The Oxidation State of Iron in Silicate Minerals from the Matrices of CO Carbonaceous Chondrites

No abstract available

On the regulation, function, and localization of the DNA-dependent ATPase PICH

The putative chromatin remodeling enzyme Plk1-interacting checkpoint helicase (PICH) was discovered as an interaction partner and substrate of the mitotic kinase Plk1. During mitosis PICH associates with centromeres and kinetochores and, most interestingly, constitutes a robust marker for ultrafine DNA bridges (UFBs) that connect separating chromatids in anaphase cells. The precise roles of PICH remain to be clarified. Here, we have used antibody microinjection and siRNA-rescue experiments to study PICH function and localization during M phase progression, with particular emphasis on the role of the predicted ATPase domain and the regulation of PICH localization by Plk1. We show that interference with PICH function results in chromatin bridge formation and micronucleation and that ATPase activity is critical for PICH function. Interestingly, an intact ATPase domain of PICH is required for prevention of chromatin bridge formation but not for UFB resolution, and quantitative analyses of UFB and chromatin bridge frequencies suggest that these structures are of different etiologies. We also show that the ATPase activity of PICH is required for temporal and spatial control of PICH localization to chromatin and that Plk1 likely controls PICH localization through phosphorylation of proteins distinct from PICH itself. This work strengthens the view that PICH is an important, Plk1-regulated enzyme, whose ATPase activity is essential for maintenance of genome integrity. Although not required for the spindle assembly checkpoint, PICH is clearly important for faithful chromosome segregatio

Global Value Chains in Africa

This paper provides evidence on the extent of Global Value Chain (GVC) participation by Africa as a region and for individual African countries. We find that Africa as a whole is heavily involved in GVCs, being more engaged in GVCs than many developing country regions as well as developed countries such as the USA. This overall finding hides the fact that much of Africa's participation in GVCs is in upstream production, with African firms providing primary inputs to firms in countries further down the value chain. The possibility of upgrading within GVCs in Africa is likely to be limited therefore, something which the current analysis suggests. Despite this, we observe a great deal of heterogeneity in terms of GVC participation and upgrading across African countries, with a number of African countries participating in GVCs to a relatively large extent. (authors' abstract

Efficient CRISPR-rAAV engineering of endogenous genes to study protein function by allele-specific RNAi.

Gene knockout strategies, RNAi and rescue experiments are all employed to study mammalian gene function. However, the disadvantages of these approaches include: loss of function adaptation, reduced viability and gene overexpression that rarely matches endogenous levels. Here, we developed an endogenous gene knockdown/rescue strategy that combines RNAi selectivity with a highly efficient CRISPR directed recombinant Adeno-Associated Virus (rAAV) mediated gene targeting approach to introduce allele-specific mutations plus an allele-selective siRNA Sensitive (siSN) site that allows for studying gene mutations while maintaining endogenous expression and regulation of the gene of interest. CRISPR/Cas9 plus rAAV targeted gene-replacement and introduction of allele-specific RNAi sensitivity mutations in the CDK2 and CDK1 genes resulted in a >85% site-specific recombination of Neo-resistant clones versus ∼8% for rAAV alone. RNAi knockdown of wild type (WT) Cdk2 with siWT in heterozygotic knockin cells resulted in the mutant Cdk2 phenotype cell cycle arrest, whereas allele specific knockdown of mutant CDK2 with siSN resulted in a wild type phenotype. Together, these observations demonstrate the ability of CRISPR plus rAAV to efficiently recombine a genomic locus and tag it with a selective siRNA sequence that allows for allele-selective phenotypic assays of the gene of interest while it remains expressed and regulated under endogenous control mechanisms

Soft X-ray spectromicroscopy using ptychography with randomly phased illumination

