Unleashing the potential of a heterogeneous society Migrant-run companies as drivers of inclusive growth. Bertelsmann Stiftung Growth for Germany 2015/02 Inclusive Growth for Germany 2015/02

As compared with many of its European partners, Germany is currently in a good economic position. But looking solely at economic growth is deceptive. Growth in recent years has not been inclusive, as participation opportunities have become increasingly unequally distributed. This puts social cohesion at risk. But what might policies that achieve both goals —realizing growth potential and expanding participation opportunities—look like? As a part of its “Strategies and Investments for Inclusive Growth” project, the Bertelsmann Stiftung develops and discusses concrete recommendations for an inclusive growth model. Using current research as a basis, this discussion paper discusses the degree to which the entrepreneurial activity of immigrants and people with a migrant background are today already serving to drive inclusive growth in Germany, and how potential of this kind can be identified. The conditions rendering it possible to engage in entrepre neurial activity in a country have a direct effect even beyond that country’s national economic performance. Who founds companies and who does not, and the degree of sustainability displayed by the companies founded, says much about how participation opportunities are distributed within a society. Are conditions such that groups that still lack full equality of opportunity within economic processes, such as women, young people, and people with an experience of immigration or a migrant background, are able as business people to become pace‑setters for a successful economy? Or is their potential overlooked and unused? What specific obstacles are in place

Bank Bailouts, International Linkages and Cooperation

Financial institutions are increasingly linked internationally. As a result, financial crisis and government intervention have stronger effects beyond borders. We provide a model of international contagion allowing for bank bailouts. While a social planner trades off tax distortions, liquidation losses and intra- and intercountry income inequality, in the noncooperative game between governments there are inefficiencies due to externalities, no burden sharing and free-riding. We show that, in absence of cooperation, stronger interbank linkages make government interests diverge, whereas cross-border asset holdings tend to align them. We analyze different forms of cooperation and their effects on global and national welfare.Portfolio choice, international transmission of shocks, monetary policy

Bank Bail-Outs, International Linkages and Cooperation

Financial institutions are increasingly linked internationally and engaged in cross-border operations. As a result, financial crises and potential bail-outs by governments have important international implications. Extending Allen and Gale (2000) we provide a model of international contagion allowing for bank bail-outs financed by distortionary taxes. In the sequential game between governments, there are inefficiencies due to spillovers, free-riding and limited burden-sharing. When countries are of equal size, an increase in cross-border deposit holdings improves, in general, the non-cooperative outcome. For efficient crisis managment, ex-ante fiscal burden sharing is essential as ex-post contracts between governments do not achieve the same global welfare.bail-out, contagion, financial crisis, international institutional arrangements

Bank Bailouts, International Linkages and Cooperation

Financial institutions are increasingly linked internationally. As a result, financial crisis and government intervention have stronger effects beyond borders. We provide a model of international contagion allowing for bank bailouts. While a social planner trades off tax distortions, liquidation losses and intra- and inter-country income inequality, in the non-cooperative game between governments there are inefficiencies due to externalities, no burden sharing and free-riding. We show that, in absence of cooperation, stronger interbank linkages make government interests diverge, whereas cross-border asset holdings tend to align them. We analyze different forms of cooperation and their effects on global and national welfare.bailout, contagion, financial crisis, international institutional arrangements

Influence of Immune Status on the Airborne Colonization of Piglets with Methicillin-Resistant Staphylococcus aureus (MRSA) Clonal Complex (CC) 398

