis and ruled out peripheral neuritis. Clinical and electrical improvements were observed in eight patients (67\%) regarding shoulder flexion, shoulder abduction, and Quick-DASH scores. Four patients (33\%) did not improve after surgery. The results corroborate our hypothesis that a bifocal LTN decompression can be an effective and reliable therapeutic option in more than half of a very selective patient population suffering from serratus anterior muscle deficiency.}, language = {en} } @book{Acker2010, author = {Acker, Kristin}, title = {Die US-Expansion des deutschen Discounters Aldi - Eine Fallstudie zur Internationalisierung im Einzelhandel}, publisher = {L.I.S. Verlag}, address = {Passau}, isbn = {978-3-932820-35-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180668}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {267}, year = {2010}, abstract = {Die Internationalisierung im Einzelhandel ist eine vergleichsweise junge Entwicklung, die in den vergangenen beiden Dekaden stark vorangeschritten ist. Dabei haben viele Unternehmen die Erfahrung machen m{\"u}ssen, die Grundlage ihres im Heimatland erlangten Wettbewerbsvorteils zwar in einige M{\"a}rkte erfolgreich transferieren zu k{\"o}nnen, in andere M{\"a}rkte jedoch nicht. Worin liegen die Ursachen hierf{\"u}r? Trotz einer zunehmenden Zahl von Studien zur Internationalisierung im Einzelhandel gibt es immer noch ein mangelndes Verst{\"a}ndnis daf{\"u}r, unter welchen Bedingungen Unternehmen im Ausland erfolgreich sind, respektive wann sie scheitern. Einen theoretischen Rahmen zur Analyse der relevanten Erfolgsdeterminanten liefert die Institutionentheorie, die das Verh{\"a}ltnis zwischen Unternehmen und Gesellschaft betrachtet und gerade auch f{\"u}r interkulturelle Fragestellungen einen interessanten Untersuchungsansatz darstellt. Vor diesem Hintergrund wird in der vorliegenden Arbeit die US-amerikanische Expansion des Discounters Aldi analysiert. Aldi bietet sich f{\"u}r eine solche Fallstudie an, da der Discounter sein an den deutschen Markt angepasstes Erfolgskonzept Ende der 1970er Jahre weitestgehend unver{\"a}ndert in die USA transferiert hat - in eine institutionelle Umwelt, die sich deutlich von der deutschen unterscheidet. Wie erfolgreich kann Aldi in dieser Umwelt agieren?}, subject = {Aldi (USA)}, language = {de} } @phdthesis{Ackermann2008, author = {Ackermann, Dorothea}, title = {Gewaltakte - Disziplinarapparate : Geschlecht und Gewalt in mittel- und fr{\"u}hneuhochdeutschen M{\"a}ren}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40560}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Inhaltsverzeichnis 1 Einleitung 6 1.1 Einf{\"u}hrung in den Forschungsgegenstand und das Forschungsinteresse der Untersuchung 6 1.2 Theoretische Pr{\"a}missen 15 1.2.1 {\"U}berlegungen zur Problematik des Konstruktbegriffes 16 1.2.2 Zur Konstituierung der Konstrukte ‚Geschlecht' und ‚Gewalt' 23 1.2.2.1 Semantik der neuhochdeutschen Begriffe ‚Gewalt' und ‚Geschlecht' 23 1.2.2.1.1 ‚Gewalt' 24 1.2.2.1.2 ‚Geschlecht' 27 1.2.2.2 Judith Butlers Modell der citationality des ‚Geschlechts' 30 1.3 Mittelalterliche Geschlechtsnormen in außerliterarischen Kontexten 37 1.4 Textauswahl und Untersuchungsverlauf 41 2 Prototheorie des M{\"a}res: Geschlecht und Gewalt in den Ehestandsm{\"a}ren des Strickers 43 2.1 Der Gevatterin Rat 47 2.2 Der begrabene Ehemann 58 2.3 Die eingemauerte Frau 70 2.4 Ehescheidungsgespr{\"a}ch 86 3 Strickers Erben? Geschlecht und Gewalt in ausgew{\"a}hlten M{\"a}ren des 14. und 15. Jahrhunderts 91 3.1 Gewaltakte 92 3.1.1 Nur {\"u}ber ihre Leiche: Die undankbare Wiedererweckte 92 3.1.2 Erstarrte M{\"a}nnlichkeit im Bildschnitzer von W{\"u}rzburg II 99 3.1.3 Making Sex: Gold und Zers I 107 3.1.4 Hans Rosenpl{\"u}ts abwaschbare Tinte 114 3.2 Disziplinarapparate 120 3.2.1 Sibotes Frauenzucht. Was Disziplinarapparate leisten k{\"o}nnen ... 122 3.2.2 ... und wie sie außer Kraft gesetzt werden - Philippas abenteurig, kurzweilig red im Entt{\"a}uschten Liebhaber des Johannes Werner von Zimmern 134 3.2.3 Vorsicht, bissig! Virgils Zauberbild als weiblicher Disziplinarapparat 144 3.2.4 Entbl{\"o}ßen, Einwickeln, Bem{\"a}nteln - Disziplinarapparate in den M{\"a}ren Heinrich Kaufringers 148 3.2.4.1 B{\"u}rgermeister und K{\"o}nigssohn: Entbl{\"o}ßen und Einschließen 148 3.2.4.2 Chorherr und Schusterin: Zudecken und Bem{\"a}nteln 154 3.2.4.3 Der Schlafpelz: Die Kunst des Einwickelns 160 3.2.4.4 Die zur{\"u}ckgelassene Hose - Wie Heinrich Kaufringer Hosen Beine macht 163 4 Zusammenfassung 167 Literaturverzeichnis 183 1 Abk{\"u}rzungen 183 2 Prim{\"a}rliteratur 183 2.1 Literatur des Mittelalters 183 2.1.1 Sammelausgaben 183 2.1.2 Einzeltextverzeichnis 184 2.2 Literatur der Neuzeit 185 3 Nachschlagewerke und W{\"o}rterb{\"u}cher 186 4 Forschungsliteratur 186}, subject = {Historische Anthropologie}, language = {de} } @article{AckermannTackeWannagatetal.1979, author = {Ackermann, J. and Tacke, Reinhold and Wannagat, U. and Koke, U. and Meyer, F.}, title = {Derivate des 1-(4-Chlorphenyl)silacyclohexans mit 3-(Diethylamino)propyl- und 2-(Diethylamino)ethyl-Gruppierungen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63621}, year = {1979}, abstract = {Die Darstellung der Verbindungen 3a (sowie 3b) und 10, die sich vom 1-(4-Chlorphenyl)-1-(2~ diethylaminoethoxy)silacyclohexan (Sila-Chlorphencyclan, II a) ableiten, wird beschrieben. Die Verbindung 3 b wurde pharmakologisch und toxikologisch untersucht. Die biologischen Eigen· schaften von 3b wurden mit denen von Ila (sowie Chlorphencyclan) und seinem Hydrochiarid Ilb verglichen.}, subject = {Anorganische Chemie}, language = {de} } @article{AckermannTackeWannagatetal.1980, author = {Ackermann, J. and Tacke, Reinhold and Wannagat, U. and Koke, U. and Meyer, F.}, title = {Sila-Analoga des Chlorphencyclans}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63633}, year = {1980}, abstract = {Sila-Chlorphencyclan (8b), ein Sila-Analogon des Chlorphencyclans (8a), die Derivate 7 und 9, deren Ammoniumsalze 11, 12, 13 und 14b, das Hydrolyseprodukt 10 sowie die Vorstufen 3-6 wurden erstmalig dargestellt. Die neuen Verbindungen wurden in ihren chemischen und physikalischen Eigenschaften charakterisiert, ihre Struktur wurde sichergestellt. Chlorphencyclan, Sila-Chlorphencyclan und einige seiner Derivate wurden vergleichend pharmakologisch und toxikologisch untersucht.}, subject = {Anorganische Chemie}, language = {de} } @phdthesis{Ackermann2023, author = {Ackermann, Johannes}, title = {Entwicklung verbesserter Verfahren zur Herstellung, Modifizierung und Charakterisierung diamantbasierter Materialien}, doi = {10.25972/OPUS-27360}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-273608}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {In dieser Dissertation wird beschrieben, wie es durch systematische Anwendung unterschiedlicher Methoden zur Herstellung und Modifizierung von Diamant gezielt und verl{\"a}sslich m{\"o}glich ist, die Eigenschaften von Diamanten zu beeinflussen. Es wird gezeigt, wie durch Variation der Parameter bei dem Wachstum von Diamant Einfluss auf dessen Morphologie und Eigenschaften genommen werden kann. Des Weiteren wird ein Verfahren vorgestellt, mit dem die Oberfl{\"a}che des Diamanten durch Ozon effizient oxidiert beziehungsweise reduziert werden kann. Um diese ver{\"a}nderte Oberfl{\"a}chenbelegung m{\"o}glichst genau zu analysieren, wird im letzten Teil der Dissertation eine Methode zur qualitativen und quantitativen Analytik der Oberfl{\"a}chen von Kohlenstoffnanomaterialien beschrieben.}, subject = {Diamant}, language = {de} } @phdthesis{Ackermann2010, author = {Ackermann, Matthias}, title = {Studien zum Verhalten von Anthocyanen aus Heidelbeeren im Humanstoffwechsel - Stabilisierung und Bindung durch Proteine}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-53336}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {Identifizierung und Strukturaufkl{\"a}rung von Anthocyanen und ihrer Metabolite erfolgten mit Hilfe der mittels Hochleistungsfl{\"u}ssigchromatographie-Diodenarray-Detektion-Elektro-spray-Tan¬dem¬massen¬spektrometrie (HPLC-DAD-ESI-MS/MS). Quantitative Analysen wurden via HPLC-DAD durchgef{\"u}hrt. Die hierzu erforderlichen Referenzverbindungen wurden mittels pr{\"a}parativer HPLC aus Heidelbeeren isoliert (Reinheit zwischen 85,8\% und 99,4\%). Der Gehalt an Anthocyanen in den untersuchten Heidelbeerfr{\"u}chten lag bei 6 g/kg. Bez{\"u}glich der mengen¬m{\"a}ßigen Verteilung dominierten Delphinidin- und Cyanidin¬glykoside vor den Glykosiden von Malvidin, Petunidin und Peonidin. Als konjugierte Zucker¬reste kamen vor allem Glukose und Galaktose vor, der Gehalt an Arabinosiden war weit geringer. Bei oraler Aufnahme erfolgt ein erster Kontakt der Anthocyane mit Speichel. Daher wurde dessen Wirkung auf die Heidelbeeranthocyane in ex vivo-Studien {\"u}ber einen (unphysio-logisch langen) Zeitraum von bis zu 30 Minuten untersucht. Dabei konnte wurde ins-besondere der Einfluß des pH-Wertes auf die Stabilit{\"a}t der Anthocyane aufgezeigt werden. Zur Simulation des Verhaltens von Anthocyanen im Magen wurden die einzelnen Heidelbeeranthocyane mit k{\"u}nstlichem Magensaft (pH 1,81) {\"u}ber vier Stunden inkubiert. Hier erwiesen sich alle untersuchten Verbindungen als stabil. Die anschließend von uns mit simuliertem Duodenalsekret (pH 7,2) {\"u}ber einen Zeitraum von 24 Stunden durchgef{\"u}hrten Studien zeigten, dass die Anthocyane unterschiedlich starken Modifizierungen unterlagen. Unter den schwach alkalischen Bedingungen wurden vor allem die Glykoside des Delphinidins schnell abgebaut, aber auch die {\"u}brigen Anthocyane erwiesen sich unter diesen Bedingungen als nicht stabil; nach 24 h war kein Anthocyan mehr nachweisbar. Um die Metabolisierungsvorg{\"a}nge der Anthocyane im D{\"u}nn- und Dickdarm zu untersuchen, wurden ex vivo-Inkubationen jeweils mit frischem Ileo- bzw. Kolo¬stoma-beutel¬inhalt durchgef{\"u}hrt. W{\"a}hrend die Abbaugeschwindigkeit in der ilealen Fl{\"u}ssigkeit vor allem von der pH-Stabilit{\"a}t des Aglykons abh{\"a}nig war, konnten im Dickdarm einzig die Arabinoside nach einer Stunde noch alle in geringen Konzentrationen identifiziert werden. Die meisten Glukoside und Galaktoside waren zu diesem Zeitpunkt schon vollst{\"a}ndig abgebaut. Da im Darm von einer hydrolytischen Spaltung der Anthocyane in Anthocyanidin und Zucker ausgegangen wird, wurde die Metabolisierung von Anthocyanidinen unter physio-logischen pH-Bedingungen untersucht. Neben der jeweiligen Spaltung in das Benzoe¬s{\"a}ure-derivat des B-Ringes sowie Phloroglucinessigs{\"a}ure traten verschiedene Poly¬merisierungs¬-produkte auf, deren Strukturen nicht aufgekl{\"a}rt werden konnten. In einer weiteren Versuchsreihe wurde die renale Ausscheidung von Anthocyanen bei Ileostomieprobanden nach oraler Applikation von 300 g Heidelbeeren {\"u}ber einen Zeitraum von acht Stunden untersucht. Es zeigte sich, dass ein Stoma des terminalen Ileums keinen Einfluss auf die Absorption und Metabolisierung der Anthocyane hatte. Die Bilanzierung der Anthocyane im Urin erfolgte als {\"A}quvalente von Malvidin-3-O-glukosid, da nicht alle Anthocyanmetabolite zur Verf{\"u}gung standen. Der Zeitpunkt der maximalen renalen Anthocyanausscheidung sowie die Menge der ausgeschiedenen Anthocyane waren starken interindividuellen Schwankungen unterworfen. Das Aus¬sscheidungs¬maximum (tmax) lag zwischen 0,5 und zwei Stunden. Bei der ausge¬schiedenen Menge wurden Werte zwischen 0,007\% und 0.019\% der auf¬ge¬nommenen Anthocyane ermittelt. Aufgrund der literaturbekannten Unterschiede zwischen den in Serum und Urin gefunden Anthocyanmengen ist davon auszugehen, dass es nach Anthocyanverzehr zu Inter-aktionen mit Proteinen in Blut oder Geweben kommt. Mittels Blutfraktionierung wurde das humane Serumalbumin (HSA) als wichtigster Bindungspartner der Anthocyane im Blut identifiziert. Anhand spektroskopischer Methoden war es m{\"o}glich, die Bindungs¬parameter zu berechnen. Als Bindungsort wurde der hydrophile Eingang der lipophilen Warfarin-Bindungstasche in der Subdom{\"a}ne IIA des HSA-Molek{\"u}ls mittels "molecular modelling" identifiziert. Nasschemische Untersuchungen ergaben, dass die Bindung der Anthocyane an HSA diese vor ihrem pH-abh{\"a}ngigen Abbau sch{\"u}tzt. Eine signifikante Herab¬setzung der chemischen Abbaugeschwindig¬keit konnte auch f{\"u}r bovines Serumalbumin beobachtet werden. Diese Erkenntnis ließ sich auf andere, mit dem HSA-Molek{\"u}l nicht strukurverwandte lebensmittelrelevante Albumine {\"u}bertragen. So zeigten Anthocyane große Stabilit{\"a}t in Milch und Eiklar, wobei die Stabilisierung auf eine Wechselwirkung mit den Proteinen Laktalbumin und Ovalbumin zur{\"u}ckgef{\"u}hrt werden konnte. Die in dieser Arbeit erlangten Erkenntnisse hinsichtlich Absorption, Metabolisierung und systemischer Verf{\"u}gbarkeit im menschlichen Organismus leisten einen Beitrag zum besseren Verst{\"a}ndnis der Wirkungen von Anthocyanen. Die neuen Erkenntnisse der Protein¬bindung sind vor allem f{\"u}r die Bewertung der Verf{\"u}gbarkeit der Anthocyane in humanem Gewebe relevant.}, subject = {Heidelbeere}, language = {de} } @phdthesis{Ackermann2020, author = {Ackermann, Sabine}, title = {Auswirkungen der multimodalen Therapie und der Einf{\"u}hrung der Vorsorgekoloskopie auf die {\"U}berlebensraten beim Kolonkarzinom}, doi = {10.25972/OPUS-20611}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206118}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Ziel dieser Arbeit war es, die Auswirkungen der {\"A}nderungen der Therapiestandards in der Behandlung des Kolonkarzinoms und die Auswirkungen der Einf{\"u}hrung der Vorsorgekoloskopie auf die {\"U}berlebensraten der Patienten mit Kolonkarzinom zu untersuchen. Die umfassende Analyse der therapieabh{\"a}ngigen {\"U}berlebensraten von 1016 Patienten mit Kolonkarzinom aus 20 Jahren zeigt eine Verbesserung der {\"U}berlebenswahrscheinlichkeit durch den Einsatz adjuvanter Therapie und multimodaler Therapieregime. Durch Neuerungen in der Therapie konnten die 5-Jahres-{\"U}berlebensraten seit Anfang der 90er Jahre nahezu verdoppelt werden. Als wichtigste Pr{\"a}diktoren f{\"u}r das Langzeit{\"u}berleben stellten sich das Alter der Patienten bei Erstdiagnose, das UICC Stadium und die Art der adjuvanten Therapie heraus. Der {\"U}berlebenszeit verl{\"a}ngernde Effekt war f{\"u}r den Einsatz der heutigen Standardtherapie mit 5-Flourouracil (5-FU) schon signifikant und zeigt sich f{\"u}r die Kombination mit neueren Medikamenten, insbesondere Oxaliplatin, noch deutlicher. Neue Operationstechniken, Fortschritte in der Metastasenchirurgie, ein optimiertes supportives Management und weitere Erkenntnisse onkologischer Prinzipien beeinflussten die erzielten Erfolge synergistisch. Das Gesamt{\"u}berleben der Patienten, die per Vorsorgekoloskopie detektiert werden ist besser als das der Patienten, die aufgrund klinischer Symptome diagnostiziert werden. Neben dem signifikanten {\"U}berlebensvorteil der Fr{\"u}herkennungs-Patienten, der sich durch die niedrigeren UICC Stadien in dieser Gruppe ergibt, finden sich auch Trends bez{\"u}glich eines besseren Outcomes dieser Patienten innerhalb der selben UICC Stadien. Die Patienten, deren Tumor im Rahmen des Screenings detektiert wurde, waren signifikant j{\"u}nger, wiesen signifikant weniger Begleiterkrakungen auf und zeigten signifikant niedrigere Tumorstadien. Eine adjuvante Therapie wurde in der Screening-Gruppe signifikant h{\"a}ufiger durchgef{\"u}hrt. Mehr als einer von f{\"u}nf tumorbedingten Todesf{\"a}llen der Patienten, die augrund von Symptomen diagnostiziert wurden, h{\"a}tte in dieser Studienpopulation verhindert werden k{\"o}nnen, wenn eine routinem{\"a}ßige Vorsorgekoloskopie durchgef{\"u}hrt worden w{\"a}re. Das Fazit lautet: die Vorsorgekoloskopie ist effektiv. Die Tumorgenese kann durch Entfernung von Vor{\"a}uferl{\"a}sionen durchbrochen werden, Tumoren k{\"o}nnen in fr{\"u}hen asymptomatischen Stadien detektiert werden. Screeningprogramme sollten erweitert werden, um die Inzidenz und die Mortalit{\"a}t von Darmkrebs weiter zu senken.