Ptychography is a form of scanning diffractive imaging that can successfully retrieve the modulus and phase of both the sample transmission function and the illuminating probe. An experimental difficulty commonly encountered in diffractive imaging is the large dynamic range of the diffraction data. Here we report a novel ptychographic experiment using a randomly phased X-ray probe to considerably reduce the dynamic range of the recorded diffraction patterns. Images can be reconstructed reliably and robustly from this setup, even when scatter from the specimen is weak. A series of ptychographic reconstructions at X-ray energies around the L absorption edge of iron demonstrates the advantages of this method for soft X-ray spectromicroscopy, which can readily provide chemical sensitivity without the need for optical refocusing. In particular, the phase signal is in perfect registration with the modulus signal and provides complementary information that can be more sensitive to changes in the local chemical environment

Diversification and economic development

Diese Arbeit analysiert den Zusammenhang zwischen dem Spezialisierungsgrad einer Ökonomie und dem Level des Pro-Kopf-Einkommens, und prüft insbesondere die Hypothese eines U-förmigen Zusammenhanges zwischen diesen Größen. In der betreffenden Literatur werden theoretische Argumente und politische Empfehlungen sowohl für mehr Spezialisierung als auch für mehr Diversifizierung vorgebracht. Neuere empirische Studien zeigen, dass beide Kräfte relevant sind, aber in unterschiedlichen Bereichen des Pro-Kopf-Einkommens eines Landes. Niedrigeinkommensländer diversifizieren ihre ökonomische Struktur mit steigendem Pro-Kopf-Einkommen bis zu einem gewissen ökonomischen Niveau, bei dem Re-Spezialisierung einsetzt, wodurch eine U-Kurve entsteht. Diese Form wurde empirisch sowohl für die Produktionsstruktur als auch für die Exportstruktur bestätigt, obwohl einige Studien die verwendeten Methoden kritisieren. Die ökonometrische Analyse in dieser Arbeit zeigt, dass die vermutete U Kurve nicht robust ist, da sie sowohl von dem verwendeten Datensatz sowie in der Messmethode abhängt. Sogar in jenen Fällen, in denen eine signifikante U-Kurve beobachtet werden kann, wird diese Kurve eher von länderspezifischen Charakteristika als von einer Variation innerhalb der jeweiligen Länder geprägt. Obwohl gezeigt werden kann, dass Niedrigeinkommensländer ihre Produktions- und Exportstruktur mit steigendem Pro-Kopf-Einkommen diversifizieren, können keine robusten Schlussfolgerungen bezüglich eines Re-Spezialisierungtrends bei Hocheinkommensländern getroffen werden. Das Kontrollieren für den Einfluss von anderen Determinanten des Spezialisierungsgrades zeigt, dass andere Faktoren als das Pro-Kopf-Einkommen die Variation innerhalb von Ländern vollständig beschreiben. Folglich beschreibt die vorgeschlagene U-Kurve nicht den „Entwicklungspfad“ eines durchschnittlichen Landes.This study analyses the relationship between economic specialization and the level of income per capita and, in particular, tests the hypothesis of a U-curve between the two. In the respective literature, economic arguments and political advice are presented in favour of specialization as well as diversification. Recent empirical studies propose that both forces are relevant, albeit at different levels of income per capita. Low-income countries diversify their production with rising income per capita until they reach a certain level of economic development, at which point specialization sets in, thus resulting in a U-curve. This pattern has been confirmed for the production structure as well as that for exports, but some studies criticize the measures and methodology used in this context. The econometric analysis in this study shows that the conjectured U-curve is not robust, as it depends on the dataset used and specialization measure applied. Even in cases where a significant U-curve is observed, it is driven by country-specific fixed effects rather than within-country variation. While it can be shown that low-income countries diversify their production and export structure as income per capita rises, no robust conclusions can be drawn concerning a trend towards re-specialization for high-income countries. Controlling for other determinants reveals that the within-country variation is rather determined by factors other than income per capita. Accordingly, the proposed U-curve does not represent the “development path” of an average country

