FLT3 Length Mutations as Marker for Follow-Up Studies in Acute Myeloid Leukaemia

Length mutations within the FLT3 gene (FLT3-LM) can be found in 23% of acute myeloid leukaemia (AML) and thus are the most frequent mutations in AML. FLT3-LM are highly correlated with AML with normal karyotype and other cytogenetic aberrations of the prognostically intermediate group. This group is supposed to be a mixed group of AML with differences in the underlying pathogenesis. For more individualized treatment options it would be helpful to better characterize this large AML group not only by molecular mutations but also use these markers for the definition of minimal residual disease (MRD). However, so far the cytogenetically intermediate AML has been lacking suitable markers for PCR-based MRD detection like the fusion genes in the prognostically favourable subgroups. The suitability of the FLT3-LM as a target for PCR-based MRD was discussed controversially as it seemed to be a rather unstable marker. Thus, we aimed at the evaluation of FLT3-LM as a marker for residual disease in a large cohort of AML. Paired samples of 97 patients with AML at diagnosis and at relapse were analyzed. It could be shown that in only four cases a loss of the length mutation was detected. This is in the range of other well-characterized AML relapsing with a different geno- and/or phenotype. In contrast, a change in the ratio of the mutated allele in comparison to the wild-type allele was frequently observed. In detail, the FLT3-LM showed a tendency to accumulate during disease progression and was found more frequently at relapse than at diagnosis. In addition, 45 patients were analyzed at different time points during and after therapy. Using conventional PCR it clearly could be shown that for most of the patients positive at presentation FLT3-LM is a reliable PCR marker for monitoring treatment response. Even an early detection of relapse was possible in some cases. Copyright (C) 2004 S. Karger AG, Basel

Influence of mechanical ventilation and inhalation of pulmonary vasodilators, upon pulmonary blood flow and pulmonary vascular resistance

Peer Reviewe

Toward a Systemic Understanding of Listeria monocytogenes Metabolism during Infection

Listeria monocytogenes is a foodborne human pathogen that can cause invasive infection in susceptible animals and humans. For proliferation within hosts, this facultative intracellular pathogen uses a reservoir of specific metabolic pathways, transporter, and enzymatic functions whose expression requires the coordinated activity of a complex regulatory network. The highly adapted metabolism of L. monocytogenes strongly depends on the nutrient composition of various milieus encountered during infection. Transcriptomic and proteomic studies revealed the spatial–temporal dynamic of gene expression of this pathogen during replication within cultured cells or in vivo. Metabolic clues are the utilization of unusual C2- and C3-bodies, the metabolism of pyruvate, thiamine availability, the uptake of peptides, the acquisition or biosynthesis of certain amino acids, and the degradation of glucose-phosphate via the pentose phosphate pathway. These examples illustrate the interference of in vivo conditions with energy, carbon, and nitrogen metabolism, thus affecting listerial growth. The exploitation, analysis, and modeling of the available data sets served as a first attempt to a systemic understanding of listerial metabolism during infection. L. monocytogenes might serve as a model organism for systems biology of a Gram-positive, facultative intracellular bacterium

Ranking Theory

Ranking theory is one of the salient formal representations of doxastic states. It differs from others in being able to represent belief in a proposition (= taking it to be true), to also represent degrees of belief (i.e. beliefs as more or less firm), and thus to generally account for the dynamics of these beliefs. It does so on the basis of fundamental and compelling rationality postulates and is hence one way of explicating the rational structure of doxastic states. Thereby it provides foundations for accounts of defeasible or nonmonotonic reasoning. It has widespread applications in philosophy, it proves to be most useful in Artificial Intelligence, and it has started to find applications as a model of reasoning in psychology

Von Reallaboren zu urbanen Experimenten: Deutsche und internationale Debatten zu Skalierung und urbanen Nachhaltigkeitstransformationen

In den letzten Jahren sind Reallabore zu einem wichtigen Bestandteil der anwendungsbezogenen Nachhaltigkeitsforschung geworden. In Deutschland wurde die Forschung zu Reallaboren durch entsprechende Forschungsprogramme gefördert (z.B. "Leitinitiative Zukunftsstadt" des Bundesministeriums für Bildung und Forschung), während die EU die Entwicklung von "Urban Living Labs" finanziell förderte (z.B. "Joint Programming Initiative Urban Europe"). Derzeit verlagert sich die internationale wissenschaftliche Debatte mehr und mehr auf die Untersuchung von lokalen Experimenten. Vor diesem Hintergrund soll dieser Artikel vor allem dem Zweck dienen, die deutschsprachige Forschung zu Reallaboren innerhalb der europäischen und internationalen Debatten zu verorten und systematisch mit den Debatten zu "Urban Living Labs" und Experimenten zu vergleichen. In diesem Zusammenhang konzentrieren wir uns vor allem auf die Grundannahmen dieser drei Ansätze, ihre Entstehung und Anwendungsbereiche sowie die Bedeutung von Lernprozessen. Obwohl alle drei Ansätze auf urbane Nachhaltigkeitstransformationen abzielen, ist nur wenig über die mittel- und langfristigen Wirkungen solcher Initiativen bekannt. Deren zeitliche und räumliche Skalierung, die hier entscheidend ist, wurde zwar als Problem erkannt, aber bislang kaum systematisch untersucht. Der Artikel zielt darauf ab, die deutsche Debatte zu Reallaboren zu bereichern und sie mit der internationalen Diskussion zu verbinden.In recent years, real-world labs have become an important part of application-related sustainability research in Germany and Europe. Currently, the international academic debate is shifting more and more towards research on local experiments. Against this backdrop, this paper serves in particular the purpose of placing the German-speaking research on real-world labs within international debates, and of comparing it systematically with debates on urban living labs and experiments. In this context, we concentrate especially on the basic assumptions of these three approaches, their origins and areas of application as well as the importance of learning processes. Although all three approaches aim at urban sustainability transformations, not much is known about their medium- and long-term impacts. Their temporal and spatial scaling, which is critical here, was recognized as problem but has barely become object of systematic research. This paper follows the purpose to enrich the German debate on real-world labs and to link it to the international discussion