}, subject = {Kolonkarzinom}, language = {de} } @book{AckermannKarremannMalhotraetal.2021, author = {Ackermann, Zeno and Karremann, Isabel and Malhotra, Simi and Zaidi, Nishat}, title = {Terrains of Consciousness: Multilogical Perspectives on Globalization}, edition = {1. Auflage}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, isbn = {978-3-95826-168-6}, doi = {10.25972/WUP-978-3-95826-169-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243936}, publisher = {W{\"u}rzburg University Press}, pages = {x, 150}, year = {2021}, abstract = {TERRAINS OF CONSCIOUSNESS emerges from an Indian-German-Swiss research collaboration. The book makes a case for a phenomenology of globalization that pays attention to locally situated socioeconomic terrains, everyday practices, and cultures of knowledge. This is exemplified in relation to three topics: - the tension between 'terrain' and 'territory' in Defoe's 'Robinson Crusoe' as a pioneering work of the globalist mentality (chapter 1) - the relationship between established conceptions of feminism and the concrete struggles of women in India since the 19th century (chapter 2) - the exploration of urban space and urban life in writings on India's capital - from Ahmed Ali to Arundhati Roy (chapter 3).}, subject = {Globalisierung}, language = {en} } @incollection{AckermannSnyderKoerber2023, author = {Ackermann, Zeno and Snyder-K{\"o}rber, MaryAnn}, title = {Series Foreword : JMU Cultural Studies - Strategies for Struggling with the Obvious}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-iii}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305801}, publisher = {W{\"u}rzburg University Press}, pages = {iii-v}, year = {2023}, abstract = {No abstract available.}, subject = {Kulturwissenschaften}, language = {en} } @article{AcqualagnaBotrelVidaurreetal.2016, author = {Acqualagna, Laura and Botrel, Loic and Vidaurre, Carmen and K{\"u}bler, Andrea and Blankertz, Benjamin}, title = {Large-Scale Assessment of a Fully Automatic Co-Adaptive Motor Imagery-Based Brain Computer Interface}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0148886}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167230}, pages = {e0148886}, year = {2016}, abstract = {In the last years Brain Computer Interface (BCI) technology has benefited from the development of sophisticated machine leaning methods that let the user operate the BCI after a few trials of calibration. One remarkable example is the recent development of co-adaptive techniques that proved to extend the use of BCIs also to people not able to achieve successful control with the standard BCI procedure. Especially for BCIs based on the modulation of the Sensorimotor Rhythm (SMR) these improvements are essential, since a not negligible percentage of users is unable to operate SMR-BCIs efficiently. In this study we evaluated for the first time a fully automatic co-adaptive BCI system on a large scale. A pool of 168 participants naive to BCIs operated the co-adaptive SMR-BCI in one single session. Different psychological interventions were performed prior the BCI session in order to investigate how motor coordination training and relaxation could influence BCI performance. A neurophysiological indicator based on the Power Spectral Density (PSD) was extracted by the recording of few minutes of resting state brain activity and tested as predictor of BCI performances. Results show that high accuracies in operating the BCI could be reached by the majority of the participants before the end of the session. BCI performances could be significantly predicted by the neurophysiological indicator, consolidating the validity of the model previously developed. Anyway, we still found about 22\% of users with performance significantly lower than the threshold of efficient BCI control at the end of the session. Being the inter-subject variability still the major problem of BCI technology, we pointed out crucial issues for those who did not achieve sufficient control. Finally, we propose valid developments to move a step forward to the applicability of the promising co-adaptive methods.}, language = {en} } @phdthesis{Adae2009, author = {Adae, Jasmin}, title = {Interaktion von malignen Tumorzellen mit extrazellul{\"a}rer Matrix und Migration: Rolle von Rac und ROCK}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-52894}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2009}, abstract = {Auf dem Weg vom Prim{\"a}rtumor zur systemischen Metastasierung, der Haupttodesursache von Krebserkrankungen, ist die Einzelzellmigration von Tumorzellen durch dreidimensionales Bindegewebe ein entscheidender Schritt. Die vorliegende Arbeit zeigt Untersuchungen zur Tumorzellmigration und -plastizit{\"a}t in einem 3D-Migrationsmodell. Kleine G-Proteine kontrollieren Zytoskelettfunktionen, insbesondere Aktinpolymerisation und die Bildung von Zellprotrusionen durch Rac sowie Actomyosinkontraktion durch Rho. Durch pharmakologische Inhibitoren von Rac und dem Rho-Effektor ROCK soll deren Bedeutung f{\"u}r Einzelzellmigration in einem dreidimensionalen Modell und vor allem der Effekt auf Morphologie, Plastizit{\"a}t und Migration von Tumorzellen gekl{\"a}rt werden. Nach Inhibition von ROCK zeigen hochinvasive HT1080 Fibrosarkomzellen einen multipolar-dendritischen und sessilen Ph{\"a}notyp. Nach Hemmung von Rac wird hingegen ein rundlicher, aber ebenfalls apolarer und sessiler Ph{\"a}notyp induziert. Bei simultaner Inhibition von Rac und ROCK entstehen rundliche, apolare, sessile Zellen mit abortiven Pseudopodien. Wird das Gleichgewicht von Rac und ROCK durch konstitutive Aktivierung von ROCK gest{\"o}rt, so entsteht eine zweigeteilte Population, bestehend aus rundlichen Zellen, die Blebs bilden, und langgezogenen Zellen. Nach Sortierung nach ihrem ß1-Integrinexpressionsniveau zeigten Zellen mit niedriger Integrin-Expression einen rundlichen Migrationstyp mit blasenartigen dynamischen Protrusionen, w{\"a}hrend Zellen mit hoher Integrin-Expression langgezogen-mesenchymal migrierten. Somit steuern ROCK und Rac gemeinsam und zeitgleich die mesenchymale Einzelzellmigration. W{\"a}hrend Rac Protrusion vermittelt, ist ROCK f{\"u}r Kontraktilit{\"a}t und Retraktion verantwortlich. Erst durch Koordination von Rac und Rho/ROCK entsteht somit Polarit{\"a}t und 3D mesenchymale Migration.}, subject = {Zellmigration}, language = {de} } @article{AdakuChilakaMally2020, author = {Adaku Chilaka, Cynthia and Mally, Angela}, title = {Mycotoxin Occurrence, Exposure and Health Implications in Infants and Young Children in Sub-Saharan Africa: A Review}, series = {Foods}, volume = {9}, journal = {Foods}, number = {11}, issn = {2304-8158}, doi = {10.3390/foods9111585}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219250}, year = {2020}, abstract = {Infants and young children (IYC) remain the most vulnerable population group to environmental hazards worldwide, especially in economically developing regions such as sub-Saharan Africa (SSA). As a result, several governmental and non-governmental institutions including health, environmental and food safety networks and researchers have been proactive toward protecting this group. Mycotoxins, toxic secondary fungal metabolites, contribute largely to the health risks of this young population. In SSA, the scenario is worsened by socioeconomic status, poor agricultural and storage practices, and low level of awareness, as well as the non-establishment and lack of enforcement of regulatory limits in the region. Studies have revealed mycotoxin occurrence in breast milk and other weaning foods. Of concern is the early exposure of infants to mycotoxins through transplacental transfer and breast milk as a consequence of maternal exposure, which may result in adverse health effects. The current paper presents an overview of mycotoxin occurrence in foods intended for IYC in SSA. It discusses the imperative evidence of mycotoxin exposure of this population group in SSA, taking into account consumption data and the occurrence of mycotoxins in food, as well as biomonitoring approaches. Additionally, it discusses the health implications associated with IYC exposure to mycotoxins in SSA.}, language = {en} } @article{AdamDeimelPardoMedinaetal.2018, author = {Adam, Alexander and Deimel, Stephan and Pardo-Medina, Javier and Garc{\´i}a-Mart{\´i}nez, Jorge and Konte, Tilen and Lim{\´o}n, M. Carmen and Avalos, Javier and Terpitz, Ulrich}, title = {Protein activity of the \(Fusarium\) \(fujikuroi\) rhodopsins CarO and OpsA and their relation to fungus-plant interaction}, series = {International Journal of Molecular Sciences}, volume = {19}, journal = {International Journal of Molecular Sciences}, number = {1}, issn = {1422-0067}, doi = {10.3390/ijms19010215}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285125}, year = {2018}, abstract = {Fungi possess diverse photosensory proteins that allow them to perceive different light wavelengths and to adapt to changing light conditions in their environment. The biological and physiological roles of the green light-sensing rhodopsins in fungi are not yet resolved. The rice plant pathogen Fusarium fujikuroi exhibits two different rhodopsins, CarO and OpsA. CarO was previously characterized as a light-driven proton pump. We further analyzed the pumping behavior of CarO by patch-clamp experiments. Our data show that CarO pumping activity is strongly augmented in the presence of the plant hormone indole-3-acetic acid and in sodium acetate, in a dose-dependent manner under slightly acidic conditions. By contrast, under these and other tested conditions, the Neurospora rhodopsin (NR)-like rhodopsin OpsA did not exhibit any pump activity. Basic local alignment search tool (BLAST) searches in the genomes of ascomycetes revealed the occurrence of rhodopsin-encoding genes mainly in phyto-associated or phytopathogenic fungi, suggesting a possible correlation of the presence of rhodopsins with fungal ecology. In accordance, rice plants infected with a CarO-deficient F. fujikuroi strain showed more severe bakanae symptoms than the reference strain, indicating a potential role of the CarO rhodopsin in the regulation of plant infection by this fungus.}, language = {en} } @article{AdamBaeurleBrodskyetal.2014, author = {Adam, Christian and Baeurle, Anne and Brodsky, Jeffrey L. and Schrama, David and Wipf, Peter and Becker, J{\"u}rgen Christian and Houben, Roland}, title = {The HSP70 Modulator MAL3-101 Inhibits Merkel Cell Carcinoma}, doi = {10.1371/journal.pone.0092041}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112795}, year = {2014}, abstract = {Merkel Cell Carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer for which no effective treatment is available. MCC represents a human cancer with the best experimental evidence for a causal role of a polyoma virus. Large T antigens (LTA) encoded by polyoma viruses are oncoproteins, which are thought to require support of cellular heat shock protein 70 (HSP70) to exert their transforming activity. Here we evaluated the capability of MAL3-101, a synthetic HSP70 inhibitor, to limit proliferation and survival of various MCC cell lines. Remarkably, MAL3-101 treatment resulted in considerable apoptosis in 5 out of 7 MCC cell lines. While this effect was not associated with the viral status of the MCC cells, quantitative mRNA expression analysis of the known HSP70 isoforms revealed a significant correlation between MAL3-101 sensitivity and HSC70 expression, the most prominent isoform in all cell lines. Moreover, MAL3-101 also exhibited in vivo antitumor activity in an MCC xenograft model suggesting that this substance or related compounds are potential therapeutics for the treatment of MCC in the future.}, language = {en} } @incollection{AdamSchartlAndexingeretal.1991, author = {Adam, D. and Schartl, A. and Andexinger, S. and H{\"o}lter, S. and Wilde, B. and Schartl, Manfred}, title = {Genetic factors in tumour formation: The melanoma-inducing gene of Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86388}, publisher = {Universit{\"a}t W{\"u}rzburg}, year = {1991}, abstract = {No abstract available.}, subject = {Humangenetik}, language = {en} } @article{AdamWittbrodtTellingetal.1988, author = {Adam, D. and Wittbrodt, J. and Telling, A. and Schartl, Manfred}, title = {RFLP for an EGF-receptor related gene associated with the melanoma oncogene locus of Xiphophorus maculatus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61822}, year = {1988}, abstract = {No abstract available}, subject = {Physiologische Chemie}, language = {en} } @article{AdamDimitrijevicSchartl1993, author = {Adam, Dieter and Dimitrijevic, Nicola and Schartl, Manfred}, title = {Tumor suppression in Xiphophorus by an accidentally acquired promoter}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61630}, year = {1993}, abstract = {Melanoma formation in the teleost Xiphophorus is caused by a dominant genetic locus, Tu. This locus includes the Xmrk oncogene, which encodes a receptor tyrosine kinase. Tumor induction is. suppressed in wild-type fish by a tumor suppressor locus, R. Molecular genetic analyses revealed that the Tu locus emerged by nonhomologaus recombination of the Xmrk proto-oncogene with a previously uncharacterized sequence, D. This event generated an additional copy of Xmrk with a new promoter. Suppression of the new Xmrk promoter by R in parental fish and its deregulation in hybrids explain the genetics of melanoma formation in Xiphophorus.}, subject = {Physiologische Chemie}, language = {en} } @article{AdamMauelerSchartl1991, author = {Adam, Dieter and Maueler, Winfried and Schartl, Manfred}, title = {Transcriptional activation of the melanoma inducing Xmrk oncogene in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87584}, year = {1991}, abstract = {The melanoma inducing locus of Xiphophorus encodes a tumorigenic version of a novel putative receptor tyrosine kinase (Xmrk). To elucidate the mechanism of oncogenic activation of Xmrk, we compared the structure and expression of two oncogenic loci with the corresponding proto-oncogene. Only minor structural alterations were found to be specific for the oncogenic Xmrk genes. Marked overexpression of the oncogene transcripts in melanoma, which are approximately 1 kb shorter than the proto-oncogene transcript, correlates with the malignancy of the tumors. The tumor transcripts are derived from an alternative transcription start site that is used only in the oncogenic loci. Thus, oncogenic activation of the melanoma inducing Xmrk gene appears primarily to be due to novel transcriptional control and overexpression.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @article{AdamKircherSbieraetal.2021, author = {Adam, Pia and Kircher, Stefan and Sbiera, Iuliu and Koehler, Viktoria Florentine and Berg, Elke and Kn{\"o}sel, Thomas and Sandner, Benjamin and Fenske, Wiebke Kristin and Bl{\"a}ker, Hendrik and Smaxwil, Constantin and Zielke, Andreas and Sipos, Bence and Allelein, Stephanie and Schott, Matthias and Dierks, Christine and Spitzweg, Christine and Fassnacht, Martin and Kroiss, Matthias}, title = {FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale}, series = {Frontiers in Endocrinology}, volume = {12}, journal = {Frontiers in Endocrinology}, issn = {1664-2392}, doi = {10.3389/fendo.2021.712107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244653}, year = {2021}, abstract = {Background Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising. Materials and Methods Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable. Results PD-L1 TPS≥50\% was observed in 42\% of ATC and 26\% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30\%) than in PDTC (5\%; p<0.01) and NT (0\%, p<0.001). 