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Kaum eine andere Industrie wurde in den vergangenen beiden Jahrzehnten so massiv durch den Einzug der Informationstechnologie geprägt wie der Wertpapierhandel. Traditionelle Geschäftsmodelle haben sich grundlegend verändert. Das klassische Börsenparkett ist nahezu vollständig elektronischen Handelsplattformen gewichen.
Notenbanken haben heute nicht die Aufgabe, die Geldmenge zu kontrollieren. Ihr Job ist es, den Wert des Geldes – und damit den Preis der Wirtschaftsgüter in der jeweiligen Währung – zu stabilisieren. Doch wie ist diese Preisstabilität am besten herzustellen? Muss man dabei nicht doch die Geldmenge im Auge behalten? Unter monetären Ökonomen gibt es dazu eine wissenschaftliche Debatte.
Wie in der Medizin muss der Therapie die Diagnose vorausgehen. Allzu viele Vorschläge zur Lösung der Krise gehen nicht zuletzt deshalb in die falsche Richtung, weil sie eine adäquate Ursachenanalyse vermissen lassen. Wird der Fiskalpakt Europa aus der Krise führen? Die Europäische Währungsordnung ist ein Produkt politischer Entscheidungen, gegossen in europäisches und nationales Recht. Wie glaubwürdig ist das Versprechen, durch neues Recht, härtere vertragliche Bestimmungen, Fehlverhalten in Zukunft zu verhindern, wenn das geltende Recht so gering geachtet wird?
Die Rechnung kommt immer zum Schluss – und sie zu bezahlen, macht in der Regel keine Freude. Wenn wir aber schon eher ungern bezahlen, soll die Zahlungsmethode selbst wenigstens einfach, überall verfügbar und sehr sicher sein. Insbesondere die Sicherheit ist beim Bezahlen im 21. Jahrhundert ein wichtiges Thema, zu dem es interdisziplinäre Forschungsansätze aus Wirtschaftswissenschaften, Informatik und Recht in einem von dynamischer Entwicklung geprägten Umfeld gibt.
Eine Billion ist mathematisch leicht darstellbar. Es ist eine Eins mit 12 Nullen: 1 000 000 000 000, mathematisch kurz und prägnant als 10^12 geschrieben. Aber darstellbar heißt nicht unbedingt vorstellbar. Versuchen wir, diese Anzahlen zu veranschaulichen, entstehen teilweise surreale, aber einprägsame Bilder.
Die Geld-Welt in Zahlen
(2012)
Die ersten »Banknoten« waren Schuldscheine oder Quittungen für hinterlegte Edelmetalle. Erst mit der Abkopplung von Papier und Einlage eröffneten sich neue Möglichkeiten der Finanzierung für Banken und Staatslenker – mit den entsprechenden Risiken. Der historische Blick auf die unterschiedlichen geldpolitischen Interessen von Regierungen, Privat- und Zentralbanken wirft auch ein neues Licht auf die Hintergründe der gegenwärtigen Krise.
Wirtschaftskrisen sind nichts Neues. Sie zählen im Laufe der Jahrhunderte zu wiederkehrenden Ereignissen. Seit dem 19. Jahrhundert strahlen sie allerdings meist weit über das ökonomische Geschehen hinaus. Ihre Ursachen sind vielfältig und lassen sich nicht allein auf das Verhalten einzelner Personen oder "der Märkte" reduzieren. Die als so beunruhigend wahrgenommenen Spekulationenmüssen als ein notwendiges Moment allen wirtschaftlichen Handelns betrachtet werden und gehören zu den Rhythmen, die – so zeigen auch die jüngsten Entwicklungen – durch staatliche Interventionen nicht ohne Weiteres umzukehren sind.
