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According to the prevailing view, the purpose of digital copyright is to balance conflicting interests in exclusivity on the one hand and in access to information on the other. This article offers an alternative reading of the conflicts surrounding copyright in the digital era. It argues that two cultures of communication coexist on the internet, each of which has a different relationship to copyright. Whereas copyright institutionalizes and supports a culture of exclusivity, it is at best neutral towards a culture of free and open access. The article shows that, depending on the future regulation of copyright and the internet in general, the dynamic coexistence of these cultures may well be replaced by an overwhelming dominance of the culture of exclusivity.
In der Region Rhein-Main steht mit dem Rhein-Main-Mobilitätspanel (RMP) seit dem Jahr 2008 ein Datensatz zur Verfügung, der im Vergleich zu früheren Datensätzen eine verbesserte Beschreibung der regionalen Mobilitätsentwicklung ermöglicht. In dieser Methodenstudie wird überprüft, inwieweit Anschlussmöglichkeiten dieses Datensatzes mit anderen regionalen Datensätzen bestehen. Das Ziel dieser Studie ist somit die Prüfung, inwiefern in der Region Rhein-Main vorliegende Mobilitäts- und andere (insbesondere raumbezogene) Daten mit dem RMP kombiniert werden können, um daraus neue Erkenntnisse und Handlungsoptionen für die Entscheidungsträger vor Ort zu entwickeln. Im Rahmen der Studie werden sowohl ein Vergleich der Stichprobenzusammensetzung und der Erhebungsmethodik als auch der erfassten Kennziffern durchgeführt und Möglichkeiten zur Kombination mit Raumstrukturdaten überprüft. Weiterhin werden zentrale Mobilitätskennziffern der betrachteten Erhebungen (MiD 2002, 2008; SrV 2008; Deutsches Mobilitätspanel 2002-2008) gegenübergestellt und die Anwendbarkeit des harmonisierten und kombinierten Datensatzes hinsichtlich einer inhaltlichen Fragestellung überprüft.
Containment problems belong to the classical problems of (convex) geometry. In the proper sense, a containment problem is the task to decide the set-theoretic inclusion of two given sets, which is hard from both the theoretical and the practical perspective. In a broader sense, this includes, e.g., radii or packing problems, which are even harder. For some classes of convex sets there has been strong interest in containment problems. This includes containment problems of polyhedra and balls, and containment of polyhedra, which have been studied in the late 20th century because of their inherent relevance in linear programming and combinatorics.
Since then, there has only been limited progress in understanding containment problems of that type. In recent years, containment problems for spectrahedra, which naturally generalize the class of polyhedra, have seen great interest. This interest is particularly driven by the intrinsic relevance of spectrahedra and their projections in polynomial optimization and convex algebraic geometry. Except for the treatment of special classes or situations, there has been no overall treatment of that kind of problems, though.
In this thesis, we provide a comprehensive treatment of containment problems concerning polyhedra, spectrahedra, and their projections from the viewpoint of low-degree semialgebraic problems and study algebraic certificates for containment. This leads to a new and systematic access to studying containment problems of (projections of) polyhedra and spectrahedra, and provides several new and partially unexpected results.
The main idea - which is meanwhile common in polynomial optimization, but whose understanding of the particular potential on low-degree geometric problems is still a major challenge - can be explained as follows. One point of view towards linear programming is as an application of Farkas' Lemma which characterizes the (non-)solvability of a system of linear inequalities. The affine form of Farkas' Lemma characterizes linear polynomials which are nonnegative on a given polyhedron. By omitting the linearity condition, one gets a polynomial nonnegativity question on a semialgebraic set, leading to so-called Positivstellensaetze (or, more precisely Nichtnegativstellensaetze). A Positivstellensatz provides a certificate for the positivity of a polynomial function in terms of a polynomial identity. As in the linear case, these Positivstellensaetze are the foundation of polynomial optimization and relaxation methods. The transition from positivity to nonnegativity is still a major challenge in real algebraic geometry and polynomial optimization.
With this in mind, several principal questions arise in the context of containment problems: Can the particular containment problem be formulated as a polynomial nonnegativity (or, feasibility) problem in a sophisticated way? If so, how are positivity and nonnegativity related to the containment question in the sense of their geometric meaning? Is there a sophisticated Positivstellensatz for the particular situation, yielding certificates for containment? Concerning the degree of the semialgebraic certificates, which degree is necessary, which degree is sufficient to decide containment?
Indeed, (almost) all containment problems studied in this thesis can be formulated as polynomial nonnegativity problems allowing the application of semialgebraic relaxations. Other than this general result, the answer to all the other questions (highly) depends on the specific containment problem, particularly with regard to its underlying geometry. An important point is whether the hierarchies coming from increasing the degree in the polynomial relaxations always decide containment in finitely many steps.
We focus on the containment problem of an H-polytope in a V-polytope and of a spectrahedron in a spectrahedron. Moreover, we address containment problems concerning projections of H-polyhedra and spectrahedra. This selection is justified by the fact that the mentioned containment problems are computationally hard and their geometry is not well understood.
Derivation and characterization of a new filter for nonlinear high-dimensional data assimilation
(2015)
Data assimilation (DA) combines model forecasts with real-world observations to achieve an optimal estimate of the state of a dynamical system. The quality of predictions in nonlinear and chaotic systems such as atmospheric or oceanic circulation is strongly sensitive to the initial conditions. Therefore, beyond the consistent reconstruction of past states, a primary relevance of advanced DA methods concerns the proper model initialization. The ensemble Kalman filter (EnKF) and its deterministic variants, mostly square root filters such as the ensemble transform Kalman filter (ETKF), represent a popular alternative to variational DA schemes. They are applied in a wide range of research and operations. Their forecast step employs an ensemble integration that fully respects the nonlinear nature of the analyzed system. In the analysis step, they implicitly assume the prior state and observation errors to be Gaussian. Consequently, in nonlinear systems, the mean and covariance of the analysis ensemble are biased and these filters remain suboptimal. In contrast, the fully nonlinear, non-Gaussian particle filter (PF) relies on Bayes' theorem without further assumptions, which guarantees an exact asymptotic behavior. However, it is exposed to weight collapse, particularly in higher-dimensional settings, known as the curse of dimensionality.
This work presents a new method to obtain an analysis ensemble with mean and covariance that exactly match the corresponding Bayesian estimates. This is achieved by a deterministic matrix square root transformation of the forecast ensemble, and subsequently a suitable random rotation that significantly contributes to filter stability while preserving the required second-order statistics. The forecast step remains as in the ETKF. The algorithm, which is fairly easy to implement and computationally efficient, is referred to as the nonlinear ensemble transform filter (NETF). The limitation with respect to fully-nonlinear filtering is that the NETF only considers the mean and covariance of the Bayesian analysis density, neglecting higher-order moments.
The properties and performance of the proposed algorithm are investigated via a set of experiments. The results indicate that such a filter formulation can increase the analysis quality, even for relatively small ensemble sizes, compared to other ensemble filters in nonlinear, non-Gaussian scenarios. They also confirm that localization enhances the applicability of this PF-inspired scheme in larger-dimensional systems. Finally, the novel filter is coupled to a large-scale ocean general circulation model with a realistic observation scenario. The NETF remains stable with a small ensemble size and shows a consistent behavior. Additionally, its analyses exhibit low estimation errors, as revealed by a comparison with a free ensemble integration and the ETKF. The results confirm that, in principle, the filter can be applied successfully and as simple as the ETKF in high-dimensional problems. No further modifications are needed, even though the algorithm is only based on the particle weights. Thus, it is able to overcome the curse of dimensionality, even in deterministic systems. This proves that the NETF constitutes a promising and user-friendly method for nonlinear high-dimensional DA.
