TY - JOUR A1 - Kraft, Stephan T1 - … denn sie sagen nicht, was sie tun : zur Edition des siebten Bandes der Römischen Octavia Herzog Anton Ulrichs JF - IASL online N2 - Rezension zu Anton Ulrich Herzog zu Braunschweig und Lüneburg: Werke. Historisch kritische Ausgabe. Die Römische Octavia. Siebenter Band in vier Teilen. Hg. von Rolf Tarot in Verbindung mit Hans H. Krummacher, bearbeitet von Margarete und Rolf Tarot. (Bibliothek des Literarischen Vereins in Stuttgart 334-336, 338) Stuttgart: Anton Hiersemann 2003-2007. 1406 S. Paperback. EUR (D) 623,00. ISBN: 978-3-7772-0308-9. KW - Römische Octavia KW - Anton Ulrich Herzog zu Braunschweig und Lüneburg Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321447 UR - http://www.iaslonline.de/index.php?vorgang_id=3171 SN - 1612-0442 ET - accepted version ER - TY - JOUR A1 - Kraft, Stephan T1 - Eine Revisionsverhandlung : Der zerbrochene Krug und König Ödipus JF - Euphorion N2 - No abstract available. KW - Kleist, Heinrich von / Der zerbrochne Krug KW - Sophocles / Oedipus tyrannus Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321456 UR - https://euph.winter-verlag.de/ SN - 0014-2328 VL - 104 IS - 2 ET - accepted version ER - TY - CHAP A1 - Kraft, Stephan T1 - Komödie in der Psychiatrie – Psychiatrie als Komödie: Zur "Republik Vineta" mit einigen Anmerkungen zur Verfilmung durch Franziska Stünkel T2 - "Ich gründe eine Akademie für Selbstachtung." Moritz-Rinke-Arbeitsbuch N2 - Kein Abstract verfügbar. KW - Moritz Rinke / Republik Vineta KW - Literatur KW - Verfilmung Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252782 PB - Peter Lang CY - Frankfurt am Main ER - TY - JOUR A1 - Hansmann, T. A1 - Heinzmann, J. A1 - Wrenzycki, C. A1 - Zechner, U. A1 - Niemann, H. A1 - Haaf, T. T1 - Characterization of Differentially Methylated Regions in 3 Bovine Imprinted Genes: A Model for Studying Human Germ-Cell and Embryo Development JF - Cytogenetic and Genome Research N2 - Correct imprinting is crucial for normal fetal and placental development in mammals. Experimental evidence in animal models and epidemiological studies in humans suggest that assisted reproductive technologies (ARTs) can interfere with imprinted gene regulation in gametogenesis and early embryogenesis. Bos taurus is an agriculturally important species in which ARTs are commonly employed. Because this species exhibits a similar preimplantation development and gestation length as humans, it is increasingly being used as a model for human germ-cell and embryo development. However, in contrast to humans and mice, there is relatively little information on bovine imprinted genes. Here, we characterized the bovine intergenic IGF2-H19 imprinting control region (ICR) spanning approximately 3 kb. We identified a 300-bp differentially methylated region (DMR) approximately 6 kb upstream of the H19 promoter, containing a CpG island with CTCF-binding site and high sequence similarity with the human intergenic ICR. Additional differentially methylated CpG islands lie –6 kb to –3 kb upstream of the promoter, however these are less conserved. Both classical bisulfite sequencing and bisulfite pyrosequencing demonstrated complete methylation of the IGF2-H19 ICR in sperm, complete demethylation in parthenogenetic embryos having only the female genome, and differential methylation in placental and somatic tissues. In addition, we established pyrosequencing assays for the previously reported bovine SNRPN and PEG3 DMRs. The observed methylation patterns were consistent with genomic imprinting in all analyzed tissues/cell types. The identified IGF2-H19 ICR and the developed quantitative methylation assays may prove useful for further studies on the relationship between ARTs and imprinting defects in the bovine model. KW - bovine KW - differentially methylated region KW - IGF2-H19 KW - imprinting control region Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199051 SN - 1424-8581 SN - 1424-859X N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 132 IS - 4 ER - TY - BOOK A1 - Brauneck, Jens T1 - Late Quaternary climate changes in the Central Sahara : new evidence from palaeoenvironmental research in NE-Niger N2 - Surveys by the Universities of Wuerzburg and Berlin, starting in the 1970´s have revealed the existence of palaeolakes in remote areas in Niger. Initial research has shown that the sediments found are suitable for reconstructing its late quaternary palaeoenvironment. Although a high number of investigations focused on the succession of climatological conditions in the Central Sahara, some uncertainties still exist as the results show discontinuities and mostly are of low temporal and spatial resolution. Two expeditions in 2005 and 2006 headed to the northeastern parts of Niger to investigate the known remains of palaeolakes and search some new and undetected ones. Samples were taken at several study sites in order to receive a complete picture of the Late Quaternary environmental settings and to produce high-resolution proxies for palaeoclimate modelling. The most valuable and best-investigated study site is the sebkha of Seggedim, where a core of 15 meters length could be extracted which revealed a composition of high-resolution sections. Stratigraphical, structural and geochemical investigations as well as the analysis of thin sections allow the characterization of different environmental conditions from Early to Mid Holocene. Driven by climate and hydrogeological influence, the water body developed from a water pond of several metres depth within a stable, grass and shrub vegetated landscape, to an alternating freshwater lake in a more dynamic environmental setting. Radiocarbon dates set the beginning of the stage at about 10.6 ka cal BP, with an exceptionally stable regime to 6.6 ka cal BP (at 12.6 metres’ depth), when a major change in the sedimentation regime of the basin is recorded in the core. Increased erosion, likely due to decreased vegetation cover within the basin, led to the siltation/filling of the lake within a few hundred years and the subsequent development of a sebkha/salt pan due to massive evaporation. Due to the lack of dateable material in the upper core section, the termination of the lake stage and the onset of the subsequent sebkha stage cannot be determined precisely but can be narrowed to a period around 6 ka BP. The results obtained from the core are compared with those from terrestrial and lacustrine sediments from outside the depression, situated a few hundred kilometres further to the north. These supplementary study sites are required to validate the information obtained from the coring. Within the plateau landscape of Djado, Mangueni and Tchigai, two depressions and a valley containing lacustrine deposits, were investigated for palaeoenvironmental reconstruction. Depending on modifying local factors, these sediment archives were of shorter existence than IX the lake, but reveal additional information about the landscape dynamics from Early to Mid Holocene. A damming situation within a small tributary at Enneri Achelouma led to lacustrine sedimentation conditions at Early Holocene in the upper reaches of the valley. The remnants of the lacustrine accumulations show distinct changes in the environmental conditions within the small catchment, as the archive immediately responded to local climate-induced changes of precipitation. Radiocarbon dating of the deposited sediments revealed ages from 8780 ± 260 cal a BP to 9480 ± 80 cal a BP. The sites of Yoo Ango and Fabérgé show a completely different sedimentation milieu as they consist of basins within the foothills of the Tchigai. The study sites show increased catchment sizes, probably extending towards the Tchigai massif and are most likely influenced by groundwater charge. The widespread occurrence of wind shaped relicts and the limited amount of lacustrine remnants indicate a generally high aeolian activity in both areas. Only in wind sheltered spots, parts of the lacustrine sequences were preserved, that show ages spanning from Early to Mid Holocene (9440 ± 140 cal a BP – 6810 ±140 cal a BP) and give additional evidence of fires from pre-LGM periods. Although intensively weathered, all profiles indicate distinct changes in the sedimentation conditions by alternating geochemical values and the mineralogical composition. The information obtained from the records investigated in this work confirms the heterogeneity of reconstructed environmental succession in the Central Sahara. The Mid Holocene rapid (within decades) and uniform development from more humid to extremely arid environmental conditions cannot be confirmed for the Central Sahara. In addition, a division of Early and Mid Holocene wet periods cannot be confirmed, either. Actually, the evidences obtained from the palaeoenvironmental reconstructions revealed major variations in the timing and extend of lacustrine and aeolian periods. Evidently, a transitional time has existed between 7 to 5 ka BP where alternating influences prevailed. This is indicated by the varying sedimentation conditions in the Seggedim depression as well as the evidence of soil properties on a fossil dune, with a time of deposition dated to 6200 ± 400 cal a BP and the removal of lacustrine Sediments at the Seeterrassental at Mid Holocene. In respect to provide a complete picture of landscape succession and to avoid misinterpretation, the investigation of several dissimilar spots within a designated study area is prerequisite for further investigations. N2 - Bereits seit den 1970er Jahren sind Vorkommen von Paläoseen im Nordosten Nigers bekannt und waren Gegenstand einer Vielzahl von Untersuchungen über die Paläoumweltbedingungen der Zentralen Sahara des Spätquartärs. Trotz der großen Anzahl an Analysen bestehen noch immer Unsicherheiten in Bezug auf das zeitliche Ausmaß feuchter und trockener Phasen in diesem Gebiet, da angrenzende Areale deutlich unterschiedliche Entwicklungen aufweisen können. Im Zuge zweier Expeditionen in den Jahren 2005 und 2006 in den äußersten Nordosten Nigers, wurden an bereits untersuchten und erstmalig entdeckten Standorten Proben genommen, um ein komplettes Bild über die spätquartären Umweltbedingungen in diesem Gegend zu erlangen und um die Aussagekraft verschiedener Sedimentarchive zu überprüfen. Der wertvollste und am intensivsten untersuchte Standort ist die Sebkha von Seggedim, wo ein Bohrkern von 15 Meter Länge gewonnen werden konnte, welcher hochauflösende Sedimente einer ununterbrochenen Sequenz vom Frühen bis Mittleren Holozän aufweist. Untersuchungen zur Stratigraphie, Sedimentstruktur, Geochemie und Mineralogie ermöglichen die Unterscheidung mehrerer Stadien der Seeentwicklung und der damit verbundenen Umweltbedingungen. Durch klimatische und hydrogeologische Einflüsse geprägt, entwickelte sich der Wasserkörper zunächst zu einem wenige Meter tiefem, jedoch biologisch sehr produktivem Gewässer innerhalb einer stabilen Gras- und Strauchlandschaft. Datierungen belegen den Beginn dieser außerordentlich stabilen Phase vor ca. 10.600 Jahren und einer Dauer bis 6.600 Jahre vor heute. Ab 12,6 Meter Tiefe zeigt sich ein deutlicher Wechsel im Sedimentationsverhalten des Sees. Verstärkter Sedimenteintrag, höchstwahrscheinlich ausgelöst durch reduzierte Vegetationsbedeckung und Variationen in der Saisonalität der Niederschläge innerhalb des Einzugsgebietes, führte zur Verlandung des Sees binnen weniger Jahrhunderte und der anschließenden Entwicklung einer Sebkha (Salz-Ton-Pfanne) durch verstärkte Evaporation. Durch das Fehlen datierbaren Materials in den oberen Abschnitten des Kerns kann die Endphase des Sees und der nachfolgende Beginn der Sebkhaphase nicht exakt bestimmt werden, allerdings kann dieser Bereich auf eine Zeit um 5500 bis 6000 Jahre vor heute eingegrenzt werden. Die Ergebnisse der Bohrkernuntersuchungen sind im Folgenden mit weiteren Ergebnissen von lakustrinen Sedimenten außerhalb der Depression verknüpft worden. Diese zusätzlichen Untersuchungen dienen zur Validierung der Bohrkerndaten und zur Überprüfung potentieller überregionaler klimatischer Zusammenhänge. Einige hundert Kilometer nordwärts, inmitten der Plateaus von Djado, Mangueni und Tchigai wurden Standorte auf deren Entwicklung im Spätquartär untersucht. Aufgrund der unterschiedlichen, durch die Geographie bedingten, lokalen Faktoren weisen diese lakustrinen Sedimentarchive deutlich kürzere Lebensdauer auf, jedoch ermöglichen sie teilweise einen genaueren Einblick in die vorherrschende Dynamik innerhalb dieser Landschaften. Durch die Blockade eines tributären Tals im Enneri Achelouma wurden für einen kurzen Abschnitt im Frühholozän Seesedimente in dessen Oberlauf akkumuliert, welche kurzzeitige, aber deutliche Änderungen der Umweltbedingungen dokumentieren. Datierungen zeigen die Existenz dieser Seebecken oder Seeterrassen von 9480 ± 80 cal a BP bis 8780 ± 260 cal a BP. Durch Veränderungen im Niederschlagsregime kam es anschließend zu einer Zerschneidung und teilweisen Ausräumung des abgelagerten Materials. Die Standorte Yoo Ango und Fabérgé weisen ein komplett anderes Sedimentationsmilieu auf, da sie aus Becken innerhalb der Ausläufer des Tchigai Plateaus bestehen und deutlich größere Einzugsgebiete aufweisen. Zusätzlich sind beide Standorte grundwasserbeeinflusst und stark durch die sehr hohe äolische Aktivität in diesem Gebiet geprägt, sichtbar an dem weitverbreiteten äolischen Formenschatz sowie der geringen Anzahl erhaltener Seesedimente. Nur in wenigen windgeschützten Lokalitäten wurden lakustrine Sedimentpakete erhalten, die ebenfalls früh- bis mittelholozäne Alter aufweisen. Trotz der intensiven Verwitterung die sämtliche untersuchten Sedimente betrifft, weisen nahezu alle Profile eindeutige Veränderungen auf, sowohl in Bezug auf die geochemischen Werte als auch die mineralogische Zusammensetzung. Aus den untersuchten Profilen wird eine feuchtere Phase zu Beginn des Holozäns ersichtlich, die jedoch starken Schwankungen unterlegen war, wie in den Profilen von Achelouma zu sehen ist. In einer Phase des Übergangs im Mittelholozän endete zunächst die lakustrine Sedimentation in Achelouma, dann in der Fabérgé-Senke. Die erhöhte Niederschlagsvariabilität führte in Achelouma zur teilweisen Ausräumung der Seesedimente, während in der Fabérgé- Senke Dünen aktiv waren. Die Ergebnisse von Seggedim zeigen ebenfalls starke Veränderungen der Umweltbedingungen an, jedoch zeitlich versetzt zu den Ergebnissen aus den anderen Gebieten. Insgesamt weisen die Ergebnisse der Paläoumweltrekonstruktionen große zeitliche Unterschiede bezüglich des Endes der lakustrinen Phasen auf. Die Untersuchungen zeigen deutlich, dass lokale geographische Faktoren eine klimatische Interpretation von Klimaarchiven erschweren können. Insbesondere dann, wenn wie im Falle Seggedim, ein überregionaler Aquifer die Existenz eines Wasserkörpers in einem ansonsten ariden Gebiet verlängert und klimatische Einflussfaktoren zeitweise ausgeklammert werden. Um Fehlinterpretationen zu vermeiden und ein Gesamtbild der landschaftlichen Entwicklung eines Raumes zu erhalten, sind Informationen aus mehreren grundverschiedenen Paläoumweltarchiven erforderlich. T3 - Würzburger Geographische Arbeiten - 103 KW - Paläoklimatologie KW - Sahara KW - Westafrika KW - Mittlere Sahara KW - Niger KW - Jungquartär KW - Klimaänderung Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235146 ER - TY - BOOK A1 - Acker, Kristin T1 - Die US-Expansion des deutschen Discounters Aldi - Eine Fallstudie zur Internationalisierung im Einzelhandel N2 - Die Internationalisierung im Einzelhandel ist eine vergleichsweise junge Entwicklung, die in den vergangenen beiden Dekaden stark vorangeschritten ist. Dabei haben viele Unternehmen die Erfahrung machen müssen, die Grundlage ihres im Heimatland erlangten Wettbewerbsvorteils zwar in einige Märkte erfolgreich transferieren zu können, in andere Märkte jedoch nicht. Worin liegen die Ursachen hierfür? Trotz einer zunehmenden Zahl von Studien zur Internationalisierung im Einzelhandel gibt es immer noch ein mangelndes Verständnis dafür, unter welchen Bedingungen Unternehmen im Ausland erfolgreich sind, respektive wann sie scheitern. Einen theoretischen Rahmen zur Analyse der relevanten Erfolgsdeterminanten liefert die Institutionentheorie, die das Verhältnis zwischen Unternehmen und Gesellschaft betrachtet und gerade auch für interkulturelle Fragestellungen einen interessanten Untersuchungsansatz darstellt. Vor diesem Hintergrund wird in der vorliegenden Arbeit die US-amerikanische Expansion des Discounters Aldi analysiert. Aldi bietet sich für eine solche Fallstudie an, da der Discounter sein an den deutschen Markt angepasstes Erfolgskonzept Ende der 1970er Jahre weitestgehend unverändert in die USA transferiert hat - in eine institutionelle Umwelt, die sich deutlich von der deutschen unterscheidet. Wie erfolgreich kann Aldi in dieser Umwelt agieren? T3 - Geographische Handelsforschung - 16 KW - Aldi (USA) KW - Internationalisierung KW - Internationalisierung KW - Amerikanischer Markt KW - Discounter KW - Marktzugang KW - USA KW - Lebensmitteleinzelhandel KW - ALDI SÜD KW - Markteintrittsstrategie KW - Unternehmenserfolg Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180668 SN - 978-3-932820-35-9 N1 - Die gedruckte Version dieses Bandes ist im Buchhandel lieferbar. Nähere Informationen unter: http://www.metagis.de/MetaGIS-Fachbuch/Schriftenreihen/Reihe-GHF/reihe-ghf.html PB - L.I.S. Verlag CY - Passau ER - TY - JOUR A1 - Stellzig-Eisenhauer, Angelika A1 - Meyer-Marcotty, Philipp T1 - Interaction between otorhinolaryngology and orthodontics: correlation between the nasopharyngeal airway and the craniofacial complex JF - GMS Current Topics in Otorhinolaryngology - Head and Neck Surgery N2 - In terms of pathophysiology, an anatomically narrow airway is a predisposing factor for obstruction of the upper respiratory tract. The correlation between the nasopharyngeal airway and the craniofacial structures is discussed in this context. Thus a mutual interaction between the pharynx and the mandibular position was demonstrated, whereby the transverse dimension of the nasopharynx was significantly larger in patients with prognathism than in patients with retrognathism. The influence of chronic obstruction of the nasal airway on craniofacial development was also discussed. The form-and-function interaction, which ought to explain the causal relationship between nasal obstruction and craniofacial growth, appears to be of a multifactorial rather than a one-dimensional, linear nature. It is not disputed, however, that expanding the maxilla improves not only nasal volume and nasal flow, but also the subjective sensation of patients, although it is not possible to make a prognostic statement about the extent of this improvement because of the differing reactions of individuals. Orthodontic appliances for advancing the mandible can also be successfully used in the treatment of mild obstructive sleep apnea syndrome. This treatment method should be considered particularly for patients who are unwilling to undergo or cannot tolerate CPAP (continuous positive airway pressure) treatment. KW - craniofacial development KW - adenoids KW - rapid maxillary expansion (RME) KW - obstructive sleep apnea syndrome (OSAS) KW - mandibular advancement device (MAD) KW - nasopharyngeal airway Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140850 VL - 9 IS - Dok04 ER - TY - JOUR ED - Ramos Mendez, Carmen ED - Wildenauer-Józsa, Doris T1 - Profil. Würzburger Zeitschrift für den universitären Fremdsprachenunterricht. 02/2010: Lernerautonomie T2 - Profil N2 - Profil wird vom Zentrum für Sprachen der Universität Würzburg herausgegeben. Die Zeitschrift stellt neueste Entwicklungen des Fremdsprachenunterrichts an der Hochschule aus einer praxisorientierten Perspektive dar. Profil präsentiert Forschungsergebnisse und innovative Unterrichtsprojekte. Die Hauptbereiche der Zeitschrift sind Sprachlehr- und Lernforschung und Fremdsprachendidaktik. Ausgabe 02/2010: Lernerautonomie Summer, Theresa. Key Concept: Learner Autonomy Schmenk, Barbara. Bildungsphilosophischer Idealismus, erfahrungsgesättigte Praxisorientierung, didaktischer Hiphop? Eine kleine Geschichte der Lernerautonomie Curbelo, Ángel G. Ayudar a cruzar el puente: Un blog en la clase de lenguas para fomentar la autonomía Zhuber-Okrog, Karen. "Der Spaß und das Interesse diese Sprache zu lernen überwiegt" - Erfahrungen aus dem Selbstlernprojekt "Erste Schritte Russisch / Erste Schritte Arabisch" Asano, Yuki. Bericht einer Aktionsforschung zur Förderung autonomen Lernens in einem Japanischkurs – Aspekte selbstreflektierenden Fremdsprachenlernens Fröhlich, Brigitta; Holstein, Silke & Pilaski, Anna. Lernen bedeutet, sich auf den Weg zu machen – Lernoptimierung als Konzept im Unterricht Karagiannakis, Evangelia. Autonomes Lernen durch Beobachtung, Reflexion und Evaluation des eigenen Lernprozesses – Punktuelle und kontinuierliche Verfahren Sailer, Wolfram. epos– das elektronische Portfolio der Sprachen: ein wichtiges Instrument zur Förderung von Lernautonomie beim lebenslangen Sprachenlernen Tassinari, Maria Giovanna. Checklisten zu Lernerautonomie: Erfahrungen mit der Selbsteinschätzung Werbe, Franziska. Eigen- und Fremdevaluation im Rahmen eines Kurses "Präsentationstechniken" für ausländische Studierende Hammer, Julia. My presentation ... Presenting in English Smasal, Marc. Lernstrategien im Fremdsprachenunterricht. Ein Workshop für die fächerübergreifende Aus- und Weiterbildung von Fremdsprachenlehrkräften Breuer, Rachelle. Schreibberatung für die englische Sprache an deutschen Hochschulen: Forschungsvorhaben über die analytischen Zugänge zu Organisationsprinzipien und Beratungsstrategien Wildenauer-Józsa, Doris. "T. Claußen. Strategietraining und Lernberatung" / Rezension KW - Fremdsprachenunterricht KW - Lernerautonomie KW - learner autonomy Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152910 SN - 1869-3334 N1 - Dieses Dokument wurde aus Urheberrechtsschutzgründen erneut veröffentlicht. Der Artikel "My presentation ... Presenting in English" von Julia Hammer steht nicht mehr zur Verfügung. Die ursprüngliche Veröffentlichung war am 02.08.2010. VL - 02/2010 ER - TY - THES A1 - Schwemmer, Marius T1 - Studien zu Genealogie, Biographie und Werk von Joseph Willibald Michl (1745-1816) T1 - Studies about genealogy, biography und work of Joseph Willibald Michl (1745-1816) N2 - „Joseph Willibald Michl – Ein Komponist von vielem Kopfe“, so schrieb einst Christian Friedrich Daniel Schubart über den wohl bedeutendsten Spross einer Musikerfamilie, die über mindestens vier Generationen das Musikgeschehen der Oberpfalz, Bayerns und darüber hinaus mitgestaltete. Neben dem deutschen Dichter, Organisten, Komponisten und Journalisten Schubart, sprechen sich auch andere Zeitgenossen wie der englische Musikforscher Charles Burney oder der Historiker und Schriftsteller Lorenz von Westenrieder sprechen sich lobend über den „Churfürstlichen Kammer-Compositeur“ von Maximilian III. Joseph aus. Diese Studie untersucht die Genealogie, die Biographie und das Werk von Joseph Willibald Michl anhand neuer Quellen und schließt darüber hinaus Lücken in seinem Curriculum Vitae. Erstmals wird ein systematisch-thematisches Werkverzeichnis des Komponisten vorgelegt, um das heute noch greifbare musikalische Œuvre zu erfassen bzw. zur Klärung fraglicher oder offensichtlicher Falschzuweisungen beizutragen. In einer Analyse repräsentativ ausgewählter Werke der von Michl verwenden musikalischen Gattungen wird die Kompositionsart und Musiksprache Michls näher betrachtet. N2 - A compser with a clever mind - was the verdict of Christian Friedrich Daniel Schubart about Joseph Willibald Michl who was probably the most famous sprout of a musician’s dynasty. Over four generations Michl’s family influenced the musical scene of the time from the Upper Palatinate to Bavaria and beyond. Next to Schubart who was not only a German poet but also an organist, a composer and a journalist Michl, electoral chamber music composer of Maximilian III, was also praised by the English musicologist Charles Burney and the historian and author Lorenz von Westenrieder. By means of new sources this study researches the genealogy, biography and work of Michl and apart from that completes his curriculum vitae. The study includes the first entire list of Michl’s works recording his musical oeuvre or resolving doubtfully or obviously mistaken classification. Michl’s manner of composition and his musical language is analysed at representatively selected works of different genres. KW - Michl KW - Joseph Willibald KW - Hofkomponist KW - Landshuter Gesangbuch KW - Münchner Hof KW - Andrea (Komponist) KW - Mozart KW - Wolfgang Amadeus KW - Maximilian KW - Bernasconi KW - Kurfürst KW - Weyarn / Stift KW - Neumarkt KW - Camerloher Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145682 N1 - Dieses Dokument wurde aus rechtlichen Gründen erneut veröffentlicht. Die ursprüngliche Veröffentlichung war am 06.09.2010 ER - TY - THES A1 - Praetorius, Stefanie T1 - Einfluss der erfolgreichen Trabekulektomie auf Fluktuation und Spitzenwerte des intraokularen Druckes im Tag-Nacht-Vergleich T1 - Influence of successful trabeculectomy to the diurnal and nocturnal maximal IOP and IOP fluctuation N2 - Glaukomerkrankungen verlaufen progressiv und sind weltweit die zweithäufigste Ursa-che für Erblindung. Die einzig wirksame Therapie ist bisher die Senkung des IODs un¬ter eine individuelle Grenze. Dabei ist die Trabekulektomie diejenige Therapie mit dem stärksten drucksenkenden Effekt. Intraokulare Druckspitzen scheinen im Zusammen-hang mit progressiven Gesichtsfeldverlusten zu stehen. Die erfolgreiche Trabekulekto-mie senkt in dieser Arbeit den maximalen IOD nach einem Nachbeobachtungsintervall von 2,1 ± 1,7 Jahre auf durchschnittlich 