@article{BauerGoebelerWeissbrichetal.2015, author = {Bauer, Boris and Goebeler, Matthias and Weissbrich, Benedikt and Kerstan, Andreas}, title = {Kerinokeratosis papulosa of childhood}, series = {Dermatology}, volume = {231}, journal = {Dermatology}, number = {1}, issn = {1018-8665}, doi = {10.1159/000381539}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198997}, pages = {1 -- 4}, year = {2015}, abstract = {Background: Kerinokeratosis papulosa (KP) is considered an extremely rare genodermatosis presenting usually as waxy papules on the trunk in childhood. Objective: To describe and analyze the clinical, histological and potential etiopathological aspects of KP. Methods: The dermatoscopic features of a new case of KP of childhood are investigated. The presence of human papillomavirus (HPV) DNA in lesional skin was studied by polymerase chain reaction. Furthermore, all cases of KP of childhood reported so far were reviewed. Results: As a diagnostic tool, we describe for the first time a dermatoscopic feature, namely a cribriform pattern of KP, in an 11-year-old boy. In addition, we detected HPV (type 57) in his KP lesions. Conclusions: Dermatoscopic examination might be a useful tool to distinguish KP from other skin lesions, e.g. common warts. The detection of HPV type 57 might hint to an etiological role of HPV for KP.}, language = {en} } @article{SchneiderElHajjMuelleretal.2015, author = {Schneider, Eberhard and El Hajj, Nady and M{\"u}ller, Fabian and Navarro, Bianca and Haaf, Thomas}, title = {Epigenetic Dysregulation in the Prefrontal Cortex of Suicide Completers}, series = {Cytogenetic and Genome Research}, volume = {146}, journal = {Cytogenetic and Genome Research}, number = {1}, issn = {1424-8581}, doi = {10.1159/000435778}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199032}, pages = {19-27}, year = {2015}, abstract = {The epigenome is thought to mediate between genes and the environment, particularly in response to adverse life experiences. Similar to other psychiatric diseases, the suicide liability of an individual appears to be influenced by many genetic factors of small effect size as well as by environmental stressors. To identify epigenetic marks associated with suicide, which is considered the endpoint of complex gene-environment interactions, we compared the cortex DNA methylation patterns of 6 suicide completers versus 6 non-psychiatric sudden-death controls, using Illumina 450K methylation arrays. Consistent with a multifactorial disease model, we found DNA methylation changes in a large number of genes, but no changes with large effects reaching genome-wide significance. Global methylation of all analyzed CpG sites was significantly (0.25 percentage point) lower in suicide than in control brains, whereas the vast majority (97\%) of the top 1,000 differentially methylated regions (DMRs) were higher methylated (0.6 percentage point) in suicide brains. Annotation analysis of the top 1,000 DMRs revealed an enrichment of differentially methylated promoters in functional categories associated with transcription and expression in the brain. In addition, we performed a comprehensive literature research to identify suicide genes that have been replicated in independent genetic association, brain methylation and/or expression studies. Although, in general, there was no significant overlap between different published data sets or between our top 1,000 DMRs and published data sets, our methylation screen strengthens a number of candidate genes (APLP2, BDNF, HTR1A, NUAK1, PHACTR3, MSMP, SLC6A4, SYN2, and SYNE2) and supports a role for epigenetics in the pathophysiology of suicide.}, language = {en} } @article{Teichmann2015, author = {Teichmann, Christoph}, title = {Corporate Groups within the Legal Framework of the European Union: The Group-Related Aspects of the SUP Proposal and the EU Freedom of Establishment}, series = {European Company and Financial Law Review}, volume = {12}, journal = {European Company and Financial Law Review}, number = {2}, issn = {1613-2556}, doi = {10.1515/ecfr-2015-0202}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194513}, pages = {202 -- 229}, year = {2015}, abstract = {No abstract available.}, language = {en} } @article{Brinktrine2015, author = {Brinktrine, Ralf}, title = {Konkurrentenstreitverfahren im Beamtenrecht}, series = {JURA - Juristische Ausbildung}, volume = {37}, journal = {JURA - Juristische Ausbildung}, number = {11}, issn = {1612-7021}, doi = {10.1515/jura-2015-0237}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194866}, pages = {1192-1205}, year = {2015}, abstract = {Kein Abstract verf{\"u}gbar.}, language = {de} } @article{KolominskyRabasWiedmannWeingaertneretal.2015, author = {Kolominsky-Rabas, Peter L. and Wiedmann, Silke and Weing{\"a}rtner, Michael and Liman, Thomas G. and Endres, Matthias and Schwab, Stefan and Buchfelder, Michael and Heuschmann, Peter U.}, title = {Time Trends in Incidence of Pathological and Etiological Stroke Subtypes during 16 Years: The Erlangen Stroke Project}, series = {Neuroepidemiology}, volume = {44}, journal = {Neuroepidemiology}, number = {1}, issn = {0251-5350}, doi = {10.1159/000371353}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196503}, pages = {24-29}, year = {2015}, abstract = {Background: Population-based data, which continuously monitors time trends in stroke epidemiology are limited. We investigated the incidence of pathological and etiological stroke subtypes over a 16 year time period. Methods: Data were collected within the Erlangen Stroke Project (ESPro), a prospective, population-based stroke register in Germany covering a total study population of 105,164 inhabitants (2010). Etiology of ischemic stroke was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results: Between January 1995 and December 2010, 3,243 patients with first-ever stroke were documented. The median age was 75 and 55\% were females. The total stroke incidence decreased over the 16 year study period in men (Incidence Rate Ratio 1995-1996 vs. 2009-2010 (IRR) 0.78; 95\% CI 0.58-0.90) but not in women. Among stroke subtypes, a decrease in ischemic stroke incidence (IRR 0.73; 95\% CI 0.57-0.93) and of large artery atherosclerotic stroke (IRR 0.27; 95\% CI 0.12-0.59) was found in men and an increase of stroke due to small artery occlusion in women (IRR 2.33; 95\% CI 1.39-3.90). Conclusions: Variations in time trends of pathological and etiological stroke subtypes were found between men and women that might be linked to gender differences in the development of major vascular risk factors in the study population.}, language = {en} } @article{PootHaaf2015, author = {Poot, Martin and Haaf, Thomas}, title = {Mechanisms of Origin, Phenotypic Effects and Diagnostic Implications of Complex Chromosome Rearrangements}, series = {Molecular Syndromology}, volume = {6}, journal = {Molecular Syndromology}, number = {3}, issn = {1661-8769}, doi = {10.1159/000438812}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196524}, pages = {110-134}, year = {2015}, abstract = {Complex chromosome rearrangements (CCRs) are currently defined as structural genome variations that involve more than 2 chromosome breaks and result in exchanges of chromosomal segments. They are thought to be extremely rare, but their detection rate is rising because of improvements in molecular cytogenetic technology. Their population frequency is also underestimated, since many CCRs may not elicit a phenotypic effect. CCRs may be the result of fork stalling and template switching, microhomology-mediated break-induced repair, breakage-fusion-bridge cycles, or chromothripsis. Patients with chromosomal instability syndromes show elevated rates of CCRs due to impaired DNA double-strand break responses during meiosis. Therefore, the putative functions of the proteins encoded by ATM, BLM, WRN, ATR, MRE11, NBS1, and RAD51 in preventing CCRs are discussed. CCRs may exert a pathogenic effect by either (1) gene dosage-dependent mechanisms, e.g. haploinsufficiency, (2) mechanisms based on disruption of the genomic architecture, such that genes, parts of genes or regulatory elements are truncated, fused or relocated and thus their interactions disturbed - these mechanisms will predominantly affect gene expression - or (3) mixed mutation mechanisms in which a CCR on one chromosome is combined with a different type of mutation on the other chromosome. Such inferred mechanisms of pathogenicity need corroboration by mRNA sequencing. Also, future studies with in vitro models, such as inducible pluripotent stem cells from patients with CCRs, and transgenic model organisms should substantiate current inferences regarding putative pathogenic effects of CCRs. The ramifications of the growing body of information on CCRs for clinical and experimental genetics and future treatment modalities are briefly illustrated with 2 cases, one of which suggests KDM4C(JMJD2C) as a novel candidate gene for mental retardation.}, language = {en} } @article{SchmidSteinlein2015, author = {Schmid, Michael and Steinlein, Claus}, title = {Chromosome Banding in Amphibia. XXXII. The Genus Xenopus (Anura, Pipidae)}, series = {Cytogenetic and Genome Research}, volume = {145}, journal = {Cytogenetic and Genome Research}, number = {3-4}, issn = {1424-8581}, doi = {10.1159/000433481}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196727}, pages = {201-217}, year = {2015}, abstract = {Mitotic chromosomes of 16 species of the frog genus Xenopus were prepared from kidney and lung cell cultures. In the chromosomes of 7 species, high-resolution replication banding patterns could be induced by treating the cultures with 5-bromodeoxyuridine (BrdU) and deoxythymidine (dT) in succession, and in 6 of these species the BrdU/dT-banded chromosomes could be arranged into karyotypes. In the 3 species of the clade with 2n = 20 and 4n = 40 chromosomes (X. tropicalis, X. epitropicalis, X. new tetraploid 1), as well as in the 3 species with 4n = 36 chromosomes (X. laevis, X. borealis, X. muelleri), the BrdU/dT-banded karyotypes show a high degree of homoeology, though differences were detected between these groups. Translocations, inversions, insertions or sex-specific replication bands were not observed. Minor replication asynchronies found between chromosomes probably involve heterochromatic regions. BrdU/dT replication banding of Xenopus chromosomes provides the landmarks necessary for the exact physical mapping of genes and repetitive sequences. FISH with an X. laevis 5S rDNA probe detected multiple hybridization sites at or near the long-arm telomeric regions in most chromosomes of X. laevis and X. borealis, whereas in X. muelleri, the 5S rDNA sequences are located exclusively at the long-arm telomeres of a single chromosome pair. Staining with the AT base pair-specific fluorochrome quinacrine mustard revealed brightly fluorescing heterochromatic regions in the majority of X. borealis chromosomes which are absent in other Xenopus species.}, language = {en} } @article{SchmidEvansBogart2015, author = {Schmid, Michael and Evans, Ben J. and Bogart, James P.}, title = {Polyploidy in Amphibia}, series = {Cytogenetic and Genome Research}, volume = {145}, journal = {Cytogenetic and Genome Research}, number = {3-4}, issn = {1424-8581}, doi = {10.1159/000431388}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196730}, pages = {315-330}, year = {2015}, abstract = {This review summarizes the current status of the known extant genuine polyploid anuran and urodelan species, as well as spontaneously originated and/or experimentally produced amphibian polyploids. The mechanisms by which polyploids can originate, the meiotic pairing configurations, the diploidization processes operating in polyploid genomes, the phenomenon of hybridogenesis, and the relationship between polyploidization and sex chromosome evolution are discussed. The polyploid systems in some important amphibian taxa are described in more detail.}, language = {en} } @article{MatsudaUnoKondoetal.2015, author = {Matsuda, Yoichi and Uno, Yoshinobu and Kondo, Mariko and Gilchrist, Michael J. and Zorn, Aaron M. and Rokhsar, Daniel S. and Schmid, Michael and Taira, Masanori}, title = {A New Nomenclature of Xenopus laevis Chromosomes Based on the Phylogenetic Relationship to Silurana/Xenopus tropicalis}, series = {Cytogenetic and Genome Research}, volume = {145}, journal = {Cytogenetic and Genome Research}, number = {3-4}, issn = {1424-8581}, doi = {10.1159/000381292}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196748}, pages = {187-191}, year = {2015}, abstract = {Xenopus laevis (XLA) is an allotetraploid species which appears to have undergone whole-genome duplication after the interspecific hybridization of 2 diploid species closely related to Silurana/Xenopus tropicalis (XTR). Previous cDNA fluorescence in situ hybridization (FISH) experiments have identified 9 sets of homoeologous chromosomes in X. laevis, in which 8 sets correspond to chromosomes 1-8 of X. tropicalis (XTR1-XTR8), and the last set corresponds to a fusion of XTR9 and XTR10. In addition, recent X. laevis genome sequencing and BAC-FISH experiments support this physiological relationship and show no gross chromosome translocation in the X. laevis karyotype. Therefore, for the benefit of both comparative cytogenetics and genome research, we here propose a new chromosome nomenclature for X. laevis based on the phylogenetic relationship and chromosome length, i.e. XLA1L, XLA1S, XLA2L, XLA2S, and so on, in which the numbering of XLA chromosomes corresponds to that in X. tropicalis and the postfixes 'L' and 'S' stand for 'long' and 'short' chromosomes in the homoeologous pairs, which can be distinguished cytologically by their relative size. The last chromosome set is named XLA9L and XLA9S, in which XLA9 corresponds to both XTR9 and XTR10, and hence, to emphasize the phylogenetic relationship to X. tropicalis, XLA9_10L and XLA9_10S are also used as synonyms.