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Die Spinozerebelläre Ataxie Typ 2 (SCA2) ist eine autosomal dominant vererbte neurodegenerative Krankheit, welche durch die Expansion des Trinukleotids Cytosin-Adenin-Guanin von ~22/23 auf >32 im Ataxin-2 Gen (ATXN2) verursacht wird. Dieses Trinukleotid codiert für die Aminosäure Glutamin weshalb SCA2 auch zu den Polyglutaminerkrankungen zählt. Zu dieser Gruppe zählen außerdem fünf weitere SCA-Subtypen sowie drei weitere neurodegenerative Erkrankungen, darunter die Huntington-Krankheit.
SCA2 wurde 1971 zum ersten Mal von Wadia und Swami beschrieben und unterscheidet sich von den anderen SCAs aufgrund der typischen Störung der sakkadischen Augenbewegungen. Weitere klinische Symptome von SCA2 sind Ataxie, Tremor, Dysmetrie, Dysarthrie, Hyporeflexie und Dysdiadochokinese. Die Symptome gehen auf einen neuronalen Verlust insbesondere im Cerebellum, aber auch in anderen Hirnregionen wie zum Beispiel dem Hirnstamm zurück.
Atxn2 wird in weiten Teilen des Zentralnervensystems aber auch in vielen nicht-neuronalen Geweben exprimiert. Es handelt sich um ein überwiegend cytoplasmatisch lokalisiertes Protein, welches im Gegensatz zu vielen anderen SCA-Proteinen cytoplasmatische und nur selten nukleäre Aggregate bildet. Die exakte Funktion von Atxn2 ist bisher unklar, es wurde allerdings mehrfach gezeigt, dass es in die mRNA Translation involviert ist aufgrund seiner Interaktion mit dem PolyA-bindenden Protein PABPC1.
Eine Expansion des Trinukleotids in Ataxin-2 kann nicht nur zu SCA2 führen, sondern stellt bei Wiederholungen zwischen 27 und 32 CAGs auch ein erhöhtes Risiko für eine Erkrankung an Amyotropher Lateralsklerose (ALS) und anderen neurodegenerativen Krankheiten dar. Eine Interaktion zwischen ATXN2 und dem ALS-verursachenden TDP43 (Tardbp) wurde bereits zahlreich beforscht, da Aggregate von ATXN2 in Motoneuronen des Rückenmarks von ALS-Patienten und aggregiertes TDP43 in SCA2-Neuronen beobachtet wurden.
Generell sind die Mechanismen, die zur Pathologie von SCA2 und ALS führen, noch weitgehend unklar. Ziel dieser Arbeit war es daher auf der einen Seite einen Einblick in den Pathomechanismus von SCA2 zu erhalten, indem mögliche oder bereits bekannte Interaktoren in etablierten Atxn2-Mausmodellen untersucht wurden. Auf der anderen Seite wurden zwei neue Mausmodelle charakterisiert, um ihre Eignung für die Erforschung von ALS und SCA2 zu prüfen.
Für den ersten Teil der Arbeit dienten Daten aus mehreren Transkriptomstudien von Atxn2-Knock-Out (KO) und Atxn2-CAG42-Knock-In (KIN) Mäusen als Grundlage. Konnten die Daten mit einer unabhängigen Methode bestätigt werden, folgten weitere Untersuchungen auf mRNA und Proteinebene sowie unter zusätzlicher Verwendung von Zellkultur und Patientenmaterial. Dadurch konnten neue Interaktionspartner von ATXN2 identifiziert und bereits bekannte in diesen Mausmodellen bestätigt werden.
So wurde zum Beispiel eine Interaktion von ATXN2 mit der E3-Ubiquitin-Protein-Ligasekomponente FBXW8 gezeigt und deren Beteiligung am Abbau von expandiertem ATXN2. Außerdem wurde eine Interaktion von FBXW8 mit dem bereits bekannten ATXN2-degradierenden Protein PARK2 gezeigt. Eine Hochregulierung des Fbxw8 Transkripts wurde sowohl im Atxn2-CAG42-KIN-Mausmodell als auch in SCA2-Patientenfibroblasten gefunden, während Park2 in keinem der Modelle signifikant veränderte Transkriptspiegel aufwies. Diese Daten belegen die Relevanz von Fbxw8 für den Abbau von moderat-expandiertem Atxn2 und begründen weitere Studien zur genauen Funktion dieses Proteins im Pathomechanismus von Atxn2.
