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Introduction The prolactin-Janus-kinase-2-signal transducer and activator of transcription-5 (JAK2-STAT5) pathway is essential for the development and functional differentiation of the mammary gland. The pathway also has important roles in mammary tumourigenesis. Prolactin regulated target genes are not yet well defined in tumour cells, and we undertook, to the best of our knowledge, the first large genetic screen of breast cancer cells treated with or without exogenous prolactin. We hypothesise that the identification of these genes should yield insights into the mechanisms by which prolactin participates in cancer formation or progression, and possibly how it regulates normal mammary gland development. Methods We used subtractive hybridisation to identify a number of prolactin-regulated genes in the human mammary carcinoma cell line SKBR3. Northern blotting analysis and luciferase assays identified the gene encoding heat shock protein 90-alpha (HSP90A) as a prolactin-JAK2-STAT5 target gene, whose function was characterised using apoptosis assays. Results We identified a number of new prolactin-regulated genes in breast cancer cells. Focusing on HSP90A, we determined that prolactin increased HSP90A mRNA in cancerous human breast SKBR3 cells and that STAT5B preferentially activated the HSP90A promoter in reporter gene assays. Both prolactin and its downstream protein effector, HSP90α, promote survival, as shown by apoptosis assays and by the addition of the HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in both untransformed HC11 mammary epithelial cells and SKBR3 breast cancer cells. The constitutive expression of HSP90A, however, sensitised differentiated HC11 cells to starvation-induced wild-type p53-independent apoptosis. Interestingly, in SKBR3 breast cancer cells, HSP90α promoted survival in the presence of serum but appeared to have little effect during starvation. Conclusions In addition to identifying new prolactin-regulated genes in breast cancer cells, we found that prolactin-JAK2-STAT5 induces expression of the HSP90A gene, which encodes the master chaperone of cancer. This identifies one mechanism by which prolactin contributes to breast cancer. Increased expression of HSP90A in breast cancer is correlated with increased cell survival and poor prognosis and HSP90α inhibitors are being tested in clinical trials as a breast cancer treatment. Our results also indicate that HSP90α promotes survival depending on the cellular conditions and state of cellular transformation.
The possible role of a first order QCD phase transition at nonvanishing quark chemical potential and temperature for cold neutron stars and for supernovae is delineated. For cold neutron stars, we use the NJL model with nonvanishing color superconducting pairing gaps, which describes the phase transition to the 2SC and the CFL quark matter phases at high baryon densities. We demonstrate that these two phase transitions can both be present in the core of neutron stars and that they lead to the appearance of a third family of solution for compact stars. In particular, a core of CFL quark matter can be present in stable compact star configurations when slightly adjusting the vacuum pressure to the onset of the chiral phase transition from the hadronic model to the NJL model. We show that a strong first order phase transition can have strong impact on the dynamics of core collapse supernovae. If the QCD phase transition sets in shortly after the first bounce, a second outgoing shock wave can be generated which leads to an explosion. The presence of the QCD phase transition can be read off from the neutrino and antineutrino signal of the supernova.
In a combined NMR/MD study, the temperature-dependent changes in the conformation of two members of the RNA YNMG-tetraloop motif (cUUCGg and uCACGg) have been investigated at temperatures of 298, 317 and 325 K. The two members have considerable different thermal stability and biological functions. In order to address these differences, the combined NMR/MD study was performed. The large temperature range represents a challenge for both, NMR relaxation analysis (consistent choice of effective bond length and CSA parameter) and all-atom MD simulation with explicit solvent (necessity to rescale the temperature). A convincing agreement of experiment and theory is found. Employing a principle component analysis of the MD trajectories, the conformational distribution of both hairpins at various temperatures is investigated. The ground state conformation and dynamics of the two tetraloops are indeed found to be very similar. Furthermore, both systems are initially destabilized by a loss of the stacking interactions between the first and the third nucleobase in the loop region. While the global fold is still preserved, this initiation of unfolding is already observed at 317 K for the uCACGg hairpin but at a significantly higher temperature for the cUUCGg hairpin.
