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The role of RNA interference in the developmental separation of blood and lymphatic vasculature
(2014)
Background: Dicer is an RNase III enzyme that cleaves double stranded RNA and generates functional interfering RNAs that act as important regulators of gene and protein expression. Dicer plays an essential role during mouse development because the deletion of the dicer gene leads to embryonic death. In addition, dicer-dependent interfering RNAs regulate postnatal angiogenesis. However, the role of dicer is not yet fully elucidated during vascular development.
Methods: In order to explore the functional roles of the RNA interference in vascular biology, we developed a new constitutive Cre/loxP-mediated inactivation of dicer in tie2 expressing cells.
Results: We show that cell-specific inactivation of dicer in Tie2 expressing cells does not perturb early blood vessel development and patterning. Tie2-Cre; dicerfl/fl mutant embryos do not show any blood vascular defects until embryonic day (E)12.5, a time at which hemorrhages and edema appear. Then, midgestational lethality occurs at E14.5 in mutant embryos. The developing lymphatic vessels of dicer-mutant embryos are filled with circulating red blood cells, revealing an impaired separation of blood and lymphatic vasculature.
Conclusion: Thus, these results show that RNA interference perturbs neither vasculogenesis and developmental angiogenesis, nor lymphatic specification from venous endothelial cells but actually provides evidence for an epigenetic control of separation of blood and lymphatic vasculature.
The recent approval by the US Food and Drug Administration of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (VMA), often associated with vitreomacular traction (VMT) and macular hole (MH), has brought new attention to the field of pharmacologic vitreolysis. The need for an enzyme to split the vitreomacular interface, which is formed by a strong adhesive interaction between the posterior vitreous cortex and the internal limiting membrane, historically stems from pediatric eye surgery. This review summarizes the different anatomic classifications of posterior vitreous detachment or anomalous posterior vitreous detachment and puts these in the context of clinical pathologies commonly observed in clinical practice of the vitreoretinal specialist, such as MH, VMT, age-related macular degeneration, and diabetic macular edema. We revisit the outcome of the Phase II studies that indicated ocriplasmin was a safe and effective treatment for selected cases of symptomatic VMA and MH. Release of VMA at day 28 was achieved by 26.5% of patients in the ocriplasmin group versus 10.1% in the placebo group (P<0.001). Interestingly, for MHs, the numbers were more remarkable. Predictive factors for successful ocriplasmin treatment were identified for VMT (VMA diameter smaller than 1,500 µm) and MH (smaller than 250 µm). In comparison with the highly predictable outcome after vitrectomy, the general success rate of ocriplasmin not under clinical trial conditions has not fully met expectations and needs to be proven in real-world clinical settings. The ocriplasmin data will be compared in the future with observational data on spontaneous VMA release, will help retina specialists make more accurate predictions, and will improve outcome rates.
Die Struktur der makroprudenziellen Politik in der Europäischen Union ist ausgesprochen komplex und für den außenstehenden Betrachter fast undurchdringlich geworden. Deshalb wurde mit den Titeln der drei Kapitel des vorliegenden Aufsatzes „Der Prozess“, „Das Schloss“ und „Das Urteil“ bewusst auf Werke von Franz Kafka angespielt. Während sich der erste Teil der Arbeit vor allem mit der Komplexität des funktionellen Transmissionsprozesses in der makroprudenziellen Politik beschäftigt, widmet sich das zweite Kapitel, also der „Schloss-Teil“, ihren institutionellen Verflechtungen. Und am Ende werden die Ausführungen in einem „Wert-Urteil“ zusammengefasst.
On January 29, 2014, EU Commissioner Barnier published a draft law proposing a ban for proprietary trading by big banks in Europe. In this opinion piece, published in a German newspaper on 30 January, 2014, Jan Pieter Krahnen, who was a member of the Liikanen Commission, argues that the proposal could prove to be effective in preventing systemic risk.
Ein Freibrief für die Notenbank bedeutet, genau genommen, die Bankrotterklärung des demokratischen Verfassungsstaates vor technokratischen Beliebigkeiten, schreibt Helmut Siekmann in diesem Namensbeitrag. Er betont, dass die Europäische Union eine unverzichtbare Einrichtung ist und ein echter Bundesstaat sein sollte. Sie sei aber im Wesentlichen (nur) ein Rechtskonstrukt, weshalb es umso wichtiger sei, dass die rechtlichen Regeln, auf denen sie beruht, genauestens beachtet werden.