53\% of PDTC samples had PD-L1 expression ≤5\%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS. Conclusion High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.}, language = {en} } @phdthesis{Adam2024, author = {Adam, Pia Sophie}, title = {Expression von PD-L1 und FGFR1-4 beim anaplastischen und gering differenzierten Schilddr{\"u}senkarzinom - Evaluation als pr{\"a}klinische diagnostische Marker}, doi = {10.25972/OPUS-35939}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359391}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Background: Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising. Materials and methods: Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable. Results: PD-L1 TPS≥50\% was observed in 42\% of ATC and 26\% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30\%) than in PDTC (5\%; p<0.01) and NT (0\%, p<0.001). 53\% of PDTC samples had PD-L1 expression ≤5\%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS. Conclusion: High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.}, subject = {Schilddr{\"u}senkrebs}, language = {de} } @article{AdamAhrweilerSahaMoelleretal.1993, author = {Adam, W. and Ahrweiler, M. and Saha-M{\"o}ller, C. R. and Sauter, M. and Sch{\"o}nberger, A. and Epe, B. and M{\"u}ller, E. and Schiffmann, D. and Stopper, Helga and Wild, D.}, title = {Genotoxicity studies of benzofuran dioxetanes and epoxides with isolated DNA, bacteria and mammalian cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63420}, year = {1993}, abstract = {1.2-Dioxetanes, very reactive and high energy molecules. are involved as labile intermediates in dioxygenase- activated aerobic metabolism and in physiological processes. Various toxico1ogica1 tests reveal that dioxetanes are indeed genotoxic. In supercoiled DNA of bacteriophage PM2 they induce endonucleasesensitive sites, most of them are FPG protein-sensitive base modifications (8-hydroxyguanine, fonnamidopyrimidines). Pyrimidinedimersand sites ofbase loss (AP sites) which were probed by UV endonuclease and exonuclease 111 are minor lesions in this system. While the alky1-substituted dioxetanes do not show any significant mutagenic activity in different Salmonella typhimurium strains, heteroarene dioxetanes such as benzofuran and furocoumarin dioxetanes are strongly mutagenic in S. typhimurium strain TA I 00. DNA adducts formed with an intermediary alkyJating agent appear to be responsible for the mutagenic activity of benzofuran dioxetane. We assume that the benzofuran epoxides, generated in situ from benzofuran dioxetanes by deoxygenation are the ultimate mutagens of the latter. since benzofuran epoxides are highly mutagenic in the S. typhimurium strain TAIOO and they form DNA adducts. as detected by the 212Ppostlabelling technique. Our results imply that the type of D NA darnage promoted by dioxetanes is dependent on the structural feature of dioxetanes. Furthermore, the direct photochemical DNA darnage by energy transfer. i.e., pyrimidine dimers, plays a minor role in the genotoxicity of dioxetanes. Instead, photooxidation dominates in isolated DNA. while radical darnage and alkylation prevail in the cellular system.}, subject = {Toxikologie}, language = {en} } @phdthesis{Adamek2008, author = {Adamek, Anna Katharina}, title = {Einfluss des Immunsystems und der endothelialen NO-Synthase auf den myokardialen isch{\"a}mischen Schaden}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-35795}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Die Entwicklung von therapeutischen Strategien, die den infarktbedingten Untergang des Myokardgewebes minimieren und die Gewebsheilung nach abgelaufenem Myokardinfarkt unterst{\"u}tzen, geh{\"o}rt zu dem Hauptziel in der modernen Kardiologie. Bis jedoch eine spezifische Intervention als Therapieform anerkannt wird, ist ein detailliertes Entschl{\"u}sseln der zellul{\"a}ren und molekularen Mechanismen w{\"a}hrend und nach der Myokardsch{\"a}digung notwendig. Die vorliegende Arbeit besch{\"a}ftigt sich intensiv mit den Vorg{\"a}ngen der Stickstoffmonoxid- (NO) Produktion und der Inflammation nach Okklusion von Kranzarterien. Im ersten Teil der Dissertation steht die endotheliale NO-Synthase-Expression (eNOS) im Mittelpunkt der Untersuchung. eNOS ist als wichtiger Katalysator an der Biosynthese von Stickstoffmonoxid, das als protektiver Faktor f{\"u}r die Gef{\"a}ßhom{\"o}ostase seit Jahren bekannt ist, beteiligt. Ferner besteht experimentell sehr gute Evidenz daf{\"u}r, dass der endothelialen NO-Synthase am Ausmaß des kardialen Isch{\"a}mie-/ Reperfusionsschadens eine entscheidende Rolle zukommt. Folglich wurde mittels der Substanz AVE 9488 versucht, die eNOS-Expression in M{\"a}usen zu steigern und den Effekt auf das Infarktgeschehen n{\"a}her zu betrachten. Die Behandlung mit AVE 9488 erzielte einen signifikant reduzierten Isch{\"a}mie-/Reperfusionsschaden. Bei anschließenden Isch{\"a}mie-/Reperfusionsveruchen mit eNOS defizienten M{\"a}usen war der protektive Effekt wieder aufgehoben. Der Erfolg dieser Substanz wird in der signifikanten Reduktion des oxidativen Stresses vermutet. Ein zus{\"a}tzlicher wichtiger Parameter, der w{\"a}hrend der Isch{\"a}mie/Reperfusion aktiviert wird, ist der Schl{\"u}ssel-Transkriptionsfaktor Nuclear Factor kappa B (NF-kB). Durch seine Bindung an bestimmte Enhancer und Promotoren reguliert der Faktor die Entz{\"u}ndungsprozesse, indem er die Genexpression proinflammatorischer Marker verst{\"a}rkt. Folglich wurden eine Reduktion der Inflammation sowie ein protektiver Effekt nach erfolgter isch{\"a}mischer Sch{\"a}digung durch Hemmung von NF-kB angenommen. Zur Pr{\"u}fung dieser Hypothese wurden NF-kB-Untereinheit p50 defiziente M{\"a}use (p50 KO) einer Okklusion einer Herzkranzarterie unterzogen. Durch die Hemmung der NF-kB-Aktivierung kam es zu einer signifikanten Reduzierung des Infarktareals im Vergleich zu den entsprechenden Wildtyp-M{\"a}usen. Der große Benefit konnte auf die geringere Einwanderung der neutrophilen Granulozyten in das infarzierte Gebiet zur{\"u}ckgef{\"u}hrt werden. Knochenmarktransplantationsversuche mit p50 KO- und Wildtyp-Knochenmark untermauerten die Beobachtung, dass die beeintr{\"a}chtigte Aktivierung von NF-kB in p50 defizienten Leukozyten protektive Effekte in der Isch{\"a}mie/Reperfusion vermittelt. Die Aktivierung der proinflammatorischen Proteine w{\"a}hrend des linksventrikul{\"a}ren Remodelings nach Myokardinfarkt geh{\"o}rt zum Fokus des dritten Teils dieser Arbeit. Dieser Teil besch{\"a}ftigt sich mit der Frage, inwieweit eine hochdosierte Aspirin-Therapie die linksventrikul{\"a}ren Umbauprozesse g{\"u}nstig beeinflussen kann. Daf{\"u}r wurden M{\"a}use f{\"u}r 4 Wochen mit Placebo oder Aspirin (120 mg/kg pro Tag) mittels osmotischer Mini-Pumpen, die 2 Stunden nach Ligatur der Kranzarterie implantiert wurden, behandelt. In beiden Gruppen kam es zur erwarteten linksventrikul{\"a}ren Dilatation nach Myokardinfarkt, jedoch ohne signifikanten Unterschied zwischen Placebo- und Aspirin-behandelten Tieren. Es kam allerdings zu einer erwarteten Reduktion proinflammatorischer Proteine durch die Aspirin-Therapie. So war die Expression von Tumor-Nekrose-Faktor-alpha; (TNF-alpha) und Interleukin-1ß (IL-ß) in der Aspirin-Gruppe signifikant reduziert. Zusammenfassend l{\"a}sst sich sagen, dass durch die gezielte Beeinflussung bestimmter Faktoren in der Isch{\"a}mie/Reperfusion wie z. B. die Verst{\"a}rkung der eNOS-Expression oder die Hemmung der NF-kB-Aktivierung die Isch{\"a}miesch{\"a}digung signifikant reduziert werden kann.}, subject = {Isch{\"a}mie}, language = {de} } @phdthesis{Adamek2011, author = {Adamek, Julian}, title = {Classical and Quantum Aspects of Anisotropic Cosmology}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65908}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {The idea that our observable Universe may have originated from a quantum tunneling event out of an eternally inflating false vacuum state is a cornerstone of the multiverse paradigm. Modern theories that are considered as an approach towards the ultraviolet-complete fundamental theory of particles and gravity, such as the various types of string theory, even suggest that a vast landscape of different vacuum configurations exists, and that gravitational tunneling is an important mechanism with which the Universe can explore this landscape. The tunneling scenario also presents a unique framework to address the initial conditions of our observable Universe. In particular, it allows to introduce deviations from the cosmological concordance model in a controlled and well-motivated way. These deviations are a central topic of this work. An important feature in most of the theories mentioned above is the presumed existence of additional space dimensions in excess of the three which we observe in our every-day experience. It was realized that these extra dimensions could avoid our detection if they are compactified to microscopic length scales far beyond the reach of current experiments. There also seem to be natural mechanisms available for dynamical compactification in those theories. These typically lead to a vast landscape of different vacuum configurations which also may differ in the number of macroscopic dimensions, only the total number of dimensions being determined by the theory. Transitions between these vacuum configurations may hence open up new directions which were previously compact, spontaneously compactify some previously macroscopic directions, or otherwise re-arrange the configuration of compact and macroscopic dimensions in a more general way. From within the bubble Universe, such a process may be perceived as an anisotropic background spacetime - intuitively, the dimensions which open up may give rise to preferred directions. If our 3+1 dimensional observable Universe was born in a process as described above, one may expect to find traces of a preferred direction in cosmological observations. For instance, two directions could be curved like on a sphere, while the third space direction is flat. Using a scenario of gravitational tunneling to fix the initial conditions, I show how the primordial signatures in such an anisotropic Universe can be obtained in principle and work out a particular example in more detail. A small deviation from isotropy also has phenomenological consequences for the later evolution of the Universe. I discuss the most important effects and show that backreaction can be dynamically important. In particular, under certain conditions, a buildup of anisotropic stress in different components of the cosmic fluid can lead to a dynamical isotropization of the total stress-energy tensor. The mechanism is again demonstrated with the help of a physical example.}, subject = {Kosmologie}, language = {en} } @article{AdamiDragstedEnigetal.1993, author = {Adami, Hans-Olov and Dragsted, Lars and Enig, Bent and Hansen, Jens and Haraldsd{\´o}ttir, J{\´o}hanna and Hill, Michael J. and Holm, Lars Erik and Knudsen, Ib and Larsen, Jens-Jorgen and Lutz, Werner K. and Osler, Merete and Overvad, Kim and Sabroe, Svend and Sanner, Tore and Strube, Michael and Sorensen, Thorkild I. A. and Thorling, Eivind B.}, title = {Report from the working group on diet and cancer.}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-71601}, year = {1993}, abstract = {No abstract available.}, subject = {Krebs }, language = {en} } @phdthesis{AdelAbdelrehimMohamedSoliman2019, author = {Adel Abdelrehim Mohamed Soliman, Hadya}, title = {Structural Equation Modeling of Factors Influencing EFL Reading comprehension: Comparative study between Egypt and Germany}, doi = {10.25972/OPUS-18695}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186957}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {In most foreign language learning contexts, there are only rare chance for contact with native speakers of the target language. In such a situation, reading plays an important role in language acquisition as well as in gaining cultural information about the target language and its speakers. Previous research indicated that reading in foreign language is a complex process, which is influenced by various linguistic, cognitive and affective factors. The aim of the present study was to test two structural models of the relationship between reading comprehension in native language (L1), English language (L2) reading motivation, metacognitive awareness of L2 reading strategies, and reading comprehension of English as a foreign language among the two samples. Furthermore, the current study aimed to examine the differences between Egyptian and German students in their perceived usage of reading strategies during reading English texts, as well as to explore the pattern of their motivation toward reading English texts. For this purpose, 401 students were recruited from Germany (n=200) and Egypt (n=201) to participate in the current study. In order to have information about metacognitive awareness of reading strategies, a self-report questionnaire (SORS) developed by Moktari and Sheory (2002) was used. While the L2 reading motivation variable, was measured by a reading motivation survey (L2RMQ) which was based on reviewed reading motivation research. In addition, two reading tests were administrated one to measure reading comprehension for native language (German/Arabic) and the other to measure English reading comprehension. To analyze the collected data, descriptive statistics and independent t-tests were performed. In addition, further analysis using structural equation modeling was applied to test the strength of relationships between the variables under study. The results from the current research revealed that L1 reading comprehension, whether in a German or Arabic language, had the strongest relationship with L2 reading comprehension. However, the relationship between L2 intrinsic reading motivation was not proven to be significant in either the German or Egyptian models. On the other hand, the relationship between L2 extrinsic reading motivation, metacognitive awareness of reading strategies, and L2 reading comprehension was only proven significant in the German sample. The discussion of these results along with their pedagogical implications for education and practice will be illustrated in the following study.