Due to recent technical developments, a high number of long non-coding RNAs (lncRNAs) have been discovered in mammals. Although it has been shown that lncRNAs are regulated differently among tissues and disease statuses, functions of these transcripts are still unknown in most cases. GeneChip Exon 1.0 ST Arrays (exon arrays) from Affymetrix, Inc. have been used widely to profile genome-wide expression changes and alternative splicing of protein-coding genes. Here, we demonstrate that re-annotation of exon array probes can be used to profile expressions of tens of thousands of lncRNAs. With this annotation, a detailed inspection of lncRNAs and their isoforms is possible. To allow for a general usage to the research community, we developed a user-friendly web interface called 'noncoder'. By uploading CEL files from exon arrays and with a few mouse clicks and parameter settings, exon array data will be normalized and analysed to identify differentially expressed lncRNAs. Noncoder provides the detailed annotation information of lncRNAs and is equipped with unique features to allow for an efficient search for interesting lncRNAs to be studied further. The web interface is available at http://noncoder.mpi-bn.mpg.de.
Jager, Saskia C. A. de ; Bongaerts, Brenda W. C. ; Weber, Michael ; Kraaijeveld, Adriaan O. ; Rousch, Mat ; Dimmeler, Stefanie ; Dieijen-Visser, Marja P. van ; Cleutjens, Kitty B. J. M. ; Nelemans, Patty J. ; Berkel, Theo J. C. van ; Biessen, Erik A. L.
Cytokines play an important role in ischemic injury and repair. However, little is known about their prognostic value in cardiovascular disease. The aim of this study was to investigate the prognostic importance of chemokines CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC for the risk of future cardiovascular events in patients with acute coronary syndromes (ACS). Baseline levels of CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC were determined in ACS patients from the Bad Nauheim ACS II registry (n = 609). During the following 200 days, patients were monitored for the occurrence of fatal and non-fatal cardiovascular events. Patients with CCL3/MIP1α, CCL5/RANTES and CCL18/PARC concentrations in the highest tertile were associated with an increased risk of a fatal event during follow-up (HR: 2.19, 95%CI: 1.04–4.61 for CCL3/MIP1α, HR: 3.45, 95%CI: 1.54–7.72 for CCL5/RANTES and HR: 3.14, 95%CI: 1.33–7.46 for CCL18/PARC). This risk was highest for patients with all three biomarkers concentrations in the upper tertile (HR: 2.52, 95%CI: 1.11–5.65). Together with known risk predictors of cardiovascular events, CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC combined improved the c-statistics from 0.74 to 0.81 (p = 0.007). In conclusion, CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC are independently associated with the risk of short-term mortality in ACS patients. Combining all three biomarkers further increased their prognostic value.
Loot, Annemarieke E. ; Moneke, Isabelle ; Keserü, Benjamin ; Oelze, Matthias ; Syzonenko, Tetyana ; Daiber, Andreas ; Fleming, Ingrid
In the systemic circulation, 11,12-epoxyeicosatrienoic acid (11,12-EET) elicits nitric oxide (NO)- and prostacyclin-independent vascular relaxation, partially through the activation of large conductance Ca2+-activated potassium (BK) channels. However, in the lung 11,12-EET contributes to hypoxia-induced pulmonary vasoconstriction. Since pulmonary artery smooth muscle cells also express BK channels, we assessed the consequences of BKβ1 subunit deletion on pulmonary responsiveness to 11,12-EET as well as to acute hypoxia. In buffer-perfused mouse lungs, hypoxia increased pulmonary artery pressure and this was significantly enhanced in the presence of NO synthase (NOS) and cyclooxygenase (COX) inhibitors. Under these conditions the elevation of tissue EET levels using an inhibitor of the soluble epoxide hydrolase (sEH-I), further increased the hypoxic contraction. Direct administration of 11,12-EET also increased pulmonary artery pressure, and both the sEH-I and 11,12-EET effects were prevented by iberiotoxin and absent in BKβ1−/− mice. In pulmonary artery smooth muscle cells treated with NOS and COX inhibitors and loaded with the potentiometric dye, di-8-ANEPPS, 11,12-EET induced depolarization while the BK channel opener NS1619 elicited hyperpolarization indicating there was no effect of the EET on classical plasma membrane BK channels. In pulmonary artery smooth muscle cells a subpopulation of BK channels is localized in mitochondria. In these cells, 11,12-EET elicited an iberiotoxin-sensitive loss of mitochondrial membrane potential (JC-1 fluorescence) leading to plasma membrane depolarization, an effect not observed in BKβ1−/− cells. Mechanistically, stimulation with 11,12-EET time-dependently induced the association of the BK α and β1 subunits. Our data indicate that in the absence of NO and prostacyclin 11,12-EET contributes to pulmonary vasoconstriction by stimulating the association of the α and β1 subunits of mitochondrial BK channels. The 11,12-EET-induced activation of BK channels results in loss of the mitochondrial membrane potential and depolarization of the pulmonary artery smooth muscle cells.