Des Weiteren wurden diverse Kalziumhomöostasefaktoren untersucht, welche eine konsistente Herunterregulierung der Transkripte in beiden Mausmodellen aufwiesen. Auf Proteinebene zeigten sich jedoch Unterschiede zwischen den Modellen. Diese Daten belegen, dass zwar ähnliche Transkriptveränderungen im KIN- und KO-Modell auftreten, diesen aber vermutlich verschiedene Mechanismen zugrunde liegen. Welche Mechanismen dies genau sind bleibt zu klären, es ist jedoch wahrscheinlich, dass im KIN-Modell die Aggregatbildung sowie in beiden Modellen die Beteiligung von ATXN2 an der Translationregulation eine Rolle spielen. Die Ergebnisse dieser Studie unterstreichen die Relevanz des Ca2+ Signalwegs für die Entwicklung von SCA2.
Der zweite Teil der Arbeit beinhaltet die Charakterisierung einer ATXN2/TDP43 Doppelmutante auf Verhaltensebene sowie die gründliche Evaluierung des Phänotyps einer vollkommen neuen SCA2 Mausmutante. Während in der Doppelmutante trotz doppelter Genmutation nur ein sehr schwacher Phänotyp auf Verhaltensebene festgestellt werden konnte und bis zu einem Alter von 12 Monaten keine Potenzierung der Mutationen zu beobachten war, zeigte die Atxn2-CAG100-KIN Maus signifikante und früh auftretende Pathologie. Neben einer verminderten Überlebensrate, einem Gewichtsverlust und diversen motorischen Störungen, konnten auch Aggregate des mutierten Proteins in diversen Hirnregionen identifiziert werden. Der Atxn2-CAG100-KIN Phänotyp spiegelt die humanen Symptome daher recht gut wider, weshalb diese Mausmutante ein wertvolles Modell für die weitere SCA2-Forschung darstellt.
Zusammengefasst zeigt diese Arbeit die Bedeutung des ATXN2-Interaktors FBXW8 im SCA2-Mausmodell als auch im Patientenmaterial. Sie betont die Relevanz des Atxn2-KO-Modells in Bezug auf Störungen der Kalziumhomöostase und dokumentiert die Alters- und Gewebespezifität dieser Veränderungen. Außerdem beinhaltet sie die vorläufige Beschreibung eines kombinierten Atxn2/TDP43-Mausmodells und schließlich die ausführliche Charakterisierung eines vollkommen neuen und äußerst wertvollen SCA2-Mausmodells.
The frequency of intensional and non-first-order definable operators in natural languages constitutes a challenge for automated reasoning with the kind of logical translations that are deemed adequate by formal semanticists. Whereas linguists employ expressive higher-order logics in their theories of meaning, the most successful logical reasoning strategies with natural language to date rely on sophisticated first-order theorem provers and model builders. In order to bridge the fundamental mathematical gap between linguistic theory and computational practice, we present a general translation from a higher-order logic frequently employed in the linguistics literature, two-sorted Type Theory, to first-order logic under Henkin semantics. We investigate alternative formulations of the translation, discuss their properties, and evaluate the availability of linguistically relevant inferences with standard theorem provers in a test suite of inference problems stated in English. The results of the experiment indicate that translation from higher-order logic to first-order logic under Henkin semantics is a promising strategy for automated reasoning with natural languages.