}, subject = {Leseverstehen}, language = {en} } @phdthesis{Adelfinger2012, author = {Adelfinger, Marion}, title = {Pr{\"a}klinische Verwendung verschiedener onkolytischer Vaccinia-Viren zur Therapie von Human- und Hundetumoren}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70688}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {Nach Einsch{\"a}tzung der Weltgesundheitsorganisation WHO wird Krebs im Jahr 2013 die weltweit h{\"a}ufigste Todesursache bei Menschen und Haustieren sein. Diese Situation erfordert die Entwicklung neuer therapeutischer Ans{\"a}tze. Hauptziel einer Tumortherapie ist es, sowohl den Prim{\"a}rtumor als auch die Metastasen m{\"o}glichst vollst{\"a}ndig zu entfernen. Dabei wird nach Methoden gesucht, die im Gegensatz zu den meisten gegenw{\"a}rtigen therapeutischen Eins{\"a}tzen, wie der chirurgischen Entfernung b{\"o}sartiger Neubildungen, Chemotherapie und Strahlentherapie, selektiv die b{\"o}sartigen Zellen erkennen und zerst{\"o}ren k{\"o}nnen. Eine faszinierende M{\"o}glichkeit in dieser Hinsicht ist die Verwendung von onkolytischen Viren, die die F{\"a}higkeit besitzen, sich selektiv sowohl in Prim{\"a}rtumoren als auch in Metastasen anzusiedeln und die Krebszellen dort zu zerst{\"o}ren. Das Konzept, dass Viren n{\"u}tzlich f{\"u}r die Bek{\"a}mpfung von Krebs sein k{\"o}nnten, ist nicht neu. Allerdings konnte erst in den letzten Jahren durch zahlreiche Studien best{\"a}tigt werden, dass verschiedene Viren in der Lage sind, eine signifikante Antitumorwirkung in vivo auszu{\"u}ben. Zu den erfolgversprechenden onkolytischen Viren z{\"a}hlen insbesondere Adenovirus, Herpes simplex Virus, Reovirus und Vaccinia-Virus, die sich bereits in Phase III der klinischen Studien befinden oder kurz davor sind. Die therapeutische Nutzung von tumorspezifischen onkolytischen Viren beim Menschen hat bereits begonnen. Im Rahmen der vorliegenden Doktorarbeit wurden verschiedene Aspekte der Wirkungsweise von Vaccinia-Virus-St{\"a}mmen bei der Therapie verschiedener Tumore aus Mensch und Hund im Xenotransplantat-Mausmodell bearbeitet: die Onkolyse der Krebszellen und Inhibition des Tumorwachstums sowie die Effekte der Virusinfektion auf das Tumormikromilieu und die Mitwirkung des angeborenen Immunsystems bei der Virotherapie. Das Tumormikromilieu (Stroma) setzt sich aus einer Vielzahl verschiedener Zellen und Komponenten der extrazellul{\"a}ren Matrix zusammen. Die Krebszellen bilden unter anderem mit Endothelzellen des Blut- und Lymphsystems und verschiedenen Immunzellen eine komplexe Organ-{\"a}hnliche Struktur. Weitere wichtige Bestandteile des Stromas sind Wachstumsfaktoren, Chemokine und Zytokine und die Tumorvaskulatur. Diese ist durch zahlreiche strukturelle und funktionelle Abnormalit{\"a}ten charakterisiert, wodurch die Effektivit{\"a}t von Strahlen- und Chemotherapie herabgesetzt wird. Weiterhin ist das Tumormikromilieu durch seine {\"A}hnlichkeit mit einer chronischen Entz{\"u}ndungsreaktion gekennzeichnet und wirkt immunsupprimierend auf rekrutierte Leukozyten, die wiederum die Inflammation verst{\"a}rken und die Angiogenese und das Tumorwachstum weiter f{\"o}rdern. Aufgrund dieser vielen Komponenten ist die Zusammensetzung jedes Tumors einzigartig, weswegen Standardtherapien h{\"a}ufig nicht zu einer Heilung f{\"u}hren. Die Wirkung der Viren bei der Virotherapie beruht vermutlich auf 4 Mechanismen, die einzeln oder in Kombination auftreten k{\"o}nnen: die direkte Onkolyse der Krebszellen, die Zerst{\"o}rung des Tumorblutgef{\"a}ßsystems, die Aktivierung des Immunsystems des Wirts und die Suppression der microRNA-Expression des Wirtes. Zus{\"a}tzlich kann die Expression therapeutischer Gene die onkolytische Wirkung verst{\"a}rken. Zum Nachweis der Onkolyse der Krebszellen und Inhibition des Tumorwachstums wurde zuerst das Virus GLV-1h68 in einem autologen humanen Melanomzellpaar, 888-MEL und 1936-MEL, eingesetzt. Das GLV-1h68-Virus wurde auf Basis des Wildtyp Vaccinia-Virus LIVP durch die Insertion von 3 Expressionskassetten in den drei Genloci F14.5L, J2R und A56 genetisch konstruiert. 888-MEL, eine zu einem fr{\"u}hen Zeitpunkt der Krebserkrankung aus einer Metastase isolierte Zelllinie, zeigt nach Infektion mit GLV-1h68 im Mausmodell Tumornekrose („Responder"), w{\"a}hrend 1936-MEL aus einer sp{\"a}ten Metastasierungsphase kaum mit Onkolyse auf eine Virusinfektion reagiert („Poor-Responder"). Die onkolytische Wirkung konnte mittels Durchflusszytometrie in Tumoren beider Zelllinien zu einem fr{\"u}hen Zeitpunkt nach Virusinfektion nachgewiesen werden. In 888-MEL-Tumoren wurde hierbei eine große Zahl infizierter und toter Zellen nach Virusinfektion gefunden. Gleichzeitig wurde eine hohe Zahl an Immunzellen detektiert, die nach Virusinfektion reduziert war. In den schw{\"a}cher reagierenden 1936-MEL-Tumoren konnte eine Onkolyse bei Infektion mit h{\"o}herer Virusmenge und zu einem fr{\"u}heren Zeitpunkt demonstriert werden, wodurch mehr Zellen infiziert wurden. Zus{\"a}tzlich wurde eine Steigerung der nur in geringer Zahl vorhandenen Immunzellen nachgewiesen. Trotz des unterschiedlichen Tumormikromilieus konnte somit ein onkolytischer Effekt in beiden Tumormodellen erzielt werden. ...}, subject = {Vaccinia-Virus}, language = {de} } @article{AdelfingerBesslerCeciletal.2015, author = {Adelfinger, Marion and Bessler, Simon and Cecil, Alexander and Langbein-Laugwitz, Johanna and Frentzen, Alexa and Gentschev, Ivaylo and Szalay, Aladar A.}, title = {Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti-VEGF Single-Chain Antibody for Canine Cancer Therapy}, series = {Viruses}, volume = {7}, journal = {Viruses}, doi = {10.3390/v7072811}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125705}, pages = {4075-4092}, year = {2015}, abstract = {Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a novel approach for canine cancer therapy. Here we describe, for the first time, the characterization and the use of VACV strain GLV-5b451 expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as therapeutic agent against different canine cancers. Cell culture data demonstrated that GLV-5b451 efficiently infected and destroyed all four tested canine cancer cell lines including: mammary carcinoma (MTH52c), mammary adenoma (ZMTH3), prostate carcinoma (CT1258), and soft tissue sarcoma (STSA-1). The GLV-5b451 virus-mediated production of GLAF-2 antibody was observed in all four cancer cell lines. In addition, this antibody specifically recognized canine VEGF. Finally, in canine soft tissue sarcoma (CSTS) xenografted mice, a single systemic administration of GLV-5b451 was found to be safe and led to anti-tumor effects resulting in the significant reduction and substantial long-term inhibition of tumor growth. A CD31-based immuno-staining showed significantly decreased neo-angiogenesis in GLV-5b451-treated tumors compared to the controls. In summary, these findings indicate that GLV-5b451 has potential for use as a therapeutic agent in the treatment of CSTS.}, language = {en} } @article{AdelfingerGentschevdeGuibertetal.2014, author = {Adelfinger, Marion and Gentschev, Ivaylo and de Guibert, Julio Grimm and Weibel, Stephanie and Langbein-Laugwitz, Johanna and H{\"a}rtl, Barbara and Escobar, Hugo Murua and Nolte, Ingo and Chen, Nanhai G. and Aguilar, Richard J. and Yu, Yong A. and Zhang, Qian and Frentzen, Alexa and Szalay, Aladar A.}, title = {Evaluation of a New Recombinant Oncolytic Vaccinia Virus Strain GLV-5b451 for Feline Mammary Carcinoma Therapy}, series = {PLoS ONE}, volume = {9}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0104337}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119387}, pages = {e104337}, year = {2014}, abstract = {Virotherapy on the basis of oncolytic vaccinia virus (VACV) infection is a promising approach for cancer therapy. In this study we describe the establishment of a new preclinical model of feline mammary carcinoma (FMC) using a recently established cancer cell line, DT09/06. In addition, we evaluated a recombinant vaccinia virus strain, GLV-5b451, expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as an oncolytic agent against FMC. Cell culture data demonstrate that GLV-5b451 virus efficiently infected, replicated in and destroyed DT09/06 cancer cells. In the selected xenografts of FMC, a single systemic administration of GLV-5b451 led to significant inhibition of tumor growth in comparison to untreated tumor-bearing mice. Furthermore, tumor-specific virus infection led to overproduction of functional scAb GLAF-2, which caused drastic reduction of intratumoral VEGF levels and inhibition of angiogenesis. In summary, here we have shown, for the first time, that the vaccinia virus strains and especially GLV-5b451 have great potential for effective treatment of FMC in animal model.}, language = {en} } @phdthesis{Adelhardt2007, author = {Adelhardt, Melanie}, title = {Einfluß der Dialysetherapie auf den Genomschaden von Nierenpatienten in einer prospektiven Studie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-23123}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {Patienten mit terminaler Niereninsuffizienz haben im Vergleich zur Normalbev{\"o}lkerung eine deutlich erh{\"o}hte Inzidenz maligner Erkrankungen. Fr{\"u}here Untersuchungen zeigten, dass periphere Blutlymphozyten dieser Patienten einen h{\"o}heren genetischen Schaden aufweisen, wodurch das Risiko einer malignen Entartung steigt. In dieser Arbeit wurde der genetische Schaden mithilfe zweier Testverfahren, Comet Assay und Mikrokerntest, untersucht. Es handelte sich um eine prospektive Studie mit zwei Patientenkollektiven. Die erste Gruppe bestand aus Patienten, die aufgrund einer terminalen Niereninsuffizienz innerhalb der n{\"a}chsten Monate eine Dialysetherapie mittels konventioneller H{\"a}modialyse beginnen mußten. Die zweite Gruppe bildeten Dialysepatienten, die im Verlauf von konventioneller Dialyse auf H{\"a}modiafiltration umgestellt wurden. Bei allen Patienten wurde der genetische Schaden der peripheren Blutlymphozyten in den Monaten vor und nach Therapiebeginn bzw. Therapieumstellung regelm{\"a}ßig untersucht. Unsere Ergebnisse zeigen, dass 4 der 10 Pr{\"a}dialysepatienten nach Beginn der Dialyse einen niedrigeren genetischen Schaden hatten, 2 Patienten hatten unterschiedliche Werte in Comet Assay und Mikrokerntest und bei 2 Patienten ergab sich im Verlauf eine h{\"o}here DNA-Sch{\"a}digung. Die verbliebenen 2 Patienten mußten aufgrund einer konstant bleibenden Niereninsuffizienz nicht mit der Dialysetherapie beginnen. Bei Zusammenfassung aller Einzelwerte zeigte sich, dass das Kollektiv der Pr{\"a}dialysepatienten insgesamt vom Beginn der Behandlung profitiert hat. In der Gruppe der Dialysepatienten hatte 2 von 7 Patienten nach Umstellung auf H{\"a}modiafiltration eine geringere DNA-Sch{\"a}digung, 2 Patienten zeigten unterschiedliche Ergebnisse im Comet Assay und Mikrokerntest und 2 weitere Patienten wiesen eine h{\"o}heren genetischen Schaden in den Lymphozyten auf. Ein Patient konnte bei fehlenden Vorwerten nicht ber{\"u}cksichtigt werden. Im Gruppenvergleich zeigte sich f{\"u}r alle Dialysepatienten ein gleichbleibender DNA-Schaden, gemessen mithilfe des Comet Assays bei leicht erh{\"o}hten Mikrokernraten. Jedoch hatte sich die Zellproliferation ebenfalls etwas verbessert. Zusammenfassend ergibt sich somit in beiden Gruppen kein eindeutiges Ergebnis, woraus neue Therapieempfehlungen f{\"u}r Patienten mit terminaler Niereninsuffizienz abzuleiten w{\"a}ren. Um weiter Einflußvariablen auf die H{\"o}he des genetischen Schadens festzustellen, sind weiter Untersuchungen mit gr{\"o}ßeren Patientenkollektiven erforderlich.}, language = {de} } @article{AdemmerHornQuast2022, author = {Ademmer, Martin and Horn, Wolfram and Quast, Josefine}, title = {Stock market dynamics and the relative importance of domestic, foreign, and common shocks}, series = {International Journal of Finance \& Economics}, volume = {27}, journal = {International Journal of Finance \& Economics}, number = {4}, doi = {10.1002/ijfe.2194}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225729}, pages = {3911 -- 3923}, year = {2022}, abstract = {We quantify the contemporaneous relationships among stock markets in the euro area, the United States, and a group of emerging economies over the period from 2008 to 2017. Exploiting the heteroskedasticity in the stock market data, we identify shocks that originated in the respective domestic markets and shocks that are common to all markets. Our results underline the leading role of the United States in international equity markets, but also point to the importance of indirect spillovers for all economies. Variance decompositions show that while domestic shocks explain the bigger part of the variation in each stock market, a substantial part of the variation in the euro area and the emerging economies can be attributed to foreign shocks. A comparison with a sample covering the pre-crisis period from 1999 to 2007 suggests a strengthening of the linkages among global stock markets in recent years. In particular, the spillovers from advanced to emerging economies have become more pronounced.}, language = {en} } @phdthesis{Adenugba2021, author = {Adenugba, Akinbami Raphael}, title = {Functional analysis of the gene organization of the pneumoviral attachment protein G}, doi = {10.25972/OPUS-12814}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128146}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {The putative attachment protein G of pneumonia virus of mice (PVM), a member of the Pneumoviruses, is an important virulence factor with so far ambiguous function in a virus-cell as well as in virus-host context. The sequence of the corresponding G gene is characterized by significant heterogeneity between and even within strains, affecting the gene and possibly the protein structure. This accounts in particular for the PVM strain J3666 for which two differing G gene organizations have been described: a polymorphism in nucleotide 65 of the G gene results in the presence of an upstream open reading frame (uORF) that precedes the main ORF in frame (GJ366665A) or extension of the major G ORF for 18 codons (GJ366665U). Therefore, this study was designed to analyse the impact of the sequence variations in the respective G genes of PVM strains J3666 and the reference strain 15 on protein expression, replication and virulence. First, the controversy regarding the consensus sequence of PVM J3666 was resolved. The analysis of 45 distinct cloned fragments showed that the strain separated into two distinct virus populations defined by the sequence and structure of the G gene. This division was further supported by nucleotide polymorphisms in the neighbouring M and SH genes. Sequential passage of this mixed strain in the cell line standardly used for propagation of virus stocks resulted in selection for the GJ366665A-containing population in one of two experiments pointing towards a moderate replicative advantage. The replacement of the G gene of the recombinant PVM 15 with GJ366665A or GJ366665U, respectively, using a reverse genetic approach indicated that the presence of uORF within the GJ366665A significantly reduced the expression of the main G ORF on translational level while the potential extension of the ORF in GJ366665U increased G protein expression. In comparison, the effect of the G gene-structure on virus replication was inconsistent and dependent on cell line and type. While the presence of uORF correlated with a replication advantage in the standardly used BHK-21 cells and primary murine embryonic fibroblasts, replication in the murine macrophage cell line RAW 264.7 did not. In comparison, the GJ366665U variant was not associated with any effect on replication in cultured cells at all. Nonetheless, in-vivo analysis of the recombinant viruses associated the GJ366665U gene variant, and hence an increased G expression, with higher virulence whereas the GJ366665A gene, and therefore an impaired G expression, conferred an attenuated phenotype to the virus. To extend the study to other G gene organizations, a recombinant PVM expressing a G protein without the cytoplasmic domain and for comparison a G-deletion mutant, both known to be attenuated in vivo, were studied. Not noticed before, this structure of the G gene was associated with a 75\% reduction in G protein expression and a significant attenuation of replication in macrophage-like cells. This attenuation was even more prominent for the virus lacking G. Taking into consideration the higher reduction in G protein levels compared to the GJ366665A variant indicates that a threshold amount of G is required for efficient replication in these cells. In conclusion, the results gathered indicated that the expression levels of the G protein were modulated by the sequence of the 5' untranslated region of the gene. At the same time the G protein levels modulated the virulence of PVM.