In der Dissertation mit dem Titel „Verrechtlichung von Geschichte. Parlamentarische Debatten um die gesetzlichen Bestimmungen gegen Holocaustleugnung in Österreich und Deutschland“ wurden die strafrechtlichen Bestimmungen gegen Holocaust-Leugnung in Deutschland und Österreich untersucht. Im Vordergrund stand die Frage, wie ein historisches Ereignis mit Hilfe politischer und juristischer Terminologie so gefasst und normiert werden konnte, dass die Leugnung desselben seitdem mit Hilfe des Rechts bestraft werden kann. Dazu wurden vor allem jene parlamentarischen Vorgänge und Debatten untersucht, die der Verabschiedung der Gesetze vorausgegangen sind. Die Auswertung dieser Quellen hilft auch zu verstehen, weshalb und in welcher Form die Logik dieser Gesetze in den letzten zwanzig Jahren von anderen Staaten übernommen und auf andere historische Ereignisse ausgeweitet worden ist. Neben diesem umfangreichen empirischen Teil, der auf die jeweiligen historischen Spezifika eingeht, beinhaltet die Dissertation einen stärker analytisch ausgerichteten resümierenden Schlussteil, in dem versucht wurde, mit thesenhaften Beobachtungen das Phänomen und die ideengeschichtliche Genese der Holocaust-Leugnungsgesetze nachzuzeichnen. Diese Beobachtungen umfassen unter anderem die Bereiche Geschichtspolitik, Rechtspolitik, Sprachpolitik oder auch Wissenschaftspolitik und gehen aus unterschiedlichen Blickwinkeln der Frage nach, auf welche Weise die Gesetze begründet, legitimiert und kritisiert worden sind und immer noch werden.
Amphibians have existed on the planet for over 300 million years and are today one of the most diverse vertebrate classes in the world with over 7000 known species and still many more to be discovered. However, several studies assume that approximately one third of the world´s known living amphibians are directly threatened with extinction, making it the most endangered vertebrate class. In relation to the relatively small land mass that is occupied by the state of Panama, it supports one of the most diverse amphibian faunas. However, in many cases the ecological role of single species in a wider context and their habitat preferences are still poorly understood and subject to ongoing research. Modern taxonomic approaches in other tropical regions have shown that former assumptions of amphibian diversity were distinct underestimations of the actual species diversity; a situation that is probably also true for Panama. Concurrently, the collection of amphibian diversity data and the description of new species is a race against time. The amphibian fauna of the world and that of Panama in particular, has suffered from an unprecedented loss of diversity over the last 30 years. The reasons are manifold and include destruction, alteration, and fragmentation of their natural habitats as the main causes, but also the deadly amphibian disease chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). In Panama and Costa Rica, this Emerging Infectious Disease (EID) spread in a wave-like manner from west to east causing mass die-offs and reduced amphibian diversity even in well-preserved habitats. The disease has primarily affected stream-associated highland species. The last large-scale evaluation of the conservation status of Panama´s amphibians through the IUCN Red List of Threatened Species in 2004 concluded that approximately 30% of the known species are acutely threatened with extinction. Furthermore, around 17% of the amphibian species that have been known back then lacked adequate data to be assessed. In view of Panama´s already overwhelming amphibian diversity, as well as the variety of habitats and the large number of sites that have not been examined with regard to amphibians before, I started this study with the conviction that the inventory of Panama´s amphibian diversity is far from being completed. Furthermore, when I started this study, it was uncertain if there would be any surviving amphibian species in areas where chytridiomycosis had emerged. The loss of whole amphibian communities in upland western Panama following Bd arrival led to a shift of amphibian research to lowland sites in central and eastern Panama aiming primarily on pathogen arrival and the documentation of epizootic outbreak and subsequent population decline. The situation of amphibian communities in areas post-decline was therefore largely unknown. Accordingly, the main goals of my study were to add to the taxonomic inventory of amphibians in Panama and to assess the situation of amphibian populations in habitats where chytrid-driven declines have been observed. To address these tasks I conducted fieldwork in western Panama with a focus on mountainous elevations between 1000 and 3475 m asl. Additionally, I visited different lowland sites between sea level and 1000 m asl to collect comparative material. In the period between 2008 and 2013, I conducted five collection trips to Panama that add up to a total of approximately 13 months in the field. I have sampled nine regions in western Panama and collected 767 specimens together with student collaborators, 531 of which were collected under my personal field number. Additional data obtained from those specimens include 68 male anuran call recordings, 102 standardized color descriptions of specimens in life, and 259 tissue samples that to date yielded 185 16S mtDNA sequences. This comprises the most comprehensive data set for amphibians of Panama and the first large-scale DNA barcoding approach for western Panama to date. After a preliminary DNA barcoding and subsequent comparative examination of morphological und bioacoustic data of all specimens collected, the number of taxonomic problems that needed to be addressed was higher than I previously anticipated. For most genetic lineages deeper taxonomic analyses were required to reach conclusive results. A selection had to be made with which lineages to proceed in the analyses, in view of the substantial financial and time expenditure that would be needed for a complete taxonomic revision. Therefore, I chose to run deeper analyses on one genus from each of the three amphibian orders in Panama. The genera selection depended largely on the availability of sufficient material and the scientific relevance of the respective genus.
I selected the genus Diasporus from the order Anura. These small frogs are omnipresent in many habitats and thus relatively easy to find. In addition, the genus is underrepresented in taxonomic studies. This is the first taxonomic study on the genus Diasporus to include a molecular phylogeny and the first comparison of advertisement calls between several populations from western Panama. In total, I collected 67 Diasporus specimens throughout western Panama and compared them morphologically with 49 additional specimens from Central America in collections, including the primary types of D. diasporus and D. hylaeformis. Additional comparative data were taken from literature. The DNA barcoding analysis of a fragment of the 16S rRNA gene included 43 own sequences that were complemented with 15 relevant GenBank sequences. In addition, I compared the advertisement calls of 26 male individuals among each other and with call descriptions from the literature. The DNA barcoding approach revealed several unnamed genetic lineages, but in some cases also resulted in the lumping of morphologically and bioacoustically distinct specimens. Generally, the morphological examination of the collected material revealed almost no specific characters that could be used to distinguish between genetic lineages. However, it was possible to identify species using a combination of several morphological characteristics. Which ones are relevant in the individual case depends on the respective species. My extensive collection of call recordings made it possible to test for the first time the intraspecific call variation of D. hylaeformis in dependency of various parameters. This analysis showed that the dominant frequency depends significantly on the body size of the calling male; the smaller the calling male, the higher the frequency of the call. A similar relationship was observed between the call rate and temperature: the lower the temperature during calling, the lower the call rate. I suppose that these general patterns, which have already been observed in other anuran genera, are also true in other Diasporus species that could not be tested in this study. Taking into account the intraspecific variation of Diasporus advertisement calls, I consider comparative call analyses to be the best way to distinguish between species. This is especially true in syntopic species. Integration of the three lines of evidence (i.e., morphology, DNA barcoding, and bioacoustics) led to the identification of four new species, two of which (i.e., D. citrinobapheus and D. igneus) colleagues and I have already formally described.
I conducted an integrative taxonomic analysis of the western Panamanian representatives of the genus Bolitoglossa from the order Caudata, the larger of the two Panamanian salamander genera. Bolitoglossa is very species-rich with a centre of diversification in the high mountains of Costa Rica and western Panama. I collected 53 Bolitoglossa specimens and compared them to twelve specimens in collection, including the holotype and one paratype of B. gomezi. The dataset was complemented with information from the literature. Among the sampled specimens were two species considered to be endangered that have not been collected or observed for several decades; B. magnifica has not been seen for 34 years and B. anthracina has not been seen for 22 years. Further, I collected salamanders at several new locations. To date, my 16S mtDNA barcoding analysis represents the densest taxon sampling for Panamanian Bolitoglossa composed of 21 own sequences that were combined in the final alignment with 47 GenBank sequences. Even though the molecular phylogeny is based only on a single marker, the received trees largely coincide with previous studies and the nodes received high statistical support. In these trees, I retrieve all previously defined subgenera and species groups. On the basis of this molecular phylogeny, I placed B. anthracina, here sequenced for the first time, in the B. subpalmata species group. Due to the fact that B. anthracina is a large and dark colored species it had previously been placed by implication in the B. schizodactyla species group along with other large black salamanders of the B. nigrescens species complex. Moreover, I found deep divergent genetic lineages among geographically separated populations of B. minutula. However, until now there were no additional morphological characteristics detectable to distinguish between these lineages. Additionally, my colleagues and I described a new deep divergent lineage in the B. robinsoni species group as B. jugivagans, a species new to science. In contrast, I found only minor genetic differences between specimens of B. sombra and B. nigrescens. After combining morphometric data and tooth counts from literature of both species with additional data from specimens of B. sombra that I collected near the type locality, the distinguishing features blurred. In particular, including much larger specimens of B. sombra, not yet known at the time of its description, showed that the tooth count difference is dependent on the size and age of the specimen examined. Larger specimens have more maxillary and vomerine teeth. Based on this evidence I regard B. sombra as a junior synonym of B. nigrescens. Further, I revised the Panamanian distribution of the two relatively common lowland salamanders, B. colonnea and B. lignicolor. Besides filling the gaps in the fragmentary known distributions of these species, I assessed the molecular and morphological variation of both species among populations in Panama. While there was little variation in B. lignicolor, I found divergent genetic lineages among geographically distinct populations of B. colonnea that require further taxonomic examination.
