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 - 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 - 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 - 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 - 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 -