}, subject = {G glycoprotein}, language = {en} } @article{AdeyemoSiren1992, author = {Adeyemo, M. and Sir{\´e}n, Anna-Leena}, title = {Cardio-respiratory changes and mortality in the conscious rat induced by (+)- and (±)- anatoxin-a}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63027}, year = {1992}, abstract = {0. M. ADEYEMO and A.-L. SIREN. Cardio-respiratory changes and mortality in the conscious rat induced by ( + )- and ( ± )-anatoxin-a. Toxicon 30, 899-905, 1992.-Anatoxin-a (AnTx-a) isapotent nicotinic cholinergic receptor agonist. The relative potencies of the ( + )-AnTx-a and the racemic mixture ( ± )-AnTxa were investigated in the conscious rat by comparing their effects on mean arterial blood pressure (BP), heart rate (HR), blood oxygen and carbon dioxide pressures (p02 and pC02, respective1y), acid-base balance (pH) and mortality. The present experiments show that while both forms of AnTx-a produce dose-dependent increases in BP and decreases in HR, ( + )-AnTx-a is about IO-fo1d morepotent than the optically inactive isomer. ( + )-AnTx-a was also 6-fo1d more potent than ( ± )-AnTx-a in produclog severe hypoxemia, and more than 4-fold as potent as the (±}-AnTx-a in producing significant hypercapnia accompanied with severe acidosis. The approximate median Iethai dose (Ln so) of ( + )-AnTx-a was about 5-fold less than that of ( ± )-AnTx-a. We conclude that ( + )-AnTx-a is more potent than the ( ± )-AnTx-a racemic mixture in causing detrimental cardio-respiratory changes and therefore increased mortality in the rat.}, subject = {Neurobiologie}, language = {en} } @article{AdeyemoShapiraTombaccinietal.1991, author = {Adeyemo, O. M. and Shapira, S. and Tombaccini, D. and Pollard, H. and Feuerstein, G. and Sir{\´e}n, Anna-Leena}, title = {A goldfish model for evaluation of the neurotoxicit of \(\omega\)-conotoxin GVIA and screening of monoclonal antibodies}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63087}, year = {1991}, abstract = {A Goldfish Model for Evaluation of the Neurotaxicity of \(\omega\)-Conotoxin GVI A and Screening of Monoclonal Antibodies. ADEYEMO, 0. M .. SHAPIRA, S., TOMBACCINI, D., POLLARD, H. 8 .• FEUERSTEIN, G .. AND SIREN, A-L. ( 1991 ). Toxicol. App/. Pharmaco/. 108, 489-496. The neurotoxicity of \(\omega\)-conotoxin (\(\omega\)-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. \(\omega\)-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. \(\omega\)CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antiborlies was investigated in vivo by either ( l) preincubation of the antibody with w-CgTx at 4°C overnight, or (2) pretreatment with antibody, 30 min before \(\omega\)CgTx injection in a 10:1 antibody/\(\omega\)-CgTx molar ratio. The LD50 dose of \(\omega\)-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with \(\omega\)-CgTx (5 nmol/kg ip) significantly (p < 0.05) reduced mortality. ASB, and toxicity time. The antitoxin activity of the monoclonal antiborlies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by \(\omega\)-CgTx (0.03 nmol/rat icv) were significantly (p < 0.02 and p < 0.0 l, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple. accurate, and inexpensive in vivo model for the study of the toxicity of \(\omega\)CgTx}, subject = {Neurobiologie}, language = {en} } @phdthesis{Adhikari2024, author = {Adhikari, Bikash}, title = {Targeted degradation of Myc-interacting oncoproteins}, doi = {10.25972/OPUS-31732}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317326}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {The hallmark oncoprotein Myc is a major driver of tumorigenesis in various human cancer entities. However, Myc's structural features make it challenging to develop small molecules against it. A promising strategy to indirectly inhibit the function of Myc is by targeting its interactors. Many Myc-interacting proteins have reported scaffolding functions which are difficult to target using conventional occupancy- driven inhibitors. Thus, in this thesis, the proteolysis targeting chimera (PROTAC) approach was used to target two oncoproteins interacting with Myc which promote the oncogenicity of Myc, Aurora-A and WDR5. PROTACs are bifunctional small molecules that bind to the target protein with one ligand and recruit a cellular E3- ligase with the other ligand to induce target degradation via the ubiquitin- proteasome system. So far, the most widely used E3-ligases for PROTAC development are Cereblon (CRBN) and von Hippel-Lindau tumor suppressor (VHL). Furthermore, there are cases of incompatibility between some E3-ligases and proteins to bring about degradation. Hence there is a need to explore new E3- ligases and a demand for a tool to predict degradative E3-ligases for the target protein in the PROTAC field. In the first part, a highly specific mitotic kinase Aurora-A degrader, JB170, was developed. This compound utilized Aurora-A inhibitor alisertib as the target ligand and thalidomide as the E3-ligase CRBN harness. The specificity of JB170 and the ternary complex formation was supported by the interactions between Aurora-A and CRBN. The PROTAC-mediated degradation of Aurora-A induced a distinct S- phase defect rather than mitotic arrest, shown by its catalytic inhibition. The finding demonstrates that Aurora-A has a non-catalytic role in the S-phase. Furthermore, the degradation of Aurora-A led to apoptosis in various cancer cell lines. In the second part, two different series of WDR5 PROTACs based on two protein- protein inhibitors of WDR5 were evaluated. The most efficient degraders from both series recruited VHL as a E3-ligase and showed partial degradation of WDR5. In addition, the degradation efficiency of the PROTACs was significantly affected by the linker nature and length, highlighting the importance of linker length and composition in PROTAC design. The degraders showed modest proliferation defects at best in cancer cell lines. However, overexpression of VHL increased the degradation efficiency and the antiproliferative effect of the PROTACs. In the last part, a rapamycin-based assay was developed to predict the degradative E3-ligase for a target. The assay was validated using the WDR5/VHL and Aurora- A/CRBN pairs. The result that WDR5 is degraded by VHL but not CRBN and Aurora-A is degraded by CRBN, matches observations made with PROTACs. This technique will be used in the future to find effective tissue-specific and essential E3-ligases for targeted degradation of oncoproteins using PROTACs. Collectively, the work presented here provides a strategy to improve PROTAC development and a starting point for developing Aurora-A and WDR5 PROTACs for cancer therapy.}, subject = {Degradation}, language = {en} } @phdthesis{Adler2021, author = {Adler, Florian Rudolf}, title = {Electronic Correlations in Two-dimensional Triangular Adatom Lattices}, doi = {10.25972/OPUS-24175}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241758}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Two-dimensional triangular lattices of group IV adatoms on semiconductor substrates provide a rich playground for the investigation of Mott-Hubbard physics. The possibility to combine various types of adatoms and substrates makes members of this material class versatile model systems to study the influence of correlation strength, band filling and spin-orbit coupling on the electronic structure - both experimentally and with dedicated many-body calculation techniques. The latter predict exotic ground states such as chiral superconductivity or spin liquid behavior for these frustrated lattices, however, experimental confirmation is still lacking. In this work, three different systems, namely the \(\alpha\)-phases of Sn/SiC(0001), Pb/Si(111), and potassium-doped Sn/Si(111) are investigated with scanning tunneling microscopy and photoemission spectroscopy in this regard. The results are potentially relevant for spintronic applications or quantum computing. For the novel group IV triangular lattice Sn/SiC(0001), a combined experimental and theoretical study reveals that the system features surprisingly strong electronic correlations because they are boosted by the substrate through its partly ionic character and weak screening capabilities. Interestingly, the spectral function, measured for the first time via angle-resolved photoemission, does not show any additional superstructure beyond the intrinsic \(\sqrt{3} \times \sqrt{3} R30^{\circ}\) reconstruction, thereby raising curiosity regarding the ground-state spin pattern. For Pb/Si(111), preceding studies have noted a phase transition of the surface reconstruction from \(\sqrt{3} \times \sqrt{3} R30^{\circ}\) to \(3 \times 3\) at 86 K. In this thesis, investigations of the low-temperature phase with high-resolution scanning tunneling microscopy and spectroscopy unveil the formation of a charge-ordered ground state. It is disentangled from a concomitant structural rearrangement which is found to be 2-up/1-down, in contrast to previous predictions. Applying an extended variational cluster approach, a phase diagram of local and nonlocal Coulomb interactions is mapped out. Based on a comparison of theoretical spectral functions with scattering vectors found via quasiparticle interference, Pb/Si(111) is placed in said phase diagram and electronic correlations are found to be the driving force of the charge-ordered state. In order to realize a doped Mott insulator in a frustrated geometry, potassium was evaporated onto the well-known correlated Sn/Si(111) system. Instead of the expected insulator-to-metal transition, scanning tunneling spectroscopy data indicates that the electronic structure of Sn/Si(111) is only affected locally around potassium atoms while a metallization is suppressed. The potassium atoms were found to be adsorbed on empty \(T_4\) sites of the substrate which eventually leads to the formation of two types of K-Sn alloys with a relative potassium content of 1/3 and 1/2, respectively. Complementary measurements of the spectral function via angle-resolved photoemission reveal that the lower Hubbard band of Sn/Si(111) gradually changes its shape upon potassium deposition. Once the tin and potassium portion on the surface are equal, this evolution is complete and the system can be described as a band insulator without the need to include Coulomb interactions.}, subject = {Rastertunnelmikroskopie}, language = {en} } @phdthesis{Adler2012, author = {Adler, Melanie}, title = {New approaches to improve prediction of drug-induced liver injury}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69512}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {Das h{\"a}ufige Scheitern neuer Arzneistoffkandidaten aufgrund von Lebertoxizit{\"a}t in pr{\"a}klinischen und klinischen Studien stellt ein erhebliches Problem in der Entwicklung von neuen Arzneimitteln dar. Deshalb ist es wichtig, neue Ans{\"a}tze zu entwickeln, mit deren Hilfe unerw{\"u}nschte Wirkungen von Arzneimitteln fr{\"u}her und zuverl{\"a}ssiger erkannt werden k{\"o}nnen. Um die Vorhersage von Lebertoxizit{\"a}t in pr{\"a}klinischen Studien zu verbessern, wurden im Rahmen dieser Arbeit zwei wesentliche Ans{\"a}tze gew{\"a}hlt: 1) die Evaluierung neuer Biomarker, durch die Lebertoxizit{\"a}t zuverl{\"a}ssiger und empfindlicher detektiert werden k{\"o}nnte und 2.) wirkmechanistische Untersuchungen mittels Toxcicogenomics f{\"u}r ein besseres Verst{\"a}ndnis der zugrunde liegenden Mechanismen der Arzneimittel-induzierten Toxizit{\"a}t. Ein Ziel dieser Arbeit war, die F{\"a}higkeit einiger neuer potenzieller Biomarker (NGAL, Thiostatin, Clusterin und PON1) zu bewerten, Arzmeimittel-induzierte Lebertoxizit{\"a}t in Ratten fr{\"u}hzeitig zu erkennen. Die Ergebnisse zeigen, dass PON1 und Clusterin infolge eines durch die verabreichten Arzneistoffkandidaten verursachten Leberschadens nicht konsistent ver{\"a}ndert waren. Diese beiden Marker sind daher, verglichen mit bestehenden klinisch-chemischen Markern, nicht f{\"u}r eine sichere Vorhersage von Arzneistoff-induzierten Lebersch{\"a}den geeignet. Bei Thiostatin und NGAL zeigte sich hingegen ein zeit- und dosisabh{\"a}ngiger Anstieg im Serum und Urin behandelter Tiere. Diese Ver{\"a}nderungen, die gut mit der mRNA Expression im Zielorgan {\"u}bereinstimmten, korrelierten mit dem Schweregrad der Arzneistoff-induzierten Lebersch{\"a}den. Die Analyse mittels ROC zeigte, Thiostatin im Serum, nicht aber NGAL, ein besserer Indikator f{\"u}r Arzneimittel-induzierte hepatobili{\"a}re Sch{\"a}den ist als die routinem{\"a}ßig verwendeten klinische-chemischen Marker, wie z.B. die Leberenzyme ALP, ALT und AST. Thiostatin wird jedoch als Akute-Phase-Protein in einer Vielzahl von Geweben exprimiert und kann somit nicht spezifisch als Lebermarker betrachtet werden. Dennoch zeigen unsere Ergebnisse, dass Thiostatin als sensitiver, minimal-invasiver diagnostischer Marker f{\"u}r Entz{\"u}ndungsprozesse und Gewebesch{\"a}den eine sinnvolle Erg{\"a}nzung in der pr{\"a}klinischen Testung auf Lebertoxizit{\"a}t darstellt. Im zweiten Teil dieser Arbeit wurde mittels RNA-Interferenz das pharmakologische Target des Arzneistoffkandidaten BAY16, der Glukagonrezeptor, auf mRNA-Ebene gehemmt und anhand von Genexpressionsanalysen untersucht, ob die pharmakologisch-bedingte Modulation des Glukagonrezeptors eine Rolle in der Toxizit{\"a}t von BAY16 spielt. Desweiteren sollten diese Arbeiten Aufschluss geben, welche molekularen Ver{\"a}nderungen auf die pharmakologische Wirkung des Arzneistoffs zur{\"u}ckzuf{\"u}hren sind, und daher f{\"u}r den Mechanismus der Toxizit{\"a}t m{\"o}glicherweise wenig relevant sind. W{\"a}hrend BAY16 in Konzentrationen von 75 µM starke zytotoxische Wirkungen aufwies, hatte die siRNA vermittelte Depletion des Glukagonrezeptors keinen Einfluss auf die Vitalit{\"a}t prim{\"a}rer Rattenhepatozyten. Daraus l{\"a}sst sich ableiten, dass die Hepatotoxizi{\"a}t von BAY16 in vitro und in vivo nicht mit der pharmakologischen Modulation des Glukagonrezeptors assoziiert ist. Diese Ergebnisse wurden durch die Tatsache gest{\"u}tzt, dass die meisten der durch BAY16 induzierten Genexpressionsver{\"a}nderungen unabh{\"a}ngig von der pharmakologischen Modulation des Glucagonrezeptors auftraten. Diese beobachteten off-target-Effekte beinhalteten Ver{\"a}nderungen im Fremdstoffmetabolismus, oxidativer Stress, erh{\"o}hte Fetts{\"a}uresynthese und Ver{\"a}nderungen im Cholesterol- und Gallens{\"a}uremetabolismus. Obwohl Ver{\"a}nderungen in diesen molekularen Mechanismen zum Fortschreiten eines Leberschadens beitragen k{\"o}nnen, ist es anhand dieser Daten nicht m{\"o}glich einen eindeutigen Mechanismus f{\"u}r die Toxizit{\"a}t von BAY16 abzuleiten. In dieser Arbeit konnte jedoch gezeigt werden, dass die Anwendung der siRNA-Technologie einen neuen methodischen Ansatz darstellt, um Mechanismen arzneimittelbedingter Toxizit{\"a}t besser verstehen zu k{\"o}nnen.}, subject = {Biomarker}, language = {en} } @phdthesis{Adler2022, author = {Adler, Philipp}, title = {Erfolgsrate wurzelkanalgef{\"u}llter Z{\"a}hne in Abh{\"a}ngigkeit von der Obturationstechnik: Adh{\"a}sive Obturation mit Continuous-Wave-Technik versus Single-Cone-Obturation mit silikonbasiertem oder epoxidharzbasiertem Sealer}, doi = {10.25972/OPUS-27815}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278158}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Bei der vorliegenden Arbeit handelt es sich um eine klinische und radiologische Nachuntersuchung von insgesamt 114 Patientinnen und Patienten, die zwischen 2009 und 2012 in der Poliklinik f{\"u}r Zahnerhaltung und Parodontologie der Universit{\"a}t W{\"u}rzburg von approbierten Zahn{\"a}rztinnen und Zahn{\"a}rzten endodontisch behandelt wurden. Dabei kamen drei verschiedene Obturationsmethoden zum Einsatz. 