Caecilians (order Gymnophiona) are among the least investigated terrestrial vertebrates. After I received a first specimen of the predominantly South American genus Oscaecilia (family Caeciliidae) in western Panama, I started to work more extensively on the taxonomy of Caeciliidae in Central America. The specimens from western Panama were not readily assignable to a single described species, but shared characters with O. elongata and O. osae. While O. osae was only known from the holotype, the type material of O. elongata was destroyed during World War II. On the basis of the original description, the unique feature in O. elongata within Oscaecilia is the absence of subdermal scales in the posterior part of the body. In a referred specimen of O. elongata mentioned in the original description from eastern Panama, this characteristic cannot be examined as it consists of head and neck only. Therefore, I used non-destructive high-resolution, synchrotron-based X-ray micro CT imaging (HRμCT) to examine cranial characters in the specimens in question and took normal radiographs to count vertebrae and to make subdermal scales visible. I found that the fragmented specimen from eastern Panama likely belongs to the well-sampled species O. ochrocephala and has not much in common with O. osae or the specimens from western Panama. Contrarily, O. osae and the specimens from western Panama share many morphological characters, but also show some differences. Genetic barcoding revealed that both species are close relatives, but the genetic distance could not be finally resolved, because 16S sequences obtained from blood samples of living O. osae were of poor quality. Thus, I compare the Oscaecilia from western Panama to O. osae in this study, but postpone a taxonomic decision until further material becomes available. Further, I designate O. elongata a nomen dubium, because the type material is lost, the type locality is not defined in more detail than “Panama”, and the original description does not allow for a definite assignment. Since previous molecular studies only considered O. ochrocephala, the monophyly of Oscaecilia was never tested before. So far, the genus Oscaecilia is based largely on a single cranial character, the eyes covered with bone. Here, I combined two 16S mtDNA sequences of O. osae from Costa Rica and two sequences from O. sp. from western Panama with two sequences of O. ochrocephala and ten sequences of four species of the genus Caecilia, the sister genus of Oscaecilia. The resulted phylogeny contains two well-supported clades, one clade containing two species of Caecilia, one from Panama and one from western Ecuador and all species of Oscaecilia tested. The other clade consists of two species of Caecilia from the Amazon basin. I therefore assume that the split in both clades is due to the rise of the Andes, what led to today’s cis-trans-Andean distribution of the two clades. For now, to restore monophyly, I suggest to place Oscaecilia within the synonymy of Caecilia until more taxa have been tested. When assessing the conservation status of the amphibian species in mountainous western Panama, I first compiled a list of known species that I potentially could have found during my fieldwork. Using the IUCN categories, I analyzed how many of the endangered species I actually found and how these are distributed over families and species groups. Surprisingly, my rediscoveries of lost species were not equally distributed among the four families that comprise most endangered amphibian species (i.e., Bufonidae, Craugastoridae, Hylidae, and Plethodontidae). While I discovered ten of eleven endangered hylids and six of nine endangered plethodontids, I found only one of four endangered bufonids and none of the nine endangered craugastorids. I assume that the secretive living plethodontids, for which no Bd related declines have been documented, were just overlooked in the past decades. In contrast, I propose that hylids, in which Bd related population decline is well documented, developed distinct evolutionary solutions permitting coexistence with the pathogen. The situation is obviously different in bufonids and craugastorids, where I found no signs of population recoveries at present. So far, the only surviving populations of species from these families exist in climatic or physiographic niches that have probably shielded them from Bd. My data confirm the current view that the risk for naïve amphibian populations to decline during Bd epizootics is predicted by ecological traits (e.g., aquatic index, vertical distribution) and not dependent on taxonomic affiliation. However, I propose that only certain amphibian families (e.g., hylids and centrolenids) have the ability to acquire immunity solutions to coexist with the pathogen during enzootic stages. This is a very new perspective on the worst infectious disease in amphibians worldwide, allowing for new research approaches to understand the host-pathogen dynamics. Moreover, I examined where the share of surviving endangered amphibian species is particularly high in mountainous western Panama. As was to be expected, most of the endangered species are found within the boundaries of protected areas. One exception is the unprotected Cerro Colorado region in the Comarca Ngöbe-Buglé that provides habitat for a wide variety of endangered and undiscovered amphibian species. Nonetheless, planned open pit mining would destroy the forests in a large part of the area. This demonstrates once again that human activities are the biggest threat to amphibians in Panama and elsewhere.
Epigenetic silencing of transgene expression represents a major obstacle for the efficient genetic modification of multipotent and pluripotent stem cells. We and others have demonstrated that a 1.5 kb methylation-free CpG island from the human HNRPA2B1-CBX3 housekeeping genes (A2UCOE) effectively prevents transgene silencing and variegation in cell lines, multipotent and pluripotent stem cells, and their differentiated progeny. However, the bidirectional promoter activity of this element may disturb expression of neighboring genes. Furthermore, the epigenetic basis underlying the anti-silencing effect of the UCOE on juxtaposed promoters has been only partially explored. In this study we removed the HNRPA2B1 moiety from the A2UCOE and demonstrate efficient anti-silencing properties also for a minimal 0.7 kb element containing merely the CBX3 promoter. This DNA element largely prevents silencing of viral and tissue-specific promoters in multipotent and pluripotent stem cells. The protective activity of CBX3 was associated with reduced promoter CpG-methylation, decreased levels of repressive and increased levels of active histone marks. Moreover, the anti-silencing effect of CBX3 was locally restricted and when linked to tissue-specific promoters did not activate transcription in off target cells. Thus, CBX3 is a highly attractive element for sustained, tissue-specific and copy-number dependent transgene expression in vitro and in vivo.
In the present work, mismatch negativity (MMN) was used to examine the contribution of spectral vs. temporal perceptual features to vowel length discrimination in children and adults. Three age groups (adults vs. 9-10 years vs. 10-11 years olds) have been taken to examine developmental effects on vowel length perception. Natural (i.e., spectrotemporal) vowel length differences were compared with (artificially modified) stimulus pairs varying only in temporal or spectral characteristics to contrast spectral, temporal and spectrotemporal processing.
The result indicates that, while adults integrate spectral and temporal aspects of the speech signal in an additive way, children of 9-10 years of age sequentially process both features. However, vowel length processing is found to become adultlike at the age of 10-11 years.
This thesis covers the analysis of radix sort, radix select and the path length of digital trees under a stochastic input assumption known as the Markov model.
The main results are asymptotic expansions of mean and variance as well as a central limit theorem for the complexity of radix sort and the path length of tries, PATRICIA tries and digital search trees.
Concerning radix select, a variety of different models for ranks are discussed including a law of large numbers for the worst case behavior, a limit theorem for the grand averages model and the first order asymptotic of the average complexity in the quantile model.
Some of the results are achieved by moment transfer techniques, the limit laws are based on a novel use of the contraction method suited for systems of stochastic recurrences.
Diesmal kein Hinweis auf einen lesenswerten Text, sondern auf eine Veranstaltung, die von Genocide Alert mit der Deutschen Atlantischen Gesellschaft in Berlin organisiert wird: Am 15.6. um 18:30 Uhr diskutieren im Presse- und Informationsamt der Bundesregierung Dr. Klaus Kinkel, ehemaliger Bundesaußenminister a.D., Alfred Grannas vom Auswärtiges Amt, Prof. Dr. Axel Hagedorn, der Anwalt der Stiftung “Mütter von Srebrenica” sowie Prof. Dr. Wolfgang Höpken von der Uni Leipzig über das Massaker, das im Jahr 1995 in Srebrenica stattgefunden hat...
Hematopoietic stem cells (HSCs) have the unique abilities of life-long self-renewal and multi-lineage differentiation. They are routinely used in BM or stem cell transplantations to reconstitute the blood system of patients suffering from malignant or monogenic blood disorders. For an adequate production of each blood cell lineage in homeostasis and under stress conditions, the fate choice of HSCs to either self-renew or to differentiate must be strictly controlled. The incomplete understanding of the molecular mechanisms that control this balance makes it still impossible to maintain or expand undifferentiated HSCs in culture for advanced regenerative medical purposes.