Das medulläre Schilddrüsencarcinom ist ein maligner Tumor der parafollikulären calcitoninbildenden C-Zellen der Schilddrüse. In der Nachsorge der Patienten mit MTC stellt die Bestimmung des Calcitonin und CEA-Wertes im Serum zurzeit den Gold-Standard dar. In den letzten Jahren hat die Einführung der in hohem Maße sensitiven RT-PCR-Technik die Diagnose und den frühen Nachweis von Metastasen bei einigen Krebsformen verbessert. Die vorliegende Arbeit beschreibt eine Methode, mit welcher der molekulare Nachweis der Calcitonin-mRNA und carcinoembryonale Antigen-mRNA im peripheren Blut von Patienten mit medullärem Schilddrüsencarcinom und nachgewiesenen Fernmetastasen durchgeführt wurde. Bei keinem der untersuchten Patienten konnte CT-mRNA im peripheren Blut nachwiesen werden, obwohl die CT-Werte im Serum bei allen MTC Patienten erhöht waren. CEA mRNA wurde häufiger bei Patienten mit MTC (54 %) als in der Kontrollgruppe (34,4%) nachgewiesen. Der Grund für den hohen Anteil falsch positiver CEA-mRNA Nachweise bei Kontrollpatienten ist unbekannt. Vermutet wird eine „illegitime Transkription“. Die Ergebnisse zeigen, daß Calcitonin mRNA kein geeigneter Parameter für den Nachweis zirkulierender Tumorzellen bei Patienten mit medullärem Schilddrüsencarcinom ist. Im Gegensatz dazu könnte der Nachweis der CEA mRNA eine Verbesserung der frühen Diagnose des metastasierten medullären Schilddrüsencarcinoms darstellen.
One of the current trends in international law scholarship is the question of which influences specific legal cultures have on the understanding of international law. This contribution will trace the conditions of a German perspective and analyse the debate against the background of positive law. We will try to assess what the debate adds to the general theory of international law, how it fits into demands of legitimacy of international governance, and whether it contributes to a sensible reconstruction of current law. Furthermore, we try to develop our own perspective that matches the system of international law and is plausible in terms of international legal theory. For that purpose, we will first take It is probably in this context that the contention has to be understood that the ongoing debate on the constitutionalisation of public international law is particularly European, if not German. Whether or not this is the case is difficult to investigate with a lawyer’s tools. However, the idea that international law is the constitution of mankind has found many adherents in German legal writings. This contribution will trace the conditions of a German perspective and analyse the debate against the background of positive law. We will try to assess what the debate adds to the general theory of international law, how it fits into demands of legitimacy of international governance, and whether it contributes to a sensible reconstruction of current law. Furthermore, we try to develop our own perspective that matches the system of international law and is plausible in terms of international legal theory. For that purpose, we will first take up the debate and find its place in the landscape of international legal theory. In this context, we try to shed light on the central concepts used or presupposed when constitutionalisation is discussed by German-speaking scholars (see below, section B). Furthermore, we will discuss structures in positive law which are used as arguments in the debate (section C). Finally, we will try to give an account of constitutionalisation in terms of both sources doctrine and legal theory (section D), before drawing conclusions from the discussion (section E).
Ich freue mich mit Ihnen über diese ganz besondere Ehre, die Ihnen heute zuteil wird. Die Medaille, die Ihnen im Namen und im Andenken an Johann Wilhelm Meigen verliehen wird, wurde zur Förderung der entomologischen Forschung auf dem Gebiet der Systematik und Faunistik gestiftet. Mir fällt nun die Aufgabe zu, Ihre Verdienste um ebendiese Gebiete zu skizzieren. Dies ist eine ebenso leichte wie schwierige Aufgabe, möchte ich doch sowohl dem Menschen als auch dem Werk in allen Facetten gerecht werden. Leicht erscheint mir die Aufgabe vor allem deshalb, weil ich Herrn Remane schon sehr lange kenne – ich begegnete ihm vor etwas mehr als 30 Jahren, gleich am ersten Tag meines Studiums in Marburg, als ich in die Bestimmungsübungen marschierte und den jugendlich wirkenden Mann in Lederjacke, der so gar nicht aussah, wie ich mir einen Professor vorgestellt hatte, erst mal ganz locker mit „Du“ ansprach. Wie peinlich war es mir, als er sich bei Kursbeginn dann mit Titel vorstellte! In den folgenden 10 Jahren haben wir mehr Zeit miteinander verbracht als mit unseren jeweiligen Familien. Bitte erwarten Sie also keine objektive Darstellung von mir – ich bin sozusagen im besten Sinne des Wortes „befangen“ und kann nur aus meiner subjektiven Sicht berichten. Zunächst allerdings ein paar „Highlights“ aus Ihrer Vita. Inspiriert durch sein familiäres Umfeld, interessierte sich Herr Remane bereits als Schüler für die Lebewesen seiner unmittelbaren Umgebung. Zunächst waren es die Wanzen, denen er sich mit großer Begeisterung zuwandte, und er publizierte noch als Schüler mit 18 Jahren seinen ersten wissenschaftlichen Beitrag in einem...