Colonized vertebrates including humans and pigs are to date the main reservoirs of livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA). Currently, the mechanisms underlying colonization of pigs are not fully understood. We investigated the influence of piglet pre-immune status on airborne MRSA colonization. Three groups of MRSA-negative piglets were primed and exposed to airborne LA-MRSA (104 colony forming units (cfu)/m3) in an aerosol chamber for 24 h. One group was treated intramuscularly with dexamethasone (1 mg/kg body weight) to imitate weaning stress. The second group was exposed to bacterial endotoxin containing MRSA aerosol. Both conditions play a role in the development of multifactorial diseases and may promote MRSA colonization success. The third group served as control. The piglets' MRSA status was monitored for 21 days via swab samples. At necropsy, specific tissues and organs were analyzed. Blood was collected to examine specific immunological parameters. The duration of MRSA colonization was not extended in both treated groups compared to the control group, indicating the two immune-status influencing factors do not promote MRSA colonization. Blood sample analysis confirmed a mild dexamethasone-induced immune suppression and typical endotoxin-related changes in peripheral blood. Of note, the low-dose dexamethasone treatment showed a trend of increased MRSA clearance

Chirale Phasentransfer-Katalysatoren zur asymmetrischen Darstellung von a,b-Epoxycarbonylverbindungen

Die hier vorliegende Arbeit beschreibt die Synthesen neuartiger chiraler Phasentransfer-Katalysatoren auf Basis der Cinchona-Alkaloide Chinin und Chinidin und deren Anwendung zur Darstellung von a,b-Epoxycarbonylverbindungen. Die erhaltenen Ergebnisse bei der Epoxidierung von 1,4-Naphthochinonen, speziell Vitamin-K3, sind bislang die besten hinsichtlich der erzielten Enantioselektivitäten. Erste kinetische Studien lieferten Hinweise auf die reale Katalysatorstruktur in der Reaktionsmischung. Durch die entwickelten PTCs konnte auch eine asymmetrische Induktion bei der Darzens-Reaktion zu 2,3-Epoxyzimtsäureamiden bewirkt werden. Dies stellt die erste Anwendung von Cinchona-Alkaloid abgeleiteten PTCs zum asymmetrischen Aufbau dieser Verbindungsklasse dar. Des Weiteren konnte erstmalig eine Methodik zur Epoxidierung von elektronenarmen Enonen unter Weitz-Scheffer-Bedingungen in Mikroemulsionen etabliert werden. Mit dieser Methodik wurden beachtliche Reaktionsbeschleunigungen bei sehr guten Ausbeuten realisiert

Hinder and standardize. On prevention as a mode of optimizing the nutrition of children

Die Autorin untersucht solche Praktiken aus der Perspektive der historischen Anthropologie bzw. einer kulturwissenschaftlich ausgerichteten Erziehungswissenschaft am Beispiel der Ernährung von Kindern, die zunehmend im Rahmen von Imperativen und Strategien der Optimierung gedacht wird. Dabei wird die Ernährung einer präventiven Logik unterstellt, womit die Lebensführung und eine darauf bezogene Erziehung zunehmend von Risikovermeidungsstrategien bestimmt werden. (DIPF/Orig.

Struktur-Funktionsanalyse der PEX3-PEX19 Interaktion: ein verbessertes Verständnis der peroxisomalen Membranbiogenese