Mitochondria are involved in the aging processes that ultimately lead to neurodegeneration and the development of Alzheimer’s disease (AD). A healthy lifestyle, including a diet rich in antioxidants and polyphenols, represents one strategy to protect the brain and to prevent neurodegeneration. We recently reported that a stabilized hexanic rice bran extract (RBE) rich in vitamin E and polyphenols (but unsuitable for human consumption) has beneficial effects on mitochondrial function in vitro and in vivo (doi:10.1016/j.phrs.2013.06.008, 10.3233/JAD-132084). To enable the use of RBE as food additive, a stabilized ethanolic extract has been produced. Here, we compare the vitamin E profiles of both extracts and their effects on mitochondrial function (ATP concentrations, mitochondrial membrane potential, mitochondrial respiration and mitochondrial biogenesis) in PC12 cells. We found that vitamin E contents and the effects of both RBE on mitochondrial function were similar. Furthermore, we aimed to identify components responsible for the mitochondria-protective effects of RBE, but could not achieve a conclusive result. α-Tocotrienol and possibly also γ-tocotrienol, α-tocopherol and δ-tocopherol might be involved, but hitherto unknown components of RBE or a synergistic effect of various components might also play a role in mediating RBE’s beneficial effects on mitochondrial function.
Background: The peroneal muscles are the most effective lateral stabilisers whose tension braces the ankle joint complex against excessive supination. The purpose of this study was to identify the morphological and biomechanical effects of two machine-based shank muscle training methods.
Methods: Twenty-two healthy male recreationally active sports students performed ten weeks of single-set high resistance strength training with 3 training sessions per week. The subjects conducted subtalar pronator/supinator muscle training (ST) with the right leg by using a custom-made apparatus; the left foot muscles were exercised with machine-based talocrural plantar and dorsiflexor training (TT). Muscle strength (MVIC), muscle volume and foot biomechanics (rearfoot motion, ground reaction forces, muscle reaction times) during a sudden ankle supination were recorded before and after the intervention.
Results: Compared to TT, ST resulted in significantly higher pronator (14% vs. 8%, P<0.01) and supinator MVIC (25% vs. 12%, P<0.01). During sudden foot inversions, both ST and TT resulted in reduced supination velocity (-12%; P<0.01). The muscle reaction onset time was faster after the training in peroneus longus (PL) (P<0.01). Muscle volume of PL (P<0.01) and TA (P<0.01) increased significantly after both ST and TT.
Conclusion: After both ST and TT, the ankle joint complex is mechanically more stabilised against sudden supinations due to the muscle volume increase of PL and TA. As the reduced supination velocities indicate, the strength training effects are already present during free-fall. According to a sudden ankle supination in standing position, both machine-based dorsiflexor and pronator strength training is recommended for enhancing the mechanical stability of the ankle.
Die vorliegende Bachelorarbeit leistet einen Beitrag zur wissenschaftlichen Identifikation von intergenerationalen Unterschieden verschiedener Arbeitnehmergruppen. Insbesondere werden sowohl die Unterschiede zwischen den Generationen X und Y, in der Arbeitsbereitschaft, in unterschiedlichen Abschnitten des Berufslebens, als auch die Unterschiede zwischen der Wahrnehmung der Wichtigkeit von Arbeitgeberattraktivitätsattributen jener Generationen betrachtet. Ein besonderes Augenmerk liegt hierbei auf der Betrachtung von High-Potentials.
Highlights
• A panel of 20 biomarkers was identified capable of differentiating BD patients from controls.
• Excellent discrimination between established BD patients and controls.
• Good to excellent discrimination between misdiagnosed BD patients and first onset MDD patients.
• Fair to good discrimination between pre-diagnostic BD patients and controls.
• Study demonstrates the potential utility of a protein biomarker panel as a diagnostic test for BD.
Abstract
Background: Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD.
Methods and findings: We performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies.
We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC) ⩾ 0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel.
Conclusions: An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.
The solution structure of the lantibiotic immunity protein NisI and its interactions with nisin
(2015)
Many Gram-positive bacteria produce lantibiotics, genetically encoded and posttranslationally modified peptide antibiotics, which inhibit the growth of other Gram-positive bacteria. To protect themselves against their own lantibiotics these bacteria express a variety of immunity proteins including the LanI lipoproteins. The structural and mechanistic basis for LanI-mediated lantibiotic immunity is not yet understood. Lactococcus lactis produces the lantibiotic nisin, which is widely used as a food preservative. Its LanI protein NisI provides immunity against nisin but not against structurally very similar lantibiotics from other species such as subtilin from Bacillus subtilis. To understand the structural basis for LanI-mediated immunity and their specificity we investigated the structure of NisI. We found that NisI is a two-domain protein. Surprisingly, each of the two NisI domains has the same structure as the LanI protein from B. subtilis, SpaI, despite the lack of significant sequence homology. The two NisI domains and SpaI differ strongly in their surface properties and function. Additionally, SpaI-mediated lantibiotic immunity depends on the presence of a basic unstructured N-terminal region that tethers SpaI to the membrane. Such a region is absent from NisI. Instead, the N-terminal domain of NisI interacts with membranes but not with nisin. In contrast, the C-terminal domain specifically binds nisin and modulates the membrane affinity of the N-terminal domain. Thus, our results reveal an unexpected structural relationship between NisI and SpaI and shed light on the structural basis for LanI mediated lantibiotic immunity.