The aim of this thesis was the identification and molecular characterisation of mechanisms that control the decision of HSCs to self-renew or to differentiate, and how they are connected to extrinsic cytokine signaling control. Prior to this thesis, a screening for genes upregulated under self-renewal promoting thrombopoietin (TPO) signaling via the transcription factors STAT5A/B in HSCs was conducted, and Growth arrest and DNA damage inducible 45 gamma (Gadd45g) was one of the regulated genes. GADD45G was described as stress sensor, DNA-damage response and tumor suppressor gene, that is epigenetically silenced in many solid tumors and leukemia. Furthermore, Gadd45g is upregulated in aged HSCs with impaired multi-lineage reconstitution abilities, and it is induced by differentiation promoting cytokines in GM-committed cells. However, the function of GADD45G in LT-HSCs was unknown. All these points warrant further investigation to unravel the function of GADD45G on early cell fate decisions of HSCs in hematopoiesis.
The expression of Gadd45g was stimulated by hematopoietic cytokines TPO, IL3 and IL6 both in HSCs and MPPs, making GADD45G an interesting target to focus on. To simulate the cytokine-induced expression GADD45G was lentivirally transduced in HSCs. Surprisingly, GADD45G did not induce cell cycle arrest or cell death in hematopoietic cells neither in vitro nor in vivo, as reported in many cell lines. Instead GADD45G revealed an enhanced and markedly accelerated differentiation of HSCs into mainly myelomonocytic cells, similar as observed for IL3 and IL6 containing cultures. Also in vivo, GADD45G rapidly initiates the differentiation program in HSCs at the expense of self-renewal and long-term engraftment, as shown by serial HSC transplantation experiments. Along the same line, HSCs from Gadd45g-knock out mice exhibited an increased self-renewal. In vitro, Gadd45g-/- progenitors showed higher and prolonged colony formation potential and slower expansion after cytokine stimulation. The loss of Gadd45g increased HSC self-renewal and improved repopulation in secondary recipients, determined by serial competitive transplantations. Taken together, GADD45G could be identified as molecular link between differentiation-promoting cytokine signaling and rapid differentiation induction in murine LT-HSCs.
As presented in this thesis the differentiation induction of GADD45G was mediated by the activation of the cascade of MAP3K4 – MKK6 –p38 MAPK. Small molecule inhibition of p38, but not JNK, blocked the GADD45G-induced differentiation. GADD45G binds to MAP3K4 and releases its auto-inhibitory loop by a change in confirmation, initiating this cascade. Phosphoflow cytometry demonstrated the activation of p38 and a downstream kinase MK2 by GADD45G expression in MPPs. Furthermore, the expression of constitutive active MAP3K4 and MKK6 were able to phenocopy GADD45G-induced differentiation, which could be blocked by p38 inhibition.
The other two family members GADD45A and B also induced accelerated differentiation in LT-HSCs. Interestingly, only GADD45G suppressed the differentiation into megakaryocyte and erythrocyte (Mek/E) lineage cells suggesting a role of GADD45G in lineage choice. Long-term time-lapse microscopy-based cell tracking of single LT-HSCs and their progeny revealed that, once GADD45G is expressed, the development of LT-HSCs into granulocyte-macrophage-committed progeny occurred within 36 hours, and uncovered a selective lineage choice with a severe reduction in Mek/E cells. Furthermore, no megakaryocytic-erythroid progenitors (MEPs) could develop from HSPCs in BM 2 weeks after transplantation suggesting a very early selection against Mek/E cell fates. In line with these findings, GADD45G-transduced MEPs could not expand or form colonies in vitro, demonstrating that the differentiation program induced by GADD45G is not compatible with Mek/E lineage fate. Gene expression profiling of HSCs indicated that GADD45G promotes myelomonocytic differentiation programs over programs for self-renewal or megakaryo-/ erythropoiesis. The here identified differentiation induction potential of GADD45G is so strong that the expression of GADD45G in primary acute myeloid leukemia (AML) cells inhibited their expansion accompanied by enhanced differentiation and increased apoptosis.
The here presented work shows that IL3 and IL6 induce a differentiation program in HSCs via GADD45G and p38 closing the link of extrinsic cytokine signaling and differentiation induction. Since the loss of Gadd45g increased the self-renewal and slowed HSC differentiation, this may be utilized, i.e. by p38 inhibition, to ex vivo maintain and expand HSCs by preventing cytokine-induced differentiation. Furthermore, Re-expression of GADD45G may overcome the differentiation block in leukemia to eliminate these cells by driving them into terminal differentiation and apoptosis.
In der aktuellen Ausgabe der Zeitschrift für Internationale Beziehungen analysieren Christopher Daase und Nicole Deitelhoff (Uni Frankfurt) den Ist-Zustand in der deutschen Disziplin der Internationalen Beziehungen (Fazit: nicht so gut & viel Käse) und rufen zu mehr Beteiligung auf, v.a. beim anstehenden DVPW-Kongress in Duisburg.
Die HBO-Serie The Wire erzählt eine Geschichte von Kriminalität, Polizeiarbeit und Politik in Baltimore. Eine ihrer Stärken liegt darin, wie sie die Ambivalenz des sozialen und politischen Lebens nachzeichnet. Eine zentrale Rolle spielt dabei allgegenwärtige Korruption. Ihre Ambivalenz bricht sich nicht zuletzt in der Darstellung der Figur des State Senator Clay Davis.
Die bisher nicht lückenlos aufgeklärte, vermutlich aber Gruppen der organisierten Kriminalität zuzurechnende Ermordung von über 40 Lehramtsstudenten in der südmexikanischen Kleinstadt Ayotzinapa Ende 2014 hat ebenso wie die seit dem Abschuss eines Militärhubschraubers im Mai 2015 eskalierende Gewalt im westlichen Bundesstaat Jalisco wieder einmal schmerzlich in Erinnerung gerufen, dass in Mexiko bereits seit fast neun Jahren ein blutiger Gewaltkonflikt im Gange ist, der angesichts der wirtschaftlichen Erfolge des „Aztec tiger“ teils fast schon vergessen schien.
Die vorliegende Arbeit befasst sich mit der Untersuchung einzelner chiraler Moleküle durch Koinzidenzmessungen. Ein Molekül wird chiral genannt, wenn es in zwei Varianten, sogenannten Enantiomeren auftritt, deren Strukturmodelle Spiegelbilder voneinander sind.
Da viele biologisch relevante Moleküle chiral sind, sind Methoden und Erkenntnisse dieses Gebiets von großer Bedeutung für Biochemie und Pharmazie. Bemerkenswert ist, dass in der Natur meist nur eines der beiden möglichen Enantiomere auftritt. Ob diese Wahl zufällig war, ob sie aufgrund der Anfangsbedingungen bei Entstehung des Lebens erfolgte, oder ob sie eine fundamentale Ursache hat, ist bisher ungeklärt. Seit der Entdeckung chiraler Molekülstrukturen in der zweiten Hälfte des 19. Jahrhunderts ist eine Vielzahl von Methoden entwickelt worden, um die beiden Enantiomere eines Moleküls zu unterscheiden und ihre Eigenschaften zu untersuchen. Aussagen über die mikroskopische Struktur (Absolutkonfiguration) können jedoch meist nur mithilfe theoretischer Modelle getroffen werden.
Der innovative Schritt der vorliegenden Arbeit besteht darin, eine in der Atomphysik entwickelte Technik zur Untersuchung einzelner mikroskopischer Systeme erstmals auf chirale Moleküle anzuwenden: Mit der sogenannten Cold Target Recoil Ion Momentum Spectroscopy (COLTRIMS) ist es möglich, einzelne Moleküle in der Gasphase mehrfach zu ionisieren und die entstandenen Fragmente (Ionen und Elektronen) zu untersuchen. Die gleichzeitige Detektion dieser Fragmente wird als Koinzidenzmessung bezeichnet.
Zunächst wurde das prototypische chirale Molekül CHBrClF mit einem Femtosekunden-Laserpuls mehrfach ionisiert, sodass alle fünf Atome als einfach geladene Ionen in einer sogenannten Coulomb-Explosion „auseinander fliegen“. Durch Messung der Impulsvektoren dieser Ionen konnte die mikroskopische Konfiguration einzelner Moleküle mit sehr hoher Zuverlässigkeit bestimmt werden. Somit eignet sich die Koinzidenzmethode auch dazu, die Anteile der rechts- bzw. linkshändigen Enantiomere in einer Probe zu bestimmen. Die Messungen an der verwendeten, racemischen Probe zeigen bei der Ionisation mit linear polarisiertem Licht im Rahmen der statistischen Unsicherheit wie erwartet eine Gleichverteilung der beiden Enantiomere.
