Analytic Dirac approximation for real linear algebraic groups

For a real linear algebraic group G let A(G) be the algebra of analytic vectors for the left regular representation of G on the space of superexponentially decreasing functions. We present an explicit Dirac sequence in A(G). Since A(G) acts on E for every Frechet-representation (\pi,E) of moderate growth, this yields an elementary proof of a result of Nelson that the space of analytic vectors is dense in E.Comment: 7 page

Hanger Running Tool

The disclosure relates to a hanger running tool for installation of a hanger in a well. The hanger running tool comprises a central bore and a hanger engagement arrangement configurable between an engaged position in which the engagement arrangement is coupled to a hanger, and a disengaged position in which the engagement arrangement is decoupled from a hanger. The tool also comprises a pressure-controlled anchoring actuator for actuating an anchoring arrangement, and comprising an actuation surface. The hanger engagement arrangement is configurable to the engaged position in response to an increase in pressure at a first pressure source, and is configurable to the disengaged position in response to an increase in pressure inside the central bore. The anchoring actuator is actuated in response to an increase in pressure on the actuation surface (e.g. an increase in pressure external to the tubing hanger running tool, such as an increase in the pressure in the BOP, below the slick joint) so that the anchoring arrangement anchors the hanger to an anchor point (e.g. which may be located on the wellhead, the Xmas tree, the BOP, or the like)

It’s time we reconsidered the principle that states must always repay their sovereign debt

Is it true that states must always repay their sovereign debt – even after a major regime change – to maintain their future creditworthiness? Odette Lienau writes that this conventional wisdom on sovereign debt is overly simplistic and in some cases entirely wrong. She argues that the assumptions of political neutrality, creditor uniformity, and historical constancy, upon which this common narrative rests, do not stand up to closer inspection. This suggests that more flexibility exists in terms of our understanding of government debt and how the market determines creditworthiness

An in vitro model of angiogenesis of endothelial cells from the murine myocardium and from the human neonatal foreskin and transfection of endothelial cells with different plasmid constructs