Hair concentrations of anti-malarials in returned travellers-the HAIR study: Proof of principle analysis

Background: Hair analysis to identify substance use is an established methodology. This could also be a method to monitor adherence to antimalarial drugs. We aimed to establish a methodology to determine hair concentrations of atovaquone, proguanil and mefloquine in travellers using chemoprophylaxis. Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous analysis of the antimalarial drugs -atovaquone (ATQ), proguanil (PRO) and mefloquine (MQ), in human hair. The hair samples from five volunteers were used for this proof-of-concept analysis. Three volunteers were taking daily atovaquone/proguanil (ATQ/PRO) chemoprophylaxis and two volunteers were using weekly mefloquine (MQ) chemoprophylaxis. Results: With this proof-of-principle analysis, we could show that ATQ/PRO and MQ are integrated into the hair matrix. Chemoprophylaxis could be quantified with the established method. In hair segments, maximal concentrations of 3.0 ng/mL/20 mg hair proguanil, 1.3 ng/mL/20 mg hair atovaquone and 78.3 ng/mL/20 mg hair mefloquine were measured. Moreover, malaria drug concentration changes correlated with the time interval since finishing the chemoprophylaxis regimen. Conclusions: The validated method was used successfully for the analysis of antimalarial-drug positive hair samples containing atovaquone, proguanil or mefloquine. This research shows that hair can be used for adherence monitoring of chemoprophylaxis and paves the way for larger studies and optimized procedures

Pharmazeutische Betreuung von Patientinnen mit Mammakarzinom in einem sektorenübergreifenden Versorgungsmodell

Das in dieser Arbeit beschriebene Projekt verfolgte das Ziel, öffentliche Apotheken in das sektorenübergreifende Versorgungsmodell für Mammakarzinompatientinnen „mammaNetz“ einzubinden. Die projektbegleitende explorative Studie sollte Anhaltspunkte über Machbarkeit und Nutzen einer um Case Management-Aspekte erweiterten intensivierten Pharmazeutischen Betreuung liefern. Dazu wurde ein definiertes Patientenkollektiv hinsichtlich verschiedener Endpunkte untersucht. Der Studie lag ein multizentrisches, prospektives, zweiarmiges Studiendesign zugrunde. Der Start erfolgte mit der Rekrutierung erster Patientinnen im Januar 2005. Zuvor festgelegte Kriterien sahen einen Einschluss von Patientinnen mit Mammakarzinom unter adjuvanter Therapie vor. Insgesamt wurden 92 mammaNetz-Patientinnen, jeweils 46 für die Standard- und Intensivbetreuungsgruppe, sowie 33 öffentliche Apotheken für diese Studie rekrutiert. In Bezug auf die Patientenzufriedenheit mit der Information zur Krebsbehandlung, die mit der ersten deutschen Übersetzung des PS-CaTE-Fragebogens erhoben wurde, zeigten die Ergebnisse eine höchst signifikante Überlegenheit der Intensivbetreuungsgruppe in allen Skalen und Befragungszeitpunkten (p Die Ergebnisse dieser Studie können als Indiz für die Praxistauglichkeit und eine erfolgreiche Umsetzung der Pharmazeutischen Betreuung von Mammakarzinompatientinnen in der öffentlichen Apotheke gewertet werden. Die Einbindung von 64 öffentlichen Apotheken in das sektorenübergreifende Versorgungsmodell mammaNetz war zudem ein Schritt zur Beteiligung der Apothekerschaft an neuen Versorgungsformen. Die in dieser Studie ermittelten Ergebnisse deuten darauf hin, dass die gewählten Endpunkte geeignet sind, den Nutzen einer intensivierten Pharmazeutischen Betreuung aufzuzeigen. Eine Weiterführung des Projekts unter pharmakoökonomischen Gesichtspunkten und eine flächendeckende Implementierung derartiger Betreuungskonzepte könnten Ziele zukünftiger Projekte sein