Entling, Martin H. ; Schweiger, Oliver ; Bacher, Sven ; Espadaler, Xavier ; Hickler, Thomas ; Kumschick, Sabrina ; Woodcock, Ben A. ; Nentwig, Wolfgang
We study how species richness of arthropods relates to theories concerning net primary productivity, ambient energy, water-energy dynamics and spatial environmental heterogeneity. We use two datasets of arthropod richness with similar spatial extents (Scandinavia to Mediterranean), but contrasting spatial grain (local habitat and country). Samples of ground-dwelling spiders, beetles, bugs and ants were collected from 32 paired habitats at 16 locations across Europe. Species richness of these taxonomic groups was also determined for 25 European countries based on the Fauna Europaea database. We tested effects of net primary productivity (NPP), annual mean temperature (T), annual rainfall (R) and potential evapotranspiration of the coldest month (PETmin) on species richness and turnover. Spatial environmental heterogeneity within countries was considered by including the ranges of NPP, T, R and PETmin. At the local habitat grain, relationships between species richness and environmental variables differed strongly between taxa and trophic groups. However, species turnover across locations was strongly correlated with differences in T. At the country grain, species richness was significantly correlated with environmental variables from all four theories. In particular, species richness within countries increased strongly with spatial heterogeneity in T. The importance of spatial heterogeneity in T for both species turnover across locations and for species richness within countries suggests that the temperature niche is an important determinant of arthropod diversity. We suggest that, unless climatic heterogeneity is constant across sampling units, coarse-grained studies should always account for environmental heterogeneity as a predictor of arthropod species richness, just as studies with variable area of sampling units routinely consider area.
Tober, Reinhard ; Banki, Zoltan ; Ejaz, Asim ; Muik, Alexander ; Egerer, Lisa Mareike ; Laer, Dorothee von ; Kimpel, Janine
Background: Vesicular stomatitis virus (VSV) is a potent candidate vaccine vector for various viral diseases (e.g. HIV, HCV, RSV). The biggest limitation of VSV, however, is its neurotoxicity, which limits application in humans. The second drawback is that VSV induces neutralizing antibodies rapidly and is thus ineffective as a vaccine vector upon repeated applications. Our group has recently shown that VSV pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV), VSV-GP, is not neurotoxic. The aim of this project was to evaluate the potential of VSV-GP as a vaccine vector.
Methods: For this purpose, we used Ovalbumin (OVA) as a model antigen and analyzed immunogenicity of GP-pseudotyped and wildtype VSV containing OVA (VSV-GP-OVA and VSV-OVA) in vitro and in vivo in mouse models.
Results: We showed that both vectors infected murine bone marrow-derived dendritic cells (bmDCs) in vitro. These bmDCs were able to activate OVA specific CD8+ and CD4+ T cells. Immunization experiments in mice revealed that both VSV-OVA and VSV-GP-OVA induced functional OVA-specific cytotoxic T cells (CTLs) after a single immunization. In addition, with both viruses, mice generated antibodies against OVA. However, boosting with the same virus was only possible for the GP-pseudotyped virus but not for wild type VSV. The efficacy of repeated immunization with VSV-OVA was most likely limited by high levels of neutralizing antibodies, which we detected after the first immunization. In contrast, no neutralizing antibodies against VSV-GP were induced even after boosting.