Titelblatt, Inhaltsverzeichnis, Lebenslauf 1\. Einleitung 2\. Literaturübersicht 3\. Materialien 4\. Methoden 5.1 Ergebnisse Teil 1 5.2 Ergebnisse Teil 2 6\. Diskussion 7\. Zusammenfassung 8\. Summary LiteraturverzeichnisAngiogenese, die Neubildung von Blutgefässen, kommt physiologischerweise nur im Embryo und Fetus sowie beim Adulten im Rahmen zyklischer Prozesse im Ovar, in der Plazenta und bei der Entwicklung der Milchdrüse vor (Risau, 1997). Alle anderen Formen der Angiogenese sind mit pathologischen Prozessen, insbesondere dem Tumorwachstum, verbunden. Eine hoffnungsvolle und Erfolg versprechende Alternative zu bisherigen Strategien der Tumortherapie ist die gentherapeutische Anti-Angiogenese. Eine selektive Expression des Transgens von Endothelzellen kann dabei durch Einsatz von Endothelzell-spezifischen genregulatorischen Elementen erzielt werden. Die vorliegende Arbeit verfolgte zwei Hauptziele, nämlich die Etablierung und Charakterisierung von in vitro- Modellen der Angiogenese muriner und humaner mikrovaskulärer Endothelzellen sowie die Charakterisierung verschiedener Plasmidkonstrukte auf Effizienz in diesen Modellen. Im Rahmen der Transfektionsversuche sollten zusätzlich morphologische Veränderungen transfizierter Endothelzellen auf licht- und elektronenmikroskopischer Basis untersucht werden, um einerseits Aussagen über die Aufnahme der Transfektionskomplexe in die Zellen sowie deren Weg in den Zellkern zu machen und andererseits mögliche morphologische Schädigungen der Zellen infolge der Transfektion zu beurteilen und abzuschätzen. Analog zur in vivo-Angiogenese durchliefen die eingesetzten mikrovaskulären Endothelzellen, isoliert aus der Vorhaut von Neugeborenen sowie aus dem Myokard zwei Wochen alter Mäuse, durch Stimulation mit pro-angiogenen Faktoren verschiedene Stadien der angiogenen Kaskade in vitro. Initiiert wurde die angiogene Kaskade morphologisch durch eine vollständige bzw. partielle Konfluenz der Endothelzellen (Stadium 1). Es kam zur linearen und zirkulären Aneinanderreihung von Endothelzellen (Stadium 2) und schliesslich zur Ausbildung kapillarähnlicher Strukturen mit einem zentralen Lumen (Stadium 3 und 4). Die Endothelzellen bildeten ein basalmembranähnliches Material, welches interzellulär sowie in intrazellulären Vakuolen und im Lumen kapillarähnlicher Strukturen detektiert werden konnte. Die Lumenbildung erfolgte durch Ausbildung intrazellulärer Vakuolen sowie durch Apoptose. Wýhrend die eingesetzten murinen Endothelzellen planar zur Kulturschalenoberfläche kapillarähnliche Strukturen ausbildeten (zweidimensionales in vitro-Modell der Angiogenese), konnte mit den humanen Endothelzellen erstmals ein realitätsnahes, dreidimensionales in vitro-Modell der Angiogenese etabliert werden, in dem analog zur in vivo-Angiogenese die Ausbildung kapillarähnlicher Strukturen durch Degradation eines von den Zellen selbst sezernierten basalmembranähnlichen Substrates sowie Migration bzw. Invasion, Proliferation und Differenzierung erfolgte. Im basalmembranähnlichen Material wurde immunhistochemisch Kollagen IV identifiziert. Ein besonderer Befund dieser Arbeit, beobachtet im murinen Zellkulturmodell, war der zyklische Verlauf der in vitro-Angiogenese mit dazwischen liegender „Latenzzeit". Nach dem Ablösen der kapillarähnlichen Strukturen von der Kulturschale konnte nach ca. 2 Monaten Kultivierung der auf der Kulturschale verbliebenen Endothelzellen ein erneutes Auftreten dieser Strukturen beobachtet werden. Interessant war, dass im zweiten Zyklus gerade die Zellen kapillarähnliche Strukturen ausbildeten, welche zuvor unbeteiligt an der Ausbildung dieser Strukturen waren. Die Ergebnisse indizieren, dass während der „Latenzzeit" eine Differenzierung der Endothelzellen in einen angiogenen Phänotyp erfolgte. Die Polyfektion mittels aktivierten Dendrimeren erfolgte vergleichend im Stadium der endohelialen Proliferation (Stadium 0) sowie der Bildung kapillarähnlicher Strukturen (Stadium 3 bzw. 4). Die Transfektion proliferierender Endothelzellen führte mit allen untersuchten Vektoren pJWM115 (CMV-luc), pCK5 (Ets-1l-luc), pPS12 (Ets-1k-luc) und pPS6 (E-sel-luc) zur Expression des Reportergens Luciferase, woraus zu schliessen ist, dass sowohl das Adhäsionsmolekül E-Selektin als auch der Transkriptionsfaktor Ets-1 in proliferierenden murinen und humanen Endothelzellen exprimiert werden. Insgesamt wurden mit den Vektoren pCK5 und pPS12 höhere Expressionsraten der Luciferase erzielt als mit dem pPS6-Vektor. Die Ergebnisse der Transfektion muriner und humaner Endothelzellen im Stadium der Bildung kapillarähnlicher Strukturen spiegelten die angiogenetische Situation beider in vitro-Modelle wider. Während die Transfektion muriner Endothelzellen im Stadium 3, unabhängig vom eingesetzten Vektor, zu keiner Expression der Luciferase führte, wurde nach Transfektion humaner Endothelzellen im Stadium der dreidimensionalen Organisation kapillarähnlicher Strukturen (Stadium 4) eine geringe Expression detektiert. Dabei konnte ein wichtiger Unterschied zwischen den einzelnen Versuchen im humanen Zellkulturmodell