We propose a theory characterizing information systems (IS) as language communities which use and develop domain-specific languages for communication. Our theory is anchored in Language Critique, a branch of philosophy of language. In developing our theory, we draw on Systems Theory and Cybernetics as a theoretical framework. "Organization" of a system is directly related to communication of its sub-systems. "Big systems" are self-organizing and the control of this ability is disseminated throughout the system itself. Therefore, the influence on changes of the system from its outside is limited. Operations intended to change an organization are restricted to indirect approaches. The creation of domain-specific languages by the system itself leads to advantageous communication costs compared to colloquial communication at the price of set-up costs for language communities. Furthermore, we demonstrate how our theoretical constructs help to describe and predict the behavior of IS. Finally, we discuss implications of our theory for further research and IS in general. Keywords: Language Critique, language communities, communication, self-organization, IS research
Die fünf Aspekte der Scharia und die Menschenrechte : die Auslegung des Koran auf neuen Wegen
(2008)
Auch der Koran ist das Werk seiner Zeit; heute kann er nicht ausgelegt werden, ohne seinen historischen Kontext einzubeziehen. Doch noch dominiert ein starres Verständnis des Koran, das den eigentlichen Charakter des religiösen Textes verkennt. Eine kleine, international etablierte Gruppe von islamischen Theologen postuliert eine zeitgenössische innovative Koranexegese, die berücksichtigt, dass die Worte des Koran als eine lebendige Anrede an seine realen Adressaten in Offenbarungszeit und -ort gerichtet waren, nämlich an den Propheten Muhammad, seine Gefährten, die heidnischen Araber, Juden und Christen. So eröffnet sich ein neuer Blick auf die »heilige Schrift« der Muslime.
Ich möchte im Folgenden zeigen, dass bereits das frühe Manuskript der "Berliner Chronik" eine Bearbeitung der Gattungen 'Stadtbild' und 'Autobiographie' darstellt und - das ist sein Charakteristikum - diese Bearbeitung auch in Szene setzt. Des weiteren soll nachgezeichnet werden, dass die "Chronik" auf äußerst komplexe Weise autobiographische und topographische Schreibweisen miteinander verknüpft und dabei - so meine These - zu dem maßgeblichen Text wird, in dem Benjamin die Kategorie des Raumes für sein Denken entfaltet. Anders gesagt: Im Schreiben der "Berliner Chronik" richtet der Kulturhistoriker Benjamin sein Denken räumlich aus.
Naturalness is one of the most important criteria in nature conservation. This paper examines the fundamental concepts underlying the definition and assessment of naturalness. Its role in nature conservation and forest management under conditions of global change is also discussed. The degree of naturalness may be defined in ordinal classes. The “static” concept of the potential natural vegetation (pnV), developed in the 1950ies, is mostly used as the reference state. In other cases, its reversed concept, the hemeroby (degree of articifiality) is assessed, based on the intensity and frequency of human impacts. Since the 1970ies, more attention has been given to natural dynamics than in earlier approaches, e.g. in forest succession models. At the end of the 1980ies, the previous importance was increasingly stressed of natural browsing by large herbivores and the role of predators. These large herbivors are extinct today in most cultural European landscapes. It is assumed, that they open up the canopy, and create park-like forest structures which contain a diversity of habitats for other types of organism (birds, insects). Changed and permanently changing environments and altering patterns of competition between species continue to modify natural processes today. Some of the more conspicuous effects are the extinction of native species and immigration of species to new regions. Long-lived ecosystems like forests are however not able to adapt quickly to such changes and may be unable to find a new balance with the environment. Today, such changes occur very rapidly, and are reducing the original naturalness of ecosystems. Because of this, the criterion “naturalness” must be downweighted. Conversely, more importance should be attached to other criteria: particularly originality (= original naturalness) and restorability. Forestry is contributing to this accelerated change of biocoenoses by increasing disturbances and introducing exotic tree species. Naturalisation of some exotic tree species modifies the natural processes and creates a “new allochthonous naturalness”. Because of this, forest planning should try to preserve or restore stands with attributes of the “original forest”. Exotic species should not be planted, or only in a very restricted way.