The investigated haloarchaeal species, Halobacterium salinarum, Haloferax mediterranei, and H. volcanii, have all been shown to be polyploid. They contain several replicons that have independent copy number regulation, and most have a higher copy number during exponential growth phase than in stationary phase. The possible evolutionary advantages of polyploidy for haloarchaea, most of which have experimental support for at least one species, are discussed. These advantages include a low mutation rate and high resistance toward X-ray irradiation and desiccation, which depend on homologous recombination. For H. volcanii, it has been shown that gene conversion operates in the absence of selection, which leads to the equalization of genome copies. On the other hand, selective forces might lead to heterozygous cells, which have been verified in the laboratory. Additional advantages of polyploidy are survival over geological times in halite deposits as well as at extreme conditions on earth and at simulated Mars conditions. Recently, it was found that H. volcanii uses genomic DNA as genetic material and as a storage polymer for phosphate. In the absence of phosphate, H. volcanii dramatically decreases its genome copy number, thereby enabling cell multiplication, but diminishing the genetic advantages of polyploidy. Stable storage of phosphate is proposed as an alternative driving force for the emergence of DNA in early evolution. Several additional potential advantages of polyploidy are discussed that have not been addressed experimentally for haloarchaea. An outlook summarizes selected current trends and possible future developments.
A multiple filter test for the detection of rate changes in renewal processes with varying variance
(2014)
The thesis provides novel procedures in the statistical field of change point detection in time series.
Motivated by a variety of neuronal spike train patterns, a broad stochastic point process model is introduced. This model features points in time (change points), where the associated event rate changes. For purposes of change point detection, filtered derivative processes (MOSUM) are studied. Functional limit theorems for the filtered derivative processes are derived. These results are used to support novel procedures for change point detection; in particular, multiple filters (bandwidths) are applied simultaneously in oder to detect change points in different time scales.
Inhalt:
Prof. Dr. Dr. h.c. Helmut Siekmann: Stellungnahme für den Haushalts- und Finanzausschuss des Landtags Nordrhein-Westfalen zum Entwurf eines Gesetzes zur Offenlegung der Bezüge von Sparkassenführungskräften im Internet (Drucksache 16/4165) vom 10.02.2014
Gesetzentwurf der Fraktion der Piraten Gesetz zur Offenlegung der Bezüge von Sparkassenführungskräften im Internet vom 08.10.2013
Panel Sample Selection ModelsThe empirical evidence currently available in the literature regarding the effects of a country's IMF program participation on its output growth is rather inconclusive. In this paper we propose and estimate a panel data sample selection model featuring state dependence. As in this model the output growth effects of program participation can be conditional on the realization of a state variable (conditional pooling), our framework may reconcile previous empirical evidence based on models without state-dependent effects. We find that the effects of IMF program participation on output growth vary systematically with an index reflecting a country's institutional record, and that output growth effects of program participation are significantly positive only if the program participation is coupled with sufficient improvement of the institutional record.
Das Forschungsunternehmen "Romanisch und Deutsch am Hinterrhein / GR" von Prof. Dr. Theodor Ebneter (Sprachlabor der Universität Zürich) wurde in den Jahren 1978-1992 am Phonogrammarchiv der Universität Zürich als erstes bilinguistisches Projekt durchgeführt.
Für jede der vier Talschaften des Hinterrheins waren ursprünglich zwei Bände, einer für das Deutsche und einer für das Romanische, vorgesehen. […] Da die Gewährsleute ihre jeweilige Mundart gerne mit jener von Chur vergleichen, wurde die Dissertation von Oscar Eckhardt "Die Mundart der Stadt Chur" (1991)als Band 9 veröffentlicht.
Nachdem Prof. Ebneters Leitung des Phonogrammarchivs 1992 zu Ende ging, konnte mit Unterstützung des Schweizerischen Nationalfonds Band 7 "Romanisch im Boden, in Trin und in Flims" mit seinem Umfang von 622 Seiten abgeschlossen werden, der als romanistische Ergänzung zu Urs Willis 1990 publiziertem Band 8 "Deutsch im Bezirk Imboden " die Untersuchung dieser vierten und letzten Talschaft beschliessen sollte.