16,0 ± 4,4 mmHg im Tagprofil und 16,0 ± 5,4 mmHg im Nachtprofil. Im Tagprofil bewirkt sie eine signifikante Senkung des maxi-malen IODs von 40 % vom präoperativen maximalen IOD (26,5 ± 5,9 mmHg), im Nachtprofil eine signifikante Senkung von 32 % des entsprechenden präoperativen Werts (23,4 ± 5,2 mmHg). Damit liegt der maximale IOD nach 2,1 ± 1,7 Jahren im Tagprofil bei 80 % der Patien-ten (bei 71 % ohne Medikamente) und im Nachtprofil bei 69 % (63 % ohne Medika-mente) unter oder bei 21 mmHg mit einer Reduktion gegenüber dem präoperativen IOD-Wertes von mindestens 20 %. Bei 60 % (54 % ohne Medikamente) im Tagprofil und bei 63 % (57 %) im Nachtprofil liegt der maximale IOD 2,1 ± 1,7 Jahre nach erfolgreicher Trabekulektomie unter 18 mmHg. Der erhöhte IOD ist nachweislich ein Risikofaktor für die Entstehung und die Progres-sion von Glaukomen. In den letzten Jahren zeigten einige Studien, dass die Fluktuation des IODs ein unabhängiger Risikofaktor für die Progression von Gesichtsfeldausfällen zu sein scheint. Die Auswirkung der erfolgreichen Trabekulektomie auf die Fluktuation ist bisher wenig untersucht. Die präoperative Fluktuation von 12,1 ± 4,2 mmHg im Tagesprofil beträgt 2,1 ± 1,7 Jahre nach erfolgreicher Trabekulektomie 5,6 ± 2,2 mmHg, das entspricht einer signifikanten Senkung von 54 % (6,5 ± 4,6 mmHg). Im Nachtprofil wurde eine Untergruppe betrachtet. Die präoperative Fluktuation von 7,1 ± 4,5 mmHg im Nachtprofil beträgt 2,1 ± 1,7 Jahre nach erfolgreicher Trabekulektomie 3,9 ± 4,1 mmHg, das entspricht einer nicht signifikanten Senkung von 46 % (3,3 ± 6,8 mmHg). Die Signifikanz in der Untergruppe wurde durch die geringe Fallzahl in der Untergruppe beeinträchtigt. Der IOD folgt einem circadianen Rhythmus. Einige Studien berichten von Unterschie-den im Tag-Nacht-Verhalten, weshalb in der vorliegenden Arbeit das Tagprofil und das Nachtprofil getrennt ausgewertet wurden. Der präoperative maximale IOD des Tagpro-fils lag 3,1 ± 6,1 mmHg (12 %) signifikant höher als der des Nachtprofils und wurde durch die erfolgreiche Trabekulektomie um 3,1 ± 6,6 mmHg (30 %) signifikant stärker gesenkt als der des Nachtprofils. Der postoperative maximale IOD war im Tag- und Nachtprofil im Durchschnitt fast identisch. In allen weiteren Auswertungen konnte kein signifikanter Unterschied im Tag-Nacht-Verhalten des IODs festgestellt werden. Antimetaboliten werden im Rahmen fistulierender Operationen zur Verminderung der natürlichen Wundheilung eingesetzt und erhöhen nachweislich die Erfolgsrate der Operation. Einige Studien haben festgestellt, dass die subkonjunktivale Applikation von Antimetaboliten ohne weitere Intervention drucksenkende Eigenschaften hat. In der vorliegenden Studie konnte dieser Effekt nicht bestätigt werden. Diese Studie liefert interessante Erkenntnisse zum Verhalten des IODs, insbesondere der Fluktuation des IODs nach erfolgreicher Trabekulektomie bei einer relativ langen Nachbeobachtungszeit. Über die Auswirkung der Trabekulektomie in Bezug auf die Fluktuation des IODs ist bisher wenig bekannt. Die Signifikanz der Ergebnisse könnte durch eine prospektive Studie mit größeren Fallzahlen erhöht werden. Eine wichtige Beschränkung der Aussagekraft der Ergebnisse liegt darin, dass das Verhalten des IODs bisher nicht an einem kontinuierlich erfassten IOD untersucht werden kann. N2 - High intraocular pressure (IOP) is a major risk factor for glaucoma, which is among the three most prevalent causes for blindness. Trabeculectomy (TET) is widely accepted as one of the best methods in lowering the IOP. Diurnal fluctuations of the IOP seem to be an indepentent risk factor for progression in visual field loss in case of glaucoma. In this thesis the effect of successful TET on the maximal values and the fluctuations of the IOP and the influence of intra- and postoperative use of antimetabolites (mitomycin C, 5-fluoruoracil) were studied and compared between day and night. Data were acquired retrospectively from documented diurnal and nocturnal IOP-measurements of 35 patients with medicially not controlled glaucoma who underwent successful trabeculectomy at the University of Wuerzburg and who had at least one diurnal and one nocturnal measurement of IOP before and after TET. We find that successful TET reduces the mean diurnal maximal IOP (mIOP maxD) by 40% (26,5 ± 5,9 mmHg to 16,0 ± 4,4 mmHg) (p<0,001) and the mean nocturnal maximal IOP (mIOPmaxN) by 32% (23,4 ± 5,2 mmHg to 16,0 ± 5,4 mmHg) (p<0,001). The mean diurnal pressure fluctuation after successful TET is significantly reduced by 54% (12,1 ± 4,2 mmHg to 5,6 ± 2,2 mmHg) (p<0,001). To calculate the nocturnal pressure fluctuation a smaller sub-group (7 patients) had to be built, in this group the nocturnal fluctuation is reduced by 46% (7,1 ± 4,5 mmHg to 3,9 ± 4,1 mmHg) but due to the small amount of patients the reduction is not significant (p=0,270). In this sub group the reduction of the diurnal fluctuation is averaged 49% (12,0 ± 6,1 mmHg to 6,1 ± 1,6 mmHg) with marginally significance (p<0,05). There is no significant difference between the reduction of the diurnal and nocturnal fluctuation. No influence of the intra- or/and postoperative use of antimetabolites to the maximal IOP was found in this study. For future studies larger numbers of cases, ideally deploying new techniques for continuous IOD measurement are desirable. KW - Glaukom KW - Augendruck KW - Operation KW - Fluktuation KW - Trabekulektomie KW - Tages-Nacht-Vergleich KW - Intraokularer Druck KW - glaucoma KW - intraocular pressure KW - trabeculectomy KW - fluctiation KW - nocturnal Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118511 N1 - Dieses Dokument wurde aus Datenschutzgründen - ohne inhaltliche Änderungen - erneut veröffentlicht. Die ursprüngliche Veröffentlichung war am: 12.05.2010 unter der URN http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-48129 Best. von Frau Kaiser (DNB) ist gegeben ER - TY - JOUR T1 - Campus Würzburg März (2010) N2 - Uni mal zwei - Für den doppelten Abi-Jahrgang verdoppelt sich der Campus KW - Universität Würzburg Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110184 UR - http://www.presse.uni-wuerzburg.de/publikationen/campus/ VL - 03/2010 ER - TY - JOUR T1 - Campus Würzburg Juni (2010) N2 - Un(i)gewöhnliche Orte: Mehr als Hörsaal und Mensa – so hast du den Campus noch nie gesehen KW - Universität Würzburg Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110178 UR - http://www.presse.uni-wuerzburg.de/publikationen/campus/ VL - 06/2010 ER - TY - JOUR T1 - Campus Würzburg September (2010) N2 - Da ist Musik drin - Auftakt zum neuen Semester KW - Universität Würzburg Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110151 UR - http://www.presse.uni-wuerzburg.de/publikationen/campus/ VL - 09/2010 ER - TY - THES A1 - Gogolin, Christian T1 - Pure State Quantum Statistical Mechanics T1 - Statistische Quantenmechanik mit reinen Zuständen N2 - The capabilities of a new approach towards the foundations of Statistical Mechanics are explored. The approach is genuine quantum in the sense that statistical behavior is a consequence of objective quantum uncertainties due to entanglement and uncertainty relations. No additional randomness is added by hand and no assumptions about a priori probabilities are made, instead measure concentration results are used to justify the methods of Statistical Physics. The approach explains the applicability of the microcanonical and canonical ensemble and the tendency to equilibrate in a natural way. This work contains a pedagogical review of the existing literature and some new results. The most important of which are: i) A measure theoretic justification for the microcanonical ensemble. ii) Bounds on the subsystem equilibration time. iii) A proof that a generic weak interaction causes decoherence in the energy eigenbasis. iv) A proof of a quantum H-Theorem. v) New estimates of the average effective dimension for initial product states and states from the mean energy ensemble. vi) A proof that time and ensemble averages of observables are typically close to each other. vii) A bound on the fluctuations of the purity of a system coupled to a bath. N2 - Es wird ein neuer Ansatz die Methoden der Statistischen Physik aus der Quan- tenmechanik heraus zu rechtfertigen untersucht. Der gewählte Zugang ist echt quantenmechanisch. Statistisches Verhalten wird allein durch objektive quanten- mechanische Zufälligkeit auf Grund von Verschränkung und Unbestimmtheitsre- lationen erklärt. Es werden keine Annahmen über subjective Unwissenheit oder a priori Wahrscheinlichkeiten gemacht. Der Ansatz ist in der Lage eine maß- theoretische Rechtfertigung für die Anwendbarkeit des mikrokanonischen und des kanonischen Ensembles zu geben und erklärt auf natürliche Weise das Streben ins Gleichgewicht. Diese Arbeit enthält einen Überblick über die vorhandene Literatur und eine Reihe von neuen Resultaten. Die wichtigsten neuen Ergebnisse sind: i) Eine maßtheoretische Begründung für die Anwendbarkeit des mikrokanonischen En- sembles. ii) Schranken für die Zeit bis ins Gleichgewicht. iii) Aufzeigen eines generischen Dekohärenz-Mechanismus in der lokalen Energie-Eigenbasis bei schwa- cher Kopplung. iv) Beweis eines quantenmechanischen H-Theorems. v) Neue Abschätzungen der mittleren effektiven Dimension für Produktzustände und im “mittlere Energie”-Ensemble. vi) Ein Beweis, dass Zeit und Ensemblemittel typ- ischerweise nahezu zusammenfallen. vii) Eine Schranke für die Fluktuationen der Reinheit eines an ein Bad gekoppelten Systems. KW - Quantum Mechanics KW - Statistical Physics KW - Quantenstatistik Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-106065 ER - TY - JOUR A1 - Ruhe, Ernstpeter T1 - Enjambements et envols: Assia Djebar échographe N2 - No abstract available. KW - Djebar, Assia Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-105385 ER - TY - CHAP A1 - Ruhe, Ernstpeter T1 - "Une révolution copernicienne": texte et pré-texte de la "Lettre à Maurice Thorez" N2 - No abstract available. KW - Thorez, Maurice KW - Césaire, Aimé Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-102189 ER - TY - JOUR A1 - Hommers, Wilfried A1 - Lee, Wha-Yong T1 - Unifying Kohlberg with Information Integration: The Moral Algebra of Recompense and of Kohlbergian Moral Informers JF - Psicológica N2 - In order to unify two major theories of moral judgment, a novel task is employed which combines elements of Kohlberg´s stage theory and of the theory of information integration. In contrast to the format of Kohlberg´s moral judgment interview, a nonverbal and quantitative response which makes low demands on verbal facility was used . Moral informers differing in value, i.e. high and low, are presented. The differences in effect of those two pieces of information should be substantial for a person at that specific moral stage, but small for a person at a different stage. Hence, these differences may diagnose the person's moral stage in the simplest possible way as the two levels of each of the thoughts were about typical content of the four Kohlbergian preconventional and conventional stages. The novel task allowed additionally to measure the influence of another moral concept which was about the non-Kohlbergian moral concept of recompense. After a training phase, pairs of those thoughts were presented to allow for the study of integration and individual differences. German and Korean children, 8, 10, and 12 years in age, judged deserved punishment. The patterns of means, correlations and factor loadings showed that elements of both theories can be unified, but produced unexpected results also. Additive integration of each of the two pairs of moral informers appeared, either with two Kohlbergian moral informers or with another Kohlbergian moral informer in combination with information about recompense. Also cultural independence as well as dependence, developmental changes between 8 and 10 years, and an outstanding moral impact of recompense in size and distinctiveness were observed. Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85875 UR - http://www.uv.es/psicologica/articulos3FM.10/16Hommers.pdf ER - TY - JOUR A1 - Reiserer, Andreas A. A1 - Huang, Jer-Shing A1 - Hecht, Bert A1 - Brixner, Tobias T1 - Subwavelength broadband splitters and switches for femtosecond plasmonic signals JF - Optics Express N2 - Numerical simulations and an analytic approach based on transmission line theory are used to design splitters for nano-plasmonic signal processing that allow to arbitrarily adjust the ratio of transmission from an input into two different output arms. By adjusting the geometrical parameters of the structure, either a high bandwidth or a sharp transmission resonance is obtained. Switching between the two arms can be achieved by modulating the effective refractive index of the waveguide. Employing the instantaneous Kerr effect, switching rates in the THz regime are potentially feasible. The suggested devices are of interest for future applications in nanoplasmonic information processing. Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85889 UR - http://www.opticsinfobase.org/oe/fulltext.cfm?uri=oe-18-11-11810&id=199640 ER - TY - JOUR A1 - Huenig, Siegfried A1 - Huenig, Georg T1 - Cataract Surgery With Implantation of an Artificial Lens Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85908 ER - TY - JOUR A1 - Johanssen, Sarah A1 - Hahner, Stefanie A1 - Saeger, Wolfgang A1 - Quinkler, Marcus A1 - Beuschlein, Felix A1 - Dralle, Henning A1 - Haaf, Michaela A1 - Kroiss, Matthias A1 - Jurowich, Christian A1 - Langer, Peter A1 - Oelkers, Wolfgang A1 - Spahn, Martin A1 - Willenberg, Holger S. A1 - Maeder, Uwe A1 - Allolio, Bruno A1 - Fassnacht, Martin T1 - Deficits in the Management of Patients With Adrenocortical Carcinoma in Germany N2 - Background: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Often, the physicians who first treat patients with ACC have no prior experience with the disease. The aim of our study was to evaluate the quality of medical care for patients with ACC in Germany. Methods: Data from the German ACC registry were analyzed with regard to the patients’ preoperative diagnostic evaluation, histopathological reporting, and clinical followup. The findings were compared with the recommendations of the European Network for the Study of Adrenal Tumors (ENSAT). Results: Data were analyzed from 387 patients who had been given an initial diagnosis of ACC in the years 1998 to 2009. 21% of them underwent no hormonal evaluation before surgery, and 59% underwent an inadequate hormonal evaluation. This exposed the patients to unnecessary perioperative risks and impaired their follow-up. 48% did not undergo CT scanning of the chest, even though the lungs are the most frequent site of metastases of ACC. For 13% of the patients, the diagnosis of ACC was later revised by a reference pathologist. For 11% of the patients, the histopathology report contained no information about resection status, even though this is an important determinant of further treatment and prognosis. Optimal management requires re-staging at three-month intervals, yet some patients underwent re-staging only after a longer delay, or not at all. Conclusion: We have identified significant deficits in the care of patients with ACC in Germany. We suspect that the situation is similar for other rare diseases. The prerequisite to better care is close and early cooperation of the treating physicians with specialized centers. Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85897 ER - TY - JOUR A1 - Dietl, Johannes T1 - The Marketing Effect Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85868 ER - TY - JOUR A1 - Zollner, Ursula A1 - Rehn, Monika A1 - Dietl, Johannes T1 - Perinatal Problems in Multiple Births Inconsistent Terminology Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85850 ER - TY - JOUR A1 - Ruesch, Dirk A1 - Eberhart, Leopold H. J. A1 - Wallenborn, Jan A1 - Kranke, Peter T1 - Nausea and Vomiting After Surgery Under General Anesthesia An Evidence-Based Review Concerning Risk Assessment, Prevention, and Treatment N2 - Background: The German-language recommendations for the management of postoperative nausea and vomiting(PONV) have been revised by an expert committee. Major aspects of this revision are presented here in the form of an evidence-based review article. Methods: The literature was systematically reviewed with the goal of revising the existing recommendations. New evidence-based recommendations for the management of PONV were developed, approved by consensus, and graded according to the scheme of the Scottish Intercollegiate Guidelines Network (SIGN). Results: The relevant risk factors for PONV include female sex, nonsmoker status, prior history of PONV, motion sickness, use of opioids during and after surgery, use of inhalational anesthetics and nitrous oxide, and the duration of anesthesia. PONV scoring systems provide a rough assessment of risk that can serve as the basis for a riskadapted approach. Risk-adapted prophylaxis, however, has not been shown to provide any greater benefit than fixed (combination) prophylaxis, and PONV risk scores have inherent limitations; thus, fixed prophylaxis may be advantageous. Whichever of these two approaches to manage PONV is chosen, high-risk patients must be given multimodal prophylaxis, involving both the avoidance of known risk factors and the application of multiple validated and effective antiemetic interventions. PONV should be treated as soon as it arises, to minimize patient discomfort, the risk of medical complications, and the costs involved. Conclusion: PONV lowers patient satisfaction but is treatable. The effective, evidence-based measures of preventing and treating it should be implemented in routine practice. Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85847 ER - TY - THES A1 - Bisping, Dirk T1 - Wachstum und Charakterisierung von GaInNAs-basierenden Halbleiterstrukturen für Laseranwendungen in der optischen Telekommunikation T1 - Growth and characterization of GaInNAs-based semiconductor structures for laser applications in optical communication N2 - Im Rahmen dieser Arbeit wurden mit Molekularstrahlepitaxie GaInNAs-Strukturen für mögliche Anwendungen in der Telekommunikation als GaAs-basierende Alternative für herkömmliche Laser auf InP-Substrat hergestellt und untersucht. Zunächst wurden durch Optimierung der Substrattemperaturmessung und RF-Plasmaquelle die Voraussetzungen für gutes GaInNAs-Wachstum geschaffen. Thermisches Ausheilen ist essentiell, um eine gute optische Qualität von GaInNAs-Strukturen zu erzielen. Man beobachtet einen signifikanten Einfluss von Ausheildauer und -temperatur. Exzessives Ausheilen bei zu hohen Temperaturen bzw. zu langen Zeiten führt, neben einer ebenso unerwünschten Blauverschiebung der Emission, wiederum zu einer Degradation der optischen Qualität, die sich in einer deutlichen Reduktion der Photolumineszenz(PL)-Intensität äußert. GaInNAs-Quantenfilm(QF)-Laser mit Emission um 1240 nm mit möglicher Anwendung als Pumplaser für Ramanverstärker wurden hergestellt und charakterisiert. Durch eine Optimierung des in-situ-Ausheilens dieser Laserstrukturen konnten Laser mit sehr niedrigen Schwellenstromdichten von deutlich unter 200 A/cm^2 hergestellt werden. Für eine möglichst hohe Ausgangsleistung wurde der Wirkungsgrad der Bauteile durch eine Optimierung der internen Verluste erhöht. Eine Reduktion der internen Verluste konnte durch eine Anpassung des Dotierprofils und die Verwendung von sogenannten Large-Optical-Cavities (LOCs) erreicht werden. Mit Hilfe des LOC-Designs konnten sehr niedrige interne Verluste von nur 0,5 1/cm bei einer internen Quanteneffizienz von nahezu 80 % erreicht werden. Mit optimierten Strukturen wurde stabiler Dauerstrichbetrieb bei Ausgangsleistungen von mehreren Watt über 1000~h ohne sichtbare Degradation demonstriert. Mit auf dem LOC-Design basierenden Lasern konnte schließlich eine sehr hohe Ausgangsleistung von ca. 9 W gezeigt werden. Anschließend wurden Untersuchungen zu Quantenpunkten (QPen) im Materialsystem GaInNAs vorgestellt. Mit steigendem Stickstoffgehalt beobachtet man eine Rotverschiebung der Emission bis auf 1,43 µm, allerdings gleichzeitig eine deutliche Degradation der optischen Qualität. Eine Untersuchung der QP-Morphologie ergibt eine Reduktion der Homogenität der QP-Größenverteilung, die sich im Auftreten zweier unterschiedlich großer QP-Ensembles äußert. Um diese Degradation der QPe zu vermeiden, wurde weiterhin auf den N-Einbau in den QPen verzichtet. Wider Erwarten führt der Verzicht auf N in den QPen nicht zu einer Blauverschiebung der Emission. Dieses Resultat konnte auf die veränderte QP-Morphologie zurückgeführt werden. Durch eine Erhöhung des N-Gehaltes im die QP überwachsenden QF wurde eine weitere deutliche Rotverschiebung der Emission erreicht. So konnte PL-Emission bei Raumtemperatur mit einem Emissionsmaximum bei 1600 nm demonstriert werden. Weiterhin wurden GaInNAs-QF-Strukturen für Laser im Wellenlängenbereich um 1550 nm untersucht. Da das Wachstum hier auf Grund des deutlich höheren, notwendigen N-Gehaltes wesentlich schwieriger wird, erfolgte zunächst eine detaillierte Untersuchung der wesentlichen Wachstumsparameter. Hierbei ist es essentiell, auch das Ausheilverhalten der jeweiligen Strukturen genau zu betrachten. Bei einer Untersuchung des Einflusses der Wachstumstemperatur auf GaInNAs-Teststrukturen wurden signifikante Unterschiede auch bei nur sehr geringen Änderungen in der Substrattemperatur von nur 10 °C festgestellt. Die beobachteten Effekte wurden vor dem Hintergrund des Modells der QP-ähnlichen Emitter diskutiert. Eine Variation des Arsen-Flusses zeigte einen deutlichen Einfluss auf die PL-Emission und vor allem auf das Ausheilverhalten. Das Ausheilverhalten lässt sich durch eine Anpassung des Arsen-Flusses maßgeschneidert anpassen. Während dem Überwachsen der aktiven Schicht mit Mantel- und Kontaktschicht kann es bereits zu einem Überausheilen der Strukturen kommen. Es wurden Laser mit niedrigen Schwellenstromdichten um 1 kA/cm^2 bis zu einer Wellenlänge von 1500 nm hergestellt. Für höhere Wellenlängen steigt die Schwellenstromdichte in den Bereich von 2 bis 3 kA/cm^2. Maximal wurde Laseremission bei über 1600 nm erreicht. Bei der Untersuchung der bei 1600 nm emittierenden Laserdioden wurde eine Verbreiterung der Laseremission zur hochenergetischen Seite auf bis zu 150 nm Bandbreite bei steigendem Betriebsstrom beobachtet. Dieser Effekt kann mit Hilfe des Modells der QP-ähnlichen Emitter verstanden werden. Unter Ausnutzung dieses Effekts wurden auf dem selben epitaktischen Material monomodige Distributed-Feedback(DFB)-Laser über einen Wellenlängenbereich von ca. 1500 nm bis 1600 nm gezeigt. Auf Basis der zuvor vorgestellten langwelligen Laserstrukturen mit niedrigen Schwellenstromdichten wurde erstmals Dauerstrichbetrieb von monomodigen DFB-Lasern im Bereich um 1500 nm und von multimodigen Stegwellenleiter-Lasern über 1500 nm im Materialsystems GaInNAs gezeigt. N2 - In this work, GaInNAs structures for telecom application based on GaAs in contrast to common lasers based on InP substrates have been grown by molecular beam epitaxy and subsequently characterized. First, optimizations of substrate temperature measurement and RF plasma source were incorporated to allow high quality GaInNAs growth. Thermal annealing is crucial to achieve high optical quality of GaInNAs structures. After a discussion of the microscopic processes during annealing, the influence of annealing parameters was examined. Excessive annealing with too high temperatures or too long times can, besides the typical blue-shift of the emission, also result in a decrease of the optical quality leading to a considerable reduction of the photoluminescence intensity. Laser diodes based on GaInNAs quantum wells emitting around 1240nm have been grown and characterized for a potential application as pump sources for Raman amplifiers. Using an optimization of the in-situ annealing during growth of these structures, laser diodes with very low threshold current densities well below 200 A/cm^2 have been realized. To achieve maximum output powers, the wallplug efficiencies of these devices have been increased by reducing the internal losses. Low internal losses have been achieved using an optimized doping profile or large optical cavities (LOCs). Using a LOC, very low internal losses of only 0.5 1/cm together with a high internal quantum efficiency of almost 80 % have been achieved. Stable performance for 1.000 h without degradation under continuous-wave operation was achieved. Using lasers with a LOC design, high maximum output powers of about 9 W have been demonstrated in continuous-wave operation. Afterwards, studies concerning quantum dots based on the GaInNAs material system have been shown. Increasing N-content leads to a redshift of the emissions wavelength up to 1.43 µm, but accompanied by a significant reduction of the optical quality. An examination of the quantum dot morphology also reveals a reduction in homogeneity of the quantum dot size distribution resulting in the occurence of quantum dot ensembles with two different sizes. To avoid this degradation of the quantum dots, N was not incorporated in the quantum dots, but only in the quantum well on top of the quantum dots. Unlike expectations, this doesn't involve a blueshift of the emission wavelength. This result could be explained by the different quantum dot morphology. By increasing the N-content in the quantum well the emission wavelength at room temperature was redshifted to 1600 nm. In addition, GaInNAs quantum well structures for laser diodes in the wavelength range around 1550 nm have been examined. Due to the more difficult growth resulting from the necessary higher N-content, a detailed examination of