1. Single-Cone-Technik mit Guttapercha und AH Plus® (SCGP) 2. Single-Cone-Technik mit Guttapercha und GuttaFlow® (SCGF) 3. Adh{\"a}sive Obturation in Continuous-Wave-Technik mit Resilon® (CWR) Die Erhebung der Ausgangsvariablen (zum Behandlungszeitpunkt) erfolgte retrospektiv unter Zuhilfenahme der klinischen und radiologischen Dokumentation. Die Reevaluation des periapikalen Zustands der Z{\"a}hne und die Erhebung weiterer klinischer Parameter erfolgte im Rahmen eines aktiven Patientenrecalls nach durchschnittlich 6,3 Jahren. Dabei wurden mit m{\"o}glichst hoher Standardisierung postoperative Einzelzahnaufnah-men angefertigt. Diese wurden anhand der PAI-Klassifikation ausgewertet, um den pe-riapikalen Zustand der Z{\"a}hne vor und nach Therapie zu bestimmen. PAI-Werte von 1 und 2 galten als Behandlungserfolg, Grad 3 bis 5 als Misserfolg. Im Hinblick auf die de-finierten Arbeitshypothesen wurden die Erfolgsraten innerhalb der Kohorten miteinander verglichen. Das vorrangige Ziel der hier vorliegenden Arbeit war, zu untersuchen, ob der endodontische Behandlungserfolg abh{\"a}ngig von der jeweiligen Obturationsmethode ist und ob technikspezifische Unterschiede sich einerseits auf die Qualit{\"a}t der Obturation und andererseits auf das Auftreten m{\"o}glicher Komplikationen, wie der periapikalen Extrusion von Wurzelf{\"u}llmaterial, auswirken. Ferner sollten diese Aspekte neben weite-ren zahn- und patientenbezogenen Variablen bez{\"u}glich ihres Einflusses auf die Erfolgs-rate der endodontischen Therapie analysiert werden. Es konnten keine signifikanten Unterschiede der endodontischen Erfolgsraten zwischen den hier untersuchten Obturationsmethoden ermittelt werden (p = ,16). In der SCGP-Kohorte lag die Erfolgsrate bei 85 \% (34/40) verglichen mit 68,8 \% (44/64) f{\"u}r CWR und 80 \% (8/10) f{\"u}r SCGF. Die Homogenit{\"a}t der Obturation (p = ,2) und die Extrusion von Wurzelf{\"u}llmaterial in das periapikale Gewebe (p = ,93) zeigten keine Abh{\"a}ngigkeit von der gew{\"a}hlten Obturationstechnik. Die L{\"a}nge der Wurzelkanalf{\"u}llung hingegen unter-schied sich signifikant zwischen den Kohorten (p = ,04*). Die Obturation mittels SCGP-Technik erzielte den h{\"o}chsten Anteil ad{\"a}quater Wurzelkanalf{\"u}llungen (92,5 \%, 37/40) gegen{\"u}ber SCGF (80 \%, 8/10) und CWR (71,88 \%, 46/64). Die CWR-Methode zeigte mit 18,8 \% (12/64) den h{\"o}chsten Anteil an unterf{\"u}llten Obturationen (SCGP: 7,5 \%, 3/40; SCGF: 0 \%). Unabh{\"a}ngig von der Obturationsmethodik zeigte sich der endodontische Behandlungs-erfolg im Allgemeinen unbeeinflusst von der Qualit{\"a}t der Wurzelkanalf{\"u}llungen. Die Va-riablen Obturationsl{\"a}nge (p = ,12) und -homogenit{\"a}t (p = ,11) sowie die Extrusion von Wurzelf{\"u}llmaterial in die periapikale Region (p = 1,00) zeigten keinen signifikanten Ein-fluss auf die Erfolgsrate. Das Durchschnittsalter im Patientenkollektiv betrug 60 Jahre mit einer tendenziellen {\"U}berrepr{\"a}sentation weiblicher Probandinnen (60,5 \%, 69/114). 73 \% (81/111, 3 Mis-sings) der Studienteilnehmer/-innen wurden ab einem PSI-Grad von 3 als parodontal erkrankt eingestuft und 23,7 \% (27/114) zeigten eine positive Raucheranamnese. Der BMI betrug im Durchschnitt 26,3 kg/m2. 42,3 \% (47/111, 3 Missings) der Studienteil-nehmer/-innen wurden anhand der Einnahme von Medikamenten zur Therapie bzw. Pr{\"a}vention von kardiovaskul{\"a}ren Erkrankungen und/oder oraler Antidiabetika als chro-nisch erkrankt klassifiziert (chronic disease medication, CDM). Das Recallintervall be-trug durchschnittlich 6,3 Jahre mit einem Minimum von 4,7 und einem Maximum von 8,7 Jahren. Die patientenbezogenen Variablen Alter (p = ,45), Geschlecht (p = ,67), Pa-rodontitis (p = ,08), BMI (p = ,58), CDM (p = ,19), Recallintervall (p = ,08) und Rauchen (p = ,34) zeigten keinen signifikanten Einfluss auf den endodontischen Behandlungser-folg. Unter den zahnbezogenen Variablen beeinflusste lediglich der pr{\"a}operative apikale Sta-tus den endodontischen Erfolg signifikant (p = ,007*). Z{\"a}hne mit pr{\"a}operativer apikaler L{\"a}sion zeigten eine Erfolgsrate von 66,2 \% (47/71) gegen{\"u}ber 90,7 \% (n = 39/43) bei F{\"a}llen ohne apikale L{\"a}sion. Die Misserfolgswahrscheinlichkeit bei Vorliegen einer pr{\"a}operativen L{\"a}sion war um den Faktor 4,98 erh{\"o}ht (OR = 4,98, 95 \% KI: 1.60, 15,57, p = ,006*). Zwischen Kompositf{\"u}llungen, Teilkronen, Vollkronen, Teleskopkronen und Br{\"u}ckenversorgungen konnten keine relevanten Unterschiede in den Erfolgsraten er-mittelt werden (p = ,29). Gleiches galt f{\"u}r ad{\"a}quate (76,6 \%, 82/107) und inad{\"a}quate (57,1 \%, 4/7) Restaurationen (p = ,36). Ebenso zeigten die Erfolgsraten von Wurzelka-nalrevisionen (70,5 \%, 31/44) und Prim{\"a}rbehandlungen (78,6 \%, 55/70) keine signifikan-ten Abweichungen voneinander (p = ,45). Molaren waren im Studienkollektiv mit 56,1 \% (64/114) gegen{\"u}ber Pr{\"a}molaren und Frontz{\"a}hnen mit je 21,9 \% (25/114) {\"u}berrepr{\"a}sen-tiert. Der Zahntyp (p = ,07) und die Ausgangsdiagnose (p = ,22) stellten keine relevanten Einflussfaktoren des endodontischen Erfolgs dar.}, subject = {Endodontie}, language = {de} } @article{AdolfBraunFussetal.2020, author = {Adolf, Christian and Braun, Leah T. and Fuss, Carmina T. and Hahner, Stefanie and K{\"u}nzel, Heike and Handgriff, Laura and Sturm, Lisa and Heinrich, Daniel A. and Schneider, Holger and Bidlingmaier, Martin and Reincke, Martin}, title = {Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism}, series = {Endocrine}, volume = {69}, journal = {Endocrine}, number = {3}, issn = {1355-008X}, doi = {10.1007/s12020-020-02348-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-315966}, pages = {625-633}, year = {2020}, abstract = {Context Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis. Patients and methods We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment. Study design Observational longitudinal cohort study. Setting Tertiary care hospital. Results Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers. Conclusion This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.}, language = {en} } @article{AdolfiCarreiraJesusetal.2015, author = {Adolfi, Mateus C. and Carreira, Ana C. O. and Jesus, L{\´a}zaro W. O. and Bogerd, Jan and Funes, Rejane M. and Schartl, Manfred and Sogayar, Mari C. and Borella, Maria I.}, title = {Molecular cloning and expression analysis of dmrt1 and sox9 during gonad development and male reproductive cycle in the lambari fish, Astyanax altiparanae}, series = {Reproductive Biology and Endocrinology}, volume = {13}, journal = {Reproductive Biology and Endocrinology}, number = {2}, doi = {10.1186/1477-7827-13-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126486}, year = {2015}, abstract = {Background The dmrt1 and sox9 genes have a well conserved function related to testis formation in vertebrates, and the group of fish presents a great diversity of species and reproductive mechanisms. The lambari fish (Astyanax altiparanae) is an important Neotropical species, where studies on molecular level of sex determination and gonad maturation are scarce. Methods Here, we employed molecular cloning techniques to analyze the cDNA sequences of the dmrt1 and sox9 genes, and describe the expression pattern of those genes during development and the male reproductive cycle by qRT-PCR, and related to histology of the gonad. Results Phylogenetic analyses of predicted amino acid sequences of dmrt1 and sox9 clustered A. altiparanae in the Ostariophysi group, which is consistent with the morphological phylogeny of this species. Studies of the gonad development revealed that ovary formation occurred at 58 days after hatching (dah), 2 weeks earlier than testis formation. Expression studies of sox9 and dmrt1 in different tissues of adult males and females and during development revealed specific expression in the testis, indicating that both genes also have a male-specific role in the adult. During the period of gonad sex differentiation, dmrt1 seems to have a more significant role than sox9. During the male reproductive cycle dmrt1 and sox9 are down-regulated after spermiation, indicating a role of these genes in spermatogenesis. Conclusions For the first time the dmrt1 and sox9 were cloned in a Characiformes species. We show that both genes have a conserved structure and expression, evidencing their role in sex determination, sex differentiation and the male reproductive cycle in A. altiparanae. These findings contribute to a better understanding of the molecular mechanisms of sex determination and differentiation in fish.}, language = {en} } @article{AdolfiDuKneitzetal.2021, author = {Adolfi, Mateus C. and Du, Kang and Kneitz, Susanne and Cabau, C{\´e}dric and Zahm, Margot and Klopp, Christophe and Feron, Romain and Paix{\~a}o, R{\^o}mulo V. and Varela, Eduardo S. and de Almeida, Fernanda L. and de Oliveira, Marcos A. and N{\´o}brega, Rafael H. and Lopez-Roques, C{\´e}line and Iampietro, Carole and Lluch, J{\´e}r{\^o}me and Kloas, Werner and Wuertz, Sven and Schaefer, Fabian and St{\"o}ck, Matthias and Guiguen, Yann and Schartl, Manfred}, title = {A duplicated copy of id2b is an unusual sex-determining candidate gene on the Y chromosome of arapaima (Arapaima gigas)}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-01066-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265672}, year = {2021}, abstract = {Arapaima gigas is one of the largest freshwater fish species of high ecological and economic importance. Overfishing and habitat destruction are severe threats to the remaining wild populations. By incorporating a chromosomal Hi-C contact map, we improved the arapaima genome assembly to chromosome-level, revealing an unexpected high degree of chromosome rearrangements during evolution of the bonytongues (Osteoglossiformes). Combining this new assembly with pool-sequencing of male and female genomes, we identified id2bbY, a duplicated copy of the inhibitor of DNA binding 2b (id2b) gene on the Y chromosome as candidate male sex-determining gene. A PCR-test for id2bbY was developed, demonstrating that this gene is a reliable male-specific marker for genotyping. Expression analyses showed that this gene is expressed in juvenile male gonads. Its paralog, id2ba, exhibits a male-biased expression in immature gonads. Transcriptome analyses and protein structure predictions confirm id2bbY as a prime candidate for the master sex-determiner. Acting through the TGF beta signaling pathway, id2bbY from arapaima would provide the first evidence for a link of this family of transcriptional regulators to sex determination. Our study broadens our current understanding about the evolution of sex determination genetic networks and provide a tool for improving arapaima aquaculture for commercial and conservation purposes.}, language = {en} } @article{AdolfiHerpinMartinezBengocheaetal.2021, author = {Adolfi, Mateus C. and Herpin, Amaury and Martinez-Bengochea, Anabel and Kneitz, Susanne and Regensburger, Martina and Grunwald, David J. and Schartl, Manfred}, title = {Crosstalk Between Retinoic Acid and Sex-Related Genes Controls Germ Cell Fate and Gametogenesis in Medaka}, series = {Frontiers in Cell and Developmental Biology}, volume = {8}, journal = {Frontiers in Cell and Developmental Biology}, issn = {2296-634X}, doi = {10.3389/fcell.2020.613497}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222669}, year = {2021}, abstract = {Sex determination (SD) is a highly diverse and complex mechanism. In vertebrates, one of the first morphological differences between the sexes is the timing of initiation of the first meiosis, where its initiation occurs first in female and later in male. Thus, SD is intimately related to the responsiveness of the germ cells to undergo meiosis in a sex-specific manner. In some vertebrates, it has been reported that the timing for meiosis entry would be under control of retinoic acid (RA), through activation of Stra8. In this study, we used a fish model species for sex determination and lacking the stra8 gene, the Japanese medaka (Oryzias latipes), to investigate the connection between RA and the sex determination pathway. Exogenous RA treatments act as a stress factor inhibiting germ cell differentiation probably by activation of dmrt1a and amh. Disruption of the RA degrading enzyme gene cyp26a1 induced precocious meiosis and oogenesis in embryos/hatchlings of female and even some males. Transcriptome analyzes of cyp26a1-/-adult gonads revealed upregulation of genes related to germ cell differentiation and meiosis, in both ovaries and testes. Our findings show that germ cells respond to RA in a stra8 independent model species. The responsiveness to RA is conferred by sex-related genes, restricting its action to the sex differentiation period in both sexes.}, language = {en} } @article{AdolfiHerpinRegensburgeretal.2016, author = {Adolfi, Mateus C. and Herpin, Amaury and Regensburger, Martina and Sacquegno, Jacopo and Waxman, Joshua S. and Schartl, Manfred}, title = {Retinoic acid and meiosis induction in adult versus embryonic gonads of medaka}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, doi = {10.1038/srep34281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147843}, pages = {34281}, year = {2016}, abstract = {In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage.}, language = {en} } @article{AdolphFleischhackGaabetal.2021, author = {Adolph, Jonas E. and Fleischhack, Gudrun and Gaab, Christine and Mikasch, Ruth and Mynarek, Martin and Rutkowski, Stefan and Sch{\"u}ller, Ulrich and Pfister, Stefan M. and Pajtler, Kristian W. and Milde, Till and Witt, Olaf and Bison, Brigitte and Warmuth-Metz, Monika and Kortmann, Rolf-Dieter and Dietzsch, Stefan and Pietsch, Torsten and Timmermann, Beate and Tippelt, Stephan}, title = {Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies}, series = {Journal of Neuro-Oncology}, volume = {155}, journal = {Journal of Neuro-Oncology}, number = {2}, organization = {German GPOH HIT-Network}, issn = {0167-594X}, doi = {10.1007/s11060-021-03867-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308302}, pages = {193-202}, year = {2021}, abstract = {Purpose Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN. Methods Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated. Results Median age at first recurrence was 7.6 years (IQR: 4.0-13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3-20.0) and 36.9 months (CI 29.7-53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74-1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50\%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found. Conclusion No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation.}, language = {en} } @article{AdrianMartinezAgeronAharonianetal.2016, author = {Adri{\´a}n-Mart{\´i}nez, S. and Ageron, M. and Aharonian, F. and Aiello, S. and Albert, A. and Ameli, F. and Annasontzis, E. and Andre, M. and Androulakis, G. and Anghinolfi, M. and Anton, G. and Ardid, M. and Avgitas, T. and Barbarino, G. and Baret, B. and Barrios-Mart{\´i}, J. and Belhorma, B. and Belias, A. and Berbee, A. and van den Berg, A. and Bertin, V. and Beurthey, S. and van Beeveren, V. and Beverini, N. and Biagi, S. and Biagioni, A. and Billault, M. and Bond{\`i}, M. and Bormuth, R. and Bouhadef, B. and Bourlis, G. and Bourret, S. and Boutonnet, C. and Bouwhuis, M. and Bozza, C. and Bruijn, R. and Brunner, J. and Buis, E. and Busto, J. and Cacopardo, G. and Caillat, L. and Calmai, M. and Calvo, D. and Capone, A. and Caramete, L. and Cecchini, S. and Celli, S. and Champion, C. and Cherkaoui El Moursli, R. and Cherubini, S. and Chiarusi, T. and Circella, M. and Classen, L. and Cocimano, R. and Coelho, J. A. B. and Coleiro, A. and Colonges, S. and Coniglione, R. and Cordelli, M. and Cosquer, A. and Coyle, P. and Creusot, A. and Cuttone, G. and D'Amico, A. and De Bonis, G. and De Rosa, G. and De Sio, C. and Di Capua, F. and Di Palma, I. and D{\´i}az Garc{\´i}a, A. F. and Distefano, C. and Donzaud, C. and Dornic, D. and Dorosti-Hasankiadeh, Q. and Drakopoulou, E. and Drouhin, D. and Drury, L. and Durocher, M. and Eberl, T. and Eichie, S. and van Eijk, D. and El Bojaddaini, I. and El Khayati, N. and Elsaesser, D. and Enzenh{\"o}fer, A. and Fassi, F. and Favali, P. and Fermani, P. and Ferrara, G. and Filippidis, C. and Frascadore, G. and Fusco, L. A. and Gal, T. and Galat{\`a}, S. and Garufi, F. and Gay, P. and Gebyehu, M. and Giordano, V. and Gizani, N. and Gracia, R. and Graf, K. and Gr{\´e}goire, T. and Grella, G. and Habel, R. and Hallmann, S. and van Haren, H. and Harissopulos, S. and Heid, T. and Heijboer, A. and Heine, E. and Henry, S. and Hern{\´a}ndez-Rey, J. J. and Hevinga, M. and Hofest{\"a}dt, J. and Hugon, C. M. F. and Illuminati, G. and James, C. W. and Jansweijer, P. and Jongen, M. and de Jong, M. and Kadler, M. and Kalekin, O. and Kappes, A. and Katz, U. F. and Keller, P. and Kieft, G. and Kießling, D. and Koffeman, E. N. and Kooijman, P. and Kouchner, A. and Kulikovskiy, V. and Lahmann, R. and Lamare, P. and Leisos, A. and Leonora, E. and Lindsey Clark, M. and Liolios, A. and Llorenz Alvarez, C. D. and Lo Presti, D. and L{\"o}hner, H. and Lonardo, A. and Lotze, M. and Loucatos, S. and Maccioni, E. and Mannheim, K. and Margiotta, A. and Marinelli, A. and Mari{\c{s}}, O. and Markou, C. and Mart{\´i}nez-Mora, J. A. and Martini, A. and Mele, R. and Melis, K. W. and Michael, T. and Migliozzi, P. and Migneco, E. and Mijakowski, P. and Miraglia, A. and Mollo, C. M. and Mongelli, M. and Morganti, M. and Moussa, A. and Musico, P. and Musumeci, M. and Navas, S. and Nicoleau, C. A. and Olcina, I. and Olivetto, C. and Orlando, A. and Papaikonomou, A. and Papaleo, R. and Păvăla{\c{s}}, G. E. and Peek, H. and Pellegrino, C. and Perrina, C. and Pfutzner, M. and Piattelli, P. and Pikounis, K. and Poma, G. E. and Popa, V. and Pradier, T. and Pratolongo, F. and P{\"u}hlhofer, G. and Pulvirenti, S. and Quinn, L. and Racca, C. and Raffaelli, F. and Randazzo, N. and Rapidis, P. and Razis, P. and Real, D. and Resvanis, L. and Reubelt, J. and Riccobene, G. and Rossi, C. and Rovelli, A. and Salda{\~n}a, M. and Salvadori, I. and Samtleben, D. F. E. and S{\´a}nchez Garc{\´i}a, A. and S{\´a}nchez Losa, A. and Sanguineti, M. and Santangelo, A. and Santonocito, D. and Sapienza, P. and Schimmel, F. and Schmelling, J. and Sciacca, V. and Sedita, M. and Seitz, T. and Sgura, I. and Simeone, F. and Siotis, I. and Sipala, V. and Spisso, B. and Spurio, M. and Stavropoulos, G. and Steijger, J. and Stellacci, S. M. and Stransky, D. and Taiuti, M. and Tayalati, Y. and T{\´e}zier, D. and Theraube, S. and Thompson, L. and Timmer, P. and T{\"o}nnis, C. and Trasatti, L. and Trovato, A. and Tsirigotis, A. and Tzamarias, S. and Tzamariudaki, E. and Vallage, B. and Van Elewyk, V. and Vermeulen, J. and Vicini, P. and Viola, S. and Vivolo, D. and Volkert, M. and Voulgaris, G. and Wiggers, L. and Wilms, J. and de Wolf, E. and Zachariadou, K. and Zornoza, J. D. and Z{\´u}{\~n}iga, J.}, title = {Letter of intent for KM3NeT 2.0}, series = {Journal of Physics G-Nuclear and Particle Physics}, volume = {43}, journal = {Journal of Physics G-Nuclear and Particle Physics}, number = {8}, doi = {10.1088/0954-3899/43/8/084001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188050}, pages = {84001}, year = {2016}, abstract = {The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and}, language = {en} } @article{AdrianMartinezAlbertAndreetal.2016, author = {Adri{\´a}n-Mart{\´i}nez, S. and Albert, A. and Andr{\´e}, M. and Anghinolfi, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Avgitas, T. and Baret, B. and Barrios-Mart{\´i}, J. and Basa, S. and Bertin, V. and Biagi, S. and Bormuth, R. and Bouwhuis, M.C. and Bruijn, R. and Brunner, J. and Busto, J. and Capone, A. and Caramete, L. and Carr, J. and Celli, S. and Chiarusi, T. and Circella, M. and Coleiro, A. and Coniglione, R. and Constantini, H. and Coyle, P. and Creusot, A. and Deschamps, A. and De Bonis, G. and Distefano, C. and Donzaud, C. and Dornic, D. and Drouhin, D. and Eberl, T. and El Bojaddaini, I. and Els{\"a}sser, D. and Enzenh{\"o}fer, A. and Fehn, K. and Felis, I. and Fusco, L.A. and Galat{\`a}, S. and Gay, P. and Geißels{\"o}der, S. and Geyer, K. and Giordano, V. and Gleixner, A. and Glotin, H. and Gracia-Ruiz, R. and Graf, K. and Hallmann, S. and van Haren, H. and Heijboer, A.J. and Hello, Y. and Hern{\´a}ndez-Rey, J.J. and H{\"o}ßl, J. and Hofest{\"a}dt, J. and Hugon, C. and Illuminati, G. and James, C.W. and de Jong, M. and Kadler, M. and Kalekin, O. and Katz, U. and Kießling, D. and Kouchner, A. and Kreter, M. and Kreykenbohm, I. and Kulikovskiy, V. and Lachaud, C. and Lahmann, R. and Lef{\`e}vre, D. and Leonora, E. and Loucatos, S. and Marcelin, M. and Margiotta, A. and Marinelli, A. and Mart{\´i}nez-Mora, J.A. and Mathieu, A. and Michael, T. and Migliozzi, P. and Moussa, A. and Mueller, C. and Nezri, E. and Pavalas, G.E. and Pellegrino, C. and Perrina, C. and Piattelli, P. and Popa, V. and Pradier, T. and Racca, C. and Riccobene, G. and Roensch, K. and Salda{\~n}a, M. and Samtleben, D.F.E. and S{\´a}nchez-Losa, A. and Sanguineti, M. and Sapienza, P. and Schnabel, J. and Sch{\"u}ssler, F. and Seitz, T. and Sieger, C. and Spurio, M. and Stolarczyk, Th. and Taiuti, M. and Trovato, A. and Tselengidou, M. and Turpin, D. and T{\"o}nnis, C. and Vallage, B. and Vall{\´e}e, C. and Van Elewyck, V. and Visser, E. and Vivolo, D. and Wagner, S. and Wilms, J. and Zornoza, J.D. and Z{\´u}{\~n}iga, J.}, title = {Constraints on the neutrino emission from the Galactic Ridge with the ANTARES telescope}, series = {Physics Letters B}, volume = {760}, journal = {Physics Letters B}, doi = {10.1016/j.physletb.2016.06.051}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166608}, pages = {143-148}, year = {2016}, abstract = {A highly significant excess of high-energy astrophysical neutrinos has been reported by the IceCube Collaboration. Some features of the energy and declination distributions of IceCube events hint at a North/South asymmetry of the neutrino flux. This could be due to the presence of the bulk of our Galaxy in the Southern hemisphere. The ANTARES neutrino telescope, located in the Mediterranean Sea, has been taking data since 2007. It offers the best sensitivity to muon neutrinos produced by galactic cosmic ray interactions in this region of the sky. In this letter a search for an extended neutrino flux from the Galactic Ridge region is presented. Different models of neutrino production by cosmic ray propagation are tested. No excess of events is observed and upper limits for different neutrino flux spectral indices Γ are set. For Γ=2.4 the 90\% confidence level flux upper limit at 100 TeV for one neutrino flavour corresponds to Φ\(^{1f}_{0}\) (100 TeV) = 2.0 · 10\(^{-17}\) GeV\(^{-1}\) cm\(^{-2}\)s\(^{-1}\)sr\(^{-1}\). Under this assumption, at most two events of the IceCube cosmic candidates can originate from the Galactic Ridge. A simple power-law extrapolation of the Fermi-LAT flux to account for IceCube High Energy Starting Events is excluded at 90\% confidence level.}, language = {en} } @article{AdrianMartinezAlbertAndreetal.2017, author = {Adri{\´a}n-Mart{\´i}nez, S. and Albert, A. and Andr{\´e}, M. and Anghinolfi, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Baret, B. and Barrios-Marti, J. and Basa, S. and Bertin, V. and Biagi, S. and Bormuth, R. and Bouwhuis, M.C. and Bruijn, R. and Brunner, J. and Buto, J. and Capone, A. and Caramete, L. and Carr, J. and Chiarusi, T. and Circella, M. and Coniglione, R. and Costantini, H. and Coyle, P. and Creusot, A. and Dekeyser, I. and Deschamps, A. and De Bonis, G. and Distefano, C.}, title = {Stacked search for time shifted high energy neutrinos from gamma ray bursts with the ANTARES neutrino telescope}, series = {European Physical Journal C}, volume = {77}, journal = {European Physical Journal C}, number = {1}, doi = {10.1140/epjc/s10052-016-4496-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181251}, pages = {10}, year = {2017}, abstract = {A search for high-energy neutrino emission correlated with gamma-ray bursts outside the electromagnetic prompt-emission time window is presented. Using a stacking approach of the time delays between reported gamma-ray burst alerts and spatially coincident muon-neutrino signatures, data from the Antares neutrino telescope recorded between 2007 and 2012 are analysed. One year of public data from the IceCube detector between 2008 and 2009 have been also investigated. The respective timing profiles are scanned for statistically significant accumulations within 40 days of the Gamma Ray Burst, as expected from Lorentz Invariance Violation effects and some astrophysical models. No significant excess over the expected accidental coincidence rate could be found in either of the two data sets. The average strength of the neutrino signal is found to be fainter than one detectable neutrino signal per hundred gamma-ray bursts in the Antares data at 90\% confidence level.}, language = {en} } @article{AdrianMartinezAlbertAndreetal.2016, author = {Adri{\´a}n-Mart{\´i}nez, S. and Albert, A. and Andr{\´e}, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Avgitas, T. and Baret, B. and Barrios-Mart{\´i}, J. and Basa, S. and Bertin, V. and Biagi, S. and Bormuth, R. and Bou-Cabo, M. and Bouwhuis, M.C. and Bruijn, R. and Brunner, J. and Busto, J. and Capone, A. and Caramete, L. and Carr, J. and Celli, S. and Chiarusi, T. and Circella, M. and Coleiro, A. and Coniglione, R. and Costantini, H. and Coyle, P. and Creusot, A. and Deschamps, A. and De Bonis, G. and Distefano, C. and Donzaud, C. and Dornic, D. and Drouhin, D. and Eberl, T. and El Bojaddaini, I. and Els{\"a}sser, D. and Enzenh{\"o}fer, A. and Fehn, K. and Felis, I. and Fusco, L.A. and Galat{\`a}, S. and Gay, P. and Geißels{\"o}der, S. and Geyer, K. and Giordano, V. and Gleixner, A. and Glotin, H. and Gracia-Ruiz, R. and Graf, K. and Hallmann, S. and van Haren, H. and Heijboer, A.J. and Hello, Y. and Hern{\´a}ndez-Rey, J.-J. and H{\"o}ßl, J. and Hofest{\"a}dt, J. and Hugon, C. and Illuminati, G. and James, C.W. and de Jong, M. and Kadler, M. and Kalekin, O. and Katz, U. and Kießling, D. and Kouchner, A. and Kreter, M. and Kreykenbohm, I. and Kulikovskiy, V. and Lachaud, C. and Lahmann, R. and Lef{\`e}vre, D. and Leonora, E. and Loucatos, S. and Marcelin, M. and Margiotta, A. and Marinelli, A. and Mart{\´i}nez-Mora, J.A. and Mathieu, A. and Michael, T. and Migliozzi, P. and Moussa, A. and Mueller, C. and Nezri, E. and Păvălaș, G.E. and Pellegrino, C. and Perrina, C. and Piattelli, P. and Popa, V. and Pradier, T. and Racca, C. and Riccobene, G. and Roensch, K. and Salda{\~n}a, M. and Samtleben, D.F.E. and Sanguineti, M. and Sapienza, P. and Schnabel, J. and Sch{\"u}ssler, F. and Seitz, T. and Sieger, C. and Spurio, M. and Stolarczyk, Th. and S{\´a}nchez-Losa, A. and Taiuti, M. and Trovato, A. and Tselengidou, M. and Turpin, D. and T{\"o}nnis, C. and Vallage, B. and Vall{\´e}e, C. and Van Elewyck, V. and Vivolo, D. and Wagner, S. and Wilms, J. and Zornoza, J.D. and Z{\´u}{\~n}iga, J.}, title = {A search for Secluded Dark Matter in the Sun with the ANTARES neutrino telescope}, series = {Journal of Cosmology and Astroparticle Physics}, volume = {2016}, journal = {Journal of Cosmology and Astroparticle Physics}, number = {5}, organization = {The ANTARES collaboration}, doi = {10.1088/1475-7516/2016/05/016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189035}, pages = {12}, year = {2016}, abstract = {A search for Secluded Dark Matter annihilation in the Sun using 2007-2012 data of the ANTARES neutrino telescope is presented. Three different cases are considered: a) detection of dimuons that result from the decay of the mediator, or neutrino detection from: b) mediator that decays into a dimuon and, in turn, into neutrinos, and c) mediator that decays directly into neutrinos. As no significant excess over background is observed, constraints are derived on the dark matter mass and the lifetime of the mediator.}, language = {en} } @article{AdrianMartinezAlbertAndreetal.2016, author = {Adri{\´a}n-Mart{\´i}nez, S. and Albert, A. and Andr{\´e}, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Avgitas, T. and Baret, B. and Barrios-Mart{\´i}, J. and Basa, S. and Bertin, V. and Biagi, S. and Bormuth, R. and Bouwhuis, M.C. and Bruijn, R. and Brunner, J. and Busto, J. and Capone, A. and Caramete, L. and Carr, J. and Celli, S. and Chiarusi, T. and Circella, M. and Coleiro, A. and Coniglione, R. and Costantini, H. and Coyle, P. and Creusot, A. and Deschamps, A. and De Bonis, G. and Distefano, C. and Donzaud, C. and Dornic, D. and Drouhin, D. and Eberl, T. and El Bojaddaini, I. and Els{\"a}sser, D. and Enzenh{\"o}fer, A. and Fehn, K. and Felis, I. and Fusco, L.A. and Galat{\`a}, S. and Gay, P. and Geißels{\"o}der, S. and Geyer, K. and Giordano, V. and Gleixner, A. and Glotin, H. and Gracia-Ruiz, R. and Graf, K. and Hallmann, S. and van Haren, H. and Heijboer, A.J. and Hello, Y. and Hern{\´a}ndez-Rey, J.J. and H{\"o}ßl, J. and Hofest{\"a}dt, J. and Hugon, C. and Illuminati, G. and James, C.W. and de Jong, M. and Jongen, M. and Kadler, M. and Kalekin, O. and Katz, U. and Kießling, D. and Kouchner, A. and Kreter, M. and Kreykenbohm, I. and Kulikovskiy, V. and Lachaud, C. and Lahmann, R. and Lef{\`e}vre, D. and Leonora, E. and Loucatos, S. and Marcelin, M. and Margiotta, A. and Marinelli, A. and Mart{\´i}nez-Mora, J.A. and Mathieu, A. and Melis, K. and Michael, T. and Migliozzi, P. and Moussa, A. and Mueller, C. and Nezri, E. and Pavalas, G.E. and Pellegrino, C. and Perrina, C. and Piattelli, P. and Popa, V. and Pradier, T. and Racca, C. and Riccobene, G. and Roensch, K. and Salda{\~n}a, M. and Samtleben, D.F.E. and S{\´a}nchez-Losa, A. and Sanguineti, M. and Sapienza, P. and Schnabel, J. and Sch{\"u}ssler, F. and Seitz, T. and Sieger, C. and Spurio, M. and Stolarczyk, Th. and Taiuti, M. and T{\"o}nnis, C. and Trovato, A. and Tselengidou, M. and Turpin, D. and Vallage, B. and Vall{\´e}e, C. and Van Elewyck, V. and Vivolo, D. and Wagner, S. and Wilms, J. and Zornoza, J.D. and Z{\´u}{\~n}iga, J.}, title = {Limits on dark matter annihilation in the sun using the ANTARES neutrino telescope}, series = {Physics Letters B}, volume = {759}, journal = {Physics Letters B}, doi = {10.1016/j.physletb.2016.05.019}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166642}, pages = {69-74}, year = {2016}, abstract = {A search for muon neutrinos originating from dark matter annihilations in the Sun is performed using the data recorded by the ANTARES neutrino telescope from 2007 to 2012. In order to obtain the best possible sensitivities to dark matter signals, an optimisation of the event selection criteria is performed taking into account the background of atmospheric muons, atmospheric neutrinos and the energy spectra of the expected neutrino signals. No significant excess over the background is observed and 90\% C.L. upper limits on the neutrino flux, the spin-dependent and spin-independent WIMP-nucleon cross-sections are derived for WIMP masses ranging from 50 GeV to 5 TeV for the annihilation channels WIMP + WIMP→ b\(\overline{b}\), W\(^{+}\)W\(^{-}\) and τ\(^{+}\)τ\(^{-}\).