Der vorliegende Band 11 der Reihe "Romanisch und Deutsch am Hinterrhein / GR" ersetzt nun Willis Band 8 und schliesst zugleich das Forschungsuntemehmen mit der germanistischen Aufarbeitung des Bodens, von Trins und von Flims ab. Dieser Band wurde von Dr. Alfred Toth und Prof. Dr. Theodor Ebneter parallel zur Herstellung von Band 10 "Die romanisch-deutsche Sprachlandschaft am unteren Hinterrhein" verfasst. Die Ersetzung von Willis Band durch den vorliegenden war auch deshalb nötig, um die die deutschen Mundarten des Bezirks Imboden betreffenden Daten in Band 10 einbauen zu können. Zu diesem Zweck wurden im Winter und Frühling 1994/95 alle Ortschaften des Bezirks Imboden mit 27 Gewährspersonen in längeren Gesprächen aufgenommen.
Band 11 orientiert sich methodisch einerseits an Band 7 über die romanistische Situation des Bezirks Imboden, dessen germanistische Ergänzung er darstellt, anderseits an Band 9 über die Mundart von Chur, der innerhalb der Reihe zum erstenmal vergleichsweise herangezogen werden konnte, nachdem alle übrigen germanistischen Bände früher erschienen waren. Aus diesem Grunde wurde der Einleitung (Kap. 1), der Phonologie (Kap. 2) und der Morphologie (Kap. 3) ein Kapitel 4 "Vergleich der Dialekte des Bezirks Imboden mit der Mundart der Stadt Chur" beigesteIlt, in dem auch Aspekte der Morphosyntax (Kap. 4.3.), der Syntax (Kap. 4.4.) sowie der Lexikologie (Kap. 4.5.) behandelt werden.
Nachdem ich meine Lizentiatsarbeit [..] abgeschlossen hatte, fragte mich Prof. Ebneter an, ob ich bereit wäre, mit dem gleichen Transkritionssystem auch eine Umfrage zu diversen Verbalformen in Graubünden zu erstellen. […] Von Prof. Ebneter bekam ich eine Liste mit den gewünschten Verbformen. Ich habe zu diesen je einen Satz konstruiert, der den Gewährspersonen vorgelegt wurde. Einmal hatten die Informantinnen und Informanten die Verbformen mit vorangestelltem Subjektpronomen und einmal mit Inversion aus der standardsprachliche Vorlage in der 1. Person Singular zu übersetzen. In der Folge habe ich dann das ganze Paradigma abgefragt.
Die Resultate meiner Erhebung sind teilweise in die Verbalmorphologie des Abschlussbandes zum Forschungsprojekt "Deutsch und Romanisch am Hinterrhein" eingeflossen. Insgesamt aber sind die Verbformen noch nie integral veröffentlicht worden. Eine eigenständige gedruckte Publikation verlangte wohl auch einen Kommentar zu den Paradigmen. Mit der Möglichkeit, Texte auch digital zu publizieren, hat sich allerdings eine neue Verbreitungsform ergeben, die es erlaubt, auch "Materialien" zu veröffentlichen, die vielleicht anderen wissenschaftlich Arbeitenden nützlich sein können. Im Zeichen des zum Teil rapiden Sprachwandels gerade in der Verbalmorphologie stellen die 1988 erfassten Verbparadigmen aber auch ein Brückendokument dar, das spannende Vergleiche zwischen den Aussagen früherer Forschungen und aktuellen Daten zulässt.
Although oil price shocks have long been viewed as one of the leading candidates for explaining U.S. recessions, surprisingly little is known about the extent to which oil price shocks explain recessions. We provide the first formal analysis of this question with special attention to the possible role of net oil price increases in amplifying the transmission of oil price shocks. We quantify the conditional recessionary effect of oil price shocks in the net oil price increase model for all episodes of net oil price increases since the mid-1970s. Compared to the linear model, the cumulative effect of oil price shocks over course of the next two years is much larger in the net oil price increase model. For example, oil price shocks explain a 3% cumulative reduction in U.S. real GDP in the late 1970s and early 1980s and a 5% cumulative reduction during the financial crisis. An obvious concern is that some of these estimates are an artifact of net oil price increases being correlated with other variables that explain recessions. We show that the explanatory power of oil price shocks largely persists even after augmenting the nonlinear model with a measure of credit supply conditions, of the monetary policy stance and of consumer confidence. There is evidence, however, that the conditional fit of the net oil price increase model is worse on average than the fit of the corresponding linear model, suggesting much smaller cumulative effects of oil price shocks for these episodes of at most 1%.