festgestellt werden. Humane Endothelzellen, die zu Beginn des Stadiums 4 in die Transfektionsexperimente einbezogen wurden, zeigten eine höhere Expression der Luciferase als Endothelzellen, die zu späteren Zeitpunkten des Stadiums 4 transfiziert wurden. Dies ist durch die unterschiedliche Proliferationsrate der Endothelzellen in diesem Stadium zu erklären. Diese Ergebnisse indizieren eine Zellzyklusabhängigkeit des verwendeten Gentransfersystems. Ein effizienter Gentransfer konnte nur in proliferierenden Endothelzellen beobachtet werden, als Resultat einer gesteigerten Aufnahme der Komplexe sowie eines effizienteren Eintritts der Komplexe bzw. Plasmid-DNA in den Kern. Die ultrastrukturelle Untersuchung liess vermuten, dass die durch Endozytose aufgenommenen Komplexe vor der Fusion mit primären Lysosomen aus den Endosomen entkommen, da freie DNA-Dendrimer-Komplexe an der Kernmembran vor dem Erscheinen multivesikulýrer Körper (späte Endosomen) in humanen Endothelzellen detektiert werden konnten. In den murinen Endothelzellen schien sich der intrazelluläre Abbau der Komplexe im Vergleich zu den humanen Endothelzellen langsamer zu vollziehen, welches die allgemein höhere Effzienz des Gentransfers in diesen Zellen zumindest partiell erklären könnte. In einer weiteren Versuchsreihe wurde die Steigerung der E-sel- Promotoraktivität (pPS6) durch die Endothelzell-spezifischen Enhancer 5xebs (pPO18) und Flk-1 (pPO14) sowie durch das HLA-Intron (pPO12) untersucht. Im Gegensatz zum HLA-Intron, welches zu einer Erhöhung der Aktivität des E-sel- Promotors um ein Vielfaches führte, konnte die Promotoraktivität durch die Endothelzell-spezifischen Enhancer nicht gesteigert werden. Dies deutet darauf hin, dass die entsprechenden Transkriptionsfaktoren wie z.B. Ets-1 in den untersuchten Zellkulturmodellen nicht in ausreichender Menge exprimiert werden. Genexpressionsanalysen oder immunhistochemische Untersuchungen der Endothelzellen in verschiedenen Stadien der angiogenen Kaskade in vitro könnten hierüber Aufschluss geben. Im Hinblick auf eine Reduktion von Tierversuchen durch Ersatz- und Ergänzungsmethoden kommt den in der vorliegenden Arbeit etablierten in vitro- Modellen der Angiogenese eine besondere Bedeutung zu. Über den Tierschutzaspekt hinaus stellen sie kostengünstige, sensitive, einfache experimentelle Systeme für weiterführende Untersuchungen dar. Während das murine Zellkulturmodell insbesondere für Gentransferstudien geeignet ist, da sich die murinen Endothelzellen effizient transfizieren lassen, steht mit dem realitätsnahen, dreidimensionalen in vitro-Modell der Angiogenese humaner Endothelzellen ein experimentelles System zur Verfügung, welches sich in der Hauptsache für Untersuchungen der in vitro-Angiogenese eignet. Aufgrund des fehlenden Einsatzes einer dreidimensionalen extrazellulären Matrix und der damit verbundenen Reduktion nicht bzw. schwierig standardisierbarer Faktoren ist dieses Modell geeignet für Untersuchungen von beispielsweise Zelladhäsionsmolekülen, Zell-Matrix-Interaktionen oder auch zur Identifizierung spezifischer Inhibitoren der Lumenbildung. Die etablierten Endothelzellkulturen werden derzeit bereits in anderen Laboratorien für ähnliche Experimente eingesetzt.Angiogenesis, the formation of new blood vessels by endothelial cells, plays an important role during prenatal growth as well as postnataly in diseases such as tumor growth. Targeting endothelial cells by gene transfer to inhibit angiogenesis offers an attractive anticancer approach. A selective expression of the transgene by endothelial cells can be achieved by use of endothelial- specific gene regulatory elements. The present work pursued two main aims, namely the establishment and characterization of in vitro-models of angiogenesis of murine and human microvascular endothelial cells as well as the characterization of different plasmid constructs on efficiency in these models. Furthermore morphological alterations of transfected endothelial cells should be examined on light and electron microscopic basis in order to make statements about the uptake of the complexes by the cells and their way to the nucleus as well as to appraise possible morphological damages of the cells caused by transfection. The angiogenic cascade of endothelial cells, isolated from the human neonatal foreskin and from the myocardium of two weeks old mice, was induced by pro- angiogenic factors. The beginning of the angiogenic cascade was initiated morphologically by a complete as well as partial confluence of the endothelial cells (stage 1). A linear and circular side by side arrangement of cells (stage 2) and the formation of capillary-like structures with an internal lumen (stage 3 and 4) could be observed. The endothelial cells produced a basement membrane-like material, which was found intercellularly as well as in intracellular vacuoles and in the lumen of capillary-like structures. In lumen formation vacuolization as well as apoptosis were involved. While the invested murine endothelial cells formed capillary-like structures planar to the culture dish