Peroxisomes are eukaryotic cellular organelles involved in metabolic functions such as the ß-oxidation of very long chain fatty acids, the synthesis of plasmalogens and the degradation of H2O2. The so-called peroxins (PEX) are proteins that mediate peroxisomal biogenesis. 14 human peroxins are known to date, of which PEX3, PEX16 and PEX19 belong to the early peroxins responsible for the formation of the peroxisomal membrane. Cells lacking one of these three peroxins do not exhibit any detectable peroxisomal membrane structures. All three variants deltaPEX3-, deltaPEX16- or deltaPEX19-cells) can be complemented upon introduction of the missing gene and are then able to generate peroxisomes de novo. PEX3 and PEX19 are engaged in the import of peroxisomal membrane proteins (PMPs). PEX19 serves as a cytosolic receptor for newly synthesized PMPs by binding to the membrane peroxisomal targeting sequence. In addition, PEX19 functions as a chaperone as it keeps PMPs in an import-competent form by shielding their hydrophobic regions from the aqueous environment. Cargo-loaded PEX19 is directed to the peroxisomal membrane, where its N-terminus interacts with the cytosolic domain of PEX3. PEX3 is anchored within the membrane via its N-terminus, which also serves as the peroxisomal targeting signal as well as the PEX16-binding site. In this work, the crystal structure of PEX3 in complex with a PEX19-derived peptide fragment was determined. Furthermore, the influence of specific mutations within surface exposed regions of PEX3 on PEX19-binding and during peroxisomal biogenesis was elucidated in detail using in vitro and in vivo experiments. The crystal structure of the cytosolic part of PEX3 (sPEX3: aar 41-373, C235S) in complex with a PEX19-derived peptide (PEX19Pep: aar 14-33) provides first insights into the details of the PEX3-PEX19 complex formation at the peroxisome membrane. sPEX3 exhibits an all alpha-helical folding that lacks homology to previously known structures. Ten alpha-helices and one 310-helix build a compact bundle with the N-terminal helix projecting towards the peroxisomal membrane in vivo. PEX19Pep forms an amphipathic alpha-helix, which is engaged by sPEX3 with high affinity (Kd = 330 nM) calculated with isothermal titration calorimety. The PEX19-binding groove lies at the membrane-distal end and is composed of three distinct regions within sPEX3. The PEX3-PEX19 interaction is mainly mediated by hydrophobic interactions including several strictly conserved residues in both proteins. A thermal denaturation assay demonstrated that sPEX3 is stabilized upon PEX19Pep-binding, shifting the melting point of sPEX3 about 10 °C towards higher temperatures. Three conserved regions were identified on the surface of sPEX3. In addition to the PEX19-binding groove, a hydrophobic groove on the base of sPEX3 and a cluster of acidic residues on the opposite side could be defined. Several amino acids within these conserved regions were mutated and analyzed in order to examine their function in PEX19-binding and in peroxisome biogenesis. Two mutations in the PEX19-binding groove (L93N, K324A) lower the affinity for PEX19 but localize correctly to peroxisomes in vivo. The ability to complement deltaPEX3-cells is reduced for the mutant PEX3-myc K324A compared to native PEX3-myc, whereas PEX3-myc L93N has completely lost this characteristic feature. Furthermore, a functional PEX3-PEX19 complex is essential for de novo formation of preperoxisomal membranes. The mutation E266A, which is located in the acidic cluster, does not interfere with PEX19-binding. In addition, both mutations in the acidic cluster are properly targeted to peroxisomes and show either no (E266A) or only a small (D275A) effect on the complementation ability of deltaPEX3-cells. The mutations in the hydrophobic groove (I140N, L165N and the double mutant I140N*L165N) do not influence PEX19-binding or the exact peroxisomal localization of PEX3-myc. However, the ability to complement deltaPEX3-cells is reduced for PEX3-myc L165N and the double mutant compared to native PEX3-myc. As the mutation at position 165 is impaired neither in the formation of preperoxisomes in de novo biogenesis nor in the affinity to PEX19, the hydrophobic groove could conceivably mediate the insertion of PMPs into the lipid bilayer. This implies a direct participation of PEX3 during PMP insertion. The findings implicate a dual function of the PEX3-PEX19 complex in peroxisome biogenesis. Further experiments are required to clarify the exact function of PEX3 and the detailed mechanism of PMP insertion.Peroxisomen sind eukaryotische Zellorganellen, die wichtige metabolische Funktionen bei der ß-Oxidation langkettiger Fettsäuren, bei der Synthese von Plasmologenen sowie beim Abbau von H2O2 ausüben. Die an der peroxisomalen Biogenese beteiligten Proteine werden Peroxine (PEX) genannt. Von den 14 bisher