}, language = {en} } @misc{Altenburger2015, author = {Altenburger, Roland}, title = {Cao, Juan: In der Sackgasse oder auf dem Weg zu einem neuen Paradigma? Die Erforschung des Romans Der Traum der roten Kammer (Rotologie) im 21. Jahrhundert (Lun Wen: Studien zur Geistesgeschichte und Literatur in China; 17). Wiesbaden: Harrassowitz Verlag, 2013. XII, 256 S. ISBN 978-3-447-06992-2}, series = {Asiatische Studien - {\´E}tudes Asiatiques}, volume = {69}, journal = {Asiatische Studien - {\´E}tudes Asiatiques}, number = {1}, issn = {0004-4717}, doi = {10.1515/asia-2015-0013}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193941}, pages = {255-261}, year = {2015}, abstract = {No abstract available.}, language = {de} } @article{Osmers2015, author = {Osmers, Maria}, title = {Zwischen Vergemeinschaftung und Anarchie. Zur Konzeption und Wahrnehmung polis{\"u}bergreifender Beziehungen in klassischer Zeit}, series = {Klio}, volume = {97}, journal = {Klio}, number = {1}, issn = {2192-7669}, doi = {10.1515/klio-2015-0002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193997}, pages = {32-58}, year = {2015}, abstract = {Der Artikel fragt zun{\"a}chst nach Konzepten, die in klassischer Zeit von Außenpolitik existierten. {\"U}berlegungen zu diesem Thema sind in den antiken philosophischen Schriften greifbar, wobei Vorstellungen von der Funktionsweise des Oikos und der Polis auf den griechischen Raum {\"u}bertragen wurden. {\"A}hnliche Kategorien, um polis{\"u}bergreifende Beziehungen zu beschreiben, griff die politische Rhetorik auf. Bezogen sich antike Autoren jedoch in allgemeinen Abhandlungen auf die Außenpolitik, wurde der Krieg als bestimmendes Element identifiziert. Das theoretische Konzept von Außenpolitik konnte demnach f{\"u}r die Zeitgenossen in der Praxis wenig Wirkung entfalten. Ursachen hierf{\"u}r waren sowohl die unsteten Verh{\"a}ltnisse des 4. Jahrhunderts als auch die konkrete Konzeption der Außenpolitik, da die Interaktion im griechischen Raum anders funktionierte als in kleineren sozialen Einheiten. Zudem wurden real existierende Mechanismen zur Befriedung von Hellas nur unzureichend in die Konzeption integriert.}, language = {de} } @misc{Tornau2015, author = {Tornau, Christian}, title = {Tobias Uhle, Augustin und die Dialektik. Eine Untersuchung der Argumentationsstruktur in den Cassiciacum-Dialogen, Studien und Texte zu Antike und Christentum 67, T{\"u}bingen (Mohr Siebeck) 2012, XIV + 293 S., ISBN 978-3-16-151985-7}, series = {Zeitschrift f{\"u}r Antikes Christentum / Journal of Ancient Christianity}, volume = {18}, journal = {Zeitschrift f{\"u}r Antikes Christentum / Journal of Ancient Christianity}, number = {3}, issn = {1612-961X}, doi = {10.1515/zac-2014-0024}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195571}, pages = {509 -- 559}, year = {2015}, abstract = {Rezension zu Tobias Uhle, Augustin und die Dialektik. Eine Untersuchung der Argumentationsstruktur in den Cassiciacum-Dialogen, Studien und Texte zu Antike und Christentum 67, T{\"u}bingen (Mohr Siebeck) 2012, XIV + 293 S., ISBN 978-3-16-151985-7}, language = {de} } @article{Dannecker2015, author = {Dannecker, Christoph}, title = {Der nemo tenetur-Grundsatz - prozessuale Fundierung und Geltung f{\"u}r juristische Personen}, series = {Zeitschrift f{\"u}r die gesamte Strafrechtswissenschaft}, volume = {127}, journal = {Zeitschrift f{\"u}r die gesamte Strafrechtswissenschaft}, number = {2}, issn = {1612-703X}, doi = {10.1515/zstw-2015-0014}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195368}, pages = {370-409}, year = {2015}, abstract = {Kein Abstract verf{\"u}gbar.}, language = {de} } @phdthesis{Ames2015, author = {Ames, Christopher}, title = {Molecular Beam Epitaxy of 2D and 3D HgTe, a Topological Insulator}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151136}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {In the present thesis the MBE growth and sample characterization of HgTe structures is investigated and discussed. Due to the first experimental discovery of the quantum Spin Hall effect (QSHE) in HgTe quantum wells, this material system attains a huge interest in the spintronics society. Because of the long history of growing Hg-based heterostructures here at the Experimentelle Physik III in W{\"u}rzburg, there are very good requirements to analyze this material system more precisely and in new directions. Since in former days only doped HgTe quantum wells were grown, this thesis deals with the MBE growth in the (001) direction of undoped HgTe quantum wells, surface located quantum wells and three dimensional bulk layers. All Hg-based layers were grown on CdTe substrates which generate strain in the layer stack and provide therefore new physical effects. In the same time, the (001) CdTe growth was investigated on n-doped (001) GaAs:Si because the Japanese supplier of CdTe substrates had a supply bottleneck due to the Tohoku earthquake and its aftermath in 2011. After a short introduction of the material system, the experimental techniques were demonstrated and explained explicitly. After that, the experimental part of this thesis is displayed. So, the investigation of the (001) CdTe growth on (001) GaAs:Si is discussed in chapter 4. Firstly, the surface preparation of GaAs:Si by oxide desorption is explored and analyzed. Here, rapid thermal desorption of the GaAs oxide with following cool down in Zn atmosphere provides the best results for the CdTe due to small holes at the surface, while e.g. an atomic flat GaAs buffer deteriorates the CdTe growth quality. The following ZnTe layer supplies the (001) growth direction of the CdTe and exhibits best end results of the CdTe for 30 seconds growth time at a flux ratio of Zn/Te ~ 1/1.2. Without this ZnTe layer, CdTe will grow in the (111) direction. However, the main investigation is here the optimization of the MBE growth of CdTe. The substrate temperature, Cd/Te flux ratio and the growth time has to be adjusted systematically. Therefore, a complex growth process is developed and established. This optimized CdTe growth process results in a RMS roughness of around 2.5 nm and a FWHM value of the HRXRD w-scan of 150 arcsec. Compared to the literature, there is no lower FWHM value traceable for this growth direction. Furthermore, etch pit density measurements show that the surface crystallinity is matchable with the commercial CdTe substrates (around 1x10^4 cm^(-2)). However, this whole process is not completely perfect and offers still room for improvements. The growth of undoped HgTe quantum wells was also a new direction in research in contrast to the previous n-doped grown HgTe quantum wells. Here in chapter 5, the goal of very low carrier densities was achieved and therefore it is now possible to do transport experiments in the n - and p - region by tuning the gate voltage. To achieve this high sample quality, very precise growth of symmetric HgTe QWs and their HRXRD characterization is examined. Here, the quantum well thickness can now determined accurate to under 0.3 nm. Furthermore, the transport analysis of different quantum well thicknesses shows that the carrier density and mobility increase with rising HgTe layer thickness. However, it is found out that the band gap of the HgTe QW closes indirectly at a thickness of 11.6 nm. This is caused by the tensile strained growth on CdTe substrates. Moreover, surface quantum wells are studied. These quantum wells exhibit no or a very thin HgCdTe cap. Though, oxidization and contamination of the surface reduces here the carrier mobility immensely and a HgCdTe layer of around 5 nm provides the pleasing results for transport experiments with superconductors connected to the topological insulator [119]. A completely new achievement is the realization of MBE growth of HgTe quantum wells on CdTe/GaAs:Si substrates. This is attended by the optimization of the CdTe growth on GaAs:Si. It exposes that HgTe quantum wells grown in-situ on optimized CdTe/GaAs:Si show very nice transport data with clear Hall plateaus, SdH oscillations, low carrier densities and carrier mobilities up to 500 000 cm^2/Vs. Furthermore, a new oxide etching process is developed and analyzed which should serve as an alternative to the standard HCl process which generates volcano defects at some time. However, during the testing time the result does not differ in Nomarski, HRXRD, AFM and transport measurements. Here, long-time tests or etching and mounting in nitrogen atmosphere may provide new elaborate results. The main focus of this thesis is on the MBE growth and standard characterization of HgTe bulk layers and is discussed in chapter 6. Due to the tensile strained growth on lattice mismatched CdTe, HgTe bulk opens up a band gap of around 22 meV at the G-point and exhibits therefore its topological surface states. The analysis of surface condition, roughness, crystalline quality, carrier density and mobility via Nomarski, AFM, XPS, HRXRD and transport measurements is therefore included in this work. Layer thickness dependence of carrier density and mobility is identified for bulk layer grown directly on CdTe substrates. So, there is no clear correlation visible between HgTe layer thickness and carrier density or mobility. So, the carrier density is almost constant around 1x10^11 cm^(-2) at 0 V gate voltage. The carrier mobility of these bulk samples however scatters between 5 000 and 60 000 cm^2/Vs almost randomly. Further experiments should be made for a clearer understanding and therefore the avoidance of unusable bad samples.But, other topological insulator materials show much higher carrier densities and lower mobility values. For example, Bi2Se3 exhibits just density values around 1019 cm^(-2) and mobility values clearly below 5000 cm2/Vs. The carrier density however depends much on lithography and surface treatment after growth. Furthermore, the relaxation behavior and critical thickness of HgTe grown on CdTe is determined and is in very good agreement with theoretical prediction (d_c = 155 nm). The embedding of the HgTe bulk layer between HgCdTe layers created a further huge improvement. Similar to the quantum well structures the carrier mobility increases immensely while the carrier density levels at around 1x10^11 cm^(-2) at 0 V gate voltage as well. Additionally, the relaxation behavior and critical thickness of these barrier layers has to be determined. HgCdTe grown on commercial CdTe shows a behavior as predicted except the critical thickness which is slightly higher than expected (d_c = 850 nm). Otherwise, the relaxation of HgCdTe grown on CdTe/GaAs:Si occurs in two parts. The layer is fully strained up to 250 nm. Between 250 nm and 725 nm the HgCdTe film starts to relax randomly up to 10 \%. The relaxation behavior for thicknesses larger than 725 nm occurs than linearly to the inverse layer thickness. A explanation is given due to rough interface conditions and crystalline defects of the CdTe/GaAs:Si compared to the commercial CdTe substrate. HRXRD and AFM data support this statement. Another point is that the HgCdTe barriers protect the active HgTe layer and because of the high carrier mobilities the Hall measurements provide new transport data which have to be interpreted more in detail in the future. In addition, HgTe bulk samples show very interesting transport data by gating the sample from the top and the back. It is now possible to manipulate the carrier densities of the top and bottom surface states almost separately. The back gate consisting of the n-doped GaAs substrate and the thick insulating CdTe buffer can tune the carrier density for Delta(n) ~ 3x10^11 cm^(-2). This is sufficient to tune the Fermi energy from the p-type into the n-type region [138]. In this thesis it is shown that strained HgTe bulk layers exhibit superior transport data by embedding between HgCdTe barrier layers. The n-doped GaAs can here serve as a back gate. Furthermore, MBE growth of high crystalline, undoped HgTe quantum wells shows also new and extended transport output. Finally, it is notable that due to the investigated CdTe growth on GaAs the Hg-based heterostructure MBE growth is partially independent from commercial suppliers.}, subject = {Quecksilbertellurid}, language = {en} } @article{SonnenbergBannert2015, author = {Sonnenberg, Christoph and Bannert, Maria}, title = {Discovering the Effects of Metacognitive Prompts on the Sequential Structure of SRL-Processes Using Process Mining Techniques}, series = {Journal of Learning Analystics}, volume = {2}, journal = {Journal of Learning Analystics}, number = {1}, issn = {1929-7750}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152362}, pages = {72-100}, year = {2015}, abstract = {According to research examining self-regulated learning (SRL), we regard individual regulation as a specific sequence of regulatory activities. Ideally, students perform various learning activities, such as analyzing, monitoring, and evaluating cognitive and motivational aspects during learning. Metacognitive prompts can foster SRL by inducing regulatory activities, which, in turn, improve the learning outcome. However, the specific effects of metacognitive support on the dynamic characteristics of SRL are not understood. Therefore, the aim of our study was to analyze the effects of metacognitive prompts on learning processes and outcomes during a computer-based learning task. Participants of the experimental group (EG, n=35) were supported by metacognitive prompts, whereas participants of the control group (CG, n=35) received no support. Data regarding learning processes were obtained by concurrent think-aloud protocols. The EG exhibited significantly more metacognitive learning events than did the CG. Furthermore, these regulatory activities correspond positively with learning outcomes. Process mining techniques were used to analyze sequential patterns. Our findings indicate differences in the process models of the EG and CG and demonstrate the added value of taking the order of learning activities into account by discovering regulatory patterns.