The European Union is at the crossroads between intelligent expansion of future horizons and frightened shrinking to a perspective of local areas. Fear of descent of the citizens on one side and a politics of crisis, that goes along with harsh injustice have made upset the national societies against each other, missing courage on the side of politicians, to bring European issues to the fore, endanger the European project. There is only one way to overcome this situation by establishing a democratic union, which conserves not only the social and civilian achievements of the national state, as well as the assets of a greater democratic political unity, that offers an unity of European citizens and European state demos.
Last week, this year’s ISA conference brought together over 5000 scholars and exhibitors from all over the world to discuss all things international, political, scholarly, hold meetings, get lunch together, and party at Mardi Gras (it was in New Orleans, after all!). Similar to last year, a lot of this discussing took also place on Twitter. Scholars-slash-tweeps rallied around the hashtag #isa2015 to talk to each other online about great (and not so great) panels, trends in IR scholarship, gender bias in academia, and (not surprisingly for an academic conference) coffee. Who was most active during ISA2015 on Twitter? What were the most hotly debated topics online? When did ISAlers tweet?
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.
I’m probably not alone in observing that there seems to be an increasing number of data articles being published in the field of conflict studies and IR. Together with some colleagues, I’m even preparing one myself at the moment! Is that perceived increase in data publication actually measurable? And does it indeed amount to “drowning”?
Vor wenigen Tagen veröffentlichte das Bundeskriminalamt eine Studie mit dem Titel „Hacktivisten„, die auf einem dreistufigen Forschungsdesign beruht: einer Literaturrecherche, einer quantitativen Fallauswertung von 78 polizeilich bekannten deutschen Fällen und einem Expertenarbeitstreffen, bei welchem Erfahrungswerte ausgetauscht wurden...
We present an accessible narrative of the Turkish economy since its great 2001 crisis. We broadly survey economic developments and pay particular attention to monetary policy. The data suggests that the Central Bank of Turkey was a strong inflation targeter early in this period but began to pay less attention to inflation after 2009. Loss of the strong nominal anchor is visible in the break we estimate in Taylor-type rules as well as in asset prices. We also argue that recent discrete jumps in Turkish asset prices, especially the exchange value of the lira, are due more to domestic factors. In the post-2009 period the Central Bank was able to stabilize expectations and asset prices when it chose to do so, but this was the exception rather than the rule.
Teil VII unserer Serie zum “Islamischen Staat”: "Blogforum 'Kalifat des Terrors: Interdisziplinäre Perspektiven auf den Islamischen Staat".
Viel ist in den letzten Wochen und Monaten über den so genannten „Islamischen Staat“, ISIS oder ISIL gesprochen und geschrieben worden. Die „abstrakte Bedrohungslage“, die von der „Terrormiliz“ und ihren Anhängern ausgeht, scheint jedoch der deutschen Öffentlichkeit kaum deutlicher vor Augen geführt zu werden, als bei den Demonstrationen, die von Dresden ausgehend seit geraumer Zeit in verschiedenen Großstädten stattfinden bzw. stattgefunden haben. Die Wendung gegen das Austragen von „Glaubenskriegen auf deutschem Boden“ und noch deutlicher die Sorge vor einer bevorstehenden „Islamisierung des Abendlandes“, speist sich bei diesen zu einem gewissen Teil auch aus den Bildern und Tönen, die von und über den Islamischen Staat mittels unterschiedlicher Medienkanäle verbreitet werden. Zudem werden Befürchtungen artikuliert, die durch den Islamischen Staat ausgelösten Flüchtlingswellen bewirkten einen signifikanten Zuzug von Muslimen, der zu tiefgreifenden sozio-kulturellen Veränderungen führe...