In einem nachfolgenden Experiment konnte gezeigt werden, dass sich die Coulomb-Explosion auch mit einzelnen hochenergetischen Photonen aus einer Synchrotronstrahlungsquelle realisieren lässt. Für beide Ionisationsmechanismen – am Laser und am Synchrotron - wurden mehrere Fragmentationskanäle untersucht. Im Hinblick auf die Erweiterung der Methode hin zu komplexeren, biologisch relevanten Molekülen ist es entscheidend zu wissen, inwieweit sich die Händigkeit bestimmen lässt, wenn nicht alle Atome des Moleküls als atomare Ionen detektiert werden. Hierbei stellte sich heraus, dass auch molekulare Ionen zur Bestimmung der Absolutkonfiguration herangezogen werden können. Eine signifikante Steigerung der Effizienz konnte für den Fall demonstriert werden, dass nicht alle Fragmente aus der Coulomb-Explosion des Moleküls detektiert wurden – hier lassen sich allerdings nur noch statistische Aussagen über die Absolutkonfiguration und die Häufigkeit der beiden Enantiomere treffen.
Um die Grenzen der Methode in Bezug auf die Massenauflösung zu testen, wurden isotopenchirale Moleküle, d.h. Moleküle, die nur aufgrund zwei verschiedener Isotope chiral sind, untersucht. Auch hier ist eine Trennung der Enantiomere möglich, wenn auch mit gewissen Einschränkungen.
Ein wichtiges Merkmal chiraler Moleküle ist das unterschiedliche Verhalten der Enantiomere bei Wechselwirkung mit zirkular polarisierter Strahlung. Diese Asymmetrie wird Zirkulardichroismus genannt. Die koinzidente Untersuchung von Ionen und Elektronen aus der Fragmentation eines Moleküls eröffnet neue Möglichkeiten für die Untersuchung des Dichroismus. So können die Impulsvektoren der Ionen mit bekannten Asymmetrien in der Elektronenverteilung (Photoelektron-Zirkulardichroismus) verknüpft werden, was zu einem besseren Verständnis der Wechselwirkung elektromagnetischer Strahlung mit chiralen Molekülen führen kann.
In dieser Arbeit wurde nach Asymmetrien in der Winkelverteilung sowohl der Ionen als auch der Elektronen nach der Ionisation von CHBrClF und Propylenoxid (C3H6O) mit zirkular polarisierter Synchrotronstrahlung gesucht. In den durchgeführten Messungen konnte kein zweifelsfreier Nachweis für einen Dichroismus bei den verwendeten experimentellen Bedingungen erbracht werden. Technische und prinzipielle Limitierungen der Methode wurden diskutiert und Verbesserungsvorschläge für zukünftige Messungen genannt.
Mit der erfolgreichen Bestimmung der Absolutkonfiguration und der prinzipiellen Möglichkeit, Asymmetrien in zuvor nicht zugänglichen Messgrößen zu untersuchen, legt diese Arbeit den Grundstein für die Anwendung der Koinzidenzspektroskopie auf Fragestellungen der Stereochemie.
Die Dissertation ist in den Bereichen der semiklassischen Quantengravitation und der pseudokomplexen Allgemeinen Relativitätstheorie (pk-ART) anzusiedeln. Dabei wird unter semiklassischer Quantengravitation die Untersuchung quantenmechanischer Phänomene in einem durch eine klassische Gravitationstheorie gegebenen gravitativen Hintergrundfeld verstanden und bei der pk-ART handelt es sich um eine Alternative zu der aktuell anerkannten klassischen Gravitationstheorie, der Allgemeinen Relativitätstheorie (ART), die die reellen Raumzeitkoordinaten der ART pseudokomplex erweitert. Dies führt zusammen mit einer Veränderung des Variationsprinzips in führender Ordnung auf eine Korrektur der Einstein- Gleichung der ART mit einem zusätzlichen Quellterm (Energie-Impuls-Tensor), dessen exakte Form jedoch bisher nicht bekannt ist.
Die Beschreibung der Gravitation als Hintergrundfeld ergibt sich zwangsläufig daraus, dass auf Basis der ART bisher keine quantisierte Beschreibung für sie gefunden werden konnte. Jedoch wird erhofft, dass die Untersuchung semiklassischer Phänomene Hinweise auf die korrekte Theorie der Quantengravitation gibt. Zudem motiviert der Mangel einer quantisierten Gravitationstheorie die Verwendung alternativer Theorien, da sich dadurch die Frage stellt, ob die ART die korrekte Beschreibung klassischer Felder ist.
Das Ziel der vorliegenden Dissertation war die grundlegenden Unterschiede zwischen der ART und der pk-ART für gebundene sphärisch symmetrische Zustände der Klein-Gordon- und der Dirac-Gleichung zu identifizieren und ein qualitatives Modell der Vakuumfluktuationen in sphärisch symmetrischen Materieverteilungen zu bestimmen, wobei der Zusammenhang der pk-ART mit den Vakuumfluktuationen in der Annahme besteht, dass ein Zusammenhang zwischen ihnen und dem zusätzlichen Quellterm der pk-ART existiert. Dafür wurden die gebundenen Zustände der Klein-Gordon- und der Dirac-Gleichung für drei verschiedene Metrikmodelle (zwei ART-Modelle und ein pk-ART-Modell) mit konstanter Dichte systematisch numerisch berechnet, einige repräsentative Grafiken erstellt, anhand derer die grundlegenden Unterschiede der Ergebnisse der ART-Modelle und des pk-ART-Modells erörtert wurden, und die ART Ergebnisse der Dirac-Gleichung soweit wie möglich mit Ergebnissen der Literatur verglichen. Insbesondere wurde dabei festgestellt, dass die Energieeigenwerte in der pk-ART im Gegensatz zu denen in der ART in Abhängigkeit der Ausdehnung des Zentralobjekts ein Minimum aufweisen. Zudem wurden die Energieeigenwerte der Klein-Gordon-Gleichung teilweise sowohl über das Eigenwertproblem einer Matrix als auch über ein Anfangswertproblem berechnet und es wurde festgestellt, dass die Beschreibung als Eigenwertproblem deutlich uneffektiver ist, wenn dafür die Basis des dreidimensionalen harmonischen Oszillators genutzt wird. Für die Entwicklung des qualitativen Vakuumfluktuationsmodells wurden zwei Näherungen für den Erwartungswert des Energie-Impuls-Tensors in führender Ordnung für die Schwarzschildmetrik (ART) verglichen und die Verwendung eines qualitativen Modells durch die dabei auftretende Diskrepanz gerechtfertigt. Danach wurden die Vakuumfluktuationen für Metriken konstanter Materiedichte mit Hilfe einer der Näherungen in führender Ordnung berechnet und ein Modell gesucht, das den gleichen qualitativen Verlauf aufweist. Im Anschluss wurde dieses Modell noch für einfache Metriken mit variabler Materiedichte verifiziert.
Die Dissertation leistet mit der Analyse der gebundenen Zustände einen Beitrag in der Identifikation der Unterschiede zwischen der pk-ART und der ART und führt somit auf weitere mögliche Messgrößen, die der Unterscheidung der beiden Theorien dienen könnten. Weiterhin ermöglicht das abgeleitete Modell eine Verfeinerung der schon publizierten Ergebnisse über Neutronensterne und die für die Erstellung nötigen Vorarbeiten leisten einen Beitrag zur Identifikation des
pk-ART Quellterms.
The endocannabinoids (EC), their synthetizing and metabolizing enzymes, and the cannabinoid (CB) receptors comprise the endocannabinoid system (ECS) that has been detected by Yasuo et al. (2010) in rodent and human brain areas essential for circadian rhythmic control and hormone secretion. The EC are secreted in the pars tuberalis formation (PT) of the pituitary gland and unfold their effect as ligands on cannabinoid receptors type 1 (CB1) in the pars distalis (PD). The CB1 is mostly expressed on folliculo-stellate (fs) cells of the PD. The fs cells execute regulative and supportive functions to adjacent hormone-producing cells (Allaerts and Venkelecom, 2005; Mitsuishi et al., 2013). The lipid and calcium binding protein Annexin A1 (Anx A1) and the cell membrane permeable compound nitric oxide (NO) have been detected in the fs cells (Woods et al., 1990; Devnath and Inoue, 2008). There are published findings indicating strong influence of Anx A1 and NO on hormone production (Taylor et al. 1993; Venkelecom et al, 1997). The hypothesis of this study is that the EC influence hormonal secretion by acting upon CB1 receptors on fs cells and thus activating or inhibiting Anx A1 and NO that directly affect adjacent glandular cells.