}, language = {en} } @article{SchilbachAlkhaledWelkeretal.2015, author = {Schilbach, Karin and Alkhaled, Mohammed and Welker, Christian and Eckert, Franziska and Blank, Gregor and Ziegler, Hendrik and Sterk, Marco and M{\"u}ller, Friederike and Sonntag, Katja and Wieder, Thomas and Braum{\"u}ller, Heidi and Schmitt, Julia and Eyrich, Matthias and Schleicher, Sabine and Seitz, Christian and Erbacher, Annika and Pichler, Bernd J. and M{\"u}ller, Hartmut and Tighe, Robert and Lim, Annick and Gillies, Stephen D. and Strittmatter, Wolfgang and R{\"o}cken, Martin and Handgretinger, Rupert}, title = {Cancer-targeted IL-12 controls human rhabdomyosarcoma by senescence induction and myogenic differentiation}, series = {OncoImmunology}, volume = {4}, journal = {OncoImmunology}, number = {7}, doi = {10.1080/2162402X.2015.1014760}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154579}, pages = {e1014760}, year = {2015}, abstract = {Stimulating the immune system to attack cancer is a promising approach, even for the control of advanced cancers. Several cytokines that promote interferon-γ-dominated immune responses show antitumor activity, with interleukin 12 (IL-12) being of major importance. Here, we used an antibody-IL-12 fusion protein (NHS-IL12) that binds histones of necrotic cells to treat human sarcoma in humanized mice. Following sarcoma engraftment, NHS-IL12 therapy was combined with either engineered IL-7 (FcIL-7) or IL-2 (IL-2MAB602) for continuous cytokine bioavailability. NHS-IL12 strongly induced innate and adaptive antitumor immunity when combined with IL-7 or IL-2. NHS-IL12 therapy significantly improved survival of sarcoma-bearing mice and caused long-term remissions when combined with IL-2. NHS-IL12 induced pronounced cancer cell senescence, as documented by strong expression of senescence-associated p16\(^{INK4a}\) and nuclear translocation of p-HP1γ, and permanent arrest of cancer cell proliferation. In addition, this cancer immunotherapy initiated the induction of myogenic differentiation, further promoting the hypothesis that efficient antitumor immunity includes mechanisms different from cytotoxicity for efficient cancer control in vivo.}, language = {en} } @article{GutknechtPoppWaideretal.2015, author = {Gutknecht, Lise and Popp, Sandy and Waider, Jonas and Sommerlandt, Frank M. J. and G{\"o}ppner, Corinna and Post, Antonia and Reif, Andreas and van den Hove, Daniel and Strekalova, Tatyana and Schmitt, Angelika and Colaςo, Maria B. N. and Sommer, Claudia and Palme, Rupert and Lesch, Klaus-Peter}, title = {Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice}, series = {Psychopharmacology}, volume = {232}, journal = {Psychopharmacology}, doi = {10.1007/s00213-015-3879-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154586}, pages = {2429 -- 2441}, year = {2015}, abstract = {Rationale While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation. Objective Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene. Results Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2\(^{-/-}\)) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2\(^{-/-}\) males displayed increased impulsivity and high aggressiveness. Tph2\(^{-/-}\) females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2\(^{-/-}\) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner. Conclusions Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.}, language = {en} } @article{Schamel2015, author = {Schamel, Johannes}, title = {Ableitung von Pr{\"a}ferenzen aus GPS-Trajektorien bei landschaftsbezogenen Erholungsaktivit{\"a}ten}, series = {AGIT - Journal f{\"u}r Angewandte Geoinformatik}, volume = {2015}, journal = {AGIT - Journal f{\"u}r Angewandte Geoinformatik}, number = {1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153590}, pages = {9}, year = {2015}, abstract = {No abstract available.}, language = {de} } @article{ZahoGhirlandoAlfonsoetal.2015, author = {Zaho, Huaying and Ghirlando, Rodolfo and Alfonso, Carlos and Arisaka, Fumio and Attali, Ilan and Bain, David L. and Bakhtina, Marina M. and Becker, Donald F. and Bedwell, Gregory J. and Bekdemir, Ahmet and Besong, Tabot M. D. and Birck, Catherine and Brautigam, Chad A. and Brennerman, William and Byron, Olwyn and Bzowska, Agnieszka and Chaires, Jonathan B. and Chaton, Catherine T. and Coelfen, Helmbut and Connaghan, Keith D. and Crowley, Kimberly A. and Curth, Ute and Daviter, Tina and Dean, William L. and Diez, Ana I. and Ebel, Christine and Eckert, Debra M. and Eisele, Leslie E. and Eisenstein, Edward and England, Patrick and Escalante, Carlos and Fagan, Jeffrey A. and Fairman, Robert and Finn, Ron M. and Fischle, Wolfgang and Garcia de la Torre, Jose and Gor, Jayesh and Gustafsson, Henning and Hall, Damien and Harding, Stephen E. and Hernandez Cifre, Jose G. and Herr, Andrew B. and Howell, Elizabeth E. and Isaac, Richard S. and Jao, Shu-Chuan and Jose, Davis and Kim, Soon-Jong and Kokona, Bashkim and Kornblatt, Jack A. and Kosek, Dalibor and Krayukhina, Elena and Krzizike, Daniel and Kusznir, Eric A. and Kwon, Hyewon and Larson, Adam and Laue, Thomas M. and Le Roy, Aline and Leech, Andrew P. and Lilie, Hauke and Luger, Karolin and Luque-Ortega, Juan R. and Ma, Jia and May, Carrie A. and Maynard, Ernest L. and Modrak-Wojcik, Anna and Mok, Yee-Foong and M{\"u}cke, Norbert and Nagel-Steger, Luitgard and Narlikar, Geeta J. and Noda, Masanori and Nourse, Amanda and Obsil, Thomas and Park, Chad K and Park, Jin-Ku and Pawelek, Peter D. and Perdue, Erby E. and Perkins, Stephen J. and Perugini, Matthew A. and Peterson, Craig L. and Peverelli, Martin G. and Piszczek, Grzegorz and Prag, Gali and Prevelige, Peter E. and Raynal, Bertrand D. E. and Rezabkova, Lenka and Richter, Klaus and Ringel, Alison E. and Rosenberg, Rose and Rowe, Arthur J. and Rufer, Arne C. and Scott, David J. and Seravalli, Javier G. and Solovyova, Alexandra S. and Song, Renjie and Staunton, David and Stoddard, Caitlin and Stott, Katherine and Strauss, Holder M. and Streicher, Werner W. and Sumida, John P. and Swygert, Sarah G. and Szczepanowski, Roman H. and Tessmer, Ingrid and Toth, Ronald T. and Tripathy, Ashutosh and Uchiyama, Susumu and Uebel, Stephan F. W. and Unzai, Satoru and Gruber, Anna Vitlin and von Hippel, Peter H. and Wandrey, Christine and Wang, Szu-Huan and Weitzel, Steven E and Wielgus-Kutrowska, Beata and Wolberger, Cynthia and Wolff, Martin and Wright, Edward and Wu, Yu-Sung and Wubben, Jacinta M. and Schuck, Peter}, title = {A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0126420}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151903}, pages = {e0126420}, year = {2015}, abstract = {Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304\(\pm\)0.188) S (4.4\%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of \(\pm\)0.030 S (0.7\%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.}, language = {en} } @phdthesis{BreuergebHemberger2015, author = {Breuer [geb. Hemberger], Kathrin R. F.}, title = {Effiziente 3D Magnetresonanzbildgebung schnell abfallender Signale}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150750}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {In der vorliegenden Arbeit wird die Rotated-Cone-UTE-Sequenz (RC-UTE), eine 3D k-Raum-Auslesetechnik mit homogener Verteilung der Abtastdichte, vorgestellt. Diese 3D MR-Messtechnik erm{\"o}glicht die f{\"u}r die Detektion von schnell abfallenden Signalen notwendigen kurzen Echozeiten und weist eine h{\"o}here SNR-Effizienz als konventionelle radiale Pulssequenzen auf. Die Abtastdichte ist dabei in radialer und azimutaler Richtung angepasst. Simulationen und Messungen in vivo zeigen, dass die radiale Anpassung das T2-Blurring reduziert und die SNR-Effizienz erh{\"o}ht. Die Drehung der Trajektorie in azimutale Richtung erm{\"o}glicht die Reduzierung der Unterabtastung bei gleicher Messzeit bzw. eine Reduzierung der Messzeit ohne Aufl{\"o}sungsverlust. Die RC-UTE-Sequenz wurde erfolgreich f{\"u}r die Bildgebung des Signals des kortikalen Knochens und der Lunge in vivo angewendet. Im Vergleich mit der grundlegenden UTE-Sequenz wurden die Vorteile von RC-UTE in allen Anwendungsbeispielen aufgezeigt. Die transversalen Relaxationszeit T2* des kortikalen Knochen bei einer Feldst{\"a}rke von 3.0T und der Lunge bei 1.5T und 3.0T wurde in 3D isotroper Aufl{\"o}sung gemessen. Außerdem wurde die Kombination von RC-UTE-Sequenz mit Methoden der Magnetisierungspr{\"a}paration zur besseren Kontrasterzeugung gezeigt. Dabei wurden die Doppel-Echo-Methode, die Unterdr{\"u}ckung von Komponenten mit langer Relaxationszeit T2 durch Inversionspulse und der Magnetisierungstransfer-Kontrast angewendet. Die Verwendung der RC-UTE-Sequenz f{\"u}r die 3D funktionelle Lungenbildgebung wird ebenfalls vorgestellt. Mit dem Ziel der umfassenden Charakterisierung der Lungenfunktion in 3D wurde die simultane Messung T1-gewichteter Bilder und quantitativer T2*-Karten f{\"u}r verschiedene Atemzust{\"a}nde an sechs Probanden durchgef{\"u}hrt. Mit der hier vorgestellten Methode kann die Lungenfunktion in 3D {\"u}ber T1-Wichtung, quantitative T2*-Messung und Rekonstruktion verschiedener Atemzust{\"a}nde durch Darstellung von Ventilation, Sauerstofftransport und Volumen{\"a}nderung beurteilt werden.}, subject = {Kernspintomografie}, language = {de} } @article{EspinaPaganLopezetal.2015, author = {Espina, Laura and Pag{\´a}n, Rafael and L{\´o}pez, Daniel and Garc{\´i}a-Gonzalo, Diego}, title = {Individual Constituents from Essential Oils Inhibit Biofilm Mass Production by Multi-Drug Resistant Staphylococcus aureus}, series = {Molecules}, volume = {20}, journal = {Molecules}, doi = {10.3390/molecules200611357}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151845}, pages = {11357 -- 11372}, year = {2015}, abstract = {Biofilm formation by Staphylococcus aureus represents a problem in both the medical field and the food industry, because the biofilm structure provides protection to embedded cells and it strongly attaches to surfaces. This circumstance is leading to many research programs seeking new alternatives to control biofilm formation by this pathogen. In this study we show that a potent inhibition of biofilm mass production can be achieved in community-associated methicillin-resistant S. aureus (CA-MRSA) and methicillin-sensitive strains using plant compounds, such as individual constituents (ICs) of essential oils (carvacrol, citral, and (+)-limonene). The Crystal Violet staining technique was used to evaluate biofilm mass formation during 40 h of incubation. Carvacrol is the most effective IC, abrogating biofilm formation in all strains tested, while CA-MRSA was the most sensitive phenotype to any of the ICs tested. Inhibition of planktonic cells by ICs during initial growth stages could partially explain the inhibition of biofilm formation. Overall, our results show the potential of EOs to prevent biofilm formation, especially in strains that exhibit resistance to other antimicrobials. As these compounds are food additives generally recognized as safe, their anti-biofilm properties may lead to important new applications, such as sanitizers, in the food industry or in clinical settings.}, language = {en} } @article{SperlichHolmbergReedetal.2015, author = {Sperlich, Paula F. and Holmberg, Hans-Christer and Reed, Jennifer L. and Zinner, Christoph and Mester, Joachim and Sperlich, Billy}, title = {Individual versus standardized running protocols in the determination of VO\(_{2max}\)}, series = {Journal of Sports Science and Medicine}, volume = {14}, journal = {Journal of Sports Science and Medicine}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151890}, pages = {386-393}, year = {2015}, abstract = {The purpose of this study was to determine whether an individually designed incremental exercise protocol results in greater rates of oxygen uptake VO\(_{2max}\) than standardized testing. Fourteen well-trained, male runners performed five incremental protocols in randomized order to measure their VO\(_{2max}\): i) an incremental test (INC\(_{S+I}\)) with pre-defined increases in speed (2 min at 8.64 km.h\(^{-1}\), then a rise of 1.44 km.h\(^{-1}\) every 30 s up to 14.4 km.h\(^{-1}\)) and thereafter inclination (0.5.every 30 s); ii) an incremental test (INC\(_{I}\)) at constant speed (14.4 km.h\(^{-1}\)) and increasing inclination (2 degrees every 2 min from the initial 0 degrees); iii) an incremental test (INC\(_{S}\)) at constant inclination (0 degrees) and increasing speed (0.5 km.h\(^{-1}\) every 30 s from the initial 12.0 km.h\(^{-1}\)); iv) a graded exercise protocol (GXP) at a 1 degrees incline with increasing speed (initially 8.64 km.h\(^{-1}\) + 1.44 km.h\(^{-1}\) every 5 min); v) an individual exercise protocol (INDXP) in which the runner chose the inclination and speed. VO\(_{2max}\) was lowest (-4.2\%) during the GXP (p = 0.01; d = 0.06 - 0.61) compared to all other tests. The highest rating of perceived exertion, heart rate, ventilation and end-exercise blood lactate concentration were similar between the different protocols (p < 0.05). The time to exhaustion ranged from 7 min 18 sec (INC\(_{S}\)) to 25 min 30 sec (GXP) (p = 0.01). The VO\(_{2max}\) attained by employing an individual treadmill protocol does not differ from the values derived from various standardized incremental protocols.