Von Februar bis Juni 2015 hat die Europäische Zentralbank (EZB) die Notfall-Liquiditätshilfen (emergency liquidity assistance, ELA) für griechische Banken von 50 auf etwa 90 Milliarden Euro ausgeweitet. Dies hat zu einer Diskussion unter Wissenschaftlern, Politikern und Praktikern geführt, ob diese Liquiditätshilfen rechtmäßig sind. Es wurde der Vorwurf erhoben, die EZB trage bewusst zu einer Konkursverschleppung der bereits insolventen griechischen Banken bei.
Wir nehmen diesen Vorwurf zum Anlass, die Grundsätze des ELA-Programms genauer zu betrachten und die Frage zu diskutieren, ob das Programm in der aktuellen Situation rechtmäßig war. Zunächst beschreiben wir hierfür aus finanzwirtschaftlicher Perspektive die komplexe Beziehung zwischen der Europäischen Union, der EZB und den griechischen Banken. Dabei gehen wir insbesondere auf die wirtschaftspolitischen Grundsätze einer Währungsunion mit einer unvollständigen Fiskalunion (oder Haushaltskonsolidierung) ein. Vor diesem Hintergrund analysieren wir dann die Entscheidung der EZB, weiterhin Liquiditätshilfen an griechische Banken bereitzustellen. Wir kommen zu dem Ergebnis, dass das Vorgehen der EZB nicht als Konkursverschleppung zu bezeichnen ist.
The European Central Bank (ECB) increased the emergency liquidity assistance (ELA) for Greek banks from €50 billion in February 2015 to approximately €90 billion in June 2015. Its actions were accompanied by a discussion among academics, politicians and practitioners regarding the legitimacy of the ELA. Some have even accused the ECB of deliberately delaying the bankruptcy filing of already insolvent Greek banks.
We take the claim regarding insolvency delay as an opportunity to highlight the underlying economics of the ELA program and discuss its legitimacy in the current situation. We start by characterizing the complex interrelationship of the European Union, the ECB and the Greek banks through the lens of financial economics, with a particular focus on the political economy of a monetary union with incomplete fiscal union (or fiscal consolidation). Combining these two issues, we examine the decision of the ECB to continue the provision of ELA to Greek banks. Our conclusions, drawn from the analysis, do not support the claim that the ECB’s actions are consistent with a delayed filing for insolvency.
Recent developments in medical education have created increasing challenges for medical teachers which is why the majority of German medical schools already offer educational and instructional skills trainings for their teaching staff. However, to date no framework for educational core competencies for medical teachers exists that might serve as guidance for the qualification of the teaching faculty. Against the background of the discussion about competency based medical education and based upon the international literature, the GMA Committee for Faculty and Organizational Development in Teaching developed a model of core teaching competencies for medical teachers. This framework is designed not only to provide guidance with regard to individual qualification profiles but also to support further advancement of the content, training formats and evaluation of faculty development initiatives and thus, to establish uniform quality criteria for such initiatives in German-speaking medical schools. The model comprises a framework of six competency fields, subdivided into competency components and learning objectives. Additional examples of their use in medical teaching scenarios illustrate and clarify each specific teaching competency. The model has been designed for routine application in medical schools and is thought to be complemented consecutively by additional competencies for teachers with special duties and responsibilities in a future step.
Die Entwicklungen in der Medizinischen Ausbildung der letzten Jahre konfrontieren Lehrende zunehmend mit neuen didaktischen Herausforderungen. An zahlreichen Standorten im deutschsprachigen Raum werden bereits Qualifizierungsangebote für Lehrende angeboten, jedoch fehlt bisher ein Orientierungsrahmen für medizindidaktische Kompetenzen, der ein Qualifikationsprofil für Lehrende darstellt.