Efforts to control bank risk address the wrong problem in the wrong way. They presume that the financial crisis was caused by CEOs who failed to supervise risk-taking employees. The responses focus on executive pay, believing that executives will bring non-executives into line—using incentives to manage risk-taking—once their own pay is regulated. What they overlook is the effect on non-executive pay of the competition for talent. Even if executive pay is regulated, and executives act in the bank’s best interests, they will still be trapped into providing incentives that encourage risk-taking by non-executives due to the negative externality that arises from that competition. Greater risk-taking can increase short-term profits and, in turn, the amount a non-executive receives, potentially at the expense of long-term bank value. Non-executives, therefore, have an incentive to incur significant risk upfront so long as they can depart for a new employer before any losses materialize. The result is an upward spiral in compensation—reducing an executive’s ability to set non-executive pay and the ability of any one bank to adjust compensation to reflect risk-taking and long-term outcomes. New regulation must address the tension between compensation and competition. Regulators should take account of the effect of competition on market-wide levels of pay, including by non-banks who compete for talent. The ability of non-executives to jump from a bank employer to another financial firm should also be limited. In addition, banks should be required to include a long-term equity component in non-executive pay, with subsequent employers being restricted from compensating a new employee for any losses she incurs related to her prior work.
We examine trust and trustworthiness of individuals with varying professional preferences and experiences. Our subjects study business and economics in Frankfurt, the financial center of Germany and continental Europe. In the trust game, subjects with a high interest in working in the financial industry return 25 percent less than subjects with a low interest. We find no evidence that the extent of professional experience in the financial industry has a negative impact on trustworthiness. We also do not find any evidence that the financial industry screens out less trustworthy individuals in the hiring process. In a prediction game that is strategically equivalent to the trust game, the amount sent by first-movers was significantly smaller when the second-mover indicated a high interest in working in finance. These results suggest that the financial industry attracts less trustworthy individuals, which may contribute to the current lack of trust in its employees.
In the wake of the Global Financial Crisis that started in 2007, policymakers were forced to respond quickly and forcefully to a recession caused not by short-term factors, but rather by an over-accumulation of debt by sovereigns, banks, and households: a so-called “balance sheet recession.” Though the nature of the crisis was understood relatively early on, policy prescriptions for how to deal with its consequences have continued to diverge. This paper gives a short overview of the prescriptions, the remaining challenges and key lessons for monetary policy.
n a contribution prepared for the Athens Symposium on “Banking Union, Monetary Policy and Economic Growth”, Otmar Issing describes forward guidance by central banks as the culmination of the idea of guiding expectations by pure communication. In practice, he argues, forward guidance has proved a misguided idea. What is presented as state of the art monetary policy is an example of pretence of knowledge. Forward guidance tries to give the impression of a kind of rule-based monetary policy. De facto, however, it is an overambitious discretionary approach which, to be successful, would need much more (or rather better) information than is currently available. In Issing's view, communication must be clear and honest about the limits of monetary policy in a world of uncertainty.
Die „Rente mit 63“ hat wieder einmal den Blick auf den Renteneintritt gerichtet. In der öffentlichen Debatte werden dabei zwei Ereignisse regelmäßig vermischt: das Ende des Arbeitslebens und der Beginn der Rentenzahlung. Dabei müssen beide nicht unmittelbar aufeinander folgen. Unter bestimmten Umständen kann es finanziell attraktiv sein, die staatliche Rente nicht sofort nach dem Ausstieg aus dem Erwerbsleben zu beantragen, sondern die Ausgaben bis zum späteren Rentenbeginn durch den Abbau von Finanzkapital zu finanzieren. Dieser Beitrag gibt einen kurzen Einblick in die neueste Studie von Olivia Mitchell, Andreas Hubener und Raimund Maurer zur Alterssicherung in den USA und stellt auch Berechnungen für Deutschland auf.