Prevalently cell models were used to carry out the experimental work. The TtT/GF and Tpit/F1 cell lines represent the fs cells, the AtT20/D16v stand for the ACTH-producing corticotroph (C) cells, and GH4C1 for the PRL-producing lactotroph (L) cells. Whenever comparison with an integrity model was possible tissue from C3H mice was used. Chemoluminescent and photometrical detection, enzyme-linked immunosorbent assay (ELISA), fluorescence-activated cell sorting (FACS), immunoblot (IB), immunocyto- and immunohisto-chemical analysis (ICC, IHC), in situ hybridization (ISH), and (q) PCR methods were used as assaying tools to investigate CB1, Anx A1, the Anx A1 receptor - Fpr-rs1, NO, ACTH, and PRL.
CB1 was detected on the fs, C, and L cell models. The presence of fatty acid amide hydrolase (FAAH, an EC degrading enzyme) was confirmed in the fs cells. Incubations of the fs cells with CB1 agonists (2-AG, AEA, WIN) and antagonist (otenabant) were performed and resulting increase of Anx A1, and inhibition of NO were detected. Anx A1 binding sites, known as formyl peptide like receptor – related sequence 1 (Fpr-rs1) were identified on the C and L cells. The hormone-producing cells were treated with a 2-AG, Anx A1, and NO and the resulting changes in the levels of ACTH and PRL were detected. Anx A1 acted stimulatory on ACTH in the C AtT20/D16v cell and inhibitory on PRL in the L GH4C1 cell. NO inhibited both ACTH and PRL release. Additional analysis of the levels of expression of mRNA for Anx A1 and Fpr-rs1 in murine PD tissue demonstrated that while the expression of the first was not influenced by time, the expression of the latter was activated during the subjective day.
The here presented study shows that EC influence the ACTH release stimulatory through activating Anx A1 and inhibiting NO. As for PRL, the EC unfold an inhibition through activating Anx A1, and stimulation through inhibiting NO. A clear regulatory linkeage between the EC and ACTH and PRL control is revealed, involving the fs cells with possible time-dependence.
Ausgehend von dem gesellschaftlichen Problem des Übergewichts im Kindesalter wird die besondere Bedeutung und Verantwortung des Sportunterrichts für diese Klientel herausgestellt. Dabei wird die These vertreten, dass der Sportunterricht seinem Auftrag nur dann gerecht werden kann, wenn es gelingt, auch übergewichtigen Kindern positive Erfahrungen in Bezug auf Bewegung, Spiel und Sport zu vermitteln. Im Rahmen dieses sportpädagogischen Problemfeldes wurde zunächst ein Fragebogen konzipiert und validiert, der das Wohlbefinden als Indikator für positive Erfahrungen übergewichtiger Schüler mit dem von normalgewichtigen Kindern vergleicht (n = 336). Eine anschließende qualitative Untersuchung in Form von Leitfadeninterviews (mit acht übergewichtigen/adipösen Kindern) ergänzt und konkretisiert die Ergebnisse.
Als wesentliches Resultat konnte die Erkenntnis gewonnen werden, dass das Wohlbefinden – gemessen durch ein faktorenanalytisch generiertes Modell mit den drei Faktoren „Sportunterricht/Sportlehrer“ (Faktor I), „sportliches Selbstwertgefühl“ (Faktor II) und „Mitschüler/Schulzufriedenheit“ (Faktor III) – keine signifikanten Unterschiede zwischen den Gewichtsklassen zeigt (Faktor I p = .57; Faktor II p = .04; Faktor III p = .23). Übergewichtige Schüler fühlen sich demnach nicht weniger wohl als ihre normalgewichtigen Klassenkameraden, in der Skala sportliches Selbstwertgefühl erzielten sie sogar höhere Werte (Normalgewichtige m = 2,06 ± 0,96; Übergewichtige m = 2,27 ± 0,89). Trotz dieses positiven Befundes verspüren Übergewichtige durchaus so manche Unzufriedenheit. Die Frage nach der Wichtigkeit der bzw. der Zufriedenheit mit den Komponenten Sportunterricht, eigene sportliche Leistung, Zusammenarbeit mit den Mitschülern, Figur und Sportlehrer machte deutlich, dass den Übergewichtigen Figur und sportliche Leistung sehr wichtig sind, sie jedoch nur bedingt damit zufrieden sind. Die Unterschiede in den entsprechenden Skalen erwiesen sich als hoch signifikant (Figur p = .00 d = .28; sportliche Leistung p = .01 d = .29). Die Überprüfung der Frage F1.2 hinsichtlich der geschlechtsspezifischen Unterschiede in den Aussagen zum Wohlbefinden lieferte lediglich ein signifikantes Ergebnis (p = .01) mit mittlerem Effekt (d = .48). Übergewichtige Mädchen gaben im Faktor „Mitschüler/Schulzufriedenheit“ höhere Werte an (m = 3,27 ± 0,66) als übergewichtige Jungen (m = 2,93 ± 0,75). Daraus lässt sich schließen, dass sich die weiblichen Übergewichtigen besser von ihren Mitschülern verstanden und unterstützt fühlen und sie eine allgemein größere Schulzufriedenheit verspüren als die männliche Vergleichsgruppe.
Die Auswertung in Bezug auf die Herkunft der Schüler lieferte keine signifikanten Ergebnisse. Dieser Befund deutet auf eine gelungene Integration der ausländischen Schüler hin, die aber möglicherweise aufgrund des hohen Ausländeranteils im Stadtgebiet Offenbach nicht repräsentativ ist.
Die Auswertung der Interviews zeigte, dass der positive Selbstwert auf ein hohes Maß an sozialer Anerkennung zurückzuführen ist. Entgegen zahlreichen theoretischen Vorannahmen berichtete kein Kind von anhaltenden Diskriminierungen oder Schamgefühlen aufgrund seines Gewichts. Die Bedeutung der eigenen sportlichen Leistung zeichnete sich mehrfach als Schlüsselkriterium im Umgang mit der pädagogischen Herausforderung, dem Erschaffen eines Problembewusstseins, ohne den Selbstwert und die Freude am Sporttreiben zu trüben, ab. Übergewichtige Kinder messen der Leistung einen hohen Stellenwert bei und erkennen in der Hoffnung einer möglichen Verbesserung, dass eine Reduktion des Gewichtes vorteilhaft ist.
Empirical credit demand analysis undertaken at the aggregate level obscures potential behavioral heterogeneity between various borrowing sectors. Looking at disaggregated data and analyzing bank loans to non-financial companies, to financial companies, to households for consumption and for house purchases separately with respect to a common set of macroeconomic determinants may facilitate more accurate empirical relationships and more reliable insights for economic policy. Using quarterly Euro area panel data between 2003 and 2013, empirical evidence for heterogeneity in borrowing behavior across sectors and the credit cycle with respect to interest rates, output and house prices is found. The results motivate sector-specific, counter-cyclical capital requirements.
This paper empirically investigates how organizational hierarchy affects the allocation of credit within a bank. Using an exogenous variation in organizational design, induced by a reorganization plan implemented in roughly 2,000 bank branches in India during 1999-2006, and employing a difference-in-differences research strategy, we find that increased hierarchization of a branch decreases its ability to produce "soft" information on loans, leads to increased standardization of loans and rationing of "soft information" loans. Furthermore, this loss of information brings about a reduction in performance on loans: delinquency rates and returns on similar loans are worse in more hierarchical branches. We also document how hierarchical structures perform better in environments that are characterized by a high degree of corruption, thus highlighting the benefits of hierarchical decision making in restraining rent seeking activities. Finally, we document a channel - managerial interference - through which hierarchy affects loan outcomes.
Our paper evaluates recent regulatory proposals mandating the deferral of bonus payments and claw-back clauses in the financial sector. We study a broadly applicable principal agent setting, in which the agent exerts effort for an immediately observable task (acquisition) and a task for which information is only gradually available over time (diligence). Optimal compensation contracts trade off the cost and benefit of delay resulting from agent impatience and the informational gain. Mandatory deferral may increase or decrease equilibrium diligence depending on the importance of the acquisition task. We provide concrete conditions on economic primitives that make mandatory deferral socially (un)desirable.
In its meeting on 6 September 2012, the Governing Council of the ECB took decisions on a number of technical features regarding the Eurosystem’s outright transactions in secondary sovereign bond markets (OMT). This decision was challenged in the German Federal Constitutional Court (GFCC) by a number of constitutional complaints and other petitions. In its seminal judgment of 14 January 2014, the German court expressed serious doubts on the compatibility of the ECB’s decision with the European Union law.