}, language = {en} } @unpublished{LambertVoelkerKochetal.2015, author = {Lambert, Christoph and V{\"o}lker, Sebastian F. and Koch, Federico and Schmiedel, Alexander and Holzapfel, Marco and Humeniuk, Alexander and R{\"o}hr, Merle I. S. and Mitric, Roland and Brixner, Tobias}, title = {Energy Transfer Between Squaraine Polymer Sections: From helix to zig-zag and All the Way Back}, series = {Journal of the American Chemical Society}, journal = {Journal of the American Chemical Society}, doi = {10.1021/jacs.5b03644}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159607}, year = {2015}, abstract = {Joint experimental and theoretical study of the absorption spectra of squaraine polymers in solution provide evidence that two different conformations are present in solution: a helix and a zig-zag structure. This unique situation allows investigating ultrafast energy transfer processes between different structural segments within a single polymer chain in solution. The understanding of the underlying dynamics is of fundamental importance for the development of novel materials for light-harvesting and optoelectronic applications. We combine here femtosecond transient absorption spectroscopy with time-resolved 2D electronic spectroscopy showing that ultrafast energy transfer within the squaraine polymer chains proceeds from initially excited helix segments to zig-zag segments or vice versa, depending on the solvent as well as on the excitation wavenumber. These observations contrast other conjugated polymers such as MEH-PPV where much slower intrachain energy transfer was reported. The reason for the very fast energy transfer in squaraine polymers is most likely a close matching of the density of states between donor and acceptor polymer segments because of very small reorganization energy in these cyanine-like chromophores.}, language = {en} } @phdthesis{Rotem2015, author = {Rotem, Elam}, title = {Early Basso Continuo Practice: Implicit Evidence in the Music of Emilio de' Cavalieri}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145079}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {In this work, Emilio de' Cavalieri's musical sources will serve as a platform in an attempt to overcome the lack of explicit original guidance and guidelines of performance practice of early basso continuo. It will offer a methodology that will allow the unraveling of implicit theory and practice hidden in the music sources themselves. The methodology of this work is based on the fact that Cavalieri's Rappresentatione di Anima e di Corpo (Rome, 1600) is printed using a unique continuo notation, which is detailed, precise, and coherent—more so than any other contemporaneous printed source. Through thorough investigation of this continuo notation, it will be possible to enrich our practical as well as theoretical knowledge of the early basso continuo. A wide range of evidences will emerge, covering a wide spectrum, from general questions of instrumentation up to the very notes that should be played. Using a special notation for illustration, I will demonstrate how Cavalieri's basso continuo figuration, when combined with the known rules of counterpoint, is at times equivalent to written-out realizations. As part of this study, different models of contrapuntal phenomena will be analyzed, mainly in the context of cadences but also in the context of other progressions that deserve to be recognized as formulas. Their theoretical structure will be uncovered as well as their actual application in music and their manner of execution. The prevalence of each phenomenon will be examined in order to distinguish common and recurrent phenomena from rarely-used formulas. In order to do this, and due to problematic historical terminology, it will be necessary to create a set of new terms inspired by Cavalieri's notation. Those terms will not be solely relevant to Cavalieri's music; the models were made flexible so that they may prove useful for future discussions or studies of early continuo in general. Out of the known early basso continuo sources, a "mini-compendium" of practical implications will be extracted in order to exhaust the practical knowledge implicit in them. This endeavor will be concluded with a list of rules and general advice drawn from the sources, but it will also reveal some problematic aspects of these sources. This endeavor will make it possible to compare the "new" implicit practical information deduced in this study with the explicit known continuo sources, and assess to what extant Cavalieri's continuo practices illuminate and complement the known knowledge from previously-studied yet opaque sources of basso continuo. The focus of this dissertation is on Cavalieri's music, but the findings proposed here will be traced so as to illuminate the broader realm of the early Baroque and the 17th century musical style at large. Finally, this new research about Cavalieri's music and continuo, along reevaluating of its place among the common continuo sources, calls for redistribution of source materials on the traditional "shelf" of early basso continuo sources.}, language = {en} } @article{EdenZieglerGilbertetal.2015, author = {Eden, Lars and Ziegler, Dirk and Gilbert, Fabian and Fehske, Kai and Fenwick, Annabel and Meffert, Rainer H.}, title = {Significant pain reduction and improved functional outcome after surgery for displaced midshaft clavicular fractures}, series = {Journal of Orthopaedic Surgery and Research}, volume = {10}, journal = {Journal of Orthopaedic Surgery and Research}, number = {190}, doi = {10.1186/s13018-015-0336-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146357}, year = {2015}, abstract = {Purpose Displaced midshaft clavicular fractures can be treated conservatively as well as operatively by titan elastic nail (TEN) or plate fixation. This survey was performed to evaluate the clinical results of each treatment method and elaborate advantages or possible complications of each modality. Methods Between 2008 and 2013, 102 patients were prospectively included in our study—37 patients for conservative treatment with a rucksack bandage for 4 to 6 weeks, 41 patients for plate osteosynthesis, and 24 for intramedullary stabilization with TEN. Disabilities of the Arm, Shoulder and Hand (DASH), Constant Murley Score (CMS), and visual analog scale (VAS) for pain and function as well as time of invalidity were recorded over a 1-year period. Results The clinical data collected reveals that all three different therapies lead to good or excellent clinical results after 1 year. However, one can observe advantages of operative treatment in comparison to conservative therapy in some characteristics. Conclusion Our data shows that there are several indications where operative treatment has advantages compared to conservative treatment. In special fracture types (Robinson 2B1), TEN gives the best results. Plate fixation is extraordinarily sufficient in pain reduction within the first 5 weeks and indicated in more-part fractures (Robinson 2B2). Nevertheless, conservative treatment is always a good and promising way to treat clavicular fractures, so that individual indications and thorough patient informative talks are inevitable.}, language = {en} } @phdthesis{BeitzenHeineke2015, author = {Beitzen-Heineke, Antonia}, title = {Invariant Natural Killer T cells possess immune-modulating functions during \(Aspergillus\) \(fumigatus\) infection}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144966}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Aspergillus fumigatus is the most common cause for invasive fungal infections, a disease associated with high mortality in immune-compromised patients. CD1d-restricted invariant Natural Killer T (iNKT) cells compose a small subset of T cells known to impact the immune response towards various infectious pathogens. To investigate the role of human iNKT cells during A. fumigatus infection, we studied their activation as determined by CD69 expression and cytokine production in response to distinct fungal morphotypes in the presence of different CD1d⁺ antigen presenting cells using flow cytometry and multiplex ELISA. Among CD1d⁺ subpopulations, CD1d⁺CD1c⁺ mDCs showed the highest potential to activate iNKT cells on a per cell basis. The presence of A. fumigatus decreased this effect of CD1d⁺CD1c⁺ mDCs on iNKT cells and led to reduced secretion of TNF-α, G-CSF and RANTES. Production of other Th1 and Th2 cytokines was not affected by the fungus, suggesting an immune-modulating function for human iNKT cells during A. fumigatus infection.}, subject = {Aspergillus fumigatus}, language = {en} } @phdthesis{Kutzer2015, author = {Kutzer, Pia Elfriede Seyra}, title = {Langzeitergebnisse einer steroidfreien Immunsuppression ein Jahr nach Nierentransplantation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141586}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Die Transplantation nimmt, mehr noch als die verschiedenen Dialyseverfahren, den h{\"o}chsten Stellenwert in der Therapie eines terminalen Nierenversagens ein. Eine Transplantation erfordert jedoch auch immer eine suffiziente Immunsuppression, ohne die die Funktionalit{\"a}t des Transplantats nicht gew{\"a}hrleistet werden kann. Kortikosteroide werden dabei immer noch sehr h{\"a}ufig nach Nierentransplantation eingesetzt. Jedoch bringt diese Medikation auch Risiken mit sich. In der vorliegenden retrospektiven Analyse wurden die Daten von insgesamt 809 Patienten ausgewertet. Die Patienten wurden in zwei Gruppen aufgeteilt, wobei zwischen steroidfrei und nicht-steroidfrei in Jahr zwei nach Transplantation unterschieden wurde. Untersucht wurde, ob es Unterschiede im Patienten- und Transplantat{\"u}berleben, bei akuten Abstoßungen oder bei steroidtypischen Nebenwirkungen gibt. Wir konnten ein tendenziell besseres Patienten{\"u}berleben in der steroidfreien Gruppe feststellen, vor allem zu sehen an der Zehn-Jahres-{\"U}berlebensrate (86,0\% vs. 79,8\%). Bez{\"u}glich des Transplantat{\"u}berlebens zeigte sich ein statistisch signifikanter Unterschied zugunsten der steroidfreien Patienten (nach f{\"u}nf Jahren 92,2\% vs. 79,7\%). Ein Transplantatverlust war in der steroidfreien Kohorte seltener zu beobachten (23,1\% vs. 33,8\%). Bei den in Jahr zwei steroidfreien Patienten ereigneten sich weniger akute Abstoßungsereignisse, sowohl bioptisch gesicherte als auch nur klinisch verd{\"a}chtige Episoden. Steroidtypische Nebenwirkungen, zum Beispiel ein Posttransplantationsdiabetes sowie kardiovaskul{\"a}re Ereignisse wurden tendenziell h{\"a}ufiger in der Kohorte mit fortgesetzter Steroideinnahme diagnostiziert. Im Auftreten von Malignomen gab es keinen Unterschied zwischen den beiden Gruppen. Zu beachten ist die M{\"o}glichkeit eines Selektionsbias bei der retrospektiven Auswertung. Somit ergeben sich in unserer Analyse f{\"u}r eine verk{\"u}rzte Einnahme von Steroiden nach Transplantation greifbare Vorteile f{\"u}r das Patienten- und Transplantat{\"u}berleben. Die Steroidtherapie sollte jedoch mindestens bis sechs Monate nach Transplantation beibehalten werden. Nach diesem Zeitraum erscheint das Absetzen der Steroide sicherer zu sein, da akute Abstoßungsepisoden seltener auftreten. Sowohl Patienten- und Transplantat{\"u}berleben werden durch das Absetzen der Steroidtherapie g{\"u}nstig beeinflusst. Ein fr{\"u}heres Absetzen, wie es in anderen Studien durchgef{\"u}hrt wurde, f{\"u}hrte h{\"a}ufiger zu h{\"o}heren Raten an akuten Rejektionen. Kortikosteroide waren und bleiben somit ein unverzichtbarer Teil der initialen immunsuppressiven Therapie nach Nierentransplantation.}, subject = {Nierentransplantation}, language = {de} } @phdthesis{Schwarz2015, author = {Schwarz, Christoph Benjamin}, title = {Full vector-field control of femtosecond laser pulses with an improved optical design}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142948}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {The controlled shaping of ultrashort laser pulses is a powerful technology and applied in many laser laboratories today. Most of the used pulse shapers are only able to produce linearly polarized pulses shaped in amplitude and phase. Some devices are also capable of producing limited time-varying polarization profiles, but they are not able to control the amplitude. However, for some state-of-the-art non-linear time-resolved methods, such as polarization-enhanced two-dimensional spectroscopy, the possibility of controlling the amplitude and the polarization simultaneously is desirable. Over the last years, different concepts have been developed to overcome these restrictions and to manipulate the complete vector-field of an ultrashort laser pulse with independent control over all four degrees of freedom - phase, amplitude, orientation, and ellipticity. The aim of this work was to build such a vector-field shaper. While the basic concept used for our setup is based on previous designs reported in the literature, the goal was to develop an optimized optical design that minimizes artifacts, allowing for the generation of predefined polarization pulse sequences with the highest achievable accuracy. In Chapter 3, different approaches reported in the literature for extended and unrestricted vector-field control were examined and compared in detail. Based on this analysis, we decided to follow the approach of modulating the spectral phase and amplitude of two perpendicularly polarized pulses independently from each other in two arms of an interferometer and recombining them to a single laser pulse to gain control over the complete vector field. As described in Chapter 4, the setup consists of three functional groups: i) an optical component to generate and recombine the two polarized beams, ii) a 4f setup, and iii) a refracting telescope to direct the two beams under two different angles of incidence onto the grating of the 4f setup in a common-path geometry. This geometry was chosen to overcome potential phase instabilities of an interferometric vector-field shaper. Manipulating the two perpendicularly polarized pulses simultaneously within one 4f setup and using adjacent pixel groups of the same liquid-crystal spatial light modulator (LC SLM) for the two polarizations has the advantages that only a single dual-layer LC SLM is required and that a robust and compact setup was achieved. The shaping capabilities of the presented design were optimized by finding the best parameters for the setup through numerical calculations to adjust the frequency distributions for a broad