}, language = {en} } @phdthesis{Aehnlich2022, author = {Aehnlich, Flora}, title = {Untersuchungen zur Pr{\"a}sentation kryptischer und kanonischer Peptide {\"u}ber den MHC-Klasse-I-Komplex in Patienten mit akuter myeloischer Leuk{\"a}mie}, doi = {10.25972/OPUS-27003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270036}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Die AML stellt mit einem Anteil von 80 \% an den akuten Leuk{\"a}mien bei Erwachsenen eine bedeutende Erkrankung f{\"u}r die Gesellschaft dar. Aufgrund fehlender durchbrechender Erfolge in der Therapieentwicklung liegt die durchschnittliche F{\"u}nfjahres{\"u}berlebensrate dennoch nur bei etwa 25 \%. Der Blick auf die Kraft des Graft-versus-Leuk{\"a}mie-Effekts nach allogener Stammzelltransplantation, eine Langzeitremission der AML erzielen zu k{\"o}nnen, weist jedoch auf die Immunogenit{\"a}t und Eignung der Erkrankung f{\"u}r neue immuntherapeutische Ans{\"a}tze hin. Anhand der Kartierung der in-vivo pr{\"a}sentierten MHC-Klasse-I-Peptidome auf AML-Blasten sollten in dieser Arbeit potenziell geeignete Therapietargets identifiziert werden, um eine breitere Anwendung immuntherapeutischer Strategien bei AML-Patienten zu erm{\"o}glichen. Auf prim{\"a}ren Patientenmaterialien, Zelllinien und benignen Zellen wurden hierzu {\"u}ber eine Immunoaffinit{\"a}tschromatographie mit nachfolgenden Purifizierungsschritten die MHC-pr{\"a}sentierten Peptide massenspekrometrisch-basiert identifiziert. Zus{\"a}tzlich erfolgte eine Quantifizierung der Oberfl{\"a}chen- und intrazellul{\"a}ren MHC-Klasse-I-Molek{\"u}le der verwendeten Proben durch einen indirekten Immunfluoreszenz-Assay. Unter der Gesamtheit von 17.750 identifizierten nicht-redundanten MHC-Klasse- I-pr{\"a}sentierten Peptiden konnte eine Vielzahl von 5.626 Peptiden mit Pr{\"a}sentationsfrequenzen bis zu 72 \% als AML-exklusiv beschrieben werden. Hierunter wurden 240 kryptische Peptide vermeintlich nicht-codierenden Ursprungs identifiziert. Zudem wurden mehrere potenziell CMV-kreuzreaktive AML-Peptide erfasst, die zu der reduzierten Rezidivrate bei CMV-Infektion nach allogener Stammzelltransplantation f{\"u}hren k{\"o}nnten. Bei der MHC-Quantifizierung wiesen die AML-Blasten keine verminderte MHC-Expression auf und stellten sich somit als geeignete Target-Zellen f{\"u}r eine T-Zell-Immuntherapie dar.}, subject = {Akute myeloische Leuk{\"a}mie}, language = {de} } @article{AertsEberleinHolmetal.2021, author = {Aerts, An and Eberlein, Uta and Holm, S{\"o}ren and Hustinx, Roland and Konijnenberg, Mark and Strigari, Lidia and van Leeuwen, Fijs W. B. and Glatting, Gerhard and Lassmann, Michael}, title = {EANM position paper on the role of radiobiology in nuclear medicine}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {48}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {11}, doi = {10.1007/s00259-021-05345-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265595}, pages = {3365-3377}, year = {2021}, abstract = {With an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.}, language = {en} } @article{AeschlimannBauerBayeretal.2012, author = {Aeschlimann, Martin and Bauer, Michael and Bayer, Daniela and Brixner, Tobias and Cunovic, Stefan and Fischer, Alexander and Melchior, Pascal and Pfeiffer, Walter and Rohmer, Martin and Schneider, Christian and Str{\"u}ber, Christian and Tuchscherer, Philip and Voronine, Dimitri V.}, title = {Optimal open-loop near-field control of plasmonic nanostructures}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75256}, year = {2012}, abstract = {Optimal open-loop control, i.e. the application of an analytically derived control rule, is demonstrated for nanooptical excitations using polarization-shaped laser pulses. Optimal spatial near-field localization in gold nanoprisms and excitation switching is realized by applying a shift to the relative phase of the two polarization components. The achieved near-field switching confirms theoretical predictions, proves the applicability of predefined control rules in nanooptical light-matter interaction and reveals local mode interference to be an important control mechanism.}, subject = {Chemie}, language = {en} } @article{AeschlimannBrixnerCinchettietal.2017, author = {Aeschlimann, Martin and Brixner, Tobias and Cinchetti, Mirko and Frisch, Benjamin and Hecht, Bert and Hensen, Matthias and Huber, Bernhard and Kramer, Christian and Krauss, Enno and Loeber, Thomas H. and Pfeiffer, Walter and Piecuch, Martin and Thielen, Philip}, title = {Cavity-assisted ultrafast long-range periodic energy transfer between plasmonic nanoantennas}, series = {Light: Science \& Applications}, volume = {6}, journal = {Light: Science \& Applications}, doi = {10.1038/lsa.2017.111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173265}, year = {2017}, abstract = {Radiationless energy transfer is at the core of diverse phenomena, such as light harvesting in photosynthesis\(^1\), energy-transfer-based microspectroscopies\(^2\), nanoscale quantum entanglement\(^3\) and photonic-mode hybridization\(^4\). Typically, the transfer is efficient only for separations that are much shorter than the diffraction limit. This hampers its application in optical communication and quantum information processing, which require spatially selective addressing. Here, we demonstrate highly efficient radiationless coherent energy transfer over a distance of twice the excitation wavelength by combining localized and delocalized\(^5\) plasmonic modes. Analogous to the Tavis-Cummings model, two whispering-gallery-mode antennas\(^6\) placed in the foci of an elliptical plasmonic cavity\(^7\) fabricated from single-crystal gold plates act as a pair of oscillators coupled to a common cavity mode. Time-resolved two-photon photoemission electron microscopy (TR 2P-PEEM) reveals an ultrafast long-range periodic energy transfer in accordance with the simulations. Our observations open perspectives for the optimization and tailoring of mesoscopic energy transfer and long-range quantum emitter coupling.}, language = {en} } @phdthesis{Afify2007, author = {Afify, Samar}, title = {Drug targeting delivery systems for treatment of Raf-1 induced lung tumors in mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22249}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {The aim of the present study was to design different dosage forms as carrier systems to deliver sorafenib to the lung of BXB-23 transgenic mice using different routes of administration. Three dosage forms were used one of them was an oil-in-water emulsion and the oral route was chosen for this experiment. The other delivery system was a liposome preparation for intratracheal instillation. In this case the oral route was considered as a control experiment. The last dosage form was PLGA microspheres. Before sorafenib administration it was important to develop a HPLC method to assess sorafenib absorption after its administration and to determine its concentrations in mouse serum. The HPLC method allowed sorafenib quantification in small volumes (30 µl) of mouse serum and tissues. The developed HPLC method was validated resulting in satisfactory selectivity, good linearity, good accuracy and precision over the concentration range examined. Sorafenib was successfully incorporated in a fat emulsion (o/w) using a traditional method resulting in a white homogenous emulsion and no particle aggregation was observed. Sorafenib exhibited antitumor activity on the lung adenoma in BXB-23 transgenic mice when administered orally (2 mg sorafenib per mouse) in the emulsion preparation. The determined effect was an approximately 29 \% reduction in the tumor area of the adenoma foci and a proliferation reduction. In order to improve the pharmacological effects of sorafenib on the lung adenoma in BXB-23 mice, the targeting of sorafenib directly to the site of action (the lung) was an attractive concept. For this purpose the intratracheal route was used. Since sorafenib administration by instillation required incorporation of sorafenib in a dosage form suitable for its lipophilic nature, a liposome suspension was the second dosage form used. A lyophilization method was employed for sorafenib liposome preparation utilizing dilauroylphosphatidylcholine (DLPC) which is safe and tolerable for the lung. Incorporation of sorafenib in the liposomes did not influence the particle size and its distribution. The sorafenib liposomes showed high encapsulation efficiency, good stability at 4 °C for one month and satisfactory in vitro release properties and inhibited Raf-1 mediated activation of ERK in cell culture assay. In a pharmacokinetic experiment sorafenib loaded liposomes were instilled directly into the lung. The results revealed that a significant level of sorafenib was achieved in the lung tissues after 2 hours and then reduced after 48 h and remained nearly constant for one week. On the other hand, only traces of sorafenib were found in the mice serum up to 48 h. Subsequently, the pharmacological activity of sorafenib (1 mg per mouse) was studied when delivered in a liposomal suspension intratracheally to treat the lung adenoma of BXB-23 mice. The data of this experiment demonstrated that sorafenib intratracheal instillation resulted in a reduction of tumor area of adenoma foci (67 \%) and an elevation of the percent of apoptotic cells. In contrast, prolongation of the treatment period did not further enhance sorafenib activity on the lung adenoma. This previous finding suggested a development of multidrug resistance (MDR) by the adenoma foci cells against sorafenib instillation, which was examined by immunohistochemistry staining. The percent of MDR positive cells was higher after two and three weeks sorafenib liposome instillation treatment than that after one week treatment. The last dosage form used for sorafenib was microspheres, which were prepared by emulsion-diffusion-evaporation method using biodegradable PLGA 50:50 resulting in a white lyophilized powder. The system was characterized physicochemically and revealed a good microspheres yield, high encapsulation efficiency, a homogenous particle size distribution and slow in vitro release of sorafenib. The other strategy studied in the present research project was gene delivery to target the lung bearing tumor of BXB-23 mice using a non-viral vector (polyethylenimine). Polyethylenimine (PEI) was used to investigate its efficiency in transfecting lung bearing tumor of BXB-23 mice model and its ability to transfect the adenoma foci cells. LacZ, which encodes Beta-galactosidase was used in the present study as a reporter gene and was complexed with PEI before delivered intravenously. A high LacZ expression in the alveolar region with some expression in the adenoma foci was observed. On contrary, a low LacZ expression in the alveoli and in the adenoma foci was achieved after instillation of the same polyplex intratracheally.}, subject = {Maus}, language = {en} } @article{AfonsoGrunzHoffmeierMuelleretal.2015, author = {Afonso-Grunz, Fabian and Hoffmeier, Klaus and M{\"u}ller, S{\"o}ren and Westermann, Alexander J. and Rotter, Bj{\"o}rn and Vogel, J{\"o}rg and Winter, Peter and Kahl, G{\"u}nter}, title = {Dual 3'Seq using deepSuperSAGE uncovers transcriptomes of interacting Salmonella enterica Typhimurium and human host cells}, series = {BMC Genomics}, volume = {16}, journal = {BMC Genomics}, number = {323}, doi = {10.1186/s12864-015-1489-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143230}, year = {2015}, abstract = {Background: The interaction of eukaryotic host and prokaryotic pathogen cells is linked to specific changes in the cellular proteome, and consequently to infection-related gene expression patterns of the involved cells. To simultaneously assess the transcriptomes of both organisms during their interaction we developed dual 3'Seq, a tag-based sequencing protocol that allows for exact quantification of differentially expressed transcripts in interacting pro-and eukaryotic cells without prior fixation or physical disruption of the interaction. Results: Human epithelial cells were infected with Salmonella enterica Typhimurium as a model system for invasion of the intestinal epithelium, and the transcriptional response of the infected host cells together with the differential expression of invading and intracellular pathogen cells was determined by dual 3'Seq coupled with the next-generation sequencing-based transcriptome profiling technique deepSuperSAGE (deep Serial Analysis of Gene Expression). Annotation to reference transcriptomes comprising the operon structure of the employed S. enterica Typhimurium strain allowed for in silico separation of the interacting cells including quantification of polycistronic RNAs. Eighty-nine percent of the known loci are found to be transcribed in prokaryotic cells prior or subsequent to infection of the host, while 75\% of all protein-coding loci are represented in the polyadenylated transcriptomes of human host cells. Conclusions: Dual 3'Seq was alternatively coupled to MACE (Massive Analysis of cDNA ends) to assess the advantages and drawbacks of a library preparation procedure that allows for sequencing of longer fragments. Additionally, the identified expression patterns of both organisms were validated by qRT-PCR using three independent biological replicates, which confirmed that RELB along with NFKB1 and NFKB2 are involved in the initial immune response of epithelial cells after infection with S. enterica Typhimurium.}, language = {en} } @article{AgarwalYangRiceetal.2014, author = {Agarwal, Shailesh R. and Yang, Pei-Chi and Rice, Monica and Singer, Cherie A. and Nikolaev, Viacheslav O. and Lohse, Martin J. and Clancy, Colleen E. and Harvey, Robert D.}, title = {Role of Membrane Microdomains in Compartmentation of cAMP Signaling}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {4}, issn = {1932-6203}, doi = {10.1371/journal.pone.0095835}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116673}, pages = {e95835}, year = {2014}, abstract = {Spatially restricting cAMP production to discrete subcellular locations permits selective regulation of specific functional responses. But exactly where and how cAMP signaling is confined is not fully understood. Different receptors and adenylyl cyclase isoforms responsible for cAMP production are not uniformly distributed between lipid raft and non-lipid raft domains of the plasma membrane. We sought to determine the role that these membrane domains play in organizing cAMP responses in HEK293 cells. The freely diffusible FRET-based biosensor Epac2-camps was used to measure global cAMP responses, while versions of the probe targeted to lipid raft (Epac2-MyrPalm) and non-raft (Epac2-CAAX) domains were used to monitor local cAMP production near the plasma membrane. Disruption of lipid rafts by cholesterol depletion selectively altered cAMP responses produced by raft-associated receptors. The results indicate that receptors associated with lipid raft as well as non-lipid raft domains can contribute to global cAMP responses. In addition, basal cAMP activity was found to be significantly higher in non-raft domains. This was supported by the fact that pharmacologic inhibition of adenylyl cyclase activity reduced basal cAMP activity detected by Epac2-CAAX but not Epac2-MyrPalm or Epac2-camps. Responses detected by Epac2-CAAX were also more sensitive to direct stimulation of adenylyl cyclase activity, but less sensitive to inhibition of phosphodiesterase activity. Quantitative modeling was used to demonstrate that differences in adenylyl cyclase and phosphodiesterase activities are necessary but not sufficient to explain compartmentation of cAMP associated with different microdomains of the plasma membrane.}, language = {en} }