It admitted the complaints and petitions even though actual purchases had not been executed and the control of acts of an organ of the EU in principle is not the task of the GFCC. As justification for this procedure the court resorted to its judicature on a reserved “ultra vires” control and the defense of the “constitutional identiy” of Germany. In the end, however, the court referred the case pursuant to Article 267 TFEU to the European Court of Justice (ECJ) for preliminary rulings on several questions of EU law. In substance, the German court assessed OMT as an act of economic policy which is not covered by the competences of the ECB. Furthermore, it judged OMT as a – by EU primary law – prohibited monetary financing of sovereign debt. The defense of the ECB (disruption of monetary policy transmission mechanism) was dismissed without closer scrutiny as being “irrelevant”. Finally the court opened, however, a way for a compromise by an interpretation of OMT in conformity with EU law under preconditions, specified in detail.
Procedure and findings of this judgment were harshly criticized by many economists but also by the majority of legal scholars. This criticism is largely convincing in view of the admissibility of the complaints. Even if the “ultra vires” control is in conformity with prior decisions of court it is in this judgment expanded further without compelling reasons. It is also questionable whether the standing of the complaining parties had to be accepted and whether the referral to the ECJ was indicated. The arguments of the court are, however, conclusive in respect of the transgression of competences by the ECB and – to somewhat lesser extent – in respect of the monetary debt financing. The dismissal of the defense as “irrelevant” is absolutey persuasive.
The Treaty of Maastricht imposed the strict obligation on the European Union (EU) to establish an economic and monetary union, now Article 3(4) TEU. This economic and monetary union is, however, not designed as a separate entity but as an integral part of the EU. The single currency was to become the currency of the EU and to be the legal tender in all Member States unless an exemption was explicitly granted in the primary law of the EU, as in the case of the UK and Denmark. The newly admitted Member States are obliged to introduce the euro as their currency as soon as they fulfil the admission criteria. Technically, this has been achieved by transferring the exclusive competence for the monetary policy of the Member States whose currency is the euro on the EU, Article 3(1)(c) TFEU and by bestowing the euro with the quality of legal tender, the only legal tender in the EU, Article 128(1) sentence 3 TFEU.
Savings accounts are owned by most households, but little is known about the performance of households’ investments. We create a unique dataset by matching information on individual savings accounts from the DNB Household Survey with market data on account-specific interest rates and characteristics. We document considerable heterogeneity in returns across households, which can be partly explained by financial sophistication. A one-standard deviation increase in financial literacy is associated with a 13% increase compared to the median interest rate. We isolate the usage of modern technology (online accounts) as one channel through which financial literacy has a positive association with returns.
A theory of the boundaries of banks with implications for financial integration and regulation
(2015)
We offer a theory of the "boundary of the
rm" that is tailored to banking, as it builds on a single ine¢ ciency arising from risk-shifting and as it takes into account both interbank lending as an alternative to integration and the role of possibly insured deposit funding. Amongst others, it explains both why deeper economic integration should cause also greater financial integration through both bank mergers and interbank lending, albeit this typically remains ine¢ ciently incomplete, and why economic disintegration (or "desychronization"), as currently witnessed in the European Union, should cause less interbank exposure. It also suggests that recent policy measures such as the preferential treatment of retail deposits, the extension of deposit insurance, or penalties on "connectedness" could all lead to substantial welfare losses.
In-depth analyses of cancer cell proteomes are needed to elucidate oncogenic pathomechanisms, as well as to identify potential drug targets and diagnostic biomarkers. However, methods for quantitative proteomic characterization of patient-derived tumors and in particular their cellular subpopulations are largely lacking. Here we describe an experimental set-up that allows quantitative analysis of proteomes of cancer cell subpopulations derived from either liquid or solid tumors. This is achieved by combining cellular enrichment strategies with quantitative Super-SILAC-based mass spectrometry followed by bioinformatic data analysis. To enrich specific cellular subsets, liquid tumors are first immunophenotyped by flow cytometry followed by FACS-sorting; for solid tumors, laser-capture microdissection is used to purify specific cellular subpopulations. In a second step, proteins are extracted from the purified cells and subsequently combined with a tumor-specific, SILAC-labeled spike-in standard that enables protein quantification. The resulting protein mixture is subjected to either gel electrophoresis or Filter Aided Sample Preparation (FASP) followed by tryptic digestion. Finally, tryptic peptides are analyzed using a hybrid quadrupole-orbitrap mass spectrometer, and the data obtained are processed with bioinformatic software suites including MaxQuant. By means of the workflow presented here, up to 8,000 proteins can be identified and quantified in patient-derived samples, and the resulting protein expression profiles can be compared among patients to identify diagnostic proteomic signatures or potential drug targets.
In the title compound, C20H24N2O4, both peptide bonds adopt a trans configuration with respect to the —N—H and —C=O groups. The dihedral angle between the aromatic rings is 53.58 (4)°. The molecular conformation is stabilized by an intramolecular N—H⋯O hydrogen bond. The crystal packing is characterized by zigzag chains of N—H⋯O hydrogen-bonded molecules running along the b-axis direction.
Das Hauptziel der vorliegenden Arbeit war es, die energieabhängigen Wirkungsquerschnitte von (γ,n)-Reaktionen für 169Tm, 170Yb, 176Yb und 130Te mittels der Photoaktivierungsmethode zu bestimmen.
Dazu wurden zunächst die Effizienzen der verwendeten Detektoren mithilfe von Simulationen korrigiert, da die verwendeten Targets eine ausgedehnte Geometrie aufweisen im Gegensatz zu den punktförmigen Eichquellen. Es hat sich herausgestellt, dass mit den Simulationen die Effizienzen der MCA-Detektoren energieabhängig korrigiert werden konnten, da die Simulationen die Form der gemessenen Effizienzen gut reproduzieren konnten. Bei den Effizienzen der LEPS-Detektoren hingegen konnte keine energieabhäangige Korrektur vorgenommen werden, da die LEPS-Detektoren aufgrund des geringen Abstandes zu den Detektoren hohe Summeneffekte zeigten. Im Rahmen dieser Arbeit konnten diese Summeneffekte jedoch nicht korrigiert bzw. berücksichtigt werden.
n the EU there are longstanding and ongoing pressures towards a tax that is levied on the EU level to substitute for national contributions. We discuss conditions under which such a transition can make sense, starting from what we call a "decentralization theorem of taxation" that is analogous to Oates (1972) famous result that in the absence of spill-over effects and economies of scale decentralized public good provision weakly dominates central provision. We then drop assumptions that turn out to be unnecessary for this results. While spill-over effects of taxation may call for central rules for taxation, as long as spill-over effects do not depend on the intra-regional distribution of the tax burden, decentralized taxation plus tax coordination is found superior to a union-wide tax.
Do markets correct individual behavioral biases? In an experimental asset market, we compare the outcomes of a standard market economy to those of a an island economy that removed market interactions. We observe asset price bubbles in the market economy while prices are stable in the island economy. We also find that subjects took more risk following larger losses, resulting in larger prices and consistent with a gambling for resurrection motive. This motive can translate into bubbles in the market economy because higher prices increase average losses and thus reinforce the desire to resurrect. By contrast, the absence of such a strategic complementarity in island economies can explain the more stable outcome. These results suggest that markets do not correct behavioral biases, rather the contrary.
This paper analyzes sovereign risk shift-contagion, i.e. positive and significant changes in the propagation mechanisms, using bond yield spreads for the major eurozone countries. By emphasizing the use of two econometric approaches based on quantile regressions (standard quantile regression and Bayesian quantile regression with heteroskedasticity) we find that the propagation of shocks in euro's bond yield spreads shows almost no presence of shift-contagion. All the increases in correlation we have witnessed over the last years come from larger shocks propagated with higher intensity across Europe.
Research on interbank networks and systemic importance is starting to recognise that the web of exposures linking banks balance sheets is more complex than the single-layer-of-exposure paradigm. We use data on exposures between large European banks broken down by both maturity and instrument type to characterise the main features of the multiplex structure of the network of large European banks. This multiplex network presents positive correlated multiplexity and a high similarity between layers, stemming both from standard similarity analyses as well as a core-periphery analyses of the different layers. We propose measures of systemic importance that fit the case in which banks are connected through an arbitrary number of layers (be it by instrument, maturity or a combination of both). Such measures allow for a decomposition of the global systemic importance index for any bank into the contributions of each of the sub-networks, providing a useful tool for banking regulators and supervisors. We use the dataset of exposures between large European banks to illustrate the proposed measures.