spectrum of 740 - 880 nm. Instead of using a Wollaston prism as in previous designs, a thin-film polarizer (TFP) is utilized to generate and recombine the two orthogonally polarized beams. Artifacts such as angular dispersion and phase distortions along the beam profile which arise when a Wollaston prism is used were discussed. Furthermore, it was shown by ray-tracing simulations that in combination with a telescope and the 4f setup, a significant deformation of the beam profile would be present when using a Wollaston prism since a separation of the incoming and outgoing beam in height is needed. The ray-tracing simulations also showed that most optical aberrations of the setup are canceled out when the incoming and outgoing beams propagate in the exact same plane by inverting the beam paths. This was realized by employing a TFP in the so-called crossed-polarizer arrangement which has also the advantage that the polarization-dependent efficiencies of the TFP and the other optics are automatically compensated and that a high extinction ratio in the order of 15000:1 is reached. Chromatic aberrations are, however, not compensated by the crossed-polarizer arrangement. The ray-tracing simulations confirmed that these chromatic aberrations are mainly caused by the telescope and not by the cylindrical lens of the 4f setup. Nevertheless, in the experimentally used wavelength range of 780 - 816 nm, only minor distortions of the beam profile were observed, which were thus considered to be negligible in the presented setup. The software implementation of the pulse shaper was reviewed in Chapter 5 of this thesis. In order to perform various experiments, five different parameterizations, accounting for the extended shaping capabilities of a vector-field shaper, were developed. The Pixel Basis, the Spectral Basis, and the Spectral Taylor Basis can generally be used in combination with an optimization algorithm and are therefore well suited for quantum control experiments. For multidimensional spectroscopy, the Polarized Four-Pulse Basis was established. With this parameterization pulse sequences with up to four subpulses can be created. The polarization state of each subpulse can be specified and the relative intensity, phase, and temporal delay between consecutive subpulses can be controlled. In addition, different software programs were introduced in Chapter 5 which are required to perform the experiments conducted in this work. The experimental results were presented in Chapter 6. The frequency distribution across the LC SLM was measured proving that the optimal frequency distribution was realized experimentally. Furthermore, the excellent performance of the TFP was verified. In general, satellite pulses are emitted from the TFP due to multiple internal reflections. Various measurements demonstrated that these pulses are temporally separated by at least 4.05 ps from the main pulse and that they have vanishing intensity. The phase stability between the two arms of the presented common-path setup σ = 28.3 mrad (λ/222) over 60 minutes. To further improve this stability over very long measurement times, an on-the-fly phase reduction and stabilization (OPRAS) routine utilizing the pulse shaper itself was developed. This routine automatically produces a compressed pulse with a minimized relative phase between the two polarization components. A phase stability of σ = 31.9 mrad (λ/197) over nearly 24 hours was measured by employing OPRAS. Various pulse sequences exceeding the capabilities of conventional pulse shapers were generated and characterized. The experimental results proved that shaped pulses with arbitrary phase, amplitude, and polarization states can be created. In all cases very high agreement between the target parameters and the experimental data was achieved. For the future use of the setup also possible modifications were suggested. These are not strictly required, but all of them could further improve the performance and flexibility of the setup. Firstly, it was illustrated how a "dual-output" of the setup can be realized. With this modification it would be possible to use the main intensity of the shaped pulse for an experiment while using a small fraction to characterize the pulse or to perform OPRAS simultaneously. Secondly, the basic idea of replacing the telescope by focusing mirrors in order to eliminate the chromatic aberrations was presented. Regarding the different parameterizations for vector-field shaping, some modifications increasing the flexibility of the implemented bases and the realization of a von Neumann Basis for the presented setup were proposed. In future experiments, the vector-field shaper will be used in conjunction with a photoemission electron microscope (PEEM). This approach combines the temporal resolution provided by ultrashort laser pulses with the high spatial resolution gained by electron microscopy in order to perform two-dimensional spectroscopy and coherent control on nanostructures with polarization-shaped femtosecond laser pulses. In combination with other chiral-sensitive experimental setups implemented earlier in our group, the vector-field shaper opens up new perspectives for chiral femtochemistry and chiral control. The designed vector-field shaper meets all requirements to generate high-precision polarization-shaped multipulse sequences. These can be used to perform numerous polarization-sensitive experiments. Employing the OPRAS routine, a quasi-infinitely long phase stability is achieved and complex and elaborated long-term measurements can be carried out. The fact that OPRAS demands no additional hardware and that only a single dual-layer LC SLM and inexpensive optics are required allows the building of a vector-field shaper at comparatively low costs. We hope that with the detailed insights into the optical design process as well as into the software implementation given in this thesis, vector-field shaping will become a standard technique just as conventional pulse shaping in the upcoming years.}, subject = {Ultrakurzer Lichtimpuls}, language = {en} } @phdthesis{Dischinger2015, author = {Dischinger, Ulrich Severin}, title = {Auswirkungen unterschiedlicher Haltungsbedingungen auf Ph{\"a}notyp und Genexpression im Mausmodell}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142955}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {In zahlreichen Untersuchungen konnte gezeigt werden, dass Umweltbedingungen im fr{\"u}hen Lebensalter einerseits die Entwicklung von Resilienz, d.h. Widerstandsf{\"a}higkeit gegen{\"u}ber Stressoren, andererseits aber auch die Entwicklung physischer und psychischer Erkrankungen im weiteren Lebensverlauf beeinflussen k{\"o}nnen. Dabei wird angenommen, dass sich sowohl dezidiert positive als auch in Maßen aversive Umweltbedingungen mit rezidivierender Stressbelastung g{\"u}nstig auf die Resilienz im sp{\"a}teren Leben auswirken k{\"o}nnen. Auf neurobiologischer Ebene scheinen dabei das CRH und seine Rezeptoren (CRHR1 und CRHR2), das NPY-System sowie das NPS-System (insbesondere NPS-Rezeptor) eine besondere Rolle zu spielen. Jedoch sind die exakten Zusammenh{\"a}nge und neurobiologischen Grundlagen weiterhin nur unzureichend aufgekl{\"a}rt. Dies ist insbesondere insofern bedauernswert, da weiterer Erkenntnisgewinn auf diesem Gebiet m{\"o}glicherweise Pr{\"a}ventionsstrategien und Therapieoptionen f{\"u}r den Menschen begr{\"u}nden k{\"o}nnte. Um die Auswirkung der Umweltbedingungen im fr{\"u}hkindlichen Lebensalter auf die Resilienz im sp{\"a}teren Leben weiter aufzukl{\"a}ren, wurden im Rahmen dieser Arbeit insgesamt 310 Cd1-M{\"a}use den Haltungsbedingungen "Environmental Enrichment" (EE, Stimulation durch Spielobjekte) und "Maternal separation" (MS, wiederholte Stressbelastung durch Separation der Nachkommen vom Muttertier) sowie Standardhaltungsbedingungen unterworfen. Insgesamt 31 m{\"a}nnlichen Tieren wurde im Alter von vier Wochen die Gehirne entnommen und aus diesen jeweils die Regionen Frontalcortex, Striatum, Nucleus accumbens, Hippocampus, Amygdala, dorsale Nuclei raphes und Hypothalamus herauspr{\"a}pariert. Aus den gewonnenen Proben wurde RNA extrahiert, hieraus cDNA synthetisiert und abschließend - nach Ausschluss von Kontamination und Integrit{\"a}tspr{\"u}fung - die Expressionsraten der untersuchten Gene mittels RT-qPCR quantifiziert. Um auch verhaltensbiologische Konsequenzen der unterschiedlichen Haltungsbedingungen zu erfassen, wurden außerdem 30 weibliche sowie 30 m{\"a}nnliche Tiere im weiteren Lebensverlauf verschiedenen Verhaltenstests zugef{\"u}hrt. In den Sucrose-Pr{\"a}ferenz-Tests zeigten sich Effekte der Haltungsbedingung auf Sucrose-Konsum und Pr{\"a}ferenz mit signifikant geringeren Werten der Haltungsgruppe EE. Bei der Auswertung der Openfield-Tests fanden sich Gruppen-Geschlechter-Interaktionseffekte mit signifikant geringeren Werten (Gesamtstrecke, Strecke und Aufenthaltsdauer im zentralen Bereich, Eintritte in den zentralen Bereich) der weiblichen EE-Tiere. In den Barnes Maze-Tests ben{\"o}tigten die Tiere der Haltungsgruppe EE an den meisten Testtagen signifikant weniger Zeit, um in die Escape-Box zu "entkommen". Auf neurobiologischer Ebene fanden sich signifikante Unterschiede der CRH-Expressionsraten in Amygdalae und Frontalcortex, der CRHR 1-Expressionsraten in Amygdalae und Hypothalamus sowie der CRHR2-Expressionsraten in Amygdalae und Hippocampus. Demgegen{\"u}ber konnte kein signifikanter Effekt der Haltungsbedingung auf das NPY-System gefunden werden. Jedoch ließen sich signifikante Unterschiede der NPSR1-Expressionsraten in Amygdalae, Frontalcortex, dorsalen Nuclei raphes und Hypothalamus feststellen. Es kann also grunds{\"a}tzlich von Auswirkungen unterschiedlich aversiver Haltungsbedingungen auf die Stress-Resilienz von Versuchstieren ausgegangen werden. Dies ist einerseits f{\"u}r Tierversuche allgemein von grunds{\"a}tzlicher Bedeutung. Andererseits legen die Resultate eine entsprechende fr{\"u}hkindliche "Programmierung" auch im Menschen nahe.}, subject = {Stress}, language = {de} } @inproceedings{JannidisRegerWeimeretal.2015, author = {Jannidis, Fotis and Reger, Isabella and Weimer, Lukas and Krug, Markus and Puppe, Frank}, title = {Automatische Erkennung von Figuren in deutschsprachigen Romanen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143332}, pages = {7}, year = {2015}, abstract = {Eine wichtige Grundlage f{\"u}r die quantitative Analyse von Erz{\"a}hltexten, etwa eine Netzwerkanalyse der Figurenkonstellation, ist die automatische Erkennung von Referenzen auf Figuren in Erz{\"a}hltexten, ein Sonderfall des generischen NLP-Problems der Named Entity Recognition. Bestehende, auf Zeitungstexten trainierte Modelle sind f{\"u}r literarische Texte nur eingeschr{\"a}nkt brauchbar, da die Einbeziehung von Appellativen in die Named Entity-Definition und deren h{\"a}ufige Verwendung in Romantexten zu einem schlechten Ergebnis f{\"u}hrt. Dieses Paper stellt eine anhand eines manuell annotierten Korpus auf deutschsprachige Romane des 19. Jahrhunderts angepasste NER-Komponente vor.}, subject = {Digital Humanities}, language = {de} } @phdthesis{Sieker2015, author = {Sieker, Jakob Tobias}, title = {Direkter adenoviraler Gentransfer von Bone morphogenetic protein-2 und Indian Hedgehog zur Knorpelregeneration im Kaninchenmodell}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142622}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Einleitung Fokale Gelenkknorpeldefekte treten in der Deutschen Bev{\"o}lkerung mit einer gesch{\"a}tzten Inzidenz von {\"u}ber 300 000 j{\"a}hrlichen F{\"a}llen auf. In der US-amerikanischen Bev{\"o}lkerung wird j{\"a}hrlich von {\"u}ber 600 000 F{\"a}llen ausgegangen. Aufgrund der Insuffizienz k{\"o}rpereigener Heilungskapazit{\"a}ten und verf{\"u}gbarer Therapieverfahren, schreitet die Erkrankung regelhaft zur post-traumatischen Arthrose fort. Neben der individuellen Lebensqualit{\"a}tseinschr{\"a}nkung besteht eine sozio{\"o}konomische Bedeutung mit gesch{\"a}tzten Krankheitskosten von j{\"a}hrlich {\"u}ber 10 Milliarden US Dollar in den Vereinigten Staaten. Das Versagen zellbasierter Therapieverfahren beruht unter anderem auf einer Insuffizienz der chondrogenen Differenzierung, sowie der hypertrophen Differenzierung der Chondrozyten mit nachfolgender Osteogenese analog den Vorg{\"a}ngen in der Wachstumsfuge. F{\"u}r die Induktion der chondrogenen Differenzierung stehen insbesondere Mitglieder der TGF-β Superfamilie, wie BMP-2, zur Verf{\"u}gung. Diese sind jedoch ebenso durch eine Induktion der hypertrophen Differenzierung gekennzeichnet. Zur Induktion der Chondrogenese unter Umgehung der TGF-β-Signalwege wurde IHH in-vitro als vielversprechend beschrieben. Bislang besteht jedoch kein Nachweis der in-vivo Effektivit{\"a}t von IHH zur Knorpelreparation. Die Schaffung eines Wachstumsfaktor-Milieus in der Gelenkknorpell{\"a}sion in-vivo stellt ebenso eine Herausforderung dar. Diesbez{\"u}glich wurde ein vereinfachtes Verfahren zum lokalisierten in-vivo Gentransfer mittels adenoviraler Vektoren und autologen Knochenmarkskoagulaten anhand von Markergenen beschrieben. Die Effektivit{\"a}t jenes Verfahrens zur in-vivo Knorpelreparation wurde noch nicht gezeigt. Zweck dieses kontrollierten in-vivo Experimentes ist es, mittels des oben genannten Gentransferverfahrens die Wirksamkeit von BMP-2 und IHH zur Reparation von osteochondralen Defekten in New Zealand White Rabbits nachzuweisen. Die zentrale Hypothese lautete, dass BMP2 beziehungsweise IHH Gentransfer in einer h{\"o}heren langzeit-histologischen Qualit{\"a}t des Reparationsgewebes resultiert. Explorativ sollten dabei Unterschiede in den einzelnen Dimensionen der Gewebequalit{\"a}t anhand des ICRS-II Histology Scoring Systems, sowie der Grad der Typ I (als Faserknorpelmarker), Typ II (als Marker hyalinen Gelenkknorpels) und Typ X Kollagen Deposition (als Marker hypertropher Chondrozyten) beschrieben werden. Material und Methoden Als Tiermodel wurden