surface (two-dimensional in vitro-model of angiogenesis), a realistic three-dimensional in vitro-model of angiogenesis could be established with the human endothelial cells with strong similarity with angiogenesis in vivo. Collagen IV, a basement membrane component, was identified by immunolabeling. An especial result of this work observed in the murine cell culture model was the cyclic course of in vitro-angiogenesis with a „latency time" between. After detachment of the capillary-like structures of the culture dish a reappearance of these structures could be observed after approximately 2 months cultivation of the remained cells. Interesting was, that the capillary-like structures in the second cycle were formed by endothelial cells, which were uninvolved at the formation of these structures before. The results indicate that a differentiation of the endothelial cells to an angiogenic phenotype took place during the „latency time". Endothelial cells at different stages of the angiogenic cascade (stage 0 versus 3 respectively 4) were transfected by polyfection with activated dendrimers. Transfection of proliferative endothelial cells (stage 0) led to expression of the reporter gene (luciferase) with all vectors invested pJWM115 (CMV-luc), pCK5 (Ets-1l-luc), pPS12 (Ets-1k-luc), pPS6 (E-sel-luc). This indicates the expression of the adhesion molecule E-selectin as well as of the transcription factor Ets-1 by proliferative murine and human endothelial cells. Highest transfection efficiencies were found by using the pJWM115-, pCK5- and the pPS12-vector. The results of transfection of murine and human endothelial cells forming capillary-like structures (stage 3 resp. 4) reflected the angiogenic situation in both in vitro-models. No reporter gene expression, independently from the vector used, could be detected after transfection of murine endothelial cells at stage 3. However, transfection of human endothelial cells at stage 4 led to an expression, marginal higher than control expression. An important difference between the individual experiments in the human cell culture model could be determined on that occasion. Human endothelial cells that were transfected at beginning of stage 4, showed a higher expression of the reporter gene than cells that were transfected at later times of stage 4. This is to be explained by the different proliferative rate of endothelial cells at this stage of the angiogenic cascade. These results show a cell cycle dependence of the gene transfer system used in this work. An efficient gene transfer could be observed in proliferative endothelial cells only as result of a raised uptake of complexes as well as a more efficient entry of complexes resp. plasmid DNA into the nucleus. Ultrastructural examination of transfected cells let suspect that the complexes uptaken by endocytosis escape from the endosomes before fusion with primary lysosomes since free DNA-dendrimer-complexes at the nuclear membrane could be detected before appearance of multivesicular bodies (late endosomes) in human endothelial cells. In the murine endothelial cells the intracellular degradation of the complexes seemed to take place more slowly in comparison to human cells which could at least partially explain the broadly higher efficiency of gene transfer in murine cells. In another experiment the increase of the E-sel promoter activity (pPS6) by two endothelial-specific enhancers 5xebs (pPO18) and flk-1 (pPO14) as well as by the HLA-intron (pPO12) was examined. In contrast to the HLA-intron, which led to a multiple increase of the activity of the E-sel promoter, promoter activity could not be raised by the endothelial-specific enhancers. This indicates that the corresponding transcription factors like for example Ets-1 are not expressed in the examined cell culture models in sufficient quantity. Gene expression analyses or immunohistochemical examinations of the endothelial cells at different stages of the angiogenic cascade in vitro could give more information. In view of a reduction of animal experiments through substitute and supplement methods, a special meaning comes up to the established in vitro-models of angiogenesis. In addition to the animal protection aspect, they represent cost-effective, sensitive, simple experimental systems for continuing examinations. While the murine cell culture model is suitable for gene transfer studies since murine endothelial cells can efficiently be transfected, an experimental system is available with the realistic three- dimensional in vitro-model of angiogenesis of human endothelial cells which is suitable for examinations of in vitro-angiogenesis. On the basis of the lacking use of a three-dimensional extracellular matrix and the connected reduction of not resp. difficult to standardize factors this model is suitable for examinations of cell adhesion molecules, cell matrix interactions or also for identification of specific inhibitors of lumen formation. The established endothelial cell cultures already are used for similar experiments in other laboratories at present