the growth parameters was required. Doing that, it is obligatory to take the annealing behaviour into account. A study of the influence of the substrate temperature showed a significant influence of very small differences in the range of 10 °C. Results have been discussed based on the modell of quantum dot like emitters. A variation of the arsenic flux during growth showed strong impact on photoluminescence emission and particularly annealing behaviour. The annealing behaviour can be tailored by changing the arsenic flux. Overgrowth of the quantum well with cladding and contact layers in complete laser stuctures can already result in over-annealing of the quantum well. It was possible to realize laser diodes with low threshold current densities in the range of 1 kA/cm^2 with emission wavelengths up to 1500 nm. For longer wavelengths, threshold current densities increase into the range of 2 to 3 kA/cm^2. The longest laser emission wavelength achieved was slightly above 1600 nm. Detailed examination of laser diodes emitting at 1600 nm revealed a huge broadening of the laser emission to higher energies resulting in an emission bandwidth of up to 150 nm under increasing drive current. This effect is explained using the model of quantum dot like emitters. Making use of this effect, single mode emitting distributed feedback lasers with emission wavelengths covering the whole wavelength range from 1500 to 1600 nm have been demonstrated. Based on the described long-wavelength laser diodes with low threshold current densities, continuous-wave operation of single-mode distributed feedback laser near 1500 nm and multimode ridge-waveguide lasers above 1500 nm have been shown for the first time using the GaInNAs material system. KW - Halbleiterlaser KW - Drei-Fünf-Halbleiter KW - Optoelektronik KW - verdünnte Nitride KW - Dilute Nitrides KW - Galliumarsenid KW - Molekularstrahlepitaxie KW - Telekommunikation KW - Hochleistungslaser KW - Dauerstrichbetrieb KW - Nitride Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77538 ER - TY - THES A1 - Schönemann, Kristin T1 - Der Einfluss von Steuern auf Investitions- und Desinvestitionsentscheidungen bei Immobilienvermögen : Eine ökonomische Analyse T1 - The influence of taxes on investment and divestment strategies regarding real estate - an economic analysis N2 - In der Dissertationsschrift werden die wesentlichen Merkmale von direkten und indirekten Immobilieninvestitionen in Deutschland für vier Spezialthemen der Immobilienbesteuerung dargestellt und somit ein Einblick in die vielseitige und komplexe Besteuerung von direkten und indirekten Immobilieninvestitionen gewährt. Die Investitionsmöglichkeiten in direkte Immobilienanlageformen werden in Kapitel 2 und 3 besprochen. Die indirekte Immobilienanlage und ihre Auswirkungen auf die Preisbildung werden in den Kapiteln 4 und 5 betrachtet. In der Schlussbemerkung (Kapitel 6) werden wesentliche Erkenntnisse dieser Arbeit zusammengefasst. Im Detail werden in den vier Hauptkapiteln folgende Fragestellungen bearbeitet: • Die steuerlichen Regelungen bei selbstgenutzten und vermieteten Wohnimmobilien führen stets zu Klientel-Effekten. Im Vermietungsfall bewirkt der progressive Ein-kommensteuertarif eine Begünstigung von Steuerpflichtigen mit hohen Einkom¬men. Lediglich eine steuersatzunabhängige Förderung kann dazu führen, dass ein durchschnittlich verdienender Eigenheimkäufer Förderquoten und Investitions-renditen auf demselben Niveau wie ein vermietender Spitzenverdiener erreicht. • Die Modernisierung der Immobilienförderung innerhalb der Altersvorsorge („Wohn-Riester“) ermöglicht den Einsatz des Riester-Kapitals als echtes Eigen-kapital und dominiert die klassische Eigen- und Fremdfinanzierung. Zudem ist die Tilgung eines zum Immobilienerwerb aufgenommenen Darlehens in die staatliche Förderung integriert worden und begünstigt so die Rückführung des steuerlich benachteiligten Fremdkapitals im Fall der Selbstnutzung. • Die Wahl des steuerlichen Wertansatzes bei Vermögensübertragung auf eine steuerbegünstigte Immobilienverwaltung ist nicht trivial. Die Vorteilhaftigkeit der Wertansatzalternativen ist maßgebliche durch den Abschreibungsverlauf, die Länge des Investitionszeitraums sowie den rechtsformspezifische Steuersatzdifferenzen beeinflusst. Es zeigt sich, dass eine Aufdeckung der stillen Reserven regelmäßig nur in Verbindung mit zusätzlichen Begünstigungen sinnvoll ist. Eine allgemeine Vorteilhaftigkeit für die Umwandlung in einen REIT besteht nicht. • Steuerprivilegien können durch gesetzlich erzwungene Finanzierungsstrukturen deutlich reduziert bzw. vernichtet werden. Insbesondere der REIT wird an der Ausübung seiner steueroptimierten Finanzierungsstrategie gehindert, sodass die Erlangung des REIT-Status kein Garant für niedrige Kapitalkosten ist. Die ver-mögensverwaltende Immobilien-AG stellt aufgrund der flexiblen Ausschüttungs- und Finanzierungspolitik eine Alternative zu dem stark reglementierten REIT dar. N2 - This dissertation analyzes the selected characteristics of direct and indirect real estate investments in Germany. The complex and diverse tax consequences of real estate investments are discussed for four separate topics. Therefore, the dissertations deals in chapter 2 and 3 with direct real estate investments and in chapter 4 and 5 with indirect real estate investments to show the consequences in private and business property of German investors. Chapter 6 summarizes the main results of the previous sections. The following topics are analyzed in detail: • The German tax law results in clientele effects for average income and high income tax payers in conjunction with owner occupied or leased real estate. For high income tax payers the progressive tax scale favors the lease rather than the personal use of the real estate. Only a tax subsidy independent of the tax rate will result in a similar support and yield for average income and high income tax payers. • The German private pension scheme (Riester-Rente) also includes a subsidy to create personal used real estate. This pension scheme enables the German investor to use its Riester-capital as real equity and dominates the use of the classical equity and debt financing. In addition the redemption of debt is part of the pension scheme and favors the redemption of tax-discriminated debt in the case of the personal used real estate. • The election of the fair or book value of real estate is not trivial with respect to the change of corporate form for asset managing purposes. The advantage of the respective value will depend on the depreciation rate, period of investment and tax differences resulting from the chosen legal framework. Finally a fair value approach is only favorable in connection with additional tax benefits. A change of the legal framework to a real estate investment trust (REIT) is not always advantageous. • Tax privileges can be contradicted by regulatory restrictions regarding financing. In particular a REIT suffers from the financing restrictions as these will result in a non-optimal financing strategy and higher capital costs for tax purposes. In contrast to the highly regulated REIT a German asset-managing corporation can be a advantageous alternative as this corporation is flexible regarding distribution and self-financing. KW - Deutschland KW - Immobilienanlage KW - Steuerrecht KW - Eigenheimrentenmodell KW - Eigenheimzulage KW - Kapitalkosten KW - Umwandlungsvorgänge KW - real estate KW - taxes KW - subsidies KW - corporations KW - partnerships Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-74609 ER - TY - THES A1 - Weis, Claudia T1 - Berechnungen der Lebenserkrankungswahrscheinlichkeit bei familiärem Brustkrebs - Vergleich von Methoden T1 - Lifetime risk calculation for familial breast cancer - comparison of methods N2 - Diese Arbeit vergleicht verschiedene Methoden zur Berechung der Lebenserkrankungswahrscheinlichkeit bei familiärem Brustkrebs. Dabei handelt es sich um Tabellen von Chang-Claude und die Computerprogramme Cyrillic Version 2.1 sowie IBIS Breast Cancer Risk Evaluation Tool. Es stellte sich heraus, dass sich die Ergebnisse der Modelle nicht wesentlich voneinander unterscheiden. N2 - This paper compares different models of lifetime risk calculation for familial breast cancer. These were tables of Chang-Claude and the computer programmes Cyrillic Version 2.1 and IBIS Breast Cancer Risk Evaluation Tool. It is shown that there is no distinct difference between the results of calculated risks. KW - Brustkrebs KW - Risiko KW - Berechnung KW - breast cancer KW - risk KW - calculation Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-74027 ER - TY - JOUR A1 - Schupp, Nicole A1 - Heidland, August A1 - Stopper, Helga T1 - Genomic Damage in Endstage Renal Disease - Contribution of Uremic Toxins N2 - Patients with end-stage renal disease (ESRD), whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin upplementation. KW - Toxin KW - dialysis KW - genotoxicity KW - uremic toxins Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68653 ER - TY - JOUR A1 - Schenkel, Alexander A1 - Uhlemann, Christoph F. T1 - Field Theory on Curved Noncommutative Spacetimes N2 - We study classical scalar field theories on noncommutative curved spacetimes. Following the approach of Wess et al. [Classical Quantum Gravity 22 (2005), 3511 and Classical Quantum Gravity 23 (2006), 1883], we describe noncommutative spacetimes by using (Abelian) Drinfel’d twists and the associated ?-products and ?-differential geometry. In particular, we allow for position dependent noncommutativity and do not restrict ourselves to the Moyal–Weyl deformation. We construct action functionals for real scalar fields on noncommutative curved spacetimes, and derive the corresponding deformed wave equations. We provide explicit examples of deformed Klein–Gordon operators for noncommutative Minkowski, de Sitter, Schwarzschild and Randall–Sundrum spacetimes, which solve the noncommutative Einstein equations. We study the construction of deformed Green’s functions and provide a diagrammatic approach for their perturbative calculation. The leading noncommutative corrections to the Green’s functions for our examples are derived. KW - Physik KW - noncommutative field theory KW - Drinfel’d twists KW - deformation quantization KW - field theory on curved spacetimes Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68648 ER - TY - JOUR A1 - Conrad, Christopher A1 - Fritsch, Sebastian A1 - Zeidler, Julian A1 - Rücker, Gerd A1 - Dech, Stefan T1 - Per-Field Irrigated Crop Classification in Arid Central Asia Using SPOT and ASTER Data N2 - The overarching goal of this research was to explore accurate methods of mapping irrigated crops, where digital cadastre information is unavailable: (a) Boundary separation by object-oriented image segmentation using very high spatial resolution (2.5–5 m) data was followed by (b) identification of crops and crop rotations by means of phenology, tasselled cap, and rule-based classification using high resolution (15–30 m) bi-temporal data. The extensive irrigated cotton production system of the Khorezm province in Uzbekistan, Central Asia, was selected as a study region. Image segmentation was carried out on pan-sharpened SPOT data. Varying combinations of segmentation parameters (shape, compactness, and color) were tested for optimized boundary separation. The resulting geometry was validated against polygons digitized from the data and cadastre maps, analysing similarity (size, shape) and congruence. The parameters shape and compactness were decisive for segmentation accuracy. Differences between crop phenologies were analyzed at field level using bi-temporal ASTER data. A rule set based on the tasselled cap indices greenness and brightness allowed for classifying crop rotations of cotton, winter-wheat and rice, resulting in an overall accuracy of 80 %. The proposed field-based crop classification method can be an important tool for use in water demand estimations, crop yield simulations, or economic models in agricultural systems similar to Khorezm. KW - Geologie KW - object-based classification KW - segmentation KW - tasselled cap KW - Uzbekistan KW - irrigated agriculture KW - multi-sensor Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68630 ER - TY - JOUR A1 - Landmann, Tobias A1 - Schramm, Matthias A1 - Colditz, Rene R. A1 - Dietz, Andreas A1 - Dech, Stefan T1 - Wide Area Wetland Mapping in Semi-Arid Africa Using 250-Meter MODIS Metrics and Topographic Variables N2 - Wetlands in West Africa are among the most vulnerable ecosystems to climate change. West African wetlands are often freshwater transfer mechanisms from wetter climate regions to dryer areas, providing an array of ecosystem services and functions. Often wetland-specific data in Africa is only available on a per country basis or as point data. Since wetlands are challenging to map, their accuracies are not well considered in global land cover products. In this paper we describe a methodology to map wetlands using well-corrected 250-meter MODIS time-series data for the year 2002 and over a 360,000 km2 large study area in western Burkina Faso and southern Mali (West Africa). A MODIS-based spectral index table is used to map basic wetland morphology classes. The index uses the wet season near infrared (NIR) metrics as a surrogate for flooding, as a function of the dry season chlorophyll activity metrics (as NDVI). Topographic features such as sinks and streamline areas were used to mask areas where wetlands can potentially occur, and minimize spectral confusion. 30-m Landsat trajectories from the same year, over two reference sites, were used for accuracy assessment, which considered the area-proportion of each class mapped in Landsat for every MODIS cell. We were able to map a total of five wetland categories. Aerial extend of all mapped wetlands (class “Wetland”) is 9,350 km2, corresponding to 4.3% of the total study area size. The classes “No wetland”/“Wetland” could be separated with very high certainty; the overall agreement (KHAT) was 84.2% (0.67) and 97.9% (0.59) for the two reference sites, respectively. The methodology described herein can be employed to render wide area base line information on wetland distributions in semi-arid West Africa, as a data-scarce region. The results can provide (spatially) interoperable information feeds for inter-zonal as well as local scale water assessments. KW - Geologie KW - wetland mapping KW - MODIS time-series KW - Landsat KW - land cover KW - class homogeneity KW - West Africa Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68628 ER - TY - JOUR A1 - Koetschan, Christian A1 - Foerster, Frank A1 - Keller, Alexander A1 - Schleicher, Tina A1 - Ruderisch, Benjamin A1 - Schwarz, Roland A1 - Mueller, Tobias A1 - Wolf, Matthias A1 - Schultz, Joerg T1 - The ITS2 Database III-sequences and structures for phylogeny N2 - The internal transcribed spacer 2 (ITS2) is a widely used phylogenetic marker. In the past, it has mainly been used for species level classifications. Nowadays, a wider applicability becomes apparent. Here, the conserved structure of the RNA molecule plays a vital role. We have developed the ITS2 Database (http://its2.bioapps .biozentrum.uni-wuerzburg.de) which holds information about sequence, structure and taxonomic classification of all ITS2 in GenBank. In the new version, we use Hidden Markov models (HMMs) for the identification and delineation of the ITS2 resulting in a major redesign of the annotation pipeline. This allowed the identification of more than 160 000 correct full ength and more than 50 000 partial structures. In the web interface, these can now be searched with a modified BLAST considering both sequence and structure, enabling rapid taxon sampling. Novel sequences can be annotated using the HMM based approach and modelled according to multiple template structures. Sequences can be searched for known and newly identified motifs. Together, the database and the web server build an exhaustive resource for ITS2 based phylogenetic analyses. KW - Biologie Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68390 ER - TY - JOUR A1 - Albrecht, Marco A1 - Sharma, Cynthia M. A1 - Reinhardt, Richard A1 - Vogel, Joerg A1 - Rudel, Thomas T1 - Deep sequencing-based discovery of the Chlamydia trachomatis transcriptome N2 - Chlamydia trachomatis is an obligate intracellular pathogenic bacterium that has been refractory to genetic manipulations. Although the genomes of several strains have been sequenced, very little information is available on the gene structure of these bacteria. We used deep sequencing to define the transcriptome of purified elementary bodies (EB) and reticulate bodies (RB) of C. trachomatis L2b, respectively. Using an RNAseq approach, we have mapped 363 transcriptional start sites (TSS) of annotated genes. Semiquantitative analysis of mapped cDNA reads revealed differences in the RNA levels of 84 genes isolated from EB and RB, respectively. We have identified and in part confirmed 42 genome- and 1 plasmid-derived novel non-coding RNAs. The genome encoded non-coding RNA, ctrR0332 was one of the most abundantly and differentially expressed RNA in EB and RB, implying an important role in the developmental cycle of C. trachomatis. The detailed map of TSS in a thus far unprecedented resolution as a complement to the genome sequence will help to understand the organization, control and function of genes of this important pathogen. KW - Biologie Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68389 ER - TY - JOUR A1 - Schneider, Eberhard A1 - Pliushch, Galyna A1 - El Hajj, Nady A1 - Galetzka, Danuta A1 - Puhl, Alexander A1 - Schorsch, Martin A1 - Frauenknecht, Katrin A1 - Riepert, Thomas A1 - Tresch, Achim A1 - Mueller, Annette M. A1 - Coerdt, Wiltrud A1 - Zechner, Ulrich A1 - Haaf, Thomas T1 - Spatial, temporal and interindividual epigenetic variation of functionally important DNA methylation patterns N2 - DNA methylation is an epigenetic modification that plays an important role in gene regulation. It can be influenced by stochastic events, environmental factors and developmental programs. However, little is known about the natural variation of genespecific methylation patterns. In this study, we performed quantitative methylation analyses of six differentially methylated imprinted genes (H19, MEG3, LIT1, NESP55, PEG3 and SNRPN), one hypermethylated pluripotency gene (OCT4) and one hypomethylated tumor suppressor gene (APC) in chorionic villus, fetal and adult cortex, and adult blood samples. Both average methylation level and range of methylation variation depended on the gene locus, tissue type and/or developmental stage. We found considerable variability of functionally important methylation patterns among unrelated healthy individuals and a trend toward more similar methylation levels in monozygotic twins than in dizygotic twins. Imprinted genes showed relatively little methylation changes associated with aging in individuals who are >25 years. The relative differences in methylation among neighboring CpGs in the generally hypomethylated APC promoter may not only reflect stochastic fluctuations but also depend on the tissue type. Our results are consistent with the view that most methylation variation may arise after fertilization, leading to epigenetic mosaicism. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68371 ER - TY - JOUR A1 - Rothe, D. G. A1 - Reinthaler, R. W. A1 - Liu, C-X A1 - Molenkamp, L. W. A1 - Zhang, S-C A1 - Hankiewicz, E. M. T1 - Fingerprint of different spin-orbit terms for spin transport in HgTe quantum wells N2 - Using k · p theory, we derive an effective four-band model describing the physics of the typical two-dimensional topological insulator (HgTe/CdTe quantum well (QW)) in the presence of an out-of-plane (in the z-direction) inversion breaking potential and an in-plane potential. We find that up to third order in perturbation theory, only the inversion breaking potential generates new elements to the four-band Hamiltonian that are off-diagonal in spin space. When this new effective Hamiltonian is folded into an effective twoband model for the conduction (electron) or valence (heavy hole) bands, two competing terms appear: (i) a Rashba spin–orbit interaction originating from inversion breaking potential in the z-direction and (ii) an in-plane Pauli term as a consequence of the in-plane potential. Spin transport in the conduction band is further analysed within the Landauer–Büttiker formalism. We find that for asymmetrically doped HgTe QWs, the behaviour of the spin-Hall conductance is dominated by the Rashba term. KW - Physik Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68362 ER - TY - JOUR A1 - Ueceyler, Nurcan A1 - Biko, Lydia A1 - Sommer, Claudia T1 - MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice N2 - The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). Onehundred- thirteen wild type mice of C57Bl/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal withdrawal latencies were investigated at baseline and at 1, 3, and 7 days after CCI. Three application regimens were used for MDL-28170: a) single injection 40 min before CCI; b) serial injections of MDL- 28170 40 min before and up to day three after CCI; c) sustained application via intraperitoneal osmotic pumps. The control animals received the vehicle DMSO/PEG 400. The tolerable dose of MDL-28170 for mice was 30 mg/kg body weight, higher doses were lethal within the first hours after application. Mechanical withdrawal thresholds and thermal withdrawal latencies were reduced after CCI and did not normalize after single or serial injections, nor with application of MDL-28170 via osmotic pumps. Although the calpain inhibitor MDL-28170 inhibits the early local cytokine upregulation in the sciatic nerve after CCI, pain behavior is not altered. This finding implies that local cytokine upregulation after nerve injury alone is only one factor in the induction and maintenance of neuropathic pain. KW - Medizin KW - calpain KW - neuropathic pain KW - MDL-28170 KW - chronic constriction nerve injury (CCI) Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68359 ER - TY - JOUR A1 - Chen, Yong A1 - Boettger, Michael K. A1 - Reif, Andreas A1 - Schmitt, Angelika A1 - Ueceyler, Nurcan A1 - Sommer, Claudia T1 - Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice N2 - Background: Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results: Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund’s adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1b), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1b. The increase of the antiinflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1b, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion: These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68349 ER - TY - JOUR A1 - Meierjohann, Svenja A1 - Hufnagel, Anita A1 - Wende, Elisabeth A1 - Kleinschmidt, Markus A. A1 - Wolf, Katarina A1 - Friedl, Peter A1 - Gaubatz, Stefan A1 - Schartl, Manfred T1 - MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation N2 - Background: Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. Activation of matrix metalloproteases goes along with RTK activation and usually enhances RTK-driven migration. The purpose of this study was to examine RTKdriven three-dimensional migration of melanocytes and the pro-tumorigenic role of matrix metalloproteases for melanocytes and melanoma cells. Results: Using experimental melanocyte dedifferentiation as a model for early melanomagenesis we show that an activated EGF receptor variant potentiates migration through three-dimensional fibrillar collagen. EGFR stimulation also resulted in a strong induction of matrix metalloproteases in a MAPK-dependent manner. However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. Instead, MMPs fulfilled a function in cell cycle regulation, as their inhibition resulted in strong growth inhibition of melanocytes. The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. Using sh- and siRNA techniques, we could show that MMP13 is the protease responsible for this effect. Along with decreased proliferation, knockdown of MMP13 strongly enhanced pigmentation of melanocytes. Conclusions: Our data show for the first time that growth stimuli are mediated via MMP13 in melanocytes and melanoma, suggesting an autocrine MMP13-driven loop. Given that MMP13-specific inhibitors are already developed, these results support the evaluation of these inhibitors in the treatment of melanoma. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68335 ER - TY - JOUR A1 - Puetz, Stephanie M. A1 - Vogiatzi, Fotini A1 - Stiewe, Thorsten A1 - Sickmann, Albert T1 - Malignant transformation in a defined genetic background: proteome changes displayed by 2D-PAGE N2 - Background: Cancer arises from normal cells through the stepwise accumulation of genetic alterations. Cancer development can be studied by direct genetic manipulation within experimental models of tumorigenesis. Thereby, confusion by the genetic heterogeneity of patients can be circumvented. Moreover, identification of the critical changes that convert a pre-malignant cell into a metastatic, therapy resistant tumor cell, however, is one necessary step to develop effective and selective anti-cancer drugs. Thus, for the current study a cell culture model for malignant transformation was used: Primary human fibroblasts of the BJ strain were sequentially transduced with retroviral vectors encoding the genes for hTERT (cell line BJ-T), simian virus 40 early region (SV40 ER, cell line BJ-TE) and H-Ras V12 (cell line BJ-TER). Results: The stepwise malignant transformation of human fibroblasts was analyzed on the protein level by differential proteome analysis. We observed 39 regulated protein spots and therein identified 67 different proteins. The strongest change of spot patterns was detected due to integration of SV40 ER. Among the proteins being significantly regulated during the malignant transformation process well known proliferating cell nuclear antigen (PCNA) as well as the chaperones mitochondrial heat shock protein 75 kDa (TRAP-1) and heat shock protein HSP90 were identified. Moreover, we find out, that TRAP-1 is already up-regulated by means of SV40 ER expression instead of H-Ras V12. Furthermore Peroxiredoxin-6 (PRDX6), Annexin A2 (p36), Plasminogen activator inhibitor 2 (PAI-2) and Keratin type II cytoskeletal 7 (CK-7) were identified to be regulated. For some protein candidates we confirmed our 2D-PAGE results by Western Blot. Conclusion: These findings give further hints for intriguing interactions between the p16-RB pathway, the mitochondrial chaperone network and the cytoskeleton. In summary, using a cell culture model for malignant transformation analyzed with 2D-PAGE, proteome and cellular changes can be related to defined steps of tumorigenesis. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68321 ER - TY - JOUR A1 - Pimentel-Elardo, Sheila Marie A1 - Kozytska, Svitlana A1 - Bugni, Tim S. A1 - Ireland, Chris M. A1 - Moll, Heidrun A1 - Hentschel, Ute T1 - Anti-Parasitic Compounds from Streptomyces sp. Strains Isolated from Mediterranean Sponges N2 - Actinomycetes are prolific producers of pharmacologically important compounds accounting for about 70% of the naturally derived antibiotics that are currently in clinical use. In this study, we report on the isolation of Streptomyces sp. strains from Mediterranean sponges, on their secondary metabolite production and on their screening for anti-infective activities. Bioassay-guided isolation and purification yielded three previously known compounds namely, cyclic depsipeptide valinomycin, indolocarbazole alkaloid staurosporine and butenolide. This is the first report of the isolation of valinomycin from a marine source. These compounds exhibited novel anti-parasitic activities specifically against Leishmania major (valinomycin IC50 < 0.11 μM; staurosporine IC50 5.30 μM) and Trypanosoma brucei brucei (valinomycin IC50 0.0032 μM; staurosporine IC50 0.022 μM; butenolide IC50 31.77 μM). These results underscore the potential of marine actinomycetes to produce bioactive compounds as well as the re-evaluation of previously known compounds for novel anti-infective activities. KW - Biologie KW - marine sponges KW - Streptomyces KW - valinomycin KW - staurosporine KW - butenolide KW - anti-parasitic Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68312 ER - TY - JOUR A1 - Abdelmohsen, Usama Ramadan A1 - Pimentel-Elardo, Sheila M. A1 - Hanora, Amro A1 - Radwan, Mona A1 - Abou-El-Ela, Soad H. A1 - Ahmed, Safwat A1 - Hentschel, Ute T1 - Isolation, Phylogenetic Analysis and Anti-infective Activity Screening of Marine Sponge-Associated Actinomycetes N2 - Terrestrial actinomycetes are noteworthy producers of a multitude of antibiotics, however the marine representatives are much less studied in this regard. In this study, 90 actinomycetes were isolated from 11 different species of marine sponges that had been collected from offshore Ras Mohamed (Egypt) and from Rovinj (Croatia). Phylogenetic characterization of the isolates based on 16S rRNA gene sequencing supported their assignment to 18 different actinomycete genera representing seven different suborders. Fourteen putatively novel species were identified based on sequence similarity values below 98.2% to other strains in the NCBI database. A putative new genus related to Rubrobacter was isolated on M1 agar that had been amended with sponge extract, thus highlighting the need for innovative cultivation protocols. Testing for anti-infective activities was performed against clinically relevant, Gram-positive (Enterococcus faecalis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria, fungi (Candida albicans) and human parasites (Leishmania major, Trypanosoma brucei). Bioactivities against these pathogens were documented for 10 actinomycete isolates. These results show a high diversity of actinomycetes associated with marine sponges as well as highlight their potential to produce anti-infective agents. KW - Biologie KW - actinomycetes KW - marine sponges KW - anti-infective KW - anti-parasitic KW - phylogenetic Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68307 ER - TY - JOUR A1 - Grimm, Martin A1 - Lazariotou, Maria A1 - Kircher, Stefan A1 - Stuermer, Luisa A1 - Reiber, Christoph A1 - Hoefelmayr, Andreas A1 - Gattenloehner, Stefan A1 - Otto, Christoph A1 - Germer, Christoph T. A1 - von Rahden, Burkhard H. A. T1 - MMP-1 is a (pre-)invasive factor in Barrett-associated esophageal adenocarcinomas and is associated with positive lymph node status N2 - Background: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett’s esophagus (BE) regarded as precancerous lesion. Matrix metalloproteinases (MMPs) might play a role during the multistep carcinogenetic process. Methods: Expression of MMP-1 and -13 was analyzed in esophageal cancer (n = 41 EAC with BE, n = 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC), furthermore in BE without intraepithelial neoplasia (IN) (n = 18), and the cell line OE-33. MMP-1 was co-labelled with Ki-67 (proliferation), Cdx-2 (marker for intestinal metaplasia, BE) and analyzed on mRNA level. MMP-1 staining results were correlated with clinicopatholocical parameters. Results: On protein level, MMP-1 expression was found in 39 of 41 (95%) EAC with BE, in 19 of 19 (100%) EAC without BE, in 6 of 10 (60%) ESCC, and in 10 of 18 (56%) BE without IN. No expression of MMP-13 was found in these specimens. Quantification showed 48% MMP-1 positive cells in EAC with BE, compared to 35% in adjacent BE (p < 0.05), 44% in EAC without BE, 32% in ESCC, and 4% in BE without IN. Immunofluorescence double staining experiments revealed increased MMP-1 expressing in proliferating cells (MMP-1+/Ki-67+) (r = 0.943 for BE and r = 0.811 for EAC). On mRNA-level, expression of MMP-1 was significantly higher in EAC compared to BE (p = 0.01) and confirmed immunohistochemical staining results. High MMP-1 levels were associated with lymph node metastases but not with poorer survival (p = 0.307). Conclusions: Our findings suggest that MMP-1 plays a role as preinvasive factor in BE-associated EAC. Expression of MMP-1 in proliferating BE and EAC cells suggest malignant proliferation following the clonal expansion model. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68293 ER - TY - JOUR A1 - Frey, Li­dia M. A1 - Houben, Roland A1 - Bröcker, Eva-B. T1 - Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma N2 - Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues bymeans of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intratumoral melanocytes.Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5–8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68283 ER - TY - JOUR A1 - Winter, Julia A1 - Kneitz, Hermann A1 - Bröcker, Eva-B. T1 - Blood Vessel Density in Basal Cell Carcinomas and Benign Trichogenic Tumors as a Marker for Differential Diagnosis in Dermatopathology N2 - In order to get insight into the density of blood vessels in the stroma of benign and malignant trichogenic neoplasms, immunohistological quantification of CD 31 positive vessels was performed in 112 tumors, comprised of 50 BCCs of nodular (35) or morphoeic (15) growth patterns, 17 Pinkus’ tumors, as well as 17 trichoepitheliomas of which 6 were desmoplastic, 8 trichofolliculomas, and 20 trichoblastomas. Methods. Vessel density was counted within the tumors, in the tumor-surrounding stroma, and, as a control, in the normal skin of the operation specimen. The results were compared using statistical methods. Results. Whereas, irrespective of the patients’ age and location of tumors, the vessel density in normal skin showed no significant differences (8.8 ± 2.7), the counts in the peritumoral stroma revealed significant differences between the different tumors investigated. The highest counts were obtained in BCC (24.7 ± 6.7) and the lowest in benign trichogenic neoplasms (around 14) Pinkus’ tumors revealed intermediate counts (19.7 ± 6.6). The vessel densities within the tumors were generally low, and no correlation to the dignity was found. Conclusion. Determination of blood vessel density in the peritumoral stroma may be an additional parameter for differential diagnosis of trichogenic tumors of uncertain dignity. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68275 ER - TY - JOUR A1 - Gattenlöhner, S. A1 - Etschmann, B. A1 - Kunzmann, V. A1 - Thalheimer, A. A1 - Hack, M. A1 - Kleber, G. A1 - Einsele, H. A1 - Germer, C. A1 - Müller-Hermelink, H.-K. T1 - Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy N2 - Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRASwt genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations. KW - Krebs Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68240 ER - TY - RPRT A1 - Kneitz, H. A1 - Bröcker, Eva B. A1 - Becker, JC T1 - Mycosis fungoides bullosa: a case report and review of the literature N2 - Introduction: Mycosis fungoides, the most common type of cutaneous T-cell lymphoma, can manifest in a variety of clinical and histological forms. Bulla formation is an uncommon finding in mycosis fungoides and only approximately 20 cases have been reported in the literature. Case presentation: We present a case of rapidly progressive mycosis fungoides in a 68-year-old Caucasian man who initially presented with erythematous plaques characterised by blister formation. Conclusion: Although mycosis fungoides bullosa is extremely rare, it has to be regarded as an important clinical subtype of cutaneous T-cell lymphoma. Mycosis fungoides bullosa represents a particularly aggressive form of mycosis fungoides and is associated with a poor prognosis. The rapid disease progression in our patient confirms bulla formation as an adverse prognostic sign in cutaneous T-cell lymphoma. KW - Mycosis fungoides bullosa Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68233 ER - TY - JOUR A1 - Bollazzi, Martin A1 - Roces, Flavio T1 - The thermoregulatory function of thatched nests in the South American grass-cutting ant, Acromyrmex heyeri N2 - The construction of mound-shaped nests by ants is considered as a behavioral adaptation to low environmental temperatures, i.e., colonies achieve higher and more stables temperatures than those of the environment. Besides the well-known nests of boreal Formica wood-ants, several species of South American leaf-cutting ants of the genus Acromyrmex construct thatched nests. Acromyrmex workers import plant fragments as building material, and arrange them so as to form a thatch covering a central chamber, where the fungus garden is located. Thus, the degree of thermoregulation attained by the fungus garden inside the thatched nest largely depends on how the thatch affects the thermal relations between the fungus and the environment. This work was aimed at studying the thermoregulatory function of the thatched nests built by the grass-cutting ant Acromyrmex heyeri Forel (Hymenoptera: Formicidae: Myrmicinae). Nest and environmental temperatures were measured as a function of solar radiation on the long-term. The thermal diffusivity of the nest thatch was measured and compared to that of the surrounding soil, in order to assess the influence of the building material on the nest’s thermoregulatory ability. The results showed that the average core temperature of thatched nests was higher than that of the environment, but remained below values harmful for the fungus. This thermoregulation was brought about by the low thermal diffusivity of the nest thatch built by workers with plant fragments, instead of the readily-available soil particles that have a higher thermal diffusivity. The thatch prevented diurnal nest overheating by the incoming solar radiation, and avoided losses of the accumulated daily heat into the cold air during the night. The adaptive value of thatching behavior in Acromyrmex leaf-cutting ants occurring in the southernmost distribution range is discussed. KW - Acromyrmex heyeri KW - building behaviour KW - thermal biology KW - nest material KW - heat transfer KW - leaf-cutting ants Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68225 ER - TY - JOUR A1 - Parczyk, Marco A1 - Herold, Volker A1 - Klug, Gert A1 - Bauer, Wolfgang R. A1 - Rommel, Eberhard A1 - Jakob, Peter M. T1 - Regional in vivo transit time measurements of aortic pulse wave velocity in mice with high-field CMR at 17.6 Tesla N2 - Background: Transgenic mouse models are increasingly used to study the pathophysiology of human cardiovascular diseases. The aortic pulse wave velocity (PWV) is an indirect measure for vascular stiffness and a marker for cardiovascular risk. Results: This study presents a cardiovascular magnetic resonance (CMR) transit time (TT) method that allows the determination of the PWV in the descending murine aorta by analyzing blood flow waveforms. Systolic flow pulses were recorded with a temporal resolution of 1 ms applying phase velocity encoding. In a first step, the CMR method was validated by pressure waveform measurements on a pulsatile elastic vessel phantom. In a second step, the CMR method was applied to measure PWVs in a group of five eight-month-old apolipoprotein E deficient (ApoE(-/-)) mice and an age matched group of four C57Bl/6J mice. The ApoE(-/-) group had a higher mean PWV (PWV = 3.0 ± 0.6 m/s) than the C57Bl/6J group (PWV = 2.4 ± 0.4 m/s). The difference was statistically significant (p = 0.014). Conclusions: The findings of this study demonstrate that high field CMR is applicable to non-invasively determine and distinguish PWVs in the arterial system of healthy and diseased groups of mice. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68219 ER - TY - JOUR A1 - Gattenloehner, Stefan A1 - Joerissen, H. A1 - Huhn, M. A1 - Vincent, A. A1 - Beeson, D. A1 - Tzartos, S. A1 - Mamalaki, A. A1 - Etschmann, B. A1 - Muller-Hermelink, H. K. A1 - Koscielniak, E. A1 - Barth, S. A1 - Marx, A. T1 - A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model [Research Article] N2 - Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA).While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68200 ER - TY - JOUR A1 - Kuehn, Andrea A1 - Pradel, Gabriele T1 - The Coming-Out of Malaria Gametocytes [Review Article] N2 - The tropical disease malaria, which results in more than one million deaths annually, is caused by protozoan parasites of the genus Plasmodium and transmitted by blood-feeding Anopheline mosquitoes. Parasite transition from the human host to the mosquito vector is mediated by gametocytes, sexual stages that are formed in human erythrocytes, which therefore play a crucial part in the spread of the tropical disease. The uptake by the blood-feeding mosquito triggers important molecular and cellular changes in the gametocytes, thus mediating the rapid adjustment of the parasite from the warm-blooded host to the insect host and subsequently initiating reproduction. The contact with midgut factors triggers gametocyte activation and results in their egress from the enveloping erythrocyte, which then leads to gamete formation and fertilization. This review summarizes recent findings on the role of gametocytes during transmission to themosquito and particularly focuses on the molecular mechanisms underlying gametocyte activation and emergence from the host erythrocyte during gametogenesis. KW - Malaria Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68196 ER - TY - JOUR A1 - Zeeshan, Ahmed T1 - Towards Performance Measurement and Metrics Based Analysis of PLA Applications N2 - This article is about a measurement analysis based approach to help software practitioners in managing the additional level complexities and variabilities in software product line applications. The architecture of the proposed approach i.e. ZAC is designed and implemented to perform preprocessesed source code analysis, calculate traditional and product line metrics and visualize results in two and three dimensional diagrams. Experiments using real time data sets are performed which concluded with the results that the ZAC can be very helpful for the software practitioners in understanding the overall structure and complexity of product line applications. Moreover the obtained results prove strong positive correlation between calculated traditional and product line measures. KW - Programmierbare logische Anordnung KW - Analysis KW - Measurement KW - Software product lines KW - Variability Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68188 ER - TY - JOUR A1 - Geissinger, Eva A1 - Sadler, Petra A1 - Roth, Sabine A1 - Grieb, Tina A1 - Puppe, Bernhard A1 - Mueller, Nora A1 - Reimer, Peter A1 - Vetter-Kauczok, Claudia S. A1 - Wenzel, Joerg A1 - Bonzheim, Irina A1 - Ruediger, Thomas A1 - Mueller-Hermelink, Hans Konrad A1 - Rosenwald, Andreas T1 - Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30(+) T-cell lymphoproliferations N2 - Background CD30+ T-cell lymphoproliferations comprise a spectrum of clinically heterogeneous entities, including systemic anaplastic large cell lymphomas (ALK- and ALK+) and primary cutaneous CD30+ T-cell lymphoproliferative disorders. While all these entities are characterized by proliferation of highly atypical, anaplastic CD30+ T cells, the expression of T-cell specific antigens in the tumor cells is not consistently detectable. Design and Methods We evaluated biopsies from 19 patients with primary cutaneous CD30+ lymphoproliferative disorders, 38 with ALK- and 33 with ALK+ systemic anaplastic large cell lymphoma. The biopsies were examined for the expression of T-cell receptoraβ/CD3 complex (CD3γ, δ, ε, ζ), transcription factors regulating T-cell receptor expression (ATF1, ATF2, TCF-1, TCF-1a/LEF-1, Ets1), and molecules of T-cell receptor-associated signaling cascades (Lck, ZAP-70, LAT, bcl-10, Carma1, NFATc1, c-Jun, c-Fos, Syk) using immunohistochemistry. Results In comparison to the pattern in 20 peripheral T-cell lymphomas, not otherwise specified, we detected a highly disturbed expression of the T-cell receptor/CD3 complex, TCF-1, TCF- 1a/LEF-1, Lck, ZAP-70, LAT, NFATc1, c-Jun, c-Fos and Syk in most of the systemic anaplastic large cell lymphomas. In addition, primary cutaneous CD30+ lymphoproliferative disorders showed such a similar expression pattern to that of systemic anaplastic large cell lymphomas, that none of the markers we investigated can reliably distinguish between these CD30+ T-cell lymphoproliferations. Conclusions Severely altered expression of the T-cell receptor/CD3 complex, T-cell receptor-associated transcription factors and signal transduction molecules is a common characteristic of systemic and cutaneous CD30+ lymphoproliferations, although the clinical behavior of these entities is very different. Since peripheral T-cell lymphomas, not otherwise specified retain the full expression program required for functioning T-cell receptor signaling, the differential expression of a subset of these markers might be of diagnostic utility in distinguishing peripheral T-cell lymphomas, not otherwise specified from the entire group of CD30+ lymphoproliferations. KW - Medizin KW - systemic and cutaneous CD30+ lymphoproliferations KW - anaplastic large cell lymphoma KW - lymphomatoid papulosis KW - ALCL KW - LyP KW - TCR Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68179 ER - TY - JOUR A1 - Münßinger, Jana I. A1 - Halder, Sebastian A1 - Kleih, Sonja C. A1 - Furdea, Adrian A1 - Raco, Valerio A1 - Hösle, Adi A1 - Kübler, Andrea T1 - Brain Painting: first evaluation of a new brain-computer interface application with ALS-patients and healthy volunteers N2 - Brain–computer interfaces (BCIs) enable paralyzed patients to communicate; however, up to date, no creative expression was possible. The current study investigated the accuracy and user-friendliness of P300-Brain Painting, a new BCI application developed to paint pictures using brain activity only. Two different versions of the P300-Brain Painting application were tested: A colored matrix tested by a group of ALS-patients (n = 3) and healthy participants (n = 10), and a black and white matrix tested by healthy participants (n = 10). The three ALS-patients achieved high accuracies; two of them reaching above 89% accuracy. In healthy subjects, a comparison between the P300-Brain Painting application (colored matrix) and the P300-Spelling application revealed significantly lower accuracy and P300 amplitudes for the P300-Brain Painting application. This drop in accuracy and P300 amplitudes was not found when comparing the P300-Spelling application to an adapted, black and white matrix of the P300-Brain Painting application. By employing a black and white matrix, the accuracy of the P300-Brain Painting application was significantly enhanced and reached the accuracy of the P300-Spelling application. ALS-patients greatly enjoyed P300-Brain Painting and were able to use the application with the same accuracy as healthy subjects. P300-Brain Painting enables paralyzed patients to express themselves creatively and to participate in the prolific society through exhibitions. KW - Psychologie KW - brain–computer interfaces KW - P300 KW - amyotrophic lateral sclerosis KW - event-related potential Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68168 ER - TY - JOUR A1 - Gerdes, Antje B. M. A1 - Wieser, Matthias J. A1 - Mühlberger, Andreas A1 - Weyers, Peter A1 - Alpers, Georg W. A1 - Plichta, Michael M. A1 - Breuer, Felix A1 - Pauli, Paul T1 - Brain activations to emotional pictures are differentially associated with valence and arousal ratings N2 - Several studies have investigated the neural responses triggered by emotional pictures, but the specificity of the involved structures such as the amygdala or the ventral striatum is still under debate. Furthermore, only few studies examined the association of stimuli’s valence and arousal and the underlying brain responses. Therefore, we investigated brain responses with functional magnetic resonance imaging of 17 healthy participants to pleasant and unpleasant affective pictures and afterwards assessed ratings of valence and arousal. As expected, unpleasant pictures strongly activated the right and left amygdala, the right hippocampus, and the medial occipital lobe, whereas pleasant pictures elicited significant activations in left occipital regions, and in parts of the medial temporal lobe. The direct comparison of unpleasant and pleasant pictures, which were comparable in arousal clearly indicated stronger amygdala activation in response to the unpleasant pictures. Most important, correlational analyses revealed on the one hand that the arousal of unpleasant pictures was significantly associated with activations in the right amygdala and the left caudate body. On the other hand, valence of pleasant pictures was significantly correlated with activations in the right caudate head, extending to the nucleus accumbens (NAcc) and the left dorsolateral prefrontal cortex. These findings support the notion that the amygdala is primarily involved in processing of unpleasant stimuli, particularly to more arousing unpleasant stimuli. Reward-related structures like the caudate and NAcc primarily respond to pleasant stimuli, the stronger the more positive the valence of these stimuli is. KW - Psychologie KW - emotional pictures KW - amygdala KW - caudate KW - valence KW - arousal Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68153 ER - TY - JOUR A1 - Seefried, Lothar A1 - Mueller-Deubert, Sigrid A1 - Schwarz, Thomas A1 - Lind, Thomas A1 - Mentrup, Birgit A1 - Kober, Melanie A1 - Docheva, Denitsa A1 - Liedert, Astrid A1 - Kassem, Moustapha A1 - Ignatius, Anita A1 - Schieker, Matthias A1 - Claes, Lutz A1 - Wilke, Winfried A1 - Jakob, Franz A1 - Ebert, Regina T1 - A small scale cell culture system to analyze mechanobiology using reporter gene constructs and polyurethane dishes N2 - Mechanical forces are translated into biochemical signals and contribute to cell differentiation and phenotype maintenance. Mesenchymal stem cells and their tissuespecific offspring, as osteoblasts and chondrocytes, cells of cardiovascular tissues and lung cells are sensitive to mechanical loading but molecules and mechanisms involved have to be unraveled. It is well established that cellular mechanotransduction is mediated e.g. by activation of the transcription factor SP1 and by kinase signaling cascades resulting in the activation of the AP1 complex. To investigate cellular mechanisms involved in mechanotransduction and to analyze substances, which modulate cellular mechanosensitivity reporter gene constructs, which can be transfected into cells of interest might be helpful. Suitable small-scale bioreactor systems and mechanosensitive reporter gene constructs are lacking. To analyze the molecular mechanisms of mechanotransduction and its crosstalk with biochemically induced signal transduction, AP1 and SP1 luciferase reporter gene constructs were cloned and transfected into various cell lines and primary cells. A newly developed bioreactor and small-scale 24-well polyurethane dishes were used to apply cyclic stretching to the transfected cells. 