Vor dem Hintergrund der Diskussion um die Kompetenzorientierung des Medizinstudiums und auf Grundlage aktueller internationaler Literatur wurde durch den GMA Ausschuss für Personal- und Organisationsentwicklung in der Lehre ein Kernkompetenzmodell für Lehrende in der Medizin entwickelt. Das Modell soll nicht nur den Lehrenden Orientierung zu ihrem Qualifikationsprofil geben, sondern auch die inhaltliche Ausrichtung hochschuldidaktischer (Aus-) Weiter- und Fortbildungen sowie die Evaluation von Fakultätsentwicklungsprozessen erleichtern und nicht zuletzt einheitliche Kriterien für die Beurteilung der Lehrqualifikation in deutschsprachigen Raum definieren.
Das Modell besteht aus sechs Kompetenzfeldern, für die jeweils Teilkompetenzen definiert und Lernziele beschrieben wurden. Anwendungsbeispiele sollen die jeweiligen Kompetenzen verdeutlichen.
Das Modell ist für die praktische Anwendung konzipiert und soll in einem nächsten Schritt durch spezifische Kompetenzen für Lehrende mit besonderen Aufgaben ergänzt werden.
Die Südostasienwissenschaften der Goethe-Universität Frankfurt a. M. luden in Zusammenarbeit mit der Südostasien Informationsstelle im Asienhaus Köln und dem Arbeitskreis Südostasien der Deutschen Gesellschaft für Asienkunde den 19. und 20. Juni 2015 zu der Konferenz „Die Schattenseiten des Wirtschaftswachstums in Südostasien“ nach Frankfurt ein...
We present a nucleosynthesis sensitivity study for the γ-process in a Supernova type II model within the NuGrid research platform. The simulations aimed at identifying the relevant local production and destruction rates for the p-nuclei of molybdenum and at determining the sensitivity of the final abundances to these rates. We show that local destruction rates strongly determine the abundance of 92Mo and 94Mo, and quantify the impact.
The brain vascular system is composed of specialized endothelial cells, which regulate the movement of ions, molecules and cells from the blood lumen to the central nervous system (CNS). Endothelial cells in the brain form the blood-brain barrier (BBB) that is essential to maintain the brain homeostasis and protect the CNS from pathogens and toxins for a proper neurological function. Endothelium together with other cellular components such as pericytes, astrocytes and the basement membrane, forms the neurovascular unit (NVU), the structural unit of the BBB. Breakdown of the BBB occurs in various neurological disorders, leading to edema and neuronal damage. Therapeutic strategies focusing on factors that regulate the permeability of the BBB may help to improve neurological disorders and facilitate drug delivery to the brain.
Angiopoietins (Ang) are potential candidates for therapeutic targeting the BBB due to their role in regulating the vascular permeability in periphery. They are key growth factors that control angiogenesis and vessel maturation. Ang-1 and Ang-2 possess similar binding affinities to the Tie2 receptor tyrosine kinase, which is almost exclusively expressed on endothelial cells. Ang-1 is expressed in smooth muscle cells and pericytes, and binds in a paracrine manner to Tie2. This results in phosphorylation of the receptor and induction of downstream signaling pathways leading to vessel maturation via pericyte recruitment and blood vessel stabilization. Ang-2, on the other hand, is stored in Weibel Palade bodies in endothelial cells and is released upon inflammatory or angiogenic stimuli. Therefore, in mature, stabilized blood vessels, Ang-2 expression is low. Increased level of Ang-2 is only observed during development or in pathology such as ischemia, cancer and inflammation. When Ang-2 is released, it acts in an autocrine manner and interferes with Tie2 phosphorylation in a context-dependent way. Antagonizing the receptor results in de-stabilization of the vessels, often accompanied by reduced numbers of pericytes leading to myeloid cell infiltration. In conjunction with the vascular endothelial growth factor (VEGF), Ang-2 contributes to blood vessel sprouting, whereupon in absence of VEGF it promotes vessel regression. ...
ISIS' politics of sex
(2015)
Part III of our series on ISIS : "Blogforum 'Kalifat des Terrors: Interdisziplinäre Perspektiven auf den Islamischen Staat#".