Conclusion: Taken together, we showed that the non-neurotoxic VSV-GP is able to induce specific T cell and B cell responses against the model antigen OVA to the same level as the wild type VSV vector. However, in contrast to wild type VSV, VSV-GP-OVA boosted the immune response upon repeated applications. Thus, VSV-GP is a promising novel vaccine vector.
Schulze, Johannes B. ; Voss, Sandra ; Zissler, Ulrich ; Rose, Markus A. ; Zielen, Stefan ; Schubert, Ralf
Background: Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma. However, clinical symptoms are less likely to be induced. Therefore, we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation.
Methods: A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma underwent repetitive high-dose allergen challenges with household dust mites for four consecutive days. Pulmonary function and exhaled NO were measured at every visit. Induced sputum was analysed before and after the allergen challenges for cell counts, ECP, IL-5, INF-γ, IL-8, and the transcription factor Foxp3.
Results: We found a significant decrease in pulmonary function, an increased use of salbutamol and the development of a late asthmatic response and bronchial hyperresponsiveness, as well as a significant induction of eNO, eosinophils, and Th-2 cytokines. Repeated provocation was feasible in the majority of patients. Two subjects had severe adverse events requiring prednisolone to cope with nocturnal asthma symptoms.
Conclusions: Repeated high-dose bronchial allergen challenges resulted in severe asthma symptoms and marked Th-2-mediated allergic airway inflammation. The high-dose challenge model is suitable only in an attenuated form in diseased volunteers for proof-of-concept studies and in clinical settings to reduce the risk of severe asthma exacerbations.
Trial registration: ClinicalTrials.govNCT00677209
The small leucine-rich proteoglycans (SLRPs) are biologically active components of the extracellular matrix (ECM), consisting of a protein core with leucine rich-repeat (LRR) motifs covalently linked to glycosaminoglycan (GAG) side chains. The diversity in composition resulting from the various combinations of protein cores substituted with one or more GAG chains along with their pericellular localization enables SLRPs to interact with a host of different cell surface receptors, cytokines, growth factors, and other ECM components, leading to modulation of cellular functions. SLRPs are capable of binding to: (i) different types of collagens, thereby regulating fibril assembly, organization, and degradation; (ii) Toll-like receptors (TLRs), complement C1q, and tumor necrosis factor-alpha (TNFα), regulating innate immunity and inflammation; (iii) epidermal growth factor receptor (EGF-R), insulin-like growth factor receptor (IGF-IR), and c-Met, influencing cellular proliferation, survival, adhesion, migration, tumor growth and metastasis as well as synthesis of other ECM components; (iv) low-density lipoprotein receptor-related protein (LRP-1) and TGF-β, modulating cytokine activity and fibrogenesis; and (v) growth factors such as bone morphogenic protein (BMP-4) and Wnt-I-induced secreted protein-1 (WISP-1), controlling cell proliferation and differentiation. Thus, the ability of SLRPs, as ECM components, to directly or indirectly regulate cell-matrix crosstalk, resulting in the modulation of various biological processes, aptly qualifies these compounds as matricellular proteins.
Nephronectin regulates atrioventricular canal differentiation via Bmp4-Has2 signaling in zebrafish
(2011)
Patra, Chinmoy ; Diehl, Florian ; Ferrazzi, Fulvia ; Amerongen, Machteld J. van ; Novoyatleva, Tatyana ; Schäfer, Liliana ; Mühlfeld, Christian ; Jungblut, Benno ; Engel, Felix B.