Cultural Heritage, Sustainable Development, and Climate Policy: Comparing the UNESCO World Heritage Cities of Potsdam and Bern

Developing sustainable, carbon-neutral, and climate-resilient districts seems to be particularly challenging with respect to historic city centers. However, barriers posed by legal requirements for historical buildings are counterbalanced by opportunities because historic cities have not undergone urban modernization and did not embrace the concept of functional cities, which nowadays impedes urban sustainability transformations. Thus, this paper focuses on the relationship between cultural heritage, urban sustainable development, and climate policy. We study continuity and change in the mid-sized UNESCO World Heritage cities Potsdam (Germany) and Bern (Switzerland). These matching forerunner cities share many characteristics, which enables them to transfer policies and jointly create new solutions for common problems. We find that national context matters, but we also identify functional equivalents like referenda and active citizen participation. Despite many similarities, Potsdam is ahead of Bern with respect to the institutionalization and integration of climate mitigation and adaptation. The comparative analysis (interviews and document analysis) identifies innovations that can be transferred between the two cities (e.g., Potsdam’s integrative climate policy or Bern’s efforts to become a role model for stakeholders and citizens). Moreover, the challenge to coordinate heritage management and climate governance offers chances for cooperation between matching cities like Bern and Potsda

Fernerkundungsgestütze Wärmeverlustdetektion von Dachflächen als Beitrag zur Energieeffizienzsteigerung von Stadträumen – Ergebnisse einer Fallstudie in Graz/Österreich

Der Beitrag dokumentiert die Ergebnisse eines Forschungsprojektes, das zum Ziel hat, die komplexen Zusammenhänge von Sensor, Atmosphäre, Dachbedeckung, Dachkonstruktion und Nutzung am Fallbeispiel der Gebäude des Campus der Karl-Franzens-Universität näher zu untersuchen. Die Vielzahl an unterschiedlichen Dacheindeckungen, die heterogene Altersstruktur der Bausubstanz sowie die Erfassung der Nutzung des Dachraumes geben einen differenzierten Blick auf den Aussagewert der Thermaldaten und dienen somit als ideale Testbasis zur Methodenentwicklung bzw. -verbesserung. Über eine kritische Betrachtung der Datenakquisition und des Zusammenhangs von Emissivität und Oberflächentemperatur sowie über die Erfassung der unterschiedlichen Dachbedeckungen bzw. –konstruktionen und der darunter liegenden Nutzungen kann schließlich eine qualitative Erfassung der Wärmeabgabe und der baulichen Defizitgebiete an den Dächern erfolgen

A comprehensive analysis of Helicobacter pylori plasticity zones reveals that they are integrating conjugative elements with intermediate integration specificity

Background: The human gastric pathogen Helicobacter pylori is a paradigm for chronic bacterial infections. Its persistence in the stomach mucosa is facilitated by several mechanisms of immune evasion and immune modulation, but also by an unusual genetic variability which might account for the capability to adapt to changing environmental conditions during long-term colonization. This variability is reflected by the fact that almost each infected individual is colonized by a genetically unique strain. Strain-specific genes are dispersed throughout the genome, but clusters of genes organized as genomic islands may also collectively be present or absent. Results: We have comparatively analysed such clusters, which are commonly termed plasticity zones, in a high number of H. pylori strains of varying geographical origin. We show that these regions contain fixed gene sets, rather than being true regions of genome plasticity, but two different types and several subtypes with partly diverging gene content can be distinguished. Their genetic diversity is incongruent with variations in the rest of the genome, suggesting that they are subject to horizontal gene transfer within H. pylori populations. We identified 40 distinct integration sites in 45 genome sequences, with a conserved heptanucleotide motif that seems to be the minimal requirement for integration. Conclusions: The significant number of possible integration sites, together with the requirement for a short conserved integration motif and the high level of gene conservation, indicates that these elements are best described as integrating conjugative elements (ICEs) with an intermediate integration site specificity

Single Channel Josephson Effect in a High Transmission Atomic Contact

The Josephson effect in scanning tunneling microscopy (STM) is an excellent tool to probe the properties of the superconducting order parameter on a local scale through the Ambegaokar-Baratoff (AB) relation. Using single atomic contacts created by means of atom manipulation, we demonstrate that in the extreme case of a single transport channel through the atomic junction modifications of the current-phase relation lead to significant deviations from the linear AB formula relating the critical current to the involved gap parameters. Using the full current-phase relation for arbitrary channel transmission, we model the Josephson effect in the dynamical Coulomb blockade regime because the charging energy of the junction capacitance cannot be neglected. We find excellent agreement with the experimental data. Projecting the current-phase relation onto the charge transfer operator shows that at high transmission multiple Cooper pair tunneling may occur. These deviations become non-negligible in Josephson-STM, for example, when scanning across single adatoms.Comment: 9 pages, 6 figures, including supplementary informatio