In the late summer of 2014, the international community watched helplessly as ISIS unleashed widespread serious human rights violations against civilians across Syria and Iraq. Of note, were the different forms of sexual abuse initially directed against women from the Yazidi community of Sinjar, but rapidly expanded to women from many regions and backgrounds. Far from being attributable to isolated incidents or to the behavior of a few individuals, the abuses were, and continue to be, part of the “sexual politics” implemented by ISIS in all “wilayas” (regions) under its control and endorsed by its military hierarchy. The abuses represent a clear example of the use of rape as a weapon of war, based on the “theology of sexuality” in a war zone. Fatwas and theological arguments inspired by the medieval practices of historical Muslim armies provide the justification for the policies and practices.
This paper studies a two-country production economy with complete and frictionless financial markets and international trade of final goods in which competition in R&D leads to endogenous new firm creation and economic growth. Current monopolists ("incumbents") and potential new firms ("entrants") compete in developing patents domestically. I find that this induces negative spillover in consumption, i.e. home country's consumption decreases in response to positive productivity shocks in the foreign country. Second, there is positive spillover in R&D expenditures, i.e. home country's R&D expenditures increase in response to positive foreign productivity shocks, which is consistent with empirical evidence on international technology diffusion. Furthermore, the stylized fact in international macroeconomics that the cross-country correlation of consumption growth is significantly lower than the one of output growth is explained by the model. Fourth, net exports are negatively correlated with output as in the data. Fifth, the model matches the high comovement of the risk-free rates and stock returns across countries. Finally, the model produces a positive value premium.
The Liikanen Group proposes contingent convertible (CoCo) bonds as instruments 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. The growing number of banks issuing CoCo bonds leads to a rising awareness of these hybrid securities among life insurers as they are increasingly looking for higher?yielding investments into bond?like asset classes during the current low interest rate period. Our contribution provides an insight for life insurance companies to understand the effects of holding CoCo bonds as implied by the Solvency II standards that will become effective by 2016.
Kapitalanleger wie Versicherungsnehmer werden oft konfrontiert mit komplexen Produkten und nicht durchschaubaren Unternehmensstrukturen der Anbieter. Gleichzeitig stellt die mögliche Nichterfüllung ihrer Ansprüche häufig ein existenzielles Risiko dar. Deshalb ist es Ziel der Finanzregulierung, Rahmenbedingungen im Finanzdienstleistungsbereich zu schaffen, die wirtschaftliche Abläufe gewährleisten und gleichzeitig den Konsumenten schützen. Dem Nutzen der Regulierung stehen aber auch Risiken gegenüber, die im diesem Artikel am Beispiel der Versicherungsregulierung dargelegt werden.
Investors and insurance policyholders are often confronted with complex products and providers' opaque organisational structures. At the same time, the possibility that their claims will not be honoured often poses an existential risk. Financial regulation therefore aims at putting in place a financial services framework that will safeguard market processes whilst also protecting consumers. However, benefits of regulation are accompanied by certain risks, as can be exemplified with the case of insurance regulation.
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.
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.
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.
Do economic fluctuations change the labour market attachment of mothers? How is the reentry process into the labour market after childbirth dependent on the country context women live in? Are these processes affected by occupational status? We address these questions using data from the National Longitudinal Study of Youth and the German Life History Study. Event history analyses demonstrate that in Germany and the United States, mothers who work in high occupational status jobs before birth return more quickly to their jobs and are less likely to interrupt their careers. During legally protected leave periods, mothers return at higher rates, exemplifying that family leaves strengthen mothers’ labour force attachment. Economic fluctuations mediate this latter finding, with different consequences in each country. In the United States, mothers tend to return to their jobs faster when unemployment is high. In Germany, mothers on family leave tend to return to their jobs later when unemployment is high. The cross-national comparison shows how similar market forces create distinct responses in balancing work and care.
The prefix cyber, prepended onto terms like war, peace, security, and so on, results in interesting word combinations which we construct with our spoken language. Many scholars, from political to social science, have discussed the terms and the semantics of it in order to understand the problem and to create some scientific value out of it. But this article will not be another endless discussion on whether cyberfoo exists somewhere in any computer network at the moment or not...
Objective: To investigate the accuracy, efficiency and radiation dose of a novel laser navigation system (LNS) compared to those of free-handed punctures on computed tomography (CT).