bekannten humanen Peroxinen, zählen PEX3, PEX16 und PEX19 zu den frühen Peroxinen, die bei der Entstehung der peroxisomalen Membran benötigt werden. Zellen, denen eines dieser drei Peroxine fehlt, weisen keine detektierbaren peroxisomalen Membranstrukturen auf. Diese PEX3-, PEX16- oder PEX19-defizienten Zellen (deltaPEX3-, deltaPEX16- oder deltaPEX19-Zellen) können durch Transfektion des entsprechenden Gens wieder komplementiert werden und sind danach in der Lage, de novo Peroxisomen zu bilden. PEX3 und PEX19 sind am Import peroxisomaler Membranproteine (PMP) beteiligt. PEX19 dient hierbei als cytosolischer Rezeptor für neu synthetisierte PMPs, indem es die peroxisomale Membranzielsequenz bindet. Zusätzlich wird PEX19 die Rolle eines Chaperons zugeordnet, da es hydrophobe Bereiche des Membranproteins bindet und sie auf diese Weise in einer Import-kompetenten Form konserviert. Beladenes PEX19 wird an die peroxisomale Membran dirigiert, indem der N-Terminus von PEX19 mit der cytosolischen Domäne von PEX3 interagiert. PEX3 ist in der peroxisomalen Membran mittels seines N-Terminus verankert, der zugleich die peroxisomale Zielsequenz als auch die Bindungsstelle für PEX16 darstellt. In dieser Arbeit wurde die Struktur von PEX3 in Verbindung mit einem PEX19-Peptid mittels Röntgenstreuung gelöst. Des Weiteren wurde der Einfluss spezifischer Mutationen in konservierten Oberflächen-bereichen von PEX3 auf die Binding mit PEX19 in vitro sowie auf eine mögliche Beteiligung während der peroxisomalen Biogenese in vivo untersucht. Die hier beschriebene Kristallstruktur des zytosolischen Teils von PEX3 (sPEX3: aar 41-373, C235S) im Komplex mit einem PEX19-Peptid (PEX19Pep: aar 14-33) ermöglicht einen ersten präzisen Einblick in die PEX3-PEX19-Bindung an der peroxisomalen Membran. sPEX3 weist eine rein alpha-helikale Faltung auf, die keinerlei Homologien zu bisher bekannten Strukturen besitzt. Zehn alpha-Helices und eine 310-Helix lagern sich zu einem kompakten Bündel zusammen, aus dem eine lange N-terminale Helix herausragt. Ihre Verlängerung würde in vivo die Verbindung zur peroxisomalen Membran herstellen. PEX19Pep bildet eine amphipatische Helix, die von sPEX3 mit hoher Affinität gebunden wird (Kd = 330 nM). Dies konnte mit Hilfe von kalorimetrischen Messungen ermittelt werden. Die PEX19-Bindetasche liegt auf der Membran-abgewandten Seite und wird von drei verschiedenen Bereichen innerhalb von PEX3 gebildet. PEX19Pep interagiert fast ausschließlich über hydrophobe Wechselwirkungen mit sPEX3. Mittels eines thermischen Denaturierungsexperiments konnte gezeigt werden, dass PEX3 durch die Bindung von PEX19 stabilisiert wird, da der Schmelzpunkt des sPEX3+PEX19Pep-Komplexes um 10 °C gegenüber freiem sPEX3 erhöht ist. sPEX3 weist mehrere hoch konservierte Bereiche auf, von denen drei auf der Oberfläche liegende Regionen darstellen: neben der konservierten PEX19-Bindetasche konnte eine konservierte hydrophobe Furche und ein konservierter Bereich mit einer Gruppe saurer Aminosäurereste identifiziert werden. Durch Mutation ausgewählter Aminosäuren innerhalb dieser Regionen wurde deren Beteiligung in Bezug auf die Bindung zu PEX19 sowie ihre Rolle während der peroxisomalen Biogenese analysiert. Zwei Mutationen in der PEX19-Bindetasche (L93N, K324A) sind in ihrer Affinität zu PEX19 beeinträchtigt. Dennoch werden beide PEX3-Mutanten in vivo zu Peroxisomen gebracht. Im Vergleich zu nativem PEX3-myc ist die Fähigkeit von PEX3-myc K324A deltaPEX3T-Zellen zu komplementieren, reduziert, während PEX3-myc L93N diese Eigenschaft sogar komplett verloren hat. Des Weiteren konnte gezeigt werden, dass ein funktionsfähiger PEX3-PEX19-Komplex essentiell für die de novo Entstehung präperoxisomaler Membranen ist. Von den Mutationen im sauren Cluster (E266A, D275A) beeinträchtigt die Mutation E266A nicht die Affinität zu PEX19. Zusätzlich werden beide PEX3-myc Mutanten in Peroxisomen lokalisiert und zeigen keine (E266A) oder nur eine geringe (D275A) Auswirkung auf die Komplementationsfähigkeit von deltaPEX3T-Zellen. Die Mutationen in der hydrophoben Tasche (I140N, L165N und die Doppelmutante I140N*L165N) wirken sich weder auf eine mögliche zusätzliche PEX19-Bindung noch auf die korrekte peroxisomale Lokalisation von PEX3 aus. Allerdings weisen PEX3-myc L165N und die Doppelmutante eine verringerte Komplementationsfähigkeit von deltaPEX3T-Zellen auf. Da die Mutation an Position 165 keinen Einfluss auf die Bildung von Präperoxisomen während der de novo Biogenese hat und ebenso wenig die Affinität zu PEX19 beeinflusst, könnte die hydrophobe Furche die Insertion von PMPs in die peroxisomale Membran vermitteln. Da dies der erste Hinweis auf eine direkte Beteiligung von PEX3 während der Membraninsertion von PMPs ist, bedarf es weiterführender Experimente, um diese Ergebnisse zu untermauern und die genaue Aufgabe von PEX3 sowie den Mechanismus des PMP Imports zu klären