1 Hz cyclic stretching for 30 min in this system resulted in a significant stimulation of AP1 and SP1 mediated luciferase activity compared to unstimulated cells. In summary we describe a small-scale cell culture/bioreactor system capable of analyzing subcellular crosstalk mechanisms in mechanotransduction, mechanosensitivity of primary cells and of screening the activity of putative mechanosensitizers as new targets, e.g. for the treatment of bone loss caused by both disuse and signal transduction related alterations of mechanotransduction. KW - Bioreaktor KW - Mechanical strain KW - mechanosensitive reporter KW - gene constructs KW - bioreactor Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68099 ER - TY - JOUR A1 - Elias, Johannes A1 - Schouls, Leo M. A1 - van de Pol, Ingrid A1 - Keijzers, Wendy C. A1 - Martin, Diana R. A1 - Glennie, Anne A1 - Oster, Philipp A1 - Frosch, Matthias A1 - Vogel, Ulrich A1 - van der Ende, Arie T1 - Vaccine Preventability of Meningococcal Clone, Greater Aachen Region, Germany N2 - No abstract available KW - IMD Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68083 ER - TY - JOUR A1 - Ferrante, Augusto A1 - Wimmer, Harald K. T1 - Reachability matrices and cyclic matrices N2 - We study reachability matrices R(A, b) = [b,Ab, . . . ,An−1b], where A is an n × n matrix over a field K and b is in Kn. We characterize those matrices that are reachability matrices for some pair (A, b). In the case of a cyclic matrix A and an n-vector of indeterminates x, we derive a factorization of the polynomial det(R(A, x)). KW - Mathematik KW - Reachability matrix KW - Krylow matrix KW - cyclic matrix KW - nonderogatory matrix KW - companion matrix KW - Vandermonde matrix KW - Hautus test Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68074 N1 - AMS subject classifications. 15A03, 15A15, 93B05 ER - TY - JOUR A1 - Ballester-Bolinches, A. A1 - Beidleman, J. C. A1 - Heineken, H. A1 - Pedraza-Aguilera, M. C. T1 - Local Classes and Pairwise Mutually Permutable Products of Finite Groups N2 - The main aim of the paper is to present some results about products of pairwise mutually permutable subgroups and local classes. KW - Mathematik KW - mutually permutable KW - local classes KW - p-soluble groups KW - p-supersolubility KW - finite groups Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68062 ER - TY - JOUR A1 - Braeuninger, Stefan A1 - Kleinschnitz, C. A1 - Stoll, G. T1 - Interleukin-18 does not influence infarct volume or functional outcome in the early stage after transient focal brain ischemia in mice N2 - Interleukin-18 (IL-18) is a proinflammatory cytokine of the interleukin-1 family which is upregulated after cerebral ischemia. The functional role of IL-18 in cerebral ischemia is unknown. In the present study, we compared infarct size in IL-18 knock-out and wild-type mice 24 hours and 48 hours after 1-hour transient middle cerebral artery occlusion (tMCAO). Moreover, the functional outcome was evaluated in a modified Bederson score, foot fault test and grip test. There were no significant differences in infarct size or functional outcome tests between wild-type and IL-18 knock-out mice. These data indicate that the early inflammatory response to cerebral ischemia does not involve IL-18, in contrast to other interleukin-1 family members such as interleukin-1. KW - Interleukin-18 Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68141 ER - TY - JOUR A1 - Albert-Weissenberger, Christiane A1 - Sirén, Anna-Leena T1 - Experimental traumatic brain injury N2 - Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury. KW - Trauma Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68131 ER - TY - JOUR A1 - Ehling, P. A1 - Bittner, S. A1 - Bobak, N. A1 - Schwarz, T. A1 - Wiendl, H. A1 - Budde, T. A1 - Kleinschnitz, Christoph A1 - Meuth, S. G. T1 - Two pore domain potassium channels in cerebral ischemia: a focus on K2p9.1 (TASK3, KCNK9) N2 - BACKGROUND: Recently, members of the two-pore domain potassium channel family (K2P channels) could be shown to be involved in mechanisms contributing to neuronal damage after cerebral ischemia. K2P3.1-/- animals showed larger infarct volumes and a worse functional outcome following experimentally induced ischemic stroke. Here, we question the role of the closely related K2P channel K2P9.1. METHODS: We combine electrophysiological recordings in brain-slice preparations of wildtype and K2P9.1-/- mice with an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of K2P9.1 in stroke formation. RESULTS: Patch-clamp recordings reveal that currents mediated through K2P9.1 can be obtained in slice preparations of the dorsal lateral geniculate nucleus (dLGN) as a model of central nervous relay neurons. Current characteristics are indicative of K2P9.1 as they display an increase upon removal of extracellular divalent cations, an outward rectification and a reversal potential close to the potassium equilibrium potential. Lowering extracellular pH values from 7.35 to 6.0 showed comparable current reductions in neurons from wildtype and K2P9.1-/- mice (68.31 +/- 9.80% and 69.92 +/- 11.65%, respectively). These results could be translated in an in vivo model of cerebral ischemia where infarct volumes and functional outcomes showed a none significant tendency towards smaller infarct volumes in K2P9.1-/- animals compared to wildtype mice 24 hours after 60 min of tMCAO induction (60.50 +/- 17.31 mm3 and 47.10 +/- 19.26 mm3, respectively). CONCLUSIONS: Together with findings from earlier studies on K2P2.1-/- and K2P3.1-/- mice, the results of the present study on K2P9.1-/- mice indicate a differential contribution of K2P channel subtypes to the diverse and complex in vivo effects in rodent models of cerebral ischemia. KW - Kaliumkanal KW - Ischemia Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68129 ER - TY - JOUR A1 - Pham, Mirko A1 - Helluy, X. A1 - Braeuninger, S. A1 - Jakob, P. A1 - Stoll, G. A1 - Kleinschnitz, Christoph A1 - Bendszus, M. T1 - Outcome of experimental stroke in C57Bl/6 and Sv/129 mice assessed by multimodal ultra-high field MRI N2 - Transgenic mice bred on C57Bl/6 or Sv/129 genetic background are frequently used in stroke research. It is well established that variations in cerebrovascular anatomy and hemodynamics can influence stroke outcome in different inbred mouse lines. We compared stroke development in C57Bl/6 and Sv/129 mice in the widely used model of transient middle cerebral artery occlusion (tMCAO) by multimodal ultra-high field magnetic resonance imaging (MRI). C57Bl/6 and Sv/129 mice underwent 60 min of tMCAO and were analyzed by MRI 2 h and 24 h afterwards. Structural and functional images were registered to a standard anatomical template. Probability maps of infarction were rendered by automated segmentation from quantitative T2-relaxometric images. Whole-brain segmentation of infarction was accomplished manually on high-resolution T2-weighted (T2-w) RARE images. Cerebral perfusion (cerebral blood flow, CBF) was measured quantitatively by modified continuous arterial-spin-labeling (CASL) and apparent diffusion coefficients (ADC) by spin-echo diffusion-weighted imaging (DWI). Probabilities of cortical (95.1% ± 3.1 vs. 92.1% ± 2.5; p > 0.05) and subcortical (100% vs. 100%; p > 0.05) infarctions at 24 h were similar in both groups as was the whole-brain volumetric extent of cerebral infarction. In addition, CBF and ADC values did not differ between C57Bl/6 and Sv/129 mice at any time point or region of interest. The C57Bl/6 and Sv/129 genetic background is no major confounding factor of infarct size and cerebral perfusion in the tMCAO model. KW - NMR-Tomographie Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68115 ER - TY - JOUR A1 - Kraft, P. A1 - Schwarz, T. A1 - Pochet, L. A1 - Stoll, G. A1 - Kleinschnitz, Christoph T1 - COU254, a specific 3-carboxamide-coumarin inhibitor of coagulation factor XII, does not protect mice from acute ischemic stroke N2 - Background: Anticoagulation is an important means to prevent from acute ischemic stroke but is associated with a significant risk of severe hemorrhages. Previous studies have shown that blood coagulation factor XII (FXII)- deficient mice are protected from pathological thrombus formation during cerebral ischemia without bearing an increased bleeding tendency. Hence, pharmacological blockade of FXII might be a promising and safe approach to prevent acute ischemic stroke and possibly other thromboembolic disorders but pharmacological inhibitors selective over FXII are still lacking. In the present study we investigated the efficacy of COU254, a novel nonpeptidic 3-carboxamide-coumarin that selectively blocks FXII activity, on stroke development and post stroke functional outcome in mice. Methods: C57Bl/6 mice were treated with COU254 (40 mg/kg i.p.) or vehicle and subjected to 60 min transient middle cerebral artery occlusion (tMCAO) using the intraluminal filament method. After 24 h infarct volumes were determined from 2,3,5-Triphenyltetrazoliumchloride(TTC)-stained brain sections and functional scores were assessed. Hematoxylin and eosin (H&E) staining was used to estimate the extent of neuronal cell damage. Thrombus formation within the infarcted brain areas was analyzed by immunoblot. Results: Infarct volumes and functional outcomes on day 1 after tMCAO did not significantly differ between COU254 pre-treated mice or untreated controls (p > 0.05). Histology revealed extensive ischemic neuronal damage regularly including the cortex and the basal ganglia in both groups. COU254 treatment did not prevent intracerebral fibrin(ogen) formation. Conclusions: COU254 at the given concentration of 40 mg/kg failed to demonstrate efficacy in acute ischemic stroke in this preliminary study. Further preclinical evaluation of 3-carboxamide-coumarins is needed before the antithrombotic potential of this novel class of FXII inhibitors can be finally judged. KW - Schlaganfall KW - Maus KW - COU254 Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68103 ER - TY - JOUR A1 - Keller, Alexander A1 - Foerster, Frank A1 - Mueller, Tobias A1 - Dandekar, Thomas A1 - Schultz, Joerg A1 - Wolf, Matthias T1 - Including RNA secondary structures improves accuracy and robustness in reconstruction of phylogenetic trees N2 - Background: In several studies, secondary structures of ribosomal genes have been used to improve the quality of phylogenetic reconstructions. An extensive evaluation of the benefits of secondary structure, however, is lacking. Results: This is the first study to counter this deficiency. We inspected the accuracy and robustness of phylogenetics with individual secondary structures by simulation experiments for artificial tree topologies with up to 18 taxa and for divergency levels in the range of typical phylogenetic studies. We chose the internal transcribed spacer 2 of the ribosomal cistron as an exemplary marker region. Simulation integrated the coevolution process of sequences with secondary structures. Additionally, the phylogenetic power of marker size duplication was investigated and compared with sequence and sequence-structure reconstruction methods. The results clearly show that accuracy and robustness of Neighbor Joining trees are largely improved by structural information in contrast to sequence only data, whereas a doubled marker size only accounts for robustness. Conclusions: Individual secondary structures of ribosomal RNA sequences provide a valuable gain of information content that is useful for phylogenetics. Thus, the usage of ITS2 sequence together with secondary structure for taxonomic inferences is recommended. Other reconstruction methods as maximum likelihood, bayesian inference or maximum parsimony may equally profit from secondary structure inclusion. Reviewers: This article was reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin. Open peer review: Reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin. For the full reviews, please go to the Reviewers’ comments section. KW - Phylogenie KW - phylogenetics Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67832 ER - TY - JOUR A1 - Shityakov, Sergey A1 - Dandekar, Thomas T1 - Lead expansion and virtual screening of Indinavir derivate HIV-1 protease inhibitors using pharmacophoric - shape similarity scoring function N2 - Indinavir (Crivaxan®) is a potent inhibitor of the HIV (human immunodeficiency virus) protease. This enzyme has an important role in viral replication and is considered to be very attractive target for new antiretroviral drugs. However, it becomes less effective due to highly resistant new viral strains of HIV, which have multiple mutations in their proteases. For this reason, we used a lead expansion method to create a new set of compounds with a new mode of action to protease binding site. 1300 compounds chemically diverse from the initial hit were generated and screened to determine their ability to interact with protease and establish their QSAR properties. Further computational analyses revealed one unique compound with different protease binding ability from the initial hit and its role for possible new class of protease inhibitors is discussed in this report. KW - Proteasen KW - protease; Indinavir; lead expansion; docking; pharmacophore Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67824 ER - TY - JOUR A1 - Pratihar, Pampa A1 - Ghosh, Suhrit A1 - Stepanenko, Vladimir A1 - Patwardhan, Sameer A1 - Grozema, Ferdinand C. A1 - Siebbeles, Laurens D. A. A1 - Würthner, Frank T1 - Self-assembly and semiconductivity of an oligothiophene supergelator N2 - A bis(trialkoxybenzamide)-functionalized quaterthiophene derivative was synthesized and its self-assembly properties in solution were studied. In non-polar solvents such as cyclohexane, this quaterthiophene π-system formed fibril aggregates with an H-type molecular arrangement due to synergistic effect of hydrogen bonding and π-stacking. The self-assembled fibres were found to gelate numerous organic solvents of diverse polarity. The charge transport ability of such elongated fibres of quaterthiophene π-system was explored by the pulse radiolysis time resolved microwave conductivity (PR-TRMC) technique and moderate mobility values were obtained. Furthermore, initial AFM and UV-vis spectroscopic studies of a mixture of our electron-rich quaterthiophene derivative with the electron acceptor [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) revealed a nanoscale segregated assembly of the individual building blocks in the blend. KW - Organische Chemie KW - charge transport; hydrogen bonding; oligothiophene; organogel; self-assembly Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67817 ER - TY - JOUR A1 - Homann, Arne A1 - Qamar, Riaz-ul A1 - Serim, Sevnur A1 - Dersch, Petra A1 - Seibel, Juergen T1 - Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid N2 - Sialic acids are located at the termini of mammalian cell-surface glycostructures, which participate in essential interaction processes including adhesion of pathogens prior to infection and immunogenicity. Here we present the synthesis and bioorthogonal metabolic incorporation of the sialic acid analogue N-(1-oxohex-5-ynyl)neuraminic acid (Neu5Hex) into the cell-surface glycocalyx of a human larynx carcinoma cell line (HEp-2) and its fluorescence labelling by click chemistry. KW - Organische Chemie KW - bioorthogonal metabolic glycoengineering; click chemistry; sialic acid Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67806 ER - TY - JOUR A1 - Beck, Christine A1 - Morbach, Henner A1 - Beer, Meinrad A1 - Stenzel, Martin A1 - Tappe, Dennis A1 - Gattenlöhner, Stefan A1 - Hofmann, Ulrich A1 - Raab, Peter A1 - Girschick, Hermann J. T1 - Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment N2 - Introduction: Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disorder of unknown etiology. In children and adolescents CNO predominantly affects the metaphyses of the long bones, but lesions can occur at any site of the skeleton. Prospectively followed cohorts using a standardized protocol in diagnosis and treatment have rarely been reported. Methods: Thirty-seven children diagnosed with CNO were treated with naproxen continuously for the first 6 months. If assessment at that time revealed progressive disease or no further improvement, sulfasalazine and short-term corticosteroids were added. The aims of our short-term follow-up study were to describe treatment response in detail and to identify potential risk factors for an unfavorable outcome. Results: Naproxen treatment was highly effective in general, inducing a symptom-free status in 43% of our patients after 6 months. However, four nonsteroidal anti-inflammatory drug (NSAID) partial-responders were additionally treated with sulfasalazine and short-term corticosteroids. The total number of clinical detectable lesions was significantly reduced. Mean disease activity estimated by the patient/physician and the physical aspect of health-related quality of life including functional ability (global assessment/childhood health assessment questionnaire and childhood health assessment questionnaire) and pain improved significantly. Forty-one percent of our patients showed radiological relapses, but 67% of them were clinically silent. Conclusions: Most children show a favorable clinical course in the first year of anti-inflammatory treatment with NSAIDs. Relapses and new radiological lesions can occur at any time and at any site in the skeleton but may not be clinically symptomatic. Whole-body magnetic resonance imaging proved to be very sensitive for initial and follow-up diagnostics. KW - Mikrobiologie Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67792 ER - TY - JOUR A1 - Braunschweig, Holger A1 - Damme, Alexander T1 - 1,2-Bis(dimethylamino)-1,2-bis(2,4,6-triisopropylphenyl)diborane(4) N2 - In the molecular structure of the title compound, C34H58B2N2, each B atom of the diborane(4) is connected to one dimethylamino group and one Tip ligand (Tip = 2,4,6-triisopropylphenyl). These findings indicate that the increased steric demand of the Tip groups exerts influence solely on the B—B separation but not on the overall geometry of the title compound. KW - Anorganische Chemie Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67639 ER - TY - JOUR A1 - Braunschweig, Holger A1 - Dewhurst, Rian D. A1 - Schwab, Katrin A1 - Wagner, Katharina T1 - {N ',N ''-Bis[2,6-bis(1-methylethyl)phenyl]-N,N-dimethylguanidinato-kappa N-2 ',N ''}dibromidoborane N2 - In the molecular structure of the title compound, C27H40N3BBr2, the B atom is connected to two bromide substituents and a guanidinate scaffold, forming a four– membered ring. An aryl group is connected to each N atom in the ring that contains two isopropyl groups in positions 2 and 6. KW - Anorganische Chemie Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67622 ER - TY - THES A1 - Wilhelm, Daniela Elisabeth T1 - Die Rolle von GSK3 im Rahmen der angeborenen Immunabwehr gegen Aspergillus fumigatus T1 - GSK3 in the context of innate immune response to aspergillus fumigatus N2 - Aspergillus fumigatus ist ein ubiquitär vorkommender Schimmelpilz, dessen Sporen vom Menschen täglich zu hunderten mit der Atemluft aufgenommen werden. Aufgrund ihrer geringen Größe gelangen die Konidien leicht bis in die Alveolen der Lunge, wo sie normalerweise sofort vom angeborenen Immunsystem beseitigt werden. Immunsupprimierte Menschen leiden an einer qualitativen oder quantitativen Einschränkung dieses Teiles der Immunabwehr, weshalb die Inokulation der Sporen bei ihnen zur Auslösung der lebensgefährlichen Invasiven Aspergillose führen kann, deren Mortalität in der Hochrisikogruppe der Patienten nach hämatopoetischer Stammzelltransplantation über 90% beträgt. Bei diesen Patienten gewinnt die adaptive Immunabwehr an Bedeutung. Dendritische Zellen gehören dem angeborenen Immunsystem an und besitzen einzigartige Fähigkeiten zur Aktivierung und Steuerung der erworbenen Immunabwehr. Durch die Aktivierung naiver T-Zelen und die Sekretion bestimmter immunmodulatorischer Zytokine bestimmen sie die Art der konsekutiv asugelösten T-Helferzellantwort. Lediglich eine T-Helfer 1-Zellantwort wird hierbei mit einer erhöhten Resistenz gegenüber der invasiven Aspergillose in Verbindung gebracht. Die Zytokinsekretion der Dendritischen Zellen wird durch intrazelluläre Signalkaskaden reguliert, welche sich an ihre PRRs anschließen. Für die Erkennung des bakteriellen LPS durch den TLR wurde die Regulation der immunmodulatorischen Zytokine durch die Serin-Threonin-Kinase GSK3 festgestellt. In der vorliegenden Arbeit wurde untersucht, ob es bei der Erkennung von Aspergillus fumigatus durch humane dendritische Zellen ebenfalls einen Zusammenhang mit GSK3 und der Sekretion immunmodulatorischer Zytokine gibt. Dafür wurden aus humanen Monozyten generierte dendritische Zellen mit rekombinanten Antigenen von Aspergillus fumigatus sowie verschiedenen Morphologien stiumuliert und teilweise mit dem GSK3-Inhibitor LiCl gehemmt. Anschließend wurde die Expression bestimmter immunmodulatorischer Zytokine und der GSK3 mittels quantitativer real-time RT-PCR bestimmt. Hierbei konnte für eines der getesteten Antigene, Aspf 1, ein deutlicher Einfluss auf die GSK3-Expression der Zellen festgestellt werden. Ein paralleler Anstieg der Expression proinflammatorischer Zytokine erhärtete die Annahme einer immunregulierenden Rolle der GSK3 bei der Erkennung von Aspergillus fumigatus. Einen deutlicheren Hinweis auf den Zusammenhang zwischen der Aktivität der GSK3 und der Expression proinflammatorischer Zytokine erbrachte die Inhibierung mittels LiCl. Die mit Aspergillus fumigatus stimulierten Zellen reagierten hierauf im Vergleich zu den nicht-inhibierten Zellen mit einer Reduktion der IL12p35-Expression um 86,1% sowie mit einer Reduktion der IL23-Expression um 49,5%. Der letzte Teil der Experimente sollte ausgehend von der Vorstellung, dass verschiedene Aspergillus-Morphologien von unterschiedlichen Rezeptoren erkannt werden quantitative Unterschiede der GSK3-Beteiligung bei der Erkennung von Aspergillus fumigatus durch dendritische Zellen zeigen. Obwohl alle Morphologien des Schimmelpilzes einen Einfluss auf die GSK3-Expression der Zellen zeigten, konnten hierbei keine einheitlichen quantitativen Unterschiede festgestellt werden. Zusammengefasst konnte in der vorliegenden Arbeit die Beteiligung von GSK3 bei der Erkennung von Aspergillus fumigatus durch humane dendritische Zellen gezeigt werden. Außerdem konnten Hinweise auf eine immunregulierende Rolle der GSK3 bei der Abwehr des fakultativ pathogenen Schimmelpilzes erbracht werden, wobei die genaue Einbindung der Serin-Threonin-Kinase in dieser Situation noch unklar ist und weitere Experimente erforderlich macht. N2 - Aspergillus fumigatus is a ubiquitously occurring mould. Human beings inoculate the spores each day by breathing air. Because of their small size, the conidia easily reach the alveoles, where under normal conditions, they are immediately deleted by innate immunity. Immunocompromised humans suffer from a reduction in this part of the immune system, regarding both the quality of its deletion ability and the quantity of immune cells. Therefore, the inoculation of the spores in immunocompromised cases leads to a severe disease called invasive aspergillosis. The mortality in the high-risk group of patients undergoing stem-cell transplantation is more than 90%. Thus, the adaptive immunity of these patients gains importance. Dendritic cells are a part of innate immunity, and they have unique skills to activate and control the adaptive part of the immune system. By activating naive T-cells and secreting certain immunomodulatory cytokines, they affect the consecutive T-cell response. At this time, only a T-helper 1 response is associated with an increased resistance to invasive aspergillosis. Intracellular signaling systems attached to the pathogen recognition receptors (PRRs) of the dendritic cells regulate the secretion of cytokines. The serine-threonine kinase GSK3 (glycogen synthase kinase 3) controls the expression of the immunomodulatory cytokines from the Toll-like receptor (TLR) and the bacterial Lipopolysaccharide (LPS). This research investigated whether a correlation exists between the recognition of aspergillus fumigatus by human dendritic cells and the GSK3-controlled secretion of immunomodulatory cytokines, and thereby, the control of adaptive immunity. Dendritic cells were generated from human monocytes, subsequently stimulated with recombinant antigenes or various morphologies of aspergillus fumigates, and partially inhibited with the GSK3-inhibitor lithium chloride (LiCl). The expression of certain GSK3-controlled immunomodulatory cytokines was determined using quantitative, real-time RT-PCR (reverse transcription polymerase chain reaction). For one of the tested antigenes, Aspf 1, we revealed a considerable influence on the cells GSK3-expression. A parallel increase of the proinflammatory cytokine expression confirmed the presumption of a immunoregulatory role of GSK3 in recognizing certain Aspergillus fumigatus antigenes. A further indication of the correlation between the activity of GSK3 and the expression of proinflammatory cytokines was provided by inhibiting the cells using LiCl. Hereby, the inhibited cells reacted according to the non-inhibited cells with a 86,1% diminution of the IL-12p35 expression and a 49,5% diminution of the IL-23 expression. In the last part of this work, we investigated whether there is a difference in the GSK3 involvement during the recognition of different aspergillus morphotypes by dendritic cells, as these are recognized by different PRRs. Although all morphotypes showed an influence on the GSK3-expression, no consistent differences in quantity were discovered. Summarizing our work, we revealed the involvement of GSK3 during the recognition of aspergillus fumigatus by human dendritic cells. Besides, we found some evidence of the immunoregulatory role of GSK3 in this context, however the exact integration of the serine-threonine kinase remains unclear and needs further research. KW - Aspergillus fumigatus KW - GSK3 KW - angeborene Immunabwehr KW - Aspergillus fumigatus KW - GSK3 KW - innate immunity Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-71674 