Materials and methods: Sixty punctures were performed using a phantom body to compare accuracy, timely effort, and radiation dose of the conventional free-handed procedure to those of the LNS-guided method. An additional 20 LNS-guided interventions were performed on another phantom to confirm accuracy. Ten patients subsequently underwent LNS-guided punctures.
Results: The phantom 1-LNS group showed a target point accuracy of 4.0 ± 2.7 mm (freehand, 6.3 ± 3.6 mm; p = 0.008), entrance point accuracy of 0.8 ± 0.6 mm (freehand, 6.1 ± 4.7 mm), needle angulation accuracy of 1.3 ± 0.9° (freehand, 3.4 ± 3.1°; p < 0.001), intervention time of 7.03 ± 5.18 minutes (freehand, 8.38 ± 4.09 minutes; p = 0.006), and 4.2 ± 3.6 CT images (freehand, 7.9 ± 5.1; p < 0.001). These results show significant improvement in 60 punctures compared to freehand. The phantom 2-LNS group showed a target point accuracy of 3.6 ± 2.5 mm, entrance point accuracy of 1.4 ± 2.0 mm, needle angulation accuracy of 1.0 ± 1.2°, intervention time of 1.44 ± 0.22 minutes, and 3.4 ± 1.7 CT images. The LNS group achieved target point accuracy of 5.0 ± 1.2 mm, entrance point accuracy of 2.0 ± 1.5 mm, needle angulation accuracy of 1.5 ± 0.3°, intervention time of 12.08 ± 3.07 minutes, and used 5.7 ± 1.6 CT-images for the first experience with patients.
Conclusion: Laser navigation system improved accuracy, duration of intervention, and radiation dose of CT-guided interventions.
Der Bundesgerichtshof hat mit Urteil vom 28. Januar 2015 entschieden, dass Kinder, die durch künstliche Befruchtung im Wege einer Samenspende gezeugt worden sind, gegen Reproduktionsmediziner und -kliniken einen Anspruch auf Auskunft über die Identität des Samenspenders haben können. Die Geltendmachung des Auskunftsanspruchs setzte kein bestimmtes Mindestalter der „Spenderkinder“ voraus. Der nachfolgende Beitrag analysiert die Konstruktion dieses Anspruchs vor dem Hintergrund eines durch neue Reproduktionstechnologien und gewandelte gesellschaftliche Vorstellungen veränderten Abstammungsrechts. Nach Methodenkritik und Rekonstruktion aus einer gesellschaftlich-institutionellen Perspektive eröffnen sich weitere Aussichten auf zukünftige Formen von Vaterschaft und ein entsprechend zu verwirklichendes Recht auf Kenntnis der eigenen Abstammung.
TO DERIVE OPTIMAL ORDER EXECUTION STRATEGIES THAT STRIVE TO MINIMIZE TRANSACTION COSTS, INVESTORS AS WELL AS AUTOMATED TRADING ENGINES MUST BE ABLE TO ANTICIPATE CHANGES IN THE AVAILABLE MARKET LIQUIDITY. BASED ON AN EVENT STUDY ON THE LIQUIDITY IMPACT OF AD-HOC DISCLOSURES, WE PROPOSE A NOVEL IT ARTIFACT THAT ALLOWS AUTOMATED TRADING ENGINES TO APPROPRIATELY REACT TO NEWS-RELATED LIQUIDITY SHOCKS. FURTHERMORE, WE PROVIDE A SIMULATIONBASED EVALUATION THAT SHOWS ITS ECONOMIC RELEVANCE.
Based on a cognitive notion of neo-additive capacities reflecting likelihood insensitivity with respect to survival chances, we construct a Choquet Bayesian learning model over the life-cycle that generates a motivational notion of neo-additive survival beliefs expressing ambiguity attitudes. We embed these neo-additive survival beliefs as decision weights in a Choquet expected utility life-cycle consumption model and calibrate it with data on subjective survival beliefs from the Health and Retirement Study. Our quantitative analysis shows that agents with calibrated neo-additive survival beliefs (i) save less than originally planned, (ii) exhibit undersaving at younger ages, and (iii) hold larger amounts of assets in old age than their rational expectations counterparts who correctly assess their survival chances. Our neo-additive life-cycle model can therefore simultaneously accommodate three important empirical findings on household saving behavior.