bilaterale 3,2 mm durchmessende osteochondrale Bohrlochdefekte in der Trochlea von New Zealand White Rabbits verwendet (n=10 unabh{\"a}ngige Tiere, 20 Gelenke). Die Defekte wurden mit autologen Knochenmarkkoageln gef{\"u}llt, die nach vorheriger Beckenkammaspiration gewonnen wurden. In den experimentellen Gruppen wurden die Knochenmarkkoagel beladen mit jeweils 1 x 1011 infekti{\"o}sen Partikeln adenoviraler Vektoren, die cDNA codierend f{\"u}r BMP2 (n=3 Tiere, entsprechend 6 Gelenken) oder IHH (n=4; 8) enthielten. In der Kontrollgruppe wurde das nicht-chondrogene Markergen GFP (n=3; 6) transferiert. Beide Gelenke eines Tieres wurden der gleichen Gruppe zugeordnet. Die histologische Gewebequalit{\"a}t wurde nach 13 Wochen anhand des ICRS-II Scoringsystems durch 3 unabh{\"a}ngige, verblindete Untersucher bewertet. Als prim{\"a}re Outcomes wurden der ICRS-II Parameter „Generelles Assessment", sowie die Typ II Kollagen positive Fl{\"a}che designiert. Als explorative Outcomes wurden die verbleibenden ICRS-II Parameter, sowie die Typ I und Typ X Kollagen Deposition bewertet. Die Korrelation zwischen den Untersuchern wurde nach Pearson ermittelt. Zum Test auf Signifikanz der Gruppenunterschiede wurde ein lineares gemischtes Modell verwendet, welches einer m{\"o}gliche Abh{\"a}ngigkeit beider Gelenke eines Tieres Rechnung tr{\"a}gt. Ergebnisse Qualitative Bewertung des Reparationsknorpels. Dreizehn Wochen nach der Intervention zeigten die meisten der BMP-2 behandelten Gelenke (4 von 6) und alle der IHH behandelten Gelenke (8 von 8) hyalin-artigen Reparationsknorpel, w{\"a}hrend alle GFP behandelten Kontrollgelenke (6 von 6) faserknorpel-artiges Reparationsgewebe zeigten. Zwei BMP-2 behandelten Gelenke zeigten eine ausgepr{\"a}gte intral{\"a}sionale Knochenformation. Prim{\"a}re Outcomes - ICRS-II „Generelles Assessment" und Typ II Kollagen positive Fl{\"a}che. IHH und BMP-2 behandelte Gelenke zeigten im Vergleich zu GFP h{\"o}here Punktzahlen in dem ICRS-II „Generelles Assessment" Parameter: +33.0 (95\% Konfidenzintervall: -0.4, +66.4) Punkte f{\"u}r IHH und +8.5 (-26.6, +43.7) Punkte f{\"u}r BMP-2. Beide Effekte erreichten nicht das Level statistischer Signifikanz (p=0.052 und 0.537). IHH erh{\"o}hte die Typ II Kollagen Deposition in der Defektregion, w{\"a}hrend BMP-2 Gelenke keinen Unterschied zu GFP Kontrollen zeigten: +18.7 (-4.5, +42.0) Punkte f{\"u}r IHH und +0.0 (-29.7, +29.8) Punkte f{\"u}r BMP-2. Die erh{\"o}hte Typ II Kollagendeposition erreichte nicht das konventionelle Level statistischer Signifikanz (p=0.093). Sekund{\"a}re Outcomes - ICRS-II Parameter. In dem Vergleich von BMP-2 mit GFP Kontrollen wurde in keinem der 12 untersuchten Parameter ein signifikanter Unterschied festgestellt. IHH Gentransfer resultierte hingegen in h{\"o}heren Punktzahlen in allen untersuchten Parametern, wobei der Unterschied in 5 der 12 Parameter das Niveau statistischer Signifikanz erreichte. Ein um 21.5 Punkte (+3.6, +39.4) erh{\"o}hter Score wurde f{\"u}r den Parameter „Gewebemorphologie" beobachtet, sowie +21.0 (+6.4, +35.7) f{\"u}r „Chondrozyt{\"a}res Clustering", +31.2 (+0.8, +61.5) f{\"u}r „Formation der Tidemark", +17.3 (+0.2, +34.5) f{\"u}r „Abnorme Kalzifikation/Ossifikation" und +35.0 (+4.6, +65.2) f{\"u}r das „Assessment der mittleren und tiefen Zone". Sekund{\"a}re Outcomes - Marker chondrozyt{\"a}rer Hypertrophie. Eine perizellul{\"a}re Deposition von Typ X Kollagen wurde in allen Gruppen beobachtet. Eine deutlich gesteigerte Deposition wurde nur in den Gelenken beobachtet, die nach BMP2 Gentransfer eine ausgepr{\"a}gte intral{\"a}sionale Knochenformation zeigten. Diskussion Das hier beschriebene Experiment stellt die erste Ver{\"o}ffentlichung der Wirksamkeit von IHH zur Verbesserung der histologischen Knorpelqualit{\"a}t von in-vivo therapierten Gelenkknorpeldefekten dar [175]. Die Hypothese, dass IHH zu einer verbesserten histologischen Knorpelqualit{\"a}t f{\"u}hrt wurde best{\"a}tigt, w{\"a}hrend die Hypothese zu den positiven Effekten von BMP-2 wiederlegt wurde. IHH f{\"u}hrte zu besseren Ergebnissen in allen Untersuchten Parametern, das Niveau statistischer Signifikanz wurde dabei in den Parametern „Gewebemorphologie", „Chondrozyt{\"a}res Clustering", „Formation der Tidemark", „Abnorme Kalzifikation/Ossifikation" und „Assessment der mittleren und tiefen Zone" erreicht. Das prim{\"a}re Ziel dieses Experimentes war es, den „Proof of concept" zu liefern, dass IHH auch in-vivo ein attraktiver Faktor f{\"u}r die Induktion der Chondrogenese darstellt. Das langfristige Ziel ist die Induktion der Chondrogenese unter Umgehung des TGF-β Signalweges zu erzielen, um eine folgende hypertrophe Differenzierung der Chondrozyten und die folgende Ossifikation des reparierten Defektes zu verhindern. Die Limitationen der Studie umfassen die ausschließlich histologische und immunhistochemische durchgef{\"u}hrte Bewertung der Knorpelqualit{\"a}t und eine eingeschr{\"a}nkte statistische Power. Ob IHH es vermag die hypertrophe Differenzierung zu umgehen und somit eine langfristige hyaline Knorpelreparation zu erm{\"o}glichen, ist in weiteren pr{\"a}klinischen Studien mit biochemischer und molekulargenetischer Analyse der Hypertrophie-Marker zu untersuchen. In Bezug auf den klinischen Einsatz zur Knorpelreparation erscheint der Einsatz der Wachstumsfaktoren als Protein auf funktionalisierten Matrices vielversprechend. BMP-2 wird aufgrund der hier beobachteten intral{\"a}sionalen Knochenformation nach BMP2 Gentransfer als nicht geeignet zur Unterst{\"u}tzung der Knorpelreparation in-vivo bewertet.}, subject = {Bone morphogenetic protein-2}, language = {de} } @phdthesis{BrillgebSchubert2015, author = {Brill [geb. Schubert], Sabine}, title = {Blutzuckerverlauf, hormonelle Gegenregulation und kognitive Leistungsf{\"a}higkeit unter definierter k{\"o}rperlicher Belastung bei Patienten mit Morbus Addison und Diabetes mellitus Typ 1 CANDI - Studie: Counterregulatory Hormone Production in Adrenal Insufficiency and Diabetes Type I}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142646}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Spiroergometrische Dauerbelastung von Probanden mit Morbus Addison, Diabetes mellitus Typ 1, Polyglandul{\"a}rem Autoimmunsyndrom Typ 2 (erkrankt sowohl an Mb. Addison als auch an Diabetes mellitus Typ1) und gesunden Kontrollen. Blutzuckerverlauf, hormonelle Gegenregulation und kognitive Leistungsf{\"a}higkeit vor und nach Belastung wurden gemessen. W{\"a}hrend einer spiroergometrischen Dauerbelastung von 23 Minuten zeigte sich bei keinem der 10 Probanden mit ausschließlich Morbus Addison eine Neigung zur Hypoglyk{\"a}mie trotz fehlender Einnahme der mitt{\"a}glichen Glukokortikoiddosis. Die Blutzucker blieben bei s{\"a}mtlichen Probanden stabil und es zeigte sich sogar ein leichter Anstieg in der der Ergometrie anschließenden Nachbeobachtungsphase, eventuell als Hinweis auf eine m{\"o}gliche Entwicklung einer Inulin-Resistenz. Auf die erwartungsgem{\"a}ße Mindersekretion von Adrenalin zeigte sich eine ame ehesten kompensatorisch leicht h{\"o}here Sekretion von Noradrenalin als bei den nebennierengesunden Gruppen. Die {\"u}brige Sekretion gegenregulatorischer Hormone entsprach den Vergleichsgruppen. Die geleistete Arbeit am Fahrradergometer war bei den Probandengruppen mit Morbus Addison und APS 2 nahezu identisch, die Morbus Addison - Probanden traten sogar minimal weniger Ergometerwiderstand {\"u}ber die 15 Minuten Dauerbelastung. Dennoch zeigten die Probanden mit ausschließlich M. Addison einen ad{\"a}quaten Anstieg der gegenregulatorischen Hormone ohne starke Schwankungen der Plasmaglukose, wohingegen es bei den Probanden mit APS 2, zu einem deutlichen Abfall der Plasmaglukose kam trotz deutlich niedrigerer Insulinkonzentrationen im Vergleich zur Probandengruppe mit ausschließlich Diabetes mellitus Typ 1. Die unzureichende Sekretion von Adrenalin, sowie der geringste Konzentrationsanstieg von Noradrenalin und dieser Untersuchung auch Wachstumshormon aller Probandengruppen verhinderte einen ad{\"a}quaten Wiederanstieg des Blutzuckers. Die Probanden mit Nebennierenrindeninsuffizienz verzeichneten teils signifikant schlechtere Ergebnisse bei einem Konzentrations- und einem Kurzzeitged{\"a}chtnistest im direkten Anschluss an die Ergometrie im Vergleich mit den anderen Probandengruppen. Es gab keine relevanten Unterschiede der Testergebnisse in Ruhe. Die nebenniereninsuffizienten Probanden verbesserten sich jedoch signifikant weniger nach der Ergometrie bzw. zeigten nach dem Dauertest teils sogar schlechtere Leistungen. Die Probandengruppen mit Diabetes mellitus Typ 1 und die Kontrollgruppe zeigten eine erwartungsgem{\"a}ße Verbesserung ihrer Leistung als Reaktion auf die vorherige k{\"o}rperliche Aktivit{\"a}t. Die Unterschiede in der kognitiven Performance sind am ehesten mit der unzureichenden Adrenalinsekretion und einem fehlenden akuten Cortisolanstieg der nebenniereninsuffizienten Probanden zu erkl{\"a}ren. Die Probanden mit Nebennierenrindeninsuffizienz wurden mit signifikant niedrigeren Widerst{\"a}nden am Fahrradergometer belastet als die nebennierengesunden Probanden. Ein m{\"o}glicher Erkl{\"a}rungsansatz hierf{\"u}r k{\"o}nnte eine gewisse cortisonbedingte Myopathie sein. Dies verdeutlicht nochmals die Notwendigkeit der Optimierung der Glukokortikoidsubstitutionstherapie. Neue Substitutionsregime sollten m{\"o}glichst die physiologische circadiane Sekretionsrhythmik besser imitieren und im Optimalfall die Tagesdosis an Hydrocortison reduzieren, um glukokortikoidbedingte Nebenwirkungen wie Myopathie und Insulin-Resistenz zu reduzieren. Die Probanden mit polyglandul{\"a}rem Autoimmunsyndrom Typ 2, welche sowohl an Morbus Addison als auch an Diabetes mellitus Typ 1 leiden, m{\"u}ssen im Rahmen von Patientenschulungen besonders auf das Risiko von Hypoglyk{\"a}mien bei vermehrter k{\"o}rperlicher Aktivit{\"a}t hingewiesen werden. Patienten mit Insulinpumpe sollten das Ausschalten w{\"a}hrenddessen erw{\"a}gen und dar{\"u}ber hinaus besondere Aufmerksamkeit auf die Einnahme einer zus{\"a}tzlichen Kohlenhydrateinheit f{\"u}r den Sport walten lassen. Eine zus{\"a}tzliche Einnahme des Glukokortikoids ist in diesem Zusammenhang nicht sinnvoll. [31] Ein vor dem Sport beispielsweise inhalativ appliziertes Epinephrinpr{\"a}parat w{\"a}re eine m{\"o}gliche Strategie zur Verbesserung des Plasmaglukose-Outcomes nach sportlicher Bet{\"a}tigung auf moderatem bzw. hohem Anstrengungslevel bei Patienten mit Morbus Addison und Diabetes mellitus Typ 1 und sollte Gegenstand weiterf{\"u}hrender Studien sein.}, language = {de} } @article{BurgsdorfSlabyHandleyetal.2015, author = {Burgsdorf, Ilia and Slaby, Beate M. and Handley, Kim M. and Haber, Markus and Blom, Jochen and Marshall, Christopher W. and Gilbert, Jack A. and Hentschel, Ute and Steindler, Laura}, title = {Lifestyle Evolution in Cyanobacterial Symbionts of Sponges}, series = {mBio}, volume = {6}, journal = {mBio}, number = {3}, doi = {10.1128/mBio.00391-15}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143117}, pages = {e00391-15}, year = {2015}, abstract = {The "Candidatus Synechococcus spongiarum" group includes different clades of cyanobacteria with high 16S rRNA sequence identity (~99\%) and is the most abundant and widespread cyanobacterial symbiont of marine sponges. The first draft genome of a "Ca. Synechococcus spongiarum" group member was recently published, providing evidence of genome reduction by loss of genes involved in several nonessential functions. However, "Ca. Synechococcus spongiarum" includes a variety of clades that may differ widely in genomic repertoire and consequently in physiology and symbiotic function. Here, we present three additional draft genomes of "Ca. Synechococcus spongiarum," each from a different clade. By comparing all four symbiont genomes to those of free-living cyanobacteria, we revealed general adaptations to life inside sponges and specific adaptations of each phylotype. Symbiont genomes shared about half of their total number of coding genes. Common traits of "Ca. Synechococcus spongiarum" members were a high abundance of DNA modification and recombination genes and a reduction in genes involved in inorganic ion transport and metabolism, cell wall biogenesis, and signal transduction mechanisms. Moreover, these symbionts were characterized by a reduced number of antioxidant enzymes and low-weight peptides of photosystem II compared to their free-living relatives. Variability within the "Ca. Synechococcus spongiarum" group was mostly related to immune system features, potential for siderophore-mediated iron transport, and dependency on methionine from external sources. The common absence of genes involved in synthesis of residues, typical of the O antigen of free-living Synechococcus species, suggests a novel mechanism utilized by these symbionts to avoid sponge predation and phage attack. IMPORTANCE While the Synechococcus/Prochlorococcus-type cyanobacteria are widely distributed in the world's oceans, a subgroup has established its niche within marine sponge tissues. Recently, the first genome of sponge-associated cyanobacteria, " Candidatus Synechococcus spongiarum," was described. The sequencing of three representatives of different clades within this cyanobacterial group has enabled us to investigate intraspecies diversity, as well as to give a more comprehensive understanding of the common symbiotic features that adapt "Ca. Synechococcus spongiarum" to its life within the sponge host.