Who is the Sovereign in Sovereign Debt?: Reinterpreting a Rule-of-Law Framework from the Early Twentieth Century

Combining legal interpretation with political science analysis, this Article highlights the competing statist and popular conceptions of sovereignty at stake in sovereign debt issues. It argues that these two dominant approaches do not exhaust the offerings of intellectual history and considers an alternative approach that emerged in the early twentieth century and may be of relevance again today. The Article contends that U.S. Chief Justice Taft\u27s foundational 1923 Tinoco decision, which grounds the current approach to sovereign governmental recognition, has been misinterpreted to support a purely statist or absolutist conception of sovereignty. It argues that a proper interpretation presents an intermediate or rule of law framework that coincides with Taft\u27s domestic jurisprudence and provides an alternate conception of sovereignty for the current lending system. In emphasizing the historical and theoretical contingency of the current sovereign debt regime, this Article problematizes the assumption in mainstream international finance that only a narrow conception of sovereignty and a strict practice of debt repayment are consistent with a functioning sovereign credit market. Considering the economic and geopolitical context of Taft\u27s decision, the Article also suggests that the changing nature of creditor competition may partially account for variations in the concept of sovereignty underlying sovereign debt

Method For Installing A Hanger

The disclosure relates to a hanger running tool for installation of a hanger in a well. The hanger running tool comprises a central bore and a hanger engagement arrangement configurable between an engaged position in which the engagement arrangement is coupled to a hanger, and a disengaged position in which the engagement arrangement is decoupled from a hanger. The tool also comprises a pressure-controlled anchoring actuator for actuating an anchoring arrangement, and comprising an actuation surface. The hanger engagement arrangement is configurable to the engaged position in response to an increase in pressure at a first pressure source, and is configurable to the disengaged position in response to an increase in pressure inside the central bore. The anchoring actuator is actuated in response to an increase in pressure on the actuation surface (e.g. an increase in pressure external to the tubing hanger running tool, such as an increase in the pressure in the BOP, below the slick joint) so that the anchoring arrangement anchors the hanger to an anchor point (e.g. which may be located on the wellhead, the Xmas tree, the BOP, or the like)

Certified temperature measurement

This disclosure relates to a device for measurement of a temperature in compliance with safety certificate regulations. Disclosed is also a method relating thereto and a control loop for usage of said device

The Challenge of Legitimacy in Sovereign Debt Restructuring

Since the emergence of the post-World War II international economic system, policymakers have lamented the absence of a global sovereign debt restructuring mechanism. This disappointment has only intensified in recent years, as the failure to provide prompt, comprehensive, and lasting debt relief becomes even more apparent. As a result, scholars and key international actors have argued for the development of a more coherent global approach to debt workouts. But to date this discussion lacks a sustained focus on questions of legitimacy—a fact that is exceptionally puzzling in light of the voluminous scholarship on the legitimacy deficits of international economic institutions once they have been established. This Article bridges that gap, arguing that serious attention should be paid to these questions in advance of negotiating a possible debt workout mechanism, and considering what such attentiveness might mean in practice. It highlights the political complexity and distributional ramifications of legitimacy arguments, and develops an analytical framework for understanding the concept along with a preliminary application to the debt restructuring context. It then analyzes the institutional and historical background of debt restructuring in light of this typology, and assesses how domestic insolvency regimes and investment treaty arbitrations incorporate features purported to advance legitimacy. Finally, the Article considers how a future debt workout institution might respond to calls for legitimacy—based on its initial establishment, ongoing processes, and final outcomes—and briefly discusses existing proposals and likely political obstacles in light of these themes. In foregrounding these concerns, this Article draws attention to issues and controversies that will likely be relevant for some time, and contends that the tensions, distributional issues, and power dynamics implicated in questions of legitimacy should inform negotiations on any sovereign debt workout mechanism going forward