ER - TY - THES A1 - Blankenburg, Robert T1 - Longitudinale Untersuchungen der kardialen Morphologie von knockin-Mäusen mit humanen Myosinmutationen T1 - Longitudinal analyses of cardiac morphology in knockin mice carrying human myosin mutations N2 - Longitudinale Untersuchungen der kardialen Morphologie von knockin-Mäusen mit humanen Myosinmutationen N2 - Longitudinal analyses of cardiac morphology in knockin mice carrying human myosin mutations KW - Kardiomyopathie KW - Myosin KW - HCM KW - DCM KW - Kardiomyopathie KW - Myosin KW - HCM KW - DCM KW - cardiomyopathy KW - myosin KW - HCM KW - DCM Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-71417 ER - TY - THES A1 - Nazeer, Ahmed T1 - Physiological and molecular basis of Azospirillum-Arabidopsis Interaction T1 - Physiological and molecular basis of Azospirillum-Arabidopsis Interaction N2 - The present study was aimed at revealing the early signalling events during the interaction of the diazotrophic soil bacterium Azospirillum brasilense with its host plant Arabidopsis thaliana. Furthermore, taking advantage of the micro array technique, a comprehensive overview of Arabidopsis genes has been undertaken which are affected upon association with A. brasilense The characterization of the early responses of Arabidopsis plants upon inoculation with Azospirillum brasilense strain Sp7 clearly indicated parallels with the initial events in plant pathogen interaction. For instance, not only bacterial preprations (lysates) form Azospirillum elicited an apoplastic alkalinization of the culture medium, but also the live bacteria, which were even more effective. Besides, in a luminol based assay, the bacterial lysates triggered production of the reactive oxygen species (ROS) in the Arabidopsis leaf discs. Interestingly, the elongation factor receptor mutants (efr) were completely insensitive to Azospirillum, suggesting elongation factor Tu (EF-TU) recognition as elicitor by Arabidopsis. This hypothesis was further validated with a bioinformatic approach. The N terminus initial 26 amino acids from Azospirillum EF-TU gene (elf26) showed more similarity to the elf26 sequences of bacteria like Agrobacterium tumefaciens which elicit responses in the plants through EF-TU rather than Pseudomonas syringae where the potent elicitor is flagellin 22. Universal transcriptome profiling of Arabidopsis thaliana seedlings upon inoculation with Azospirillum brasilense over a time course of six, twenty four and ninty six hours revealed very little genetic responses in the early time points. However, a bulk of genes was differentially regulated in 96 hours post inoculation (96hpi). The nature of these genes indicated that the bacterial treatment, among others, greatly affect the processes like cell wall modification, hormone metabolism, stress and secondary metabolism. Additionally expression levels of a numer of transcription factors (TFs) related to basic helix loop helix (BHLH) and MYB domain containing TF families were altered with Azospirillum inoculation. Particularly the BHLH TFs were among the most highly regulated genes. The array results from Azospirillum treated plants were further compared with the already available data emnating from treatment with flagellin 22 (flg22), oligogalacturonides (OGs) and Agrobacterium tumefaciens. Noteworthy, very different set of genes were affected upon inoculation with Azospirillum in relation to other treatments. Secondly a cluster of proteins involved in the biosynthesis of aliphatic glucosinolates (GSL) were uniquely induced upon Sp7 exposure. Genes operating in flavonoid biosynthesis also showed a distinct regulation trend in the comparative analysis. Taken together, the study in question provides insights into the early signalling events in the context of Azospirillum-Arabidopsis association and the bacterial signals recognized by the plants. The array data, at the same time, elucidates the genetic factors of Arabidopsis triggered upon association with Azospirillum brasilense. N2 - Die vorliegende Arbeit befasst sich mit den physiologischen und genetischen Reaktionen im Zuge der Interaktion von Arabidopsis thaliana mit dem freilebenden, Stickstoff-fixierenden Bodenbakterium Azospirillum brasilense. Qualitativ konnten gemeinsame Mechanismen der frühen physiologischen Antworten von Arabidopsis auf Lysate von mutualistischen (Azospirillum brasilense) oder pathogenen (Pseudomonas syringae und Agrobacterium tumefaciens) Mikroorganismen festgestellt werden. So reagierten Arabidopsis (Col-0 ) Pflanzen auf Lysate dieser Bakterien mit einem Anstieg der cytosolischen Calcium-Konzentration sowie des extrazellulären pH Werts, mit der Bildung reaktiver Sauerstoffspezies und einer Depolarisierung des Membranpotentials. Diese Antworten untschieden sich jedoch zum Teil erheblich in ihrer Amplitude. Weitere Untersuchungen konnten zeigen, dass Flagellenproteine von Azospirillum nicht durch Arabidopsis erkannt werden. Somit unterscheidet sich der Erkennungsmechanismus der Azospirillen von dem der Pseudomonaden, welche aufgrund ihrer Flagellenproteine durch den FLAGELLINSENSING-2 (FLS2) Rezeptor in Arabidopsis perzipiert werden. Die Arabidopsis Mutante ELONGATIONFACTOR RECEPTOR (efr) war insensitiv gegenüber Azospirillumlysaten. Dies legte nahe, dass die Erkennung von Azosprillum über eine Erkennung des bakteriellen Elongationsfaktors (EF-Tu) durch den EFR Rezeptor verläuft. Die anschließende Klonierung des Azospirillum EF-Tu Gens zeigte positionspezifische Unterschiede in der abgeleiteten Aminosäuresequenz gegenüber Referenzsequenzen aus Escherichia coli oder Agrobacterium tumefaciens und erklärt somit die „imperfekte“ Erkennung durch den EFR Rezeptor. Der zeitliche Verlauf der genetischen Antwort von Arabidopsis im Zuge der Interaktion mit Azospirillum wurde mit Hilfe „Micro-Array“ basierter Transkriptionansanalysen 6, 24 und 96 Stunden nach Inokulation (hpi) der Pflanzen untersucht. Dabei wurden nach 6 und 24 hpi lediglich 30 bzw. 60 differenziell regulierte Transkripte gefunden. Diese Beobachtung steht im Gegensatz zu Studien pathogener Elizitoren wie Flagellinen, in welchen bereits nach wenigen Stunden mehr als eintausend differenziell regulierte Transkripte in Arabidopsis gefunden wurden. Dieser Effekt konnte in den Interaktionsstudien mit Azospirillum erst nach 96 hpi beobachtet werden. Die Analyse der genetischen Antwort ergab, dass 96 hpi insbesondere Gene in ihrer Expression verändert waren, deren Produkte im Zusammenhang mit Zellwandmodifikationen, dem Hormonmetabolismus, der Stressanpassung sowie der sekundären Metabolismus stehen. Darüber hinaus konnten Gene aus der Familie der sog. „basic-helix-loop-helix“ und „MYB“ Transkriptionsfaktoren identifiziert werden, die einer spezifischen Regulation durch Azospirillum unterlagen. Die vergleichende Analyse der Araydaten mit Datensätzen, die im Zuge von Pathogen-Arabidopsis Interaktionen gewonnen wurden zeigte, dass insbesondere die Biosynthese von aliphatischen Glykosiden und Flavonolen eine typische Antwort der Pflanze auf die mutualistischen Azospirillum Bakterien darstellt. Die vorgestellte Arbeit liefert somit erste Erkenntnisse zur physiologischen und genetischen Antwort von Arabidopsis auf Azospirillum und ermöglicht die vergleichende Betrachtung dieser Antworten im Kontext der Interaktion von Pflanzen mit pathogenen Mikroorganismen. Die im Rahmen dieser Arbeit identifizierten, differenziell regulierten Gene bieten neue Ansatzpunkte zum vertieften Studium der Wechselwirkung von mutualistischen, wachstumsfördernden Bakterien mit höheren Pflanzen. KW - Azospirillum brasilense KW - Ackerschmalwand KW - Wechselwirkung KW - Molekularbiologie KW - Azospirillum brasilense KW - PAMPS KW - ROS KW - EF-TU KW - aliphatic glucosinolates KW - Azospirillum brasilense KW - PAMPS KW - ROS KW - EF-TU KW - aliphatic glucosinolates Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-51673 ER - TY - THES A1 - Förster, Frank T1 - Making the most of phylogeny: Unique adaptations in tardigrades and 216374 internal transcribed spacer 2 structures T1 - Einzigartige Anpassungen in Tardigraden und 216374 "internal transcribed spacer 2" Strukturen N2 - The phylum Tardigrada consists of about 1000 described species to date. The animals live in habitats within marine, freshwater and terrestrial ecosystems allover the world. Tardigrades are polyextremophiles. They are capable to resist extreme temperature, pressure or radiation. In the event of desiccation, tardigrades enter a so-called tun stage. The reason for their great tolerance capabilities against extreme environmental conditions is not discovered yet. Our Funcrypta project aims at finding answers to the question what mechanisms underlie these adaption capabilities particularly with regard to the species Milnesium tardigradum. The first part of this thesis describes the establishment of expressed sequence tags (ESTs) libraries for different stages of M. tardigradum. From proteomics data we bioinformatically identified 144 proteins with a known function and additionally 36 proteins which seemed to be specific for M. tardigradum. The generation of a comprehensive web-based database allows us to merge the proteome and transcriptome data. Therefore we created an annotation pipeline for the functional annotation of the protein and nucleotide sequences. Additionally, we clustered the obtained proteome dataset and identified some tardigrade-specific proteins (TSPs) which did not show homology to known proteins. Moreover, we examined the heat shock proteins of M. tardigradum and their different expression levels depending on the actual state of the animals. In further bioinformatical analyses of the whole data set, we discovered promising proteins and pathways which are described to be correlated with the stress tolerance, e.g. late embryogenesis abundant (LEA) proteins. Besides, we compared the tardigrades with nematodes, rotifers, yeast and man to identify shared and tardigrade specific stress pathways. An analysis of the 50 and 30 untranslated regions (UTRs) demonstrates a strong usage of stabilising motifs like the 15-lipoxygenase differentiation control element (15-LOX-DICE) but also reveals a lack of other common UTR motifs normally used, e.g. AU rich elements. The second part of this thesis focuses on the relatedness between several cryptic species within the tardigrade genus Paramacrobiotus. Therefore for the first time, we used the sequence-structure information of the internal transcribed spacer 2 (ITS2) as a phylogenetic marker in tardigrades. This allowed the description of three new species which were indistinguishable using morphological characters or common molecular markers like the 18S ribosomal ribonucleic acid (rRNA) or the Cytochrome c oxidase subunit I (COI). In a large in silico simulation study we also succeeded to show the benefit for the phylogenetic tree reconstruction by adding structure information to the ITS2 sequence. Next to the genus Paramacrobiotus we used the ITS2 to corroborate a monophyletic DO-group (Sphaeropleales) within the Chlorophyceae. Additionally we redesigned another comprehensive database—the ITS2 database resulting in a doubled number of sequence-structure pairs of the ITS2. In conclusion, this thesis shows the first insights (6 first author publications and 4 coauthor publications) into the reasons for the enormous adaption capabilities of tardigrades and offers a solution to the debate on the phylogenetic relatedness within the tardigrade genus Paramacrobiotus. N2 - Der Tierstamm Tardigrada besteht aus derzeitig etwa 1000 beschriebenen Arten. Die Tiere leben in Habitaten in marinen, limnischen und terrestrischen Ökosystemen auf der ganzen Welt. Tardigraden sind polyextremophil. Sie können extremer Temperatur, Druck oder Strahlung widerstehen. Beim Austrocknen bilden sie ein so genanntes Tönnchenstadium. Der Grund für die hohe Toleranz gegenüber extremen Umweltbedingungen ist bis jetzt nicht aufgeklärt worden. Unser Funcrypta Projekt versucht Antworten darauf zu finden, was die hinter dieser Anpassungsfähigkeit liegenden Mechanismen sind. Dabei steht die Art Milnesium tardigradum im Mittelpunkt. Der erste Teil dieser Arbeit beschreibt die Etablierung einer expressed sequence tags (ESTs) Bibliothek für verschiedene Stadien von M. tardigradum. Aus unseren Proteomansatz konnten wir bislang 144 Proteine bioinformatisch identifizieren, denen eine Funktion zugeordnet werden konnte. Darüber hinaus wurden 36 Proteine gefunden, welche spezifisch für M. tardigradum zu sein scheinen. Die Erstellung einer umfassenden internetbasierenden Datenbank erlaubt uns die Verknüpfung der Proteom und Transkriptomdaten. Dafür wurde eine Annotations-Pipeline erstellt um den Sequenzen Funktionen zuordnen zu können. Außerdem wurden die erhaltenen Proteindaten von uns geclustert. Dabei konnten wir einige Tardigraden-spezifische Proteine (tardigrade-specific protein, TSP) identifizieren die keinerlei Homologie zu bekannten Proteinen zeigen. Außerdem untersuchten wir die Hitze-Schock-Proteine von M. tardigradum und deren differenzielle Expression in Abhängigkeit vom Stadium der Tiere. In weiteren bioinformatischen Analysen konnten wir viel versprechende Proteine und Stoffwechselwege entdecken für die beschrieben ist, dass sie mit Stressreaktionen in Verbindung stehen, beispielsweise late embryogenesis abundant (LEA) Proteine. Des Weiteren verglichen wir Tardigraden mit Nematoden, Rotatorien, Hefe und dem Menschen, um gemeinsame und Tardigraden-spezifische Stoffwechselwege identifizieren zu können. Analysen der 50 und 30 untranslatierten Bereiche zeigen eine verstärkte Nutzung von stabilisierenden Motiven, wie dem 15-lipoxygenase differentiation control element (LEA). Im Gegensatz dazu werden häufig benutzte Motive, wie beispielsweise AU-reiche Bereiche, gar nicht gefunden. Der zweite Teil der Doktorarbeit beschäftigt sich mit den Verwandtschaftsverhältnissen einiger kryptischer Arten in der Tardigradengattung Paramacrobiotus. Hierfür haben wir, zum ersten Mal in Tardigraden, die Sequenz-Struktur-Informationen der internal transcribed spacer 2 Region als phylogenetischen Marker verwendet. Dies erlaubte uns die Beschreibung von drei neuen Arten, welche mit klassischen morphologischen Merkmalen oder anderen molekularen Markern wie 18S ribosomaler RNA oder Cytochrome c oxidase subunit I (COI) nicht unterschieden werden konnten. In einer umfangreichen in silico Simulationsstudie zeigten wir den Vorteil der bei der Rekonstruktion phylogenetischer Bäume unter der Hinzunahme der Strukturinformationen zur Sequenz der ITS2 entsteht. ITS2 Sequenz-Struktur-Informationen wurden außerdem auch dazu benutzt, eine monophyletische DO-Gruppe (Sphaeropleales) in den Chlorophyceae zu bestätigen. Zusätzlich haben wir eine umfassende Datenbank, die ITS2-Datenbank, überarbeitet. Dadurch konnten die Sequenz-Struktur-Informationen verdoppelt werden, die in dieser Datenbank verfügbar sind. Die vorliegende Doktorarbeit zeigt erste Einblicke (6 Erstautor- und 4 Koautor-Publikationen) in die Ursachen für die hervorragende Anpassungsfähigkeit der Tardigraden und beschreibt die erfolgreiche Aufklärung der Verwandtschaftsverhältnisse in der Tardigradengattung Paramacrobiotus. KW - Phylogenie KW - Bioinformatik KW - Würzburg / Universität / Lehrstuhl für Bioinformatik KW - Anpassung KW - Datenbank KW - ITS2 KW - Marker KW - Tardigraden KW - Bärtierchen KW - ITS2 KW - Marker KW - Tardigrades KW - Waterbear Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-51466 ER - TY - JOUR A1 - Boll, Katharina T1 - "[...] naiv leben und dann eigentlich nochmal leben im angehaltenen Augenblick, im Zustand der Fiktion" - Narrative Lebenskonstruktionen bei Monika Maron im Zeichen der Wende N2 - Das Thema der Erinnerung zieht sich wie ein roter Faden durch Monika Marons bisher erschienene Werke. Der Aufsatz zeichnet nach, welche Funktion das Motiv des Erinnerns in den Texten Monika Marons spielt. Analysiert werden in diesem Kontext die Romane "Flugasche", "Die Überläuferin", "Stille Zeile Sechs", "Animal triste" und die Familiengeschichte "Pawels Briefe". Im Hinblick auf ihre nach der Jahrtausendwende erschienenen Romane "Endmoränen" und "Ach Glück" wird erörtert, ob bzw. inwiefern der politische Umbruch 1989/90 die Schreibweise Monika Marons beeinflusst hat. KW - Maron KW - Monika KW - Erinnerung KW - Vergessen KW - Erzähltechnik Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-70524 ER - TY - THES A1 - Gläser, Theresa Constanze Pilar [geb. Marbe] T1 - Modulation der Expression der Tight Junctions in epithelialen Monolayern als Antwort auf exogene Faktoren anhand der Untersuchung zweier Proteine Occludin und ZO-1 T1 - Modulation of expression of tight junctions on an epithelial model as reaction of exogenous factors on experiences on two proteins: occludin and zo-1 N2 - Untersuchung des transepithelialen Widerstands, der Transkriptionsmenge und der fluoreszenzmikroskopischen Verteilung der Proteine Occludin und ZO-1 in Monolayern in Reaktion auf exogene Faktoren. N2 - Trials of Occludin and ZO-1 in an epithelial model by measure the transepithelial resistance, the transcriptionlevel and the microskopic distibution. KW - Tight junction KW - Occludin KW - Signalkette KW - zo-1 KW - zo-1 Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-70605 ER - TY - THES A1 - Pizon, Dorothea T1 - Prognose des raumfordernden Mediainfarktes bei konservativer vs. operativer Therapie am Universitätsklinikum Würzburg 1993-2005 T1 - Prognosis of conservative vs. surgical treatment of the space-occupying middle cerebral artery infarction at the University Hospital Wuerzburg 1993-2005 N2 - In dieser Studie wurden Schlaganfallpatienten untersucht, die einen ausgedehnten Infarkt im Versorgungsgebiet der A.cerebri media erlitten und wegen Bewusstseinstrübung (sog. Maligner Mediainfarkt) auf der Neurologischen Intensivstation des Universitätsklinikums Würzburg im Zeitraum von 1991 bis 2005 behandelt wurde, um herauszufinden, welchen Einfluss eine operative Behandlung auf den kritisch erhöhten Hirnsdrucks zusätzlich zur konservativen Intensivtherapie auf Mortalität sowie langfristige Lebensqualität hatte. Insgesamt konnten die Daten von 292 Patienten ausgewertet werden, wovon 259 konservativ und 33 operativ behandelt worden waren. Es zeigte sich insgesamt, dass eine stillschweigende günstige Selektion für eine Trepanation sprach (jünger, eher keine Aphasie, weniger Komorbiditäten). Die Hemikraniektomie senkte die Mortalität in der Akutphase hochsignifikant (K: 22, 4%, T: 3,0%; p=0,009). Sie hatte erwartungsgemäß auch einen positiven Einfluss auf das Vigilanzniveau: die Quote von wachen Patienten war bei Entlassung der Trepanierten um 66% höher als bei Aufnahme, bei den konservativ Behandelten war sie nur um 33,3 % gestiegen. Das vorherrschende Symptom bei Aufnahme und Entlassung war eine motorische bzw. sensomotorische Hemiparese. Der Anteil der Aphasiker bei den 201 konservativ therapierten Patienten, die den stationären Aufenthalt überlebt haben, ist von bei Aufnahme 56,2% auf bei Entlassung 48,6% gesunken. Bei den 32 trepanierten Patienten ist er dagegen mit 50% gleich geblieben, obwohl 2/3 aller Patienten an der nicht-dominanten Hemisphäre operiert worden waren. Es war und ist auch nicht zu erwarten, dass eine Entlastung von Hirndruck qualitativ die hirninfarktbedingten Symptome beseitigt. Die Nachbefragung der Patienten fand im Schnitt 64,7 Monate nach erlittenem Mediainfarkt statt. Inzwischen waren von den 259 konservativ Behandelten 47,1% verstorben, von den 33 Hemikraniektomierten nur 24,2%. Die poststationäre Mortalität im weiteren Verlauf war anteilsmäßig gering (K: 24%, T: 21,2%). Die Überlebensdauer der Trepanierten war dreimal so lang wie die der nicht operierten (K: 11,6 Monate, T: 34,4 Monate). Diese Unterschiede im Langzeitüberleben sind wahrscheinlicher auf die geringeren Komorbiditäten der Trepanierten zurückzuführen, als auf die stattgehabte Operation an sich. Allerdings ist nicht auszuschließen, dass die durch Trepanation frühzeitiger verbesserte Wachheit sich auch günstig auf lebensverkürzende Folgekomplikationen ausgewirkt haben könnte. In der Nachbefragung zeigte sich, dass bezüglich der erworbenen körperlichen Funktionsdefizite, gemessen am Barthel Index, zwischen den beiden Kollektiven kein signifikanter Unterschied bestand. Die ehemals konservativ behandelten Patienten kamen auf durchschnittlich 75, die trepanierten Patienten auf 60 von 100 Punkten. Im Lebensalltag schlägt sich dieser Unterschied von 15 Punkten relevant nieder, aber insgesamt liegen beide Patientenkollektive im Bereich einer leichten bis nicht vorhandenen Abhängigkeit. Die vergleichbaren Langzeitdaten von Patienten mit Mediainfarkt liegen in einem ähnlichen Bereich. Erstmalig werden hier Langzeitdaten solcher Patienten über die Lebensqualität vorgelegt, gemessen mit dem SF-36. Nachvollziehbar zeigte sich ein deutlicher Unterschied zur Lebensqualität der Durchschnittsbevölkerung, insbesondere im Bereich der körperlichen Belastbarkeit. Für uns unerwartet günstig fielen die Antworten auf der eher psychologischen Ebene aus. Es zeigten sich bei allen Punkten des SF-36 keine signifikanten Unterschiede zwischen dem konservativ behandelten und den hemikraniektomierten Patienten, so dass die Operation als solche keinen eigenständigen Einfluss auf die langfristige Lebensqualität nahm. Zusammengefasst verbesserte die osteoklastische Trepanation des raumfordernden malignen Mediainfarkts die Überlebenschance in der Akutphase signifikant, was mit inzwischen publizierten kontrollierten Studienergebnissen übereinstimmt. Der Langzeitverlauf nach überlebter Akutkrankheit gestaltet sich unabhängig von der Trepanation. Es gibt aufgrund der erworbenen Behinderung eine weiterhin relativ hohe längerfristige Sterblichkeit. Bemerkenswert ist, dass die Selbsteinschätzung der Lebensqualität von Patienten mit einer erheblichen infarktbedingen körperlichen Behinderung psychologisch-emotional nur geringfügig von der Selbstwahrnehmung in der nicht- behinderten Durchschnittsbevölkerung. Dass bedeutet, dass Spekulationen über die zukünftige Lebensqualität keinen Einfluss auf die Operationsindikation nehmen sollten. N2 - In this retrospective study we looked at the sub-group of stroke patients who suffered a large infarction in the area of the middle cerebral artery and were treated in neurological intensive care between 1991 and 2005 due to imminent or already existent decreased conscious level (so called malignant middle cerebral artery infarction) (n=292). The aim was to find out what influence a surgical treatment has on stroke-related increased intracerebral pressure additionally to the usual conservative intesive therapy with regards to acute and longterm survival. In total data from 292 intensiv care patients was evaluated, which consisted of 259 purely conservatively and 33 surgically treated patients. 