}, language = {en} } @article{WallaceLeonhardt2015, author = {Wallace, Helen Margaret and Leonhardt, Sara Diana}, title = {Do Hybrid Trees Inherit Invasive Characteristics? Fruits of Corymbia torelliana X C. citriodora Hybrids and Potential for Seed Dispersal by Bees}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {9}, doi = {10.1371/journal.pone.0138868}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141777}, pages = {e0138868}, year = {2015}, abstract = {Tree invasions have substantial impacts on biodiversity and ecosystem functioning, and trees that are dispersed by animals are more likely to become invasive. In addition, hybridisation between plants is well documented as a source of new weeds, as hybrids gain new characteristics that allow them to become invasive. Corymbia torelliana is an invasive tree with an unusual animal dispersal mechanism: seed dispersal by stingless bees, that hybridizes readily with other species. We examined hybrids between C. torelliana and C. citriodora subsp. citriodora to determine whether hybrids have inherited the seed dispersal characteristics of C. torelliana that allow bee dispersal. Some hybrid fruits displayed the characteristic hollowness, resin production and resin chemistry associated with seed dispersal by bees. However, we did not observe bees foraging on any hybrid fruits until they had been damaged. We conclude that C. torelliana and C. citriodora subsp. citriodora hybrids can inherit some fruit characters that are associated with dispersal by bees, but we did not find a hybrid with the complete set of characters that would enable bee dispersal. However, around 20,000 hybrids have been planted in Australia, and ongoing monitoring is necessary to identify any hybrids that may become invasive.}, language = {en} } @article{MuellerStoetterKalluvyaetal.2015, author = {Mueller, A. and Stoetter, L. and Kalluvya, S. and Stich, A. and Majinge, C. and Weissbrich, B. and Kasang, C.}, title = {Prevalence of hepatitis B virus infection among health care workers in a tertiary hospital in Tanzania}, series = {BMC Infectious Diseases}, volume = {15}, journal = {BMC Infectious Diseases}, number = {386}, doi = {10.1186/s12879-015-1129-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141786}, year = {2015}, abstract = {Background: Sub-Saharan Africa has a high prevalence of hepatitis B virus (HBV) infections. Health care workers (HCWs) are at high risk of contracting HBV infection through their occupation. Vaccination of HCWs against HBV is standard practice in many countries, but is often not implemented in resource-poor settings. We aimed with this cross-sectional study to determine HBV prevalence, HCW vaccination status, and the risk factors for HCWs contracting HBV infection in Tanzania. Methods: We enrolled 600 HCWs from a tertiary Tanzanian hospital. Their demographics, medical histories, HBV vaccination details and risk factors for contracting blood-borne infections were collected using a standardized questionnaire. Serum samples were tested for HBV and hepatitis C virus (HCV) markers by ELISA techniques, PCR and an anti-HBs rapid test. HCWs were divided in two subgroups: those at risk of contracting HBV (rHCW 79.2 \%) via exposure to potentially infectious materials, and those considered not at risk of contracting HBV (nrHCW, 20.8 \%). Results: The overall prevalence of chronic HBV infection (HBsAg+, anti-HBc+, anti-HBs-) was 7.0 \% (42/598). Chronic HBV infection was found in 7.4 \% of rHCW versus 5.6 \% of nrHCW(p-value = 0.484). HCWs susceptible to HBV (HBsAg-, anti-HBc-, anti-HBs-) comprised 31.3 \%. HBV immunity achieved either by healed HBV infection (HBsAg-, anti-HBc+, anti-HBs+) or by vaccination (HBsAg-, anti-HBc-, anti-HBs+) comprised 36.5 \% and 20.2 \%, respectively. 4.8 \% of participants had indeterminate results (HBsAg-, anti-HBc+, anti-HBc-IgM-, anti-HBs-). Only 77.1 \% of HCWs who received a full vaccination course had an anti-HBs titer > 10 ml/U. An anti-HBs point-of-care test was 80.7 \% sensitive and 96.9 \% specific. There was a significantly higher risk for contracting HBV (anti-HBc+) among those HCW at occupational risk (rHCW) of older age (odds ratios (OR) in rHCW 3.297, p < 0.0001 vs. nrHCW 1.385, p = 0.606) and among those HCW being employed more than 11 years (OR 2.51, p < 0.0001***). HCV prevalence was low (HCV antibodies 1.2 \% and HCV-RNA 0.3 \%). Conclusions: Chronic HBV infection is common among Tanzanian HCWs. One third of HCWs were susceptible to HBV infection, highlighting the need for vaccination. Due to high prevalence of naturally acquired immunity against HBV pre-testing might be a useful tool to identify susceptible individuals.}, language = {en} } @article{MostovayaGrootemanBasileetal.2015, author = {Mostovaya, Ira M. and Grooteman, Muriel P.C. and Basile, Carlo and Davenport, Andrew and de Roij van Zuijdewijn, Camiel L.M. and Wanner, Christoph and Nub{\´e}, Menso J. and Blankestijn, Peter J.}, title = {High convection volume in online post-dilution haemodiafiltration: relevance, safety and costs}, series = {Clinical Kidney Journal}, volume = {8}, journal = {Clinical Kidney Journal}, number = {4}, doi = {10.1093/ckj/sfv040}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149814}, pages = {368-373}, year = {2015}, abstract = {Increasing evidence suggests that treatment with online post-dilution haemodiafiltration (HDF) improves clinical outcome in patients with end-stage kidney disease, if compared with haemodialysis (HD). Although the primary analyses of three large randomized controlled trials (RCTs) showed inconclusive results, post hoc analyses of these and previous observational studies comparing online post-dilution HDF with HD showed that the risk of overall and cardiovascular mortality is lowest in patients who are treated with high-volume HDF. As such, the magnitude of the convection volume seems crucial and can be considered as the 'dose' of HDF. In this narrative review, the relevance of high convection volume in online post-dilution HDF is discussed. In addition, we briefly touch upon some safety and cost issues.}, language = {en} } @article{KleinschnitzNiemczykRehbergWeberetal.2015, author = {Kleinschnitz, Christoph and Niemczyk, Gabriele and Rehberg-Weber, Karin and Wernsd{\"o}rfer, Colin}, title = {Interferon Beta-1a (AVONEX®) as a treatment option for untreated patients with multiple sclerosis (AXIOM): a prospective, observational study}, series = {International Journal of Molecular Sciences}, volume = {16}, journal = {International Journal of Molecular Sciences}, doi = {10.3390/ijms160715271}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148487}, pages = {15271-15286}, year = {2015}, abstract = {The efficacy and safety of first-line disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in pivotal, randomized trials, but these studies do not reflect the routine care setting where treatment gaps or switches are common. The Avonex as Treatment Option for Untreated MS Patients (AXIOM) trial assessed the efficacy of newly-initiated intramuscular interferon beta-1a (IM IFNb-1a) after a treatment-free interval, with particular consideration of the previous course of disease and therapy. The AXIOM trial was an open, 12-month, observational, non-interventional study with a retrospective and a prospective part conducted in Germany. RRMS patients with a treatment-free interval of at least three months were included and treated with IFNb-1a for up to 12 months. Relapse rate, disability progression, injection-related parameters and quality of life observed during the prospective part were compared with retrospectively-collected data. Two hundred and thirty five RRMS patients participated in AXIOM. The mean relapse rate decreased from 1.1 in the three months before baseline to 0.2 per quarter during the twelve-month observational period; the Multiple Sclerosis Functional Composite score improved during twelve months of IM IFNb-1a treatment, while the Expanded Disability Status Scale score did not change over the course of this study. Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a), SC IFNb-1b, glatiramer acetate), the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. IM IFNb-1a was effective and well accepted in RRMS patients with no or discontinued previous therapy. These results from the routine care setting may inform optimization of DMT treatment in RRMS, but need confirmation in further studies.}, language = {en} } @article{ElkonLoayzaPuchKorkmazetal.2015, author = {Elkon, Ran and Loayza-Puch, Fabricio and Korkmaz, Gozde and Lopes, Rui and van Breugel, Pieter C and Bleijerveld, Onno B and Altelaar, AF Maarten and Wolf, Elmar and Lorenzin, Francesca and Eilers, Martin and Agami, Reuven}, title = {Myc coordinates transcription and translation to enhance transformation and suppress invasiveness}, series = {EMBO reports}, volume = {16}, journal = {EMBO reports}, number = {12}, doi = {10.15252/embr.201540717}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150373}, pages = {1723-1736}, year = {2015}, abstract = {c-Myc is one of the major human proto-oncogenes and is often associated with tumor aggression and poor clinical outcome. Paradoxically, Myc was also reported as a suppressor of cell motility, invasiveness, and metastasis. Among the direct targets of Myc are many components of the protein synthesis machinery whose induction results in an overall increase in protein synthesis that empowers tumor cell growth. At present, it is largely unknown whether beyond the global enhancement of protein synthesis, Myc activation results in translation modulation of specific genes. Here, we measured Myc-induced global changes in gene expression at the transcription, translation, and protein levels and uncovered extensive transcript-specific regulation of protein translation. Particularly, we detected a broad coordination between regulation of transcription and translation upon modulation of Myc activity and showed the connection of these responses to mTOR signaling to enhance oncogenic transformation and to the TGFβ pathway to modulate cell migration and invasiveness. Our results elucidate novel facets of Myc-induced cellular responses and provide a more comprehensive view of the consequences of its activation in cancer cells.}, language = {en} } @article{OPUS4-15008, title = {Search for dark matter in events with heavy quarks and missing transverse momentum in pp collisions with the ATLAS detector}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {2}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-015-3306-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150089}, pages = {92}, year = {2015}, abstract = {This article reports on a search for dark matter pair production in association with bottom or top quarks in 20.3 fb\(^{-1}\) of pp collisions collected at \(\sqrt {s}\) = 8 TeV by the ATLAS detector at the LHC. Events with large missing transverse momentum are selected when produced in association with high-momentum jets of which one or more are identified as jets containing b-quarks. Final states with top quarks are selected by requiring a high jet multiplicity and in some cases a single lepton. The data are found to be consistent with the Standard Model expectations and limits are set on the mass scale of effective field theories that describe scalar and tensor interactions between dark matter and Standard Model particles. Limits on the dark-matter-nucleon cross-section for spin-independent and spin-dependent interactions are also provided. These limits are particularly strong for low-mass dark matter. Using a simplified model, constraints are set on the mass of dark matter and of a coloured mediator suitable to explain a possible signal of annihilating dark matter.}, language = {en} } @article{OPUS4-15011, title = {Search for Higgs boson pair production in the b\(\overline{b}\)b\(\overline{b}\) final state from pp collisions at \(\sqrt {s}\) = 8 TeV with the ATLAS detector}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {9}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-015-3628-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150119}, pages = {412}, year = {2015}, abstract = {A search for Higgs boson pair production pp → hh is performed with 19.5 fb\(^{-1}\) of proton-proton collision data at \(\sqrt {s}\) = 8 TeV, which were recorded by the ATLAS detector at the Large Hadron Collider in 2012. The decay products of each Higgs boson are reconstructed as a high-momentum b\(\overline{b}\) system with either a pair of small-radius jets or a single large-radius jet, the latter exploiting jet substructure techniques and associated b-tagged track-jets. No evidence for resonant or non-resonant Higgs boson pair production is observed. The data are interpreted in the context of the Randall-Sundrum model with a warped extra dimension as well as the two-Higgs-doublet model. An upper limit on the cross-section for pp → G\(^{*}_{KK}\) → hh → b\(\overline{b}\)b\(\overline{b}\) of 3.2(2.3) fb is set for a Kaluza-Klein graviton G\(^{*}_{KK}\) mass of 1.0(1.5) TeV, at the 95 \% confidence level. The search for non-resonant Standard Model hh production sets an observed 95 \% confidence level upper limit on the production cross-section σ(pp → hh → b\(\overline{b}\)b\(\overline{b}\)) of 202 fb, compared to a Standard Model prediction of σ(pp → hh → b\(\overline{b}\)b\(\overline{b}\)) = 3.6±0.5 fb.}, language = {en} } @article{OPUS4-15012, title = {Search for invisible decays of the Higgs boson produced in association with a hadronically decaying vector boson in pp collisions at \(\sqrt {s}\) = TeV with the ATLAS detector}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {7}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-015-3551-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150126}, pages = {337}, year = {2015}, abstract = {A search for Higgs boson decays to invisible particles is performed using 20.3 fb\(^{-1}\) of pp collision data at a centre-of-mass energy of 8 TeV recorded by the ATLAS detector at the Large Hadron Collider. The process considered is Higgs boson production in association with a vector boson (V = W or Z) that decays hadronically, resulting in events with two or more jets and large missing transverse momentum. No excess of candidates is observed in the data over the background expectation. The results are used to constrain VH production followed by H decaying to invisible particles for the Higgs boson mass range 115 < m\(_{H}\) < 300 GeV. The 95 \% confidence-level observed upper limit on σ\(_{VH}\) × BR(H → inv.) varies from 1.6 pb at 115 GeV to 0.13 pb at 300 GeV. Assuming Standard Model production and including the gg → H contribution as signal, the results also lead to an observed upper limit of 78 \% at 95 \% confidence level on the branching ratio of Higgs bosons decays to invisible particles at a mass of 125 GeV.