Although banks are at the center of systemic risk, there are other institutions that contribute to it. With the publication of the leveraged lending guideline in March 2013, the U.S. regulators show that they are especially worried about the private equity firms with their high-risk deals. Given these risks and the interconnectedness of the banks through the LBO loan syndicates, I shed light on the impact of a bank’s LBO loan exposure on its systemic risk. By using 3,538 observations between 2000 and 2013 from 165 global banks, I show that banks with higher LBO exposure also have a higher level of systemic risk. Other loan purposes do not show this positive relationship. The main drivers influencing this relationship positively are the bank’s interconnectedness to other LBO financing banks and its size. Lending experience with a specific PE sponsor, experience with leading LBO syndicates or a bank’s credit rating, however, lead to a lower impact of the LBO loan exposure on systemic risk.
In the mid-1990s, institutional investors entered the syndicated loan market and started to serve borrowers as lead arrangers. Why are non-banks able to compete for this role against banks? How do the composition of syndicates and loan pricing differ among lead arrangers? By using a dataset of 12,847 leveraged loans between 1997 and 2012, I aim to answer these questions. Non-banks benefit from looser regulatory requirements, have industry expertise which helps them in the screening and monitoring of borrowers and focus on firms that ask for loans only instead of additional cross-selling of other services. I can show that non-banks specialize on more opaque and less experienced borrowers, are more likely than banks to choose participants that help to reduce potentially higher information asymmetries and earn 105 basis points more than banks.
This paper analyzes the influence Leveraged Buyouts (LBOs) have on the operating performance of the LBO target companies’ direct competitors. A unique and hand-collected data set on LBOs in the United States in the period 1985-2009 allows us to analyze the effects different restructuring activities as part of the LBO have on the competitors’ revenues. These restructuring activities include changes to leverage, governance, or operating business, as well as M&A activities of the LBO target company. We find that although LBOs itself have a negative influence on competitors’ revenue growth, some restructuring mechanisms might actually benefit competing companies.
The Liikanen Group proposes contingent convertible (CoCo) bonds as a potential mechanism to enhance financial stability in the banking industry. Especially life insurance companies could serve as CoCo bond holders as they are already the largest purchasers of bank bonds in Europe. We develop a stylized model with a direct financial connection between banking and insurance and study the effects of various types of bonds such as non-convertible bonds, write-down bonds and CoCos on banks' and insurers' risk situations. In addition, we compare insurers' capital requirements under the proposed Solvency II standard model as well as under an internal model that ex-ante anticipates additional risks due to possible conversion of the CoCo bond into bank shares. In order to check the robustness of our findings, we consider different CoCo designs (write-down factor, trigger value, holding time of bank shares) and compare the resulting capital requirements with those for holding non-convertible bonds. We identify situations in which insurers benefit from buying CoCo bonds due to lower capital requirements and higher coupon rates. Furthermore, our results highlight how the Solvency II standard model can mislead insurers in their CoCo investment decision due to economically irrational incentives.
I assess how Basel III, Solvency II and the low interest rate environment will affect the financial connection between the bank and insurance sector by changing the funding patterns of banks as well as the investment strategies of life insurance companies. Especially for life insurance companies, the current low interest rate environment poses a key risk since declining returns on investments jeopardize the guaranteed return on life insurance contracts, a core component of traditional life insurance contracts in several European countries. I consider a contingent claim framework with a direct financial connection between banks and life insurers via bank bonds. The results indicate that life insurers' demand for bank bonds increases over the mid-term but ultimately declines in the long-run. Since life insurers are the largest purchasers of bank bonds in Europe, banks could lose one of their main funding sources. In addition, I show that shareholder value driven life insurers' appetite for risk increases when the gap between asset return and liability growth diminishes. To check the robustness of the findings, I calibrate a prolonged low interest rate scenario. The results show that the insurer's risk appetite is even higher when interest rates remain persistently low. A sensitivity analysis regarding industry-specific regulatory safety levels reveals that contagion between bank and life insurer is driven by the insurers' demand for bank bonds which itself depends on the regulatory safety level of banks.
The creation of the Banking Union is likely to come with substantial implications for the governance of Eurozone banks. The European Central Bank, in its capacity as supervisory authority for systemically important banks, as well as the Single Resolution Board, under the EU Regulations establishing the Single Supervisory Mechanism and the Single Resolution Mechanism, have been provided with a broad mandate and corresponding powers that allow for far-reaching interference with the relevant institutions’ organisational and business decisions. Starting with an overview of the relevant powers, the present paper explores how these could – and should – be exercised against the backdrop of the fundamental policy objectives of the Banking Union. The relevant aspects directly relate to a fundamental question associated with the reallocation of the supervisory landscape, namely: Will the centralisation of supervisory powers, over time, also lead to the streamlining of business models, corporate and group structures of banks across the Eurozone?
This paper examines the dynamic relationship between credit risk and liquidity in the sovereign bond market in the context of the European Central Bank (ECB) interventions. Using a comprehensive set of liquidity measures obtained from a detailed, quote-level dataset of the largest interdealer market for Italian government bonds, we show that changes in credit risk, as measured by the Italian sovereign credit default swap (CDS) spread, generally drive the liquidity of the market: a 10% change in the CDS spread leads a 11% change in the bid-ask spread. This relationship is stronger, and the transmission is faster, when the CDS spread is above the 500 basis point threshold, estimated endogenously, and can be ascribed to changes in margins and collateral, as well as clientele effects. Moreover, we show that the Long-Term Refinancing Operations (LTRO) intervention by the ECB weakened the sensitivity of the liquidity provision by the market makers to changes in the Italian government's credit risk. We also document the importance of market-wide and dealer-specific funding liquidity measures in determining the market liquidity for Italian government bonds.
The European Commission has published a Green Paper outlining possible measures to create a single market for capital in Europe. Our comments on the Commission’s capital markets union project use the functional finance approach as a starting point. Policy decisions, according to the functional finance perspective, should be essentially neutral (agnostic) in terms of institutions (level playing field). Our main angle, from which we assess proposals for the capital markets union agenda, are information asymmetries and the agency problems (screening, monitoring) which arise as a result. Within this perspective, we make a number of more specific proposals.
The paper traces the developments from the formation of the European Economic and Monetary Union to this date. It discusses the fact that the primary mandate of the European System of Central Banks (ESCB) is confined to safeguarding price stability and does not include general economic policy. Finally, the paper contributes to the discussion on whether the primary law of the European Union would support a eurozone exit. The Treaty of Maastricht imposed the strict obligation on the European Union (EU) to establish an economic and monetary union, now Article 3(4) TEU. This economic and monetary union is, however, not designed as a separate entity but as an integral part of the EU. The single currency was to become the currency of the EU and to be the legal tender in all Member States unless an exemption was explicitly granted in the primary law of the EU, as in the case of the UK and Denmark. The newly admitted Member States are obliged to introduce the euro as their currency as soon as they fulfil the admission criteria. Technically, this has been achieved by transferring the exclusive competence for the monetary policy of the Member States whose currency is the euro on the EU, Article 3(1)(c) TFEU and by bestowing the euro with the quality of legal tender, the only legal tender in the EU, Article 128(1) sentence 3 TFEU.
Die deutsche Steuerpolitik kombiniert hohe Steuersätze mit zahlreichen Ausnahmen. Das reißt Gerechtigkeitslücken, lenkt Investitionen in die falschen Zwecke und verkompliziert das Steuersystem mitunter bis zur Unkenntlichkeit. Bei der Erbschaftsteuer ist dies besonders augenfällig. Der Versuch mit minimalinvasiven Korrekturen Konsistenz in die Erbschaft- und Schenkungsteuer zu bringen ist fast zwangsläufig zum Scheitern verurteilt. Vieles spricht stattdessen für deutlich abgesenkte Steuersätze und eine gleichzeitige Abschaffung der Vergünstigungen für Betriebsvermögen.
Ein kritischer Diskurs ist essentiell für die Wissenschaft. Das ist zwar banal, wird aber im gegenwärtigen Streit um „Münkler Watch“, einem Blog, in dem Studierende der Humboldt-Universität Berlin eine Vorlesung des Politikwissenschaftlers Prof. Herfried Münkler anonym kritisieren, häufig vergessen. Aber auch den Studierenden scheint es nicht um einen inhaltlichen Dialog, sondern um Aufmerksamkeit zu gehen.