Altogether there was a positive selection for surgically treated patients (younger, no aphasia, less comorbidities). Decompressive hemicraniectomy lowered the mortality in the acute phase significantly (c: 22.4%, h: 3.0%; p=0.009). As expected decompressive hemicraniectomy also positively influenced the conscious level: the number of fully alert patients on discharge was 66% higher than on admission. In the group of the conservatively treated patients this number was only 33% higher (on discharge: c: 87% and h: 90.6% fully alert).The mean physical findings on discharge from neurological intensive care showed no significant difference between the conservatively and surgically treated group. The main symptoms were – as on admission – a motor or sensomotor hemiparesis. The prevalence of aphasia dropped in the group of 201 conservatively patients who survived the hospital stay from 56.2% on admission to 48.% on discharge (p= 0.5). In the 32 patients after hemicraniectomy who survived the hospital admission the number of aphasic patients did not change from admission to discharge (50%). It is not expected that a release of intracerebral pressure completely resolves stroke-connected symptoms. During the stay on intensive care physical and neuropsychological function was not systemically assessed using stroke function scales so we cannot comment on how the symptoms changed quantatively after the treatment. There is a possibility that arguments would be pro-hemicraniectomy. On average 64.7 months passed between the stroke and the follow-up examination. In the meantime 47.1% of the 259 conservatively treated patients had died. Of 33 patients after decompressive hemicraniectomy only 24.2% had died (p=0.01). There was a significant difference in the hospital mortality (c: 24%, h: 21.2%). The longterm mortality showed a smaller difference (c: 24%, h: 21.2%). The survival period of the surgically treated patients was three times longer (c: 11.6%, h: 34.4 months). The difference in survival length is most likely due to less comorbidities in the surgically treated patients than to the hemicraniectomy itself. However it can also not be ruled out that due to the earlier achieved improvement of conscious level postoperatively potential future complications could be prevented. With regards to acquired physical functional deficits, measured with the Barthel index, both groups did not reveal any significant difference (p=0.10). The mean Barthel index in the conservatively treated patients was 75 out of 100 and 60 out of 100 in the patients after decompressive hemicraniectomy. That means that patients from both groups were either independent or slightly dependant from other people in their every day life. For the first time we were presenting longterm data on subjective quality of life from patients after middle cerebral artery infarction, measured with the SF-36 health survey [Bullinger et al. 1998]. As expected there was a major difference between our patient group and a comparable average population, especially in areas like “physical function”. The results on a more psychological level like “vitality” and “mental health” were better than expected. They only mildly differed from the average population. The SF-36 health survey did not show any significant difference between the conservatively treated and the surgically treated group. That indicates how the decompressive hemicraniectomy alone did not have an influence on longterm quality of life. In summary the survival rate was inreased significantly by decompressive hemicraniectomy in malignant middle cerebral artery infarction at the University Hospital Wuerzburg between 1991 and 2005, which was also confirmed by other publicated controlled studies [Jüttler et al. 2007; Vahedi et al. 2007; Fandino et al. 2004]. It is remarkable that the subjective quality of life of patients with a considerable disability differs only slightly from the perception of a non-impaired control group. That means that speculations about a future quality of life should not influence a decision for or against decompressive hemicraniectomy. KW - Arteria cerebri media KW - Schlaganfall KW - Arteria carotis interna KW - Carotisstenose KW - Trepanation KW - Infarkt KW - Hirndruck KW - Hirnödem KW - Sekundärprävention KW - Barthel Index KW - Rehabilitation KW - Matched pairs KW - dekompressive Hemikraniektomie KW - maligner Mediainfarkt KW - Dekompressionskraniektomie KW - Middle cerebral artery infarction KW - malignant middle cerebrial artery infarction KW - decompressive hemicraniectomy KW - Barthel Index Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-70232 ER - TY - JOUR A1 - Wilbert, Juergen A1 - Guckenberger, Matthias A1 - Polat, Buelent A1 - Sauer, Otto A1 - Vogele, Michael A1 - Flentje, Michael A1 - Sweeney, Reinhart A. T1 - Semi-robotic 6 degree of freedom positioning for intracranial high precision radiotherapy; first phantom and clinical results N2 - Background: To introduce a novel method of patient positioning for high precision intracranial radiotherapy. Methods: An infrared(IR)-array, reproducibly attached to the patient via a vacuum-mouthpiece(vMP) and connected to the table via a 6 degree-of-freedom(DoF) mechanical arm serves as positioning and fixation system. After IR-based manual prepositioning to rough treatment position and fixation of the mechanical arm, a cone-beam CT(CBCT) is performed. A robotic 6 DoF treatment couch (HexaPOD™) then automatically corrects all remaining translations and rotations. This absolute position of infrared markers at the first fraction acts as reference for the following fractions where patients are manually prepositioned to within ± 2 mm and ± 2° of this IR reference position prior to final HexaPOD-based correction; consequently CBCT imaging is only required once at the first treatment fraction. The preclinical feasibility and attainable repositioning accuracy of this method was evaluated on a phantom and human volunteers as was the clinical efficacy on 7 pilot study patients. Results: Phantom and volunteer manual IR-based prepositioning to within ± 2 mm and ± 2° in 6DoF was possible within a mean(± SD) of 90 ± 31 and 56 ± 22 seconds respectively. Mean phantom translational and rotational precision after 6 DoF corrections by the HexaPOD was 0.2 ± 0.2 mm and 0.7 ± 0.8° respectively. For the actual patient collective, the mean 3D vector for inter-treatment repositioning accuracy (n = 102) was 1.6 ± 0.8 mm while intra-fraction movement (n = 110) was 0.6 ± 0.4 mm. Conclusions: This novel semi-automatic 6DoF IR-based system has been shown to compare favourably with existing non-invasive intracranial repeat fixation systems with respect to handling, reproducibility and, more importantly, intrafraction rigidity. Some advantages are full cranial positioning flexibility for single and fractionated IGRT treatments and possibly increased patient comfort. KW - Strahlentherapie Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68613 ER - TY - JOUR A1 - Zdziarski, Jaroslaw A1 - Brzuszkiewicz, Elzbieta A1 - Wullt, Bjorn A1 - Liesegang, Heiko A1 - Biran, Dvora A1 - Voigt, Birgit A1 - Gronberg-Hernandez, Jenny A1 - Ragnarsdottir, Bryndis A1 - Hecker, Michael A1 - Ron, Eliora Z. A1 - Daniel, Rolf A1 - Gottschalk, Gerhard A1 - Hacker, Joerg A1 - Svanborg, Catharina A1 - Dobrindt, Ulrich T1 - Host Imprints on Bacterial Genomes-Rapid, Divergent Evolution in Individual Patients N2 - Bacteria lose or gain genetic material and through selection, new variants become fixed in the population. Here we provide the first, genome-wide example of a single bacterial strain’s evolution in different deliberately colonized patients and the surprising insight that hosts appear to personalize their microflora. By first obtaining the complete genome sequence of the prototype asymptomatic bacteriuria strain E. coli 83972 and then resequencing its descendants after therapeutic bladder colonization of different patients, we identified 34 mutations, which affected metabolic and virulence-related genes. Further transcriptome and proteome analysis proved that these genome changes altered bacterial gene expression resulting in unique adaptation patterns in each patient. Our results provide evidence that, in addition to stochastic events, adaptive bacterial evolution is driven by individual host environments. Ongoing loss of gene function supports the hypothesis that evolution towards commensalism rather than virulence is favored during asymptomatic bladder colonization. KW - Proteomanalyse KW - Bakterien Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68594 ER - TY - JOUR A1 - Schubert-Unkmeir, Alexandra A1 - Konrad, Christian A1 - Slanina, Heiko A1 - Czapek, Florian A1 - Hebling, Sabrina A1 - Frosch, Matthias T1 - Neisseria meningitidis Induces Brain Microvascular Endothelial Cell Detachment from the Matrix and Cleavage of Occludin: A Role for MMP-8 N2 - Disruption of the blood-brain barrier (BBB) is a hallmark event in the pathophysiology of bacterial meningitis. Several inflammatory mediators, such as tumor necrosis factor alpha (TNF-a), nitric oxide and matrix metalloproteinases (MMPs), contribute to this disruption. Here we show that infection of human brain microvascular endothelial cells (HBMEC) with Neisseria meningitidis induced an increase of permeability at prolonged time of infection. This was paralleled by an increase in MMP-8 activity in supernatants collected from infected cells. A detailed analysis revealed that MMP-8 was involved in the proteolytic cleavage of the tight junction protein occludin, resulting in its disappearance from the cell periphery and cleavage to a lower-sized 50-kDa protein in infected HBMEC. Abrogation of MMP-8 activity by specific inhibitors as well as transfection with MMP-8 siRNA abolished production of the cleavage fragment and occludin remained attached to the cell periphery. In addition, MMP-8 affected cell adherence to the underlying matrix. A similar temporal relationship was observed for MMP activity and cell detachment. Injury of the HBMEC monolayer suggested the requirement of direct cell contact because no detachment was observed when bacteria were placed above a transwell membrane or when bacterial supernatant was directly added to cells. Inhibition of MMP-8 partially prevented detachment of infected HBMEC and restored BBB permeability. Together, we established that MMP-8 activity plays a crucial role in disassembly of cell junction components and cell adhesion during meningococcal infection. KW - Neisseria meningitidis Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68589 ER - TY - JOUR A1 - Drescher, Jochen A1 - Bluethgen, Nico A1 - Schmitt, Thomas A1 - Buehler, Jana A1 - Feldhaar, Heike T1 - Societies Drifting Apart? Behavioural, Genetic and Chemical Differentiation between Supercolonies in the Yellow Crazy Ant Anoplolepis gracilipes N2 - Background: In populations of most social insects, gene flow is maintained through mating between reproductive individuals from different colonies in periodic nuptial flights followed by dispersal of the fertilized foundresses. Some ant species, however, form large polygynous supercolonies, in which mating takes place within the maternal nest (intranidal mating) and fertilized queens disperse within or along the boundary of the supercolony, leading to supercolony growth (colony budding). As a consequence, gene flow is largely confined within supercolonies. Over time, such supercolonies may diverge genetically and, thus, also in recognition cues (cuticular hydrocarbons, CHC’s) by a combination of genetic drift and accumulation of colony-specific, neutral mutations. Methodology/Principal Findings: We tested this hypothesis for six supercolonies of the invasive ant Anoplolepis gracilipes in north-east Borneo. Within supercolonies, workers from different nests tolerated each other, were closely related and showed highly similar CHC profiles. Between supercolonies, aggression ranged from tolerance to mortal encounters and was negatively correlated with relatedness and CHC profile similarity. Supercolonies were genetically and chemically distinct, with mutually aggressive supercolony pairs sharing only 33.1%617.5% (mean 6 SD) of their alleles across six microsatellite loci and 73.8%611.6% of the compounds in their CHC profile. Moreover, the proportion of alleles that differed between supercolony pairs was positively correlated to the proportion of qualitatively different CHC compounds. These qualitatively differing CHC compounds were found across various substance classes including alkanes, alkenes and mono-, di- and trimethyl-branched alkanes. Conclusions: We conclude that positive feedback between genetic, chemical and behavioural traits may further enhance supercolony differentiation through genetic drift and neutral evolution, and may drive colonies towards different evolutionary pathways, possibly including speciation. KW - Ameisen KW - Anoplolepis gracilipes Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68573 ER - TY - JOUR A1 - Doerck, Sebastian A1 - Goebel, Kerstin A1 - Weise, Gesa A1 - Schneider-Hohendorf, Tilman A1 - Reinhardt, Michael A1 - Hauff, Peter A1 - Schwab, Nicholas A1 - Linker, Ralf A1 - Maeurer, Mathias A1 - Meuth, Sven G. A1 - Wiendl, Heinz T1 - Temporal Pattern of ICAM-I Mediated Regulatory T Cell Recruitment to Sites of Inflammation in Adoptive Transfer Model of Multiple Sclerosis N2 - Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development. KW - Multiple Sklerose Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68565 ER - TY - JOUR A1 - Goetz, Andreas A1 - Eylert, Eva A1 - Eisenreich, Wolfgang A1 - Goebel, Werner T1 - Carbon Metabolism of Enterobacterial Human Pathogens Growing in Epithelial Colorectal Adenocarcinoma (Caco-2) Cells N2 - Analysis of the genome sequences of the major human bacterial pathogens has provided a large amount of information concerning their metabolic potential. However, our knowledge of the actual metabolic pathways and metabolite fluxes occurring in these pathogens under infection conditions is still limited. In this study, we analysed the intracellular carbon metabolism of enteroinvasive Escherichia coli (EIEC HN280 and EIEC 4608-58) and Salmonella enterica Serovar Typhimurium (Stm 14028) replicating in epithelial colorectal adenocarcinoma cells (Caco-2). To this aim, we supplied [U-13C6]glucose to Caco-2 cells infected with the bacterial strains or mutants thereof impaired in the uptake of glucose, mannose and/or glucose 6-phosphate. The 13C-isotopologue patterns of protein-derived amino acids from the bacteria and the host cells were then determined by mass spectrometry. The data showed that EIEC HN280 growing in the cytosol of the host cells, as well as Stm 14028 replicating in the Salmonella-containing vacuole (SCV) utilised glucose, but not glucose 6-phosphate, other phosphorylated carbohydrates, gluconate or fatty acids as major carbon substrates. EIEC 4608-58 used C3-compound(s) in addition to glucose as carbon source. The labelling patterns reflected strain-dependent carbon flux via glycolysis and/or the Entner-Doudoroff pathway, the pentose phosphate pathway, the TCA cycle and anapleurotic reactions between PEP and oxaloacetate. Mutants of all three strains impaired in the uptake of glucose switched to C3-substrate(s) accompanied by an increased uptake of amino acids (and possibly also other anabolic monomers) from the host cell. Surprisingly, the metabolism of the host cells, as judged by the efficiency of 13C-incorporation into host cell amino acids, was not significantly affected by the infection with either of these intracellular pathogens. KW - Metabolismus KW - Carbon Metabolism Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68555 ER - TY - THES A1 - Geiger, Michael T1 - Monetary Policy in China: Institutions, Targets, Instruments and Strategies T1 - Geldpolitik in China: Institutionen, Ziele, Instrumente und Strategien N2 - China’s monetary policy aims to reach two final targets: a paramount economical target (i.e. price stability) and a less important political target (i.e. economic growth). The main actor of monetary policy is the central bank, the People’s Bank of China (PBC). But the PBC is a non-independent central bank. The State Council approves the goals of monetary policy. Very limited instrument independence means that interest rates cannot be set at the PBC’s discretion, and in-sufficient personal independence fails to insulate central bank officials from political influence. Monetary policy in China applies to two sets of monetary policy instruments: (i) instruments of the PBC; and (ii) non-central bank policy instruments. The instruments of the PBC include price-based indirect and quantity-based direct instruments. Non-central bank policy instruments include price and wage controls. The simultaneous usage of all these instruments leads to various distortions that ultimately prevent the interest rate channel of monetary transmission from functioning. Moreover, the strong influences of quantity-based direct instruments and non-central bank policy instruments bring into question the approach of indirect monetary policy in general. The PBC officially follows the monetary targeting approach with monetary aggregates as intermediate targets. Domestic loan growth and the exchange rate are defined as additional intermediate targets. In an in-depth analysis of the intermediate targets two main issues are primarily explored: (i) Are the intermediate targets of the Chinese monetary policy controllable? (ii) Is a sufficient relationship between these targets and the inflation rate observable? It is then shown that monetary aggregates are very difficult to control, but they have a satisfactory relationship with the inflation rate. Similarly, domestic loan growth is difficult to control – a fact largely attributed to the interest rate elasticity of loans – while there is a particularly close relationship between credit growth and the inflation rate. The exchange rate as an intermediate target can be controlled through foreign exchange market interventions; at the same time the exchange rate appears to have a significant relationship to the domestic inflation rate. Discussing the special issue of sterilizing foreign exchange inflows, the study concludes that between 2002 and 2008 not only no costs were incurred by sterilization operations, but that the central bank was actually able to realize a profit through foreign exchange market interventions. Based on this, it is concluded that the exchange rate target has not adversely affected the domestic orientation of monetary policy on the whole. The final part of the study examines whether there are any alternative monetary policy approaches that may be able to describe the policy approach in China; special focus is placed on nominal GDP targeting, the Taylor rule, and inflation targeting. A literature review reveals that the concept of nominal GDP targeting may be able to detect inflationary tendencies in the economy and, in combination with other indicators, it could be a suitable concept to assess the overall economic situation. The author calculates a Taylor rule for China from 1994 to 2008 and concludes that there is no close relationship between the PBC lending and the Taylor rate. The author then designs an augmented Taylor rule expanded to include a credit component (credit-augmented Taylor rule). The study shows that the augmented Taylor rule does not perform much better than the original one, but that it maps high inflationary periods relatively well. This is attributed to direct interventions into the credit markets, which have played a major role in combating inflationary cycles over the past decades. The analysis ends with an introduction of the concept of inflation targeting and an examination of whether this could describe monetary policy in China. It is clear that the PBC does not currently follow the inflation targeting approach, although the Chinese authorities could actually be able to influence inflation expectations effectively, not least through direct instruments such as price controls. The author notes that the PBC indeed had a good track record of fighting inflation between 1994 and 2008, and that this may now indicate a good time to think about introducing inflation targeting in China. The central conclusion of the study is that the proven gradual approach to economic and monetary reforms in China is reaching its limit. To break the vicious cycle that relies on the continuous use of quantity-based instruments to compensate for the ineffective price-based instruments – which in turn arises from the simultaneous use of both types of instruments – a complete shift away from quantity-based instruments is needed. Only then the approach of indirect monetary policy, which was officially introduced in 1998, could come into full play. N2 - Chinas Geldpolitik verfolgt zwei Endziele: Ein alles überragendes wirtschaftliches Ziel (d.h. Preisstabilität) und ein weniger wichtiges politisches Ziel (d.h. Wirtschaftswachstum). Der Hauptakteur der Geldpolitik ist die Zentralbank, die People's Bank of China (PBC). Aber die PBC ist eine nicht-unabhängige Zentralbank. Der Staatsrat genehmigt die Ziele der Geldpolitik, und eine sehr begrenzte Instrumenten-Unabhängigkeit bedeutet, dass die Zinsen nicht vollständig nach dem Ermessen der PBC festgelegt werden können. Die ungenügende personelle Unabhängigkeit der Zentralbank schafft es nicht, die Amtsträger dem politischen Einfluss zu entziehen. Der Geldpolitik in China stehen zwei Arten von geldpolitischen Instrumenten zur Verfügung: (i) Instrumente der PBC; und (ii) Politische nicht-Notenbank Instrumente. Die Instrumente der PBC beinhalten preis-basierte indirekte und quantität-basierte direkte Instrumente. Zu den politischen nicht-Notenbank Instrumenten zählen Preis- und Lohnkontrollen. Die gleichzeitige Nutzung dieser Instrumente führt zu vielerei Verzerrungen, die letztlich verhindern, dass der Zinskanal des monetären Transmissionsmechanismus funktionieren kann. Darüber hinaus stellen die starken Einflüsse der quantität-basierten direkten Instrumente und der politischen nicht-Notenbank Instrumente den Ansatz der indirekten Geldpolitik im Allgemeinen in Frage. KW - Geldpolitik KW - China KW - Geldmengenpolitik KW - Inflation Targeting KW - Preisberwachung KW - Lohnkontrolle KW - Taylor-Regel KW - Geldmengensteuerung KW - Notenbank KW - People's Bank of China KW - Monetary Policy KW - Window Guidance KW - China KW - Monetary Sterilisation Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69945 ER - TY - JOUR A1 - Sievers, Claudia A1 - Billig, Gwendolyn A1 - Gottschalk, Kathleen A1 - Rudel, Thomas T1 - Prohibitins Are Required for Cancer Cell Proliferation and Adhesion N2 - Prohibitin 1 (PHB1) is a highly conserved protein that together with its homologue prohibitin 2 (PHB2) mainly localizes to the inner mitochondrial membrane. Although it was originally identified by its ability to inhibit G1/S progression in human fibroblasts, its role as tumor suppressor is debated. To determine the function of prohibitins in maintaining cell homeostasis, we generated cancer cell lines expressing prohibitin-directed shRNAs. We show that prohibitin proteins are necessary for the proliferation of cancer cells. Down-regulation of prohibitin expression drastically reduced the rate of cell division. Furthermore, mitochondrial morphology was not affected, but loss of prohibitins did lead to the degradation of the fusion protein OPA1 and, in certain cancer cell lines, to a reduced capability to exhibit anchorage-independent growth. These cancer cells also exhibited reduced adhesion to the extracellular matrix. Taken together, these observations suggest prohibitins play a crucial role in adhesion processes in the cell and thereby sustaining cancer cell propagation and survival. KW - Krebs Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68548 ER - TY - JOUR A1 - Carpaneto, Armando A1 - Koepsell, Hermann A1 - Bamberg, Ernst A1 - Hedrich, Rainer A1 - Geiger, Dietmar T1 - Sucrose- and H+-Dependent Charge Movements Associated with the Gating of Sucrose Transporter ZmSUT1 N2 - Background: In contrast to man the majority of higher plants use sucrose as mobile carbohydrate. Accordingly protondriven sucrose transporters are crucial for cell-to-cell and long-distance distribution within the plant body. Generally very negative plant membrane potentials and the ability to accumulate sucrose quantities of more than 1 M document that plants must have evolved transporters with unique structural and functional features. Methodology/Principal Findings: To unravel the functional properties of one specific high capacity plasma membrane sucrose transporter in detail, we expressed the sucrose/H+ co-transporter from maize ZmSUT1 in Xenopus oocytes. Application of sucrose in an acidic pH environment elicited inward proton currents. Interestingly the sucrose-dependent H+ transport was associated with a decrease in membrane capacitance (Cm). In addition to sucrose Cm was modulated by the membrane potential and external protons. In order to explore the molecular mechanism underlying these Cm changes, presteady-state currents (Ipre) of ZmSUT1 transport were analyzed. Decay of Ipre could be best fitted by double exponentials. When plotted against the voltage the charge Q, associated to Ipre, was dependent on sucrose and protons. The mathematical derivative of the charge Q versus voltage was well in line with the observed Cm changes. Based on these parameters a turnover rate of 500 molecules sucrose/s was calculated. In contrast to gating currents of voltage dependentpotassium channels the analysis of ZmSUT1-derived presteady-state currents in the absence of sucrose (I =Q/t) was sufficient to predict ZmSUT1 transport-associated currents. Conclusions: Taken together our results indicate that in the absence of sucrose, ‘trapped’ protons move back and forth between an outer and an inner site within the transmembrane domains of ZmSUT1. This movement of protons in the electric field of the membrane gives rise to the presteady-state currents and in turn to Cm changes. Upon application of external sucrose, protons can pass the membrane turning presteady-state into transport currents. KW - Sucrose Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68538 ER - TY - JOUR A1 - Kraft, Peter A1 - Benz, Peter Michael A1 - Austinat, Madeleine A1 - Brede, Marc Elmar A1 - Schuh, Kai A1 - Walter, Ulrich A1 - Stoll, Guido A1 - Kleinschnitz, Christoph T1 - Deficiency of Vasodilator-Stimulated Phosphoprotein (VASP) Increases Blood-Brain-Barrier Damage and Edema Formation after Ischemic Stroke in Mice N2 - Background: Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification. Methodology/Principal Findings: Focal cerebral ischemia was induced in Vasp2/2 mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan’s Blue tracer was applied to visualize the extent of blood-brainbarrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p,0.05) and edema volumes (1.7 mm360.5 mm3 versus 0.8 mm360.4 mm3; p,0.0001) were significantly enhanced in Vasp2/2 mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm3617.3 mm3 versus 39.3 mm3610.7 mm3, respectively; p,0.01) and a non significant trend (p.0.05) towards worse neurological outcomes. Conclusion: Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage. KW - Vasodilatator-stimuliertes Phosphoprotein KW - Vasodilator-Stimulated Phosphoprotein Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68522 ER - TY - JOUR A1 - Kraft, Peter A1 - Schwarz, Tobias A1 - Meijers, Joost C. M. A1 - Stoll, Guido A1 - Kleinschnitz, Christoph T1 - Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Deficient Mice Are Susceptible to Intracerebral Thrombosis and Ischemic Stroke N2 - Background: Thrombus formation is a key step in the pathophysiology of acute ischemic stroke and results from the activation of the coagulation cascade. Thrombin plays a central role in this coagulation system and contributes to thrombus stability via activation of thrombin-activatable fibrinolysis inhibitor (TAFIa). TAFIa counteracts endogenous fibrinolysis at different stages and elevated TAFI levels are a risk factor for thrombotic events including ischemic stroke. Although substantial in vitro data on the influence of TAFI on the coagulation-fibrinolysis-system exist, investigations on the consequences of TAFI inhibition in animal models of cerebral ischemia are still lacking. In the present study we analyzed stroke development and post stroke functional outcome in TAFI-/- mice. Methodology/Principal Findings: TAFI-/- mice and wild-type controls were subjected to 60 min transient middle cerebral artery occlusion (tMCAO) using the intraluminal filament method. After 24 hours, functional outcome scores were assessed and infarct volumes weremeasured from 2,3,5-Triphenyltetrazoliumchloride (TTC)-stained brain slices. Hematoxylin and eosin (H&E) staining was used to estimate the extent of neuronal cell damage. Thrombus formation within the infarcted brain areas was analyzed by immunoblot. Infarct volumes and functional outcomes did not significantly differ between TAFI-/- mice and controls (p.0.05). Histology revealed extensive ischemic neuronal damage regularly including the cortex and the basal ganglia in both groups. TAFI deficiency also had no influence on intracerebral fibrin(ogen) formation after tMCAO. Conclusion: Our study shows that TAFI does not play a major role for thrombus formation and neuronal degeneration after ischemic brain challenge. KW - Thrombus Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68519 ER - TY - JOUR A1 - Rivero, Olga A1 - Reif, Andreas A1 - Sanjuan, Julio A1 - Molto, Maria D. A1 - Kittel-Schneider, Sarah A1 - Najera, Carmen A1 - Toepner, Theresia A1 - Lesch, Klaus-Peter T1 - Impact of the AHI1 Gene on the Vulnerability to Schizophrenia: A Case-Control Association Study N2 - Background: The Abelson helper integration-1 (AHI1) gene is required for both cerebellar and cortical development in humans. While the accelerated evolution of AHI1 in the human lineage indicates a role in cognitive (dys)function, a linkage scan in large pedigrees identified AHI1 as a positional candidate for schizophrenia. To further investigate the contribution of AHI1 to the susceptibility of schizophrenia, we evaluated the effect of AHI1 variation on the vulnerability to psychosis in two samples from Spain and Germany. Methodology/Principal Findings: 29 single-nucleotide polymorphisms (SNPs) located in a genomic region including the AHI1 gene were genotyped in two samples from Spain (280 patients with psychotic disorders; 348 controls) and Germany (247 patients with schizophrenic disorders; 360 controls). Allelic, genotypic and haplotype frequencies were compared between cases and controls in both samples separately, as well as in the combined sample. The effect of genotype on several psychopathological measures (BPRS, KGV, PANSS) assessed in a Spanish subsample was also evaluated. We found several significant associations in the Spanish sample. Particularly, rs7750586 and rs911507, both located upstream of the AHI1 coding region, were found to be associated with schizophrenia in the analysis of genotypic (p = 0.0033, and 0.031,respectively) and allelic frequencies (p = 0.001 in both cases). Moreover, several other risk and protective haplotypes were detected (0.006,p,0.036). Joint analysis also supported the association of rs7750586 and rs911507 with the risk for schizophrenia. The analysis of clinical measures also revealed an effect on symptom severity (minimum P value = 0.0037). Conclusions/Significance: Our data support, in agreement with previous reports, an effect of AHI1 variation on the susceptibility to schizophrenia in central and southern European populations. KW - Schizophrenie KW - Abelson helper integration-1 (AHI1) Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68501 ER - TY - JOUR A1 - Harth, Stefan A1 - Kotzsch, Alexander A1 - Hu, Junli A1 - Sebald, Walter A1 - Mueller, Thomas D. T1 - A Selection Fit Mechanism in BMP Receptor IA as a Possible Source for BMP Ligand-Receptor Promiscuity N2 - Background: Members of the TGF-b superfamily are characterized by a highly promiscuous ligand-receptor interaction as is readily apparent from the numeral discrepancy of only seven type I and five type II receptors available for more than 40 ligands. Structural and functional studies have been used to address the question of how specific signals can be deduced from a limited number of receptor combinations and to unravel the molecular mechanisms underlying the protein-protein recognition that allow such limited specificity. Principal Findings: In this study we have investigated how an antigen binding antibody fragment (Fab) raised against the extracellular domain of the BMP receptor type IA (BMPR-IA) recognizes the receptor’s BMP-2 binding epitope and thereby neutralizes BMP-2 receptor activation. The crystal structure of the complex of the BMPR-IA ectodomain bound to the Fab AbD1556 revealed that the contact surface of BMPR-IA overlaps extensively with the contact surface for BMP-2 interaction. Although the structural epitopes of BMPR-IA to both binding partners coincides, the structures of BMPR-IA in the two complexes differ significantly. In contrast to the structural differences, alanine-scanning mutagenesis of BMPR-IA showed that the functional determinants for binding to the antibody and BMP-2 are almost identical. Conclusions: Comparing the structures of BMPR-IA bound to BMP-2 or bound to the Fab AbD1556 with the structure of unbound BMPR-IA shows that binding of BMPR-IA to its interaction partners follows a selection fit mechanism, possibly indicating that the ligand promiscuity of BMPR-IA is inherently encoded by structural adaptability. The functional and structural analysis of the BMPR-IA binding antibody AbD1556 mimicking the BMP-2 binding epitope may thus pave the way for the design of low-molecular weight synthetic receptor binders/inhibitors. KW - Physiologische Chemie KW - antigen binding antibody fragment (Fab) Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68497 ER - TY - JOUR A1 - Bauer, Wolfgang R. A1 - Nadler, Walter T1 - Thermodynamics of Competitive Molecular Channel Transport: Application to Artificial Nuclear Pores N2 - In an analytical model channel transport is analyzed as a function of key parameters, determining efficiency and selectivity of particle transport in a competitive molecular environment. These key parameters are the concentration of particles, solvent-channel exchange dynamics, as well as particle-in-channel- and interparticle interaction. These parameters are explicitly related to translocation dynamics and channel occupation probability. Slowing down the exchange dynamics at the channel ends, or elevating the particle concentration reduces the in-channel binding strength necessary to maintain maximum transport. Optimized in-channel interaction may even shift from binding to repulsion. A simple equation gives the interrelation of access dynamics and concentration at this transition point. The model is readily transferred to competitive transport of different species, each of them having their individual in-channel affinity. Combinations of channel affinities are determined which differentially favor selectivity of certain species on the cost of others. Selectivity for a species increases if its in-channel binding enhances the species’ translocation probablity when compared to that of the other species. Selectivity increases particularly for a wide binding site, long channels, and fast access dynamics. Recent experiments on competitive transport of in-channel binding and inert molecules through artificial nuclear pores serve as a paradigm for our model. It explains qualitatively and quantitatively how binding molecules are favored for transport at the cost of the transport of inert molecules. KW - Thermodynamik KW - Transport KW - Molekül KW - Molecular Channel Transport KW - Artificial Nuclear Pores KW - Thermodynamics Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68484 ER - TY - JOUR A1 - Monzon-Casanova, Elisa A1 - Steiniger, Birte A1 - Schweigle, Stefanie A1 - Clemen, Holger A1 - Zdzieblo, Daniela A1 - Starick, Lisa A1 - Mueller, Ingrid A1 - Wang, Chyung-Ru A1 - Rhost, Sara A1 - Cardell, Susanna A1 - Pyz, Elwira A1 - Herrmann, Thomas T1 - CD1d Expression in Paneth Cells and Rat Exocrine Pancreas Revealed by Novel Monoclonal Antibodies Which Differentially Affect NKT Cell Activation N2 - Background: CD1d is a nonpolymorphic MHC class I-like molecule which presents nonpeptide ligands, e.g. glycolipids, to NKT cells. These cells are known to have multiple effects on innate and adaptive immune responses and on the development of pathological conditions. In order to analyze CD1d expression and function in the rat, the first rat CD1dspecific monoclonal antibodies (mAbs) were generated. Methodology/Principal Findings: Two mAbs, WTH-1 and WTH-2, were generated which bound equally well to cell surfaceexpressed rat and mouse CD1d. Their non-overlapping epitopes were mapped to the CD1d heavy chain. Flow cytometry and immunohistological analyses revealed a nearly identical degree and pattern of CD1d expression for hematopoieitic cells of both species. Notable is also the detection of CD1d protein in mouse and rat Paneth cells as well as the extremely high CD1d expression in acinar exocrine cells of the rat pancreas and the expression of CD4 on rat marginal zone B cells. Both mAbs blocked a-galactosylceramide recognition by primary rat and mouse NKT cells. Interestingly, the two mAbs differed in their impact on the activation of various autoreactive T cell hybridomas, including the XV19.2 hybridoma whose activation was enhanced by the WTH-1 mAb. Conclusions/Significance: The two novel monoclonal antibodies described in this study, allowed the analysis of CD1d expression and CD1d-restricted T cell responses in the rat for the first time. Moreover, they provided new insights into mechanisms of CD1d-restricted antigen recognition. While CD1d expression by hematopoietic cells of mice and rats was extremely similar, CD1d protein was detected at not yet described sites of non-lymphatic tissues such as the rat exocrine pancreas and Paneth cells. The latter is of special relevance given the recently reported defects of Paneth cells in CD1d2/2 mice, which resulted in an altered composition of the gut flora. KW - Krebs Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68477 ER - TY - JOUR A1 - Haarmann, Axel A1 - Deiss, Annika A1 - Prochaska, Juergen A1 - Foerch, Christian A1 - Weksler, Babette A1 - Romero, Ignacio A1 - Couraud, Pierre-Olivier A1 - Stoll, Guido A1 - Rieckmann, Peter A1 - Buttmann, Mathias T1 - Evaluation of Soluble Junctional Adhesion Molecule-A as a Biomarker of Human Brain Endothelial Barrier Breakdown N2 - Background: An inducible release of soluble junctional adhesion molecule-A (sJAM-A) under pro-inflammatory conditions was described in cultured non-CNS endothelial cells (EC) and increased sJAM-A serum levels were found to indicate inflammation in non-CNS vascular beds. Here we studied the regulation of JAM-A expression in cultured brain EC and evaluated sJAM-A as a serum biomarker of blood-brain barrier (BBB) function. Methodology/Principal Findings: As previously reported in non-CNS EC types, pro-inflammatory stimulation of primary or immortalized (hCMEC/D3) human brain microvascular EC (HBMEC) induced a redistribution of cell-bound JAM-A on the cell surface away from tight junctions, along with a dissociation from the cytoskeleton. This was paralleled by reduced immunocytochemical staining of occludin and zonula occludens-1 as well as by increased paracellular permeability for dextran 3000. Both a self-developed ELISA test and Western blot analysis detected a constitutive sJAM-A release by HBMEC into culture supernatants, which importantly was unaffected by pro-inflammatory or hypoxia/reoxygenation challenge. Accordingly, serum levels of sJAM-A were unaltered in 14 patients with clinically active multiple sclerosis compared to 45 stable patients and remained unchanged in 13 patients with acute ischemic non-small vessel stroke over time. Conclusion: Soluble JAM-A was not suited as a biomarker of BBB breakdown in our hands. The unexpected non-inducibility of sJAM-A release at the human BBB might contribute to a particular resistance of brain EC to inflammatory stimuli, protecting the CNS compartment. KW - Biomarker KW - Gehirn Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68468 ER - TY - JOUR A1 - Brandl, Carolin A1 - Ortler, Sonja A1 - Herrmann, Thomas A1 - Cardell, Susanna A1 - Lutz, Manfred B. A1 - Wiendl, Heinz T1 - B7-H1-Deficiency Enhances the Potential of Tolerogenic Dendritic Cells by Activating CD1d-Restricted Type II NKT Cells N2 - Background: Dendritic cells (DC) can act tolerogenic at a semi-mature stage by induction of protective CD4+ T cell and NKT cell responses. Methodology/Principal Findings: Here we studied the role of the co-inhibitory molecule B7-H1 (PD-L1, CD274) on semimature DC that were generated from bone marrow (BM) cells of B7-H12/2 mice and applied to the model of Experimental Autoimmune Encephalomyelitis (EAE). Injections of B7-H1-deficient DC showed increased EAE protection as compared to wild type (WT)-DC. Injections of B7-H12/2 TNF-DC induced higher release of peptide-specific IL-10 and IL-13 after restimulation in vitro together with elevated serum cytokines IL-4 and IL-13 produced by NKT cells, and reduced IL-17 and IFN-c production in the CNS. Experiments in CD1d2/2 and Ja2812/2 mice as well as with type I and II NKT cell lines indicated that only type II NKT cells but not type I NKT cells (invariant NKT cells) could be stimulated by an endogenous CD1d-ligand on DC and were responsible for the increased serum cytokine production in the absence of B7-H1. Conclusions/Significance: Together, our data indicate that BM-DC express an endogenous CD1d ligand and B7-H1 to ihibit type II but not type I NKT cells. In the absence of B7-H1 on these DC their tolerogenic potential to stimulate tolerogenic CD4+ and NKT cell responses is enhanced. KW - Dendritische Zelle Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68457 ER - TY - JOUR A1 - Goeb, Eva A1 - Schmitt, Johannes A1 - Benavente, Ricardo A1 - Alsheimer, Manfred T1 - Mammalian Sperm Head Formation Involves Different Polarization of Two Novel LINC Complexes N2 - Background: LINC complexes are nuclear envelope bridging protein structures formed by interaction of SUN and KASH proteins. They physically connect the nucleus with the peripheral cytoskeleton and are critically involved in a variety of dynamic processes, such as nuclear anchorage, movement and positioning and meiotic chromosome dynamics. Moreover, they are shown to be essential for maintaining nuclear shape. Findings: Based on detailed expression analysis and biochemical approaches, we show here that during mouse sperm development, a terminal cell differentiation process characterized by profound morphogenic restructuring, two novel distinctive LINC complexes are established. They consist either of spermiogenesis-specific Sun3 and Nesprin1 or Sun1g, a novel non-nuclear Sun1 isoform, and Nesprin3. We could find that these two LINC complexes specifically polarize to opposite spermatid poles likely linking to sperm-specific cytoskeletal structures. Although, as shown in co-transfection / immunoprecipitation experiments, SUN proteins appear to arbitrarily interact with various KASH partners, our study demonstrates that they actually are able to confine their binding to form distinct LINC complexes. Conclusions: Formation of the mammalian sperm head involves assembly and different polarization of two novel spermiogenesis-specific LINC complexes. Together, our findings suggest that theses LINC complexes connect the differentiating spermatid nucleus to surrounding cytoskeletal structures to enable its well-directed shaping and elongation, which in turn is a critical parameter for male fertility. KW - Sperma KW - LINC complexes Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68449 ER - TY - JOUR A1 - Herpin, Amaury A1 - Braasch, Ingo A1 - Kraeussling, Michael A1 - Schmidt, Cornelia A1 - Thoma, Eva C. A1 - Nakamura, Shuhei A1 - Tanaka, Minoru A1 - Schartl, Manfred T1 - Transcriptional Rewiring of the Sex Determining dmrt1 Gene Duplicate by Transposable Elements N2 - Control and coordination of eukaryotic gene expression rely on transcriptional and posttranscriptional regulatory networks. Evolutionary innovations and adaptations often require rapid changes of such networks. It has long been hypothesized that transposable elements (TE) might contribute to the rewiring of regulatory interactions. More recently it emerged that TEs might bring in ready-to-use transcription factor binding sites to create alterations to the promoters by which they were captured. A process where the gene regulatory architecture is of remarkable plasticity is sex determination. While the more downstream components of the sex determination cascades are evolutionary conserved, the master regulators can switch between groups of organisms even on the interspecies level or between populations. In the medaka fish (Oryzias latipes) a duplicated copy of dmrt1, designated dmrt1bY or DMY, on the Y chromosome was shown to be the master regulator of male development, similar to Sry in mammals. We found that the dmrt1bY gene has acquired a new feedback downregulation of its expression. Additionally, the autosomal dmrt1a gene is also able to regulate transcription of its duplicated paralog by binding to a unique target Dmrt1 site nested within the dmrt1bY proximal promoter region. We could trace back this novel regulatory element to a highly conserved sequence within a new type of TE that inserted into the upstream region of dmrt1bY shortly after the duplication event. Our data provide functional evidence for a role of TEs in transcriptional network rewiring for sub- and/or neo-functionalization of duplicated genes. In the particular case of dmrt1bY, this contributed to create new hierarchies of sex-determining genes. KW - Gen KW - dmrt1 KW - sex-determining gene Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68437 ER - TY - JOUR A1 - Pinkert, Stefan A1 - Schultz, Joerg A1 - Reichardt, Joerg T1 - Protein Interaction Networks-More Than Mere Modules N2 - It is widely believed that the modular organization of cellular function is reflected in a modular structure of molecular networks. A common view is that a ‘‘module’’ in a network is a cohesively linked group of nodes, densely connected internally and sparsely interacting with the rest of the network. Many algorithms try to identify functional modules in protein-interaction networks (PIN) by searching for such cohesive groups of proteins. Here, we present an alternative approach independent of any prior definition of what actually constitutes a ‘‘module’’. In a self-consistent manner, proteins are grouped into ‘‘functional roles’’ if they interact in similar ways with other proteins according to their functional roles. Such grouping may well result in cohesive modules again, but only if the network structure actually supports this. We applied our method to the PIN from the Human Protein Reference Database (HPRD) and found that a representation of the network in terms of cohesive modules, at least on a global scale, does not optimally represent the network’s structure because it focuses on finding independent groups of proteins. In contrast, a decomposition into functional roles is able to depict the structure much better as it also takes into account the interdependencies between roles and even allows groupings based on the absence of interactions between proteins in the same functional role. This, for example, is the case for transmembrane proteins, which could never be recognized as a cohesive group of nodes in a PIN. When mapping experimental methods onto the groups, we identified profound differences in the coverage suggesting that our method is able to capture experimental bias in the data, too. For example yeast-two-hybrid data were highly overrepresented in one particular group. Thus, there is more structure in protein-interaction networks than cohesive modules alone and we believe this finding can significantly improve automated function prediction algorithms. KW - Netzwerk KW - protein-interaction networks Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68426 ER - TY - JOUR A1 - Kleinschnitz, Christoph A1 - Grund, Henrike A1 - Wingler, Kirstin A1 - Armitage, Melanie E. A1 - Jones, Emma A1 - Mittal, Manish A1 - Barit, David A1 - Schwarz, Tobias A1 - Geis, Christian A1 - Kraft, Peter A1 - Barthel, Konstanze A1 - Schuhmann, Michael K. A1 - Herrmann, Alexander M. A1 - Meuth, Sven G. A1 - Stoll, Guido A1 - Meurer, Sabine A1 - Schrewe, Anja A1 - Becker, Lore A1 - Gailus-Durner, Valerie A1 - Fuchs, Helmut A1 - Klopstock, Thomas A1 - de Angelis, Martin Hrabe A1 - Jandeleit-Dahm, Karin A1 - Shah, Ajay M. A1 - Weissmann, Norbert A1 - Schmidt, Harald H. H. W. T1 - Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration N2 - Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox42/2) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox42/2 mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy. KW - Schlaganfall Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68416 ER - TY - JOUR A1 - Helmreich, Ernst J. M. T1 - Ways and means of coping with uncertainties of the relationship of the genetic blue print to protein structure and function in the cell N2 - As one of the disciplines of systems biology, proteomics is central to enabling the elucidation of protein function within the cell; furthermore, the question of how to deduce protein structure and function from the genetic readout has gained new significance. This problem is of particular relevance for proteins engaged in cell signalling. In dealing with this question, I shall critically comment on the reliability and predictability of transmission and translation of the genetic blue print into the phenotype, the protein. Based on this information, I will then evaluate the intentions and goals of today’s proteomics and gene-networking and appraise their chances of success. Some of the themes commented on in this publication are explored in greater detail with particular emphasis on the historical roots of concepts and techniques in my forthcoming book, published in German: Von Molekülen zu Zellen. 100 Jahre experimentelle Biologie. Betrachtungen eines Biochemikers KW - Genetik Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68006 ER - TY - JOUR A1 - Merget, Benjamin A1 - Wolf, Matthias T1 - A molecular phylogeny of Hypnales (Bryophyta) inferred from ITS2 sequence-structure data N2 - Background: Hypnales comprise over 50% of all pleurocarpous mosses. They provide a young radiation complicating phylogenetic analyses. To resolve the hypnalean phylogeny, it is necessary to use a phylogenetic marker providing highly variable features to resolve species on the one hand and conserved features enabling a backbone analysis on the other. Therefore we used highly variable internal transcribed spacer 2 (ITS2) sequences and conserved secondary structures, as deposited with the ITS2 Database, simultaneously. Findings: We built an accurate and in parts robustly resolved large scale phylogeny for 1,634 currently available hypnalean ITS2 sequence-structure pairs. Conclusions: Profile Neighbor-Joining revealed a possible hypnalean backbone, indicating that most of the hypnalean taxa classified as different moss families are polyphyletic assemblages awaiting taxonomic changes. KW - Moose KW - Hypnales KW - Bryophyta Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67997 ER - TY - JOUR A1 - Hagemann, Carsten A1 - Anacker, Jelena A1 - Haas, Stefanie A1 - Riesner, Daniela A1 - Schömig, Beate A1 - Ernestus, Ralf-Ingo A1 - Vince, Giles H. T1 - Comparative expression pattern of Matrix-Metalloproteinases in human glioblastoma cell-lines and primary cultures N2 - Background: Glioblastomas (GBM), the most frequent malignant brain tumors in adults, are characterized by an aggressive local growth pattern and highly invasive tumor cells. This invasion is facilitated by expression of matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases. They mediate the degradation of protein components of the extracellular matrix. Twenty-three family members are known. Elevated levels of several of them have been reported in GBM. GBM cell-lines are used for in vitro studies of cell migration and invasion. Therefore, it is essential to know their MMP expression patterns. Only limited data for some of the cell-lines are published, yet. To fill the gaps in our knowledge would help to choose suitable model systems for analysis of regulation and function of MMPs during GBM tumorigenesis, cell migration and invasion. Findings: We analysed MMP-1, -8, -9, -10, -11, -13, -17, -19, -20, -21, -23, -24, -26, -27, and MMP-28 expression in seven GBM cell-lines (SNB-19, GaMG, U251, U87, U373, U343, U138) and in four primary cell cultures by semiquantitative RT-PCR, followed changes in the MMP expression pattern with increasing passages of cell culture and examined the influence of TNF-a and TGF-b1 stimulation on the expression of selected MMPs in U251 and U373 cells. MMP-13, -17, -19 and -24 were expressed by all analyzed cell-lines, whereas MMP-20 and MMP-21 were not expressed by any of them. The other MMPs showed variable expression, which was dependent on passage number. Primary cells displayed a similar MMP-expression pattern as the cell-lines. In U251 and U373 cells expression of MMP-9 and MMP-19 was stimulated by TNF-a. MMP-1 mRNA expression was significantly increased in U373 cells, but not in U251 cells by this cytokine. Whereas TGF-b1 had no impact on MMP expression in U251 cells, it significantly induced MMP-11 and MMP-24 expression in U373 cells. Conclusions: Literature-data and our own results suggest that the expression pattern of MMPs is highly variable, dependent on the cell-line and the cell-culture conditions used and that also regulation of MMP expression by cytokines is cell-line dependent. This is of high impact for the transfer of cell-culture experiments to clinical implementation. KW - Metalloproteinasen KW - Glioblastom KW - Glioblastomas Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67980 ER -