}, language = {en} } @article{OPUS4-15013, title = {Search for invisible particles produced in association with single-top-quarks in proton-proton collisions at \(\sqrt {s}\) = 8 TeV with the ATLAS detector}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {2}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-014-3233-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150134}, pages = {79}, year = {2015}, abstract = {A search for the production of single-top-quarks in association with missing energy is performed in proton-proton collisions at a centre-of-mass energy of \(\sqrt {s}\) =8 TeV with the ATLAS experiment at the large hadron collider using data collected in 2012, corresponding to an integrated luminosity of 20.3 fb\(^{-1}\). In this search, the W boson from the top quark is required to decay into an electron or a muon and a neutrino. No deviation from the standard model prediction is observed, and upper limits are set on the production cross-section for resonant and non-resonant production of an invisible exotic state in association with a right-handed top quark. In the case of resonant production, for a spin-0 resonance with a mass of 500 GeV, an effective coupling strength above 0.15 is excluded at 95 \% confidence level for the top quark and an invisible spin-1/2 state with mass between 0 and 100 GeV. In the case of non-resonant production, an effective coupling strength above 0.2 is excluded at 95 \% confidence level for the top quark and an invisible spin-1 state with mass between 0 and 657 GeV.}, language = {en} } @article{OPUS4-15014, title = {Search for metastable heavy charged particles with large ionisation energy loss in pp collisions at \(\sqrt {s}\) = 8 TeV using the ATLAS experiment}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {9}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-015-3609-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150149}, pages = {407}, year = {2015}, abstract = {Many extensions of the Standard Model predict the existence of charged heavy long-lived particles, such as R-hadrons or charginos. These particles, if produced at the Large Hadron Collider, should be moving non-relativistically and are therefore identifiable through the measurement of an anomalously large specific energy loss in the ATLAS pixel detector. Measuring heavy long-lived particles through their track parameters in the vicinity of the interaction vertex provides sensitivity to metastable particles with lifetimes from 0.6 ns to 30 ns. A search for such particles with the ATLAS detector at the Large Hadron Collider is presented, based on a data sample corresponding to an integrated luminosity of 18.4 fb\(^{-1}\) of pp collisions at \(\sqrt {s}\) = 8 TeV. No significant deviation from the Standard Model background expectation is observed, and lifetime-dependent upper limits on R-hadrons and chargino production are set. Gluino R-hadrons with 10 ns lifetime and masses up to 1185 GeV are excluded at 95 \% confidence level, and so are charginos with 15 ns lifetime and masses up to 482 GeV.}, language = {en} } @article{OPUS4-15015, title = {Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at \(\sqrt {s}\) = 8 TeV with the ATLAS detector}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {7}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-015-3517-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150152}, pages = {299}, year = {2015}, abstract = {Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb\(^{-1}\) of \(\sqrt {s}\) = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between E\(^{miss}_{T}\) > 150 GeV and E\(^{miss}_{T}\) > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presented.}, language = {en} } @article{OPUS4-14988, title = {Measurement of the production and lepton charge asymmetry of bosons in Pb+Pb collisions at \(\sqrt {^{S}NN}\) with the ATLAS detector}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {1}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-014-3231-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149889}, pages = {23}, year = {2015}, abstract = {A measurement of W boson production in lead-lead collisions at \(\sqrt {^{S}NN}\)=2.76 TeV is presented. It is based on the analysis of data collected with the ATLAS detector at the LHC in 2011 corresponding to an integrated luminosity of 0.14 nb\(^{-1}\) and 0.15 nb\(^{-1}\) in the muon and electron decay channels, respectively. The differential production yields and lepton charge asymmetry are each measured as a function of the average number of participating nucleons ⟨N\(_{part}\)⟩ and absolute pseudorapidity of the charged lepton. The results are compared to predictions based on next-to-leading-order QCD calculations. These measurements are, in principle, sensitive to possible nuclear modifications to the parton distribution functions and also provide information on scaling of W boson production in multi-nucleon systems.}, language = {en} } @article{KarulinCaspellDittrichetal.2015, author = {Karulin, Alexey Y. and Caspell, Richard and Dittrich, Marcus and Lehmann, Paul V.}, title = {Normal distribution of CD8+ T-cell-derived ELISPOT counts within replicates justifies the reliance on parametric statistics for identifying positive responses}, series = {Cells}, volume = {4}, journal = {Cells}, number = {1}, doi = {10.3390/cells4010096}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149968}, pages = {96-111}, year = {2015}, abstract = {Accurate assessment of positive ELISPOT responses for low frequencies of antigen-specific T-cells is controversial. In particular, it is still unknown whether ELISPOT counts within replicate wells follow a theoretical distribution function, and thus whether high power parametric statistics can be used to discriminate between positive and negative wells. We studied experimental distributions of spot counts for up to 120 replicate wells of IFN-γ production by CD8+ T-cell responding to EBV LMP2A (426 - 434) peptide in human PBMC. The cells were tested in serial dilutions covering a wide range of average spot counts per condition, from just a few to hundreds of spots per well. Statistical analysis of the data using diagnostic Q-Q plots and the Shapiro-Wilk normality test showed that in the entire dynamic range of ELISPOT spot counts within replicate wells followed a normal distribution. This result implies that the Student t-Test and ANOVA are suited to identify positive responses. We also show experimentally that borderline responses can be reliably detected by involving more replicate wells, plating higher numbers of PBMC, addition of IL-7, or a combination of these. Furthermore, we have experimentally verified that the number of replicates needed for detection of weak responses can be calculated using parametric statistics.}, language = {en} } @article{OPUS4-15017, title = {Search for resonant diboson production in the ℓℓq\(\overline{q}\) final state in pp collisions at \(\sqrt {s}\) = 8 TeV with the ATLAS detector}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {2}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-015-3261-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150171}, pages = {69}, year = {2015}, abstract = {This paper reports on a search for narrow resonances in diboson production in the ℓℓq\(\overline{q}\) final state using pp collision data corresponding to an integrated luminosity of 20 fb\(^{-1}\) collected at \(\sqrt {s}\) = 8 TeV with the ATLAS detector at the Large Hadron Collider. No significant excess of data events over the Standard Model expectation is observed. Upper limits at the 95 \% confidence level are set on the production cross section times branching ratio for Kaluza-Klein gravitons predicted by the Randall-Sundrum model and for Extended Gauge Model W′ bosons. These results lead to the exclusion of mass values below 740 and 1590 GeV for the graviton and W′ boson respectively.}, language = {en} } @article{OPUS4-14997, title = {Observation and measurements of the production of prompt and non-prompt J/ψ mesons in association with a Z boson in pp collisions at \(\sqrt {s}\)=8 TeV with the ATLAS detector}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {5}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-015-3406-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149970}, pages = {229}, year = {2015}, abstract = {The production of a Z boson in association with a J/ψ meson in proton-proton collisions probes the production mechanisms of quarkonium and heavy flavour in association with vector bosons, and allows studies of multiple parton scattering. Using 20.3fb\(^{-1}\) of data collected with the ATLAS experiment at the LHC in pp collisions at \(\sqrt {s}\) = 8 TeV, the first measurement of associated Z+J/ψ production is presented for both prompt and non-prompt J/ψ production, with both signatures having a significance in excess of 5σ. The inclusive production cross-sections for Z boson production (analysed in μ\(^{+}\)μ\(^{-}\) or e\(^{+}\)e\(^{-}\) decay modes) in association with prompt and non-prompt J/ψ(→μ\(^{+}\)μ\(^{-}\)) are measured relative to the inclusive production rate of Z bosons in the same fiducial volume to be (36.8±6.7±2.5)×10\(^{-7}\) and (65.8±9.2±4.2)×10\(^{-7}\) respectively. Normalised differential production cross-section ratios are also determined as a function of the J/ψ transverse momentum. The fraction of signal events arising from single and double parton scattering is estimated, and a lower limit of 5.3 (3.7)mb at 68 (95)\% confidence level is placed on the effective cross-section regulating double parton interactions.}, language = {en} } @article{WorkuStichDaugschiesetal.2015, author = {Worku, Netsanet and Stich, August and Daugschies, Arwid and Wenzel, Iris and Kurz, Randy and Thieme, Rene and Kurz, Susanne and Birkenmeier, Gerd}, title = {Ethyl Pyruvate Emerges as a Safe and Fast Acting Agent against Trypanosoma brucei by Targeting Pyruvate Kinase Activity}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0137353}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150002}, pages = {e0137353}, year = {2015}, abstract = {Background Human African Trypanosomiasis (HAT) also called sleeping sickness is an infectious disease in humans caused by an extracellular protozoan parasite. The disease, if left untreated, results in 100\% mortality. Currently available drugs are full of severe drawbacks and fail to escape the fast development of trypanosoma resistance. Due to similarities in cell metabolism between cancerous tumors and trypanosoma cells, some of the current registered drugs against HAT have also been tested in cancer chemotherapy. Here we demonstrate for the first time that the simple ester, ethyl pyruvate, comprises such properties. Results The current study covers the efficacy and corresponding target evaluation of ethyl pyruvate on T. brucei cell lines using a combination of biochemical techniques including cell proliferation assays, enzyme kinetics, phasecontrast microscopic video imaging and ex vivo toxicity tests. We have shown that ethyl pyruvate effectively kills trypanosomes most probably by net ATP depletion through inhibition of pyruvate kinase (Ki = 3.0\(\pm\)0.29 mM). The potential of ethyl pyruvate as a trypanocidal compound is also strengthened by its fast acting property, killing cells within three hours post exposure. This has been demonstrated using video imaging of live cells as well as concentration and time dependency experiments. Most importantly, ethyl pyruvate produces minimal side effects in human red cells and is known to easily cross the blood-brain-barrier. This makes it a promising candidate for effective treatment of the two clinical stages of sleeping sickness. Trypanosome drug-resistance tests indicate irreversible cell death and a low incidence of resistance development under experimental conditions. Conclusion Our results present ethyl pyruvate as a safe and fast acting trypanocidal compound and show that it inhibits the enzyme pyruvate kinase. Competitive inhibition of this enzyme was found to cause ATP depletion and cell death. Due to its ability to easily cross the blood-brain-barrier, ethyl pyruvate could be considered as new candidate agent to treat the hemo-lymphatic as well as neurological stages of sleeping sickness.}, language = {en} } @article{OPUS4-15003, title = {Performance of the ATLAS muon trigger in pp collisions at \(\sqrt {s}\)= 8 TeV}, series = {European Physical Journal C: Particles and Fields}, volume = {75}, journal = {European Physical Journal C: Particles and Fields}, number = {3}, organization = {ATLAS Collaboration}, doi = {10.1140/epjc/s10052-015-3325-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150032}, pages = {120}, year = {2015}, abstract = {The performance of the ATLAS muon trigger system is evaluated with proton-proton collision data collected in 2012 at the Large Hadron Collider at a centre-of-mass energy of 8 TeV. It is primarily evaluated using events containing a pair of muons from the decay of Z bosons. The efficiency of the single-muon trigger is measured for muons with transverse momentum 25 < p\(_{T}\) < 100GeV, with a statistical uncertainty of less than 0.01 \% and a systematic uncertainty of 0.6 \%. The pT range for efficiency determination is extended by using muons from decays of J/ψ mesons, W bosons, and top quarks. The muon trigger shows highly uniform and stable performance. The performance is compared to the prediction of a detailed simulation.}, language = {en} }