The extracellular matrix is crucial for organogenesis. It is a complex and dynamic component that regulates cell behavior by modulating the activity, bioavailability and presentation of growth factors to cell surface receptors. Here, we determined the role of the extracellular matrix protein Nephronectin (Npnt) in heart development using the zebrafish model system. The vertebrate heart is formed as a linear tube in which myocardium and endocardium are separated by a layer of extracellular matrix termed the cardiac jelly. During heart development, the cardiac jelly swells at the atrioventricular (AV) canal, which precedes valve formation. Here, we show that Npnt expression correlates with this process. Morpholino-mediated knockdown of Npnt prevents proper valve leaflet formation and trabeculation and results in greater than 85% lethality at 7 days post-fertilization. The earliest observed phenotype is an extended tube-like structure at the AV boundary. In addition, the expression of myocardial genes involved in cardiac valve formation (cspg2, fibulin 1, tbx2b, bmp4) is expanded and endocardial cells along the extended tube-like structure exhibit characteristics of AV cells (has2, notch1b and Alcam expression, cuboidal cell shape). Inhibition of has2 in npnt morphants rescues the endocardial, but not the myocardial, expansion. By contrast, reduction of BMP signaling in npnt morphants reduces the ectopic expression of myocardial and endocardial AV markers. Taken together, our results identify Npnt as a novel upstream regulator of Bmp4-Has2 signaling that plays a crucial role in AV canal differentiation.
Buraschi, Simone ; Neill, Thomas ; Owens, Rick T. ; Iniguez, Leonardo A. ; Purkins, George ; Vadigepalli, Rajanikanth ; Evans, Barry ; Schäfer, Liliana ; Peiper, Stephen C. ; Wang, Zi-Xuan ; Iozzo, Renato V.
Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found that decorin protein core modulated the differential expression of 374 genes within the stromal compartment of the tumor xenograft. Further, our top gene ontology classes strongly suggests an unexpected and preferential role for decorin protein core to inhibit genes necessary for immunomodulatory responses while simultaneously inducing expression of those possessing cellular adhesion and tumor suppressive gene properties. Rigorous verification of the top scoring candidates led to the discovery of three genes heretofore unlinked to malignant breast cancer that were reproducibly found to be induced in several models of tumor stroma. Collectively, our data provide highly novel and unexpected stromal gene signatures as a direct function of systemic administration of decorin protein core and reveals a fundamental basis of action for decorin to modulate the tumor stroma as a biological mechanism for the ascribed anti-tumorigenic properties.
The wild silkmoth genus Sinobirma Bryk, 1944 is a poorly known monotypic taxon from the eastern end of the Himalaya Range. It was convincingly proposed to be closely related to some members of an exclusively Afro-tropical group of Saturniidae, but its biogeographical and evolutionary history remains enigmatic. After examining recently collected material from Tibet, northern India, and northeastern Myanmar, we realized that this unique species, S. malaisei Bryk, 1944 only known so far from a few specimens and from a very restricted area near the border between north-eastern Myanmar and the Yunnan province of China, may in fact belong to a group of closely related cryptic species. In this work, we combined morphological comparative study, DNA barcoding, and the sequences of a nuclear marker (D2 expansion segment of the 28S rRNA gene) to unequivocally delimit three distinct species in the genus Sinobirma, of which two are described as new to science: S. myanmarensis sp. n. and S. bouyeri sp. n. An informative DNA barcode sequence was obtained from the female holotype of S. malaisei—collected in 1934—ensuring the proper assignation of this name to the newly collected and studied specimens. Our findings represent another example of the potential of coupling traditional taxonomy and DNA barcoding for revealing and solving difficult cases of cryptic diversity. This approach is now being generalized to the world fauna of Saturniidae, with the participation of most of the taxonomists studying these moths.
A metal–organic framework (MOF) material, [Zn2(adc)2(dabco)] (adc = anthracene-9,10-dicarboxylate, dabco = 1,4-diazabicyclo[2.2.2]octane), the fluorescence of which depends on the loading of its nanopores, was synthesized in two forms: as free-flowing nanocrystals with different shapes and as surface-attached MOFs (SURMOFs). For the latter, we used self-assembled monolayers (SAMs) bearing functional groups, such as carboxylate and pyridyl groups, capable of coordinating to the constituents of the MOF. It could be demonstrated that this directed coordination also orients the nanocrystals deposited at the surface. Using two different patterning methods, i.e., microcontact printing and electron-beam lithography, the lateral distribution of the functional groups could be determined in such a way that the highly localized deposition of the SURMOF films became possible.