Detectability of Artificial Ocean Alkalinization and Stratospheric Aerosol Injection in MPI‐ESM

To monitor the success of carbon dioxide removal (CDR) or solar radiation management (SRM) that offset anthropogenic climate change, the forced response to any external forcing is required to be detectable against internal variability. Thus far, only the detectability of SRM has been examined using both a stationary and nonstationary detection and attribution method. Here, the spatiotemporal detectability of the forced response to artificial ocean alkalinization (AOA) and stratospheric aerosol injection (SAI) as exemplary methods for CDR and SRM, respectively, is compared in Max Planck Institute Earth System Model (MPI-ESM) experiments using regularized optimal fingerprinting and single-model estimates of internal variability, while working under a stationary or nonstationary null hypothesis. Although both experiments are forced by emissions according to the Representative Concentration Pathway 8.5 (RCP8.5) and target the climate of the RCP4.5 scenario using AOA or SAI, detection timescales reflect the fundamentally different forcing agents. Moreover, detectability timescales are sensitive to the choice of null hypothesis. Globally, changes in the CO2 system in seawater are detected earlier than the response in temperature to AOA but later in the case of SAI. Locally, the detection time scales depend on the physical, chemical, and radiative impacts of CDR and SRM forcing on the climate system, as well as patterns of internal variability, which is highlighted for oceanic heat and carbon storage

Anticoagulation for radiation-induced neurotoxicity revisited

No effective treatment for delayed radiation-induced neurotoxicity has been established. Its natural course is highly variable, but spontaneous recovery has been well documented. Here we report our experience with therapeutic anticoagulation in patients with cerebral lesions (n=3), cranial nerve lesions (n=1) or myelopathy (n=4) attributed to irradiation. Two of three patients with cerebral lesions and the patient with cranial nerve lesions showed a minor improvement of clinical symptoms. In contrast, none of the patients with radiation myelopathy improved. No patient suffered hemorrhage or other adverse effects of anticoagulation. Overall, anticoagulation therapy demonstrates only modest activity for delayed radiation-induced neurotoxicity in this small case serie