Common agenda or Europe's agenda? International protection, human rights and migration from the Horn of Africa

This paper examines the relationship between international protection, human rights and migration in the context of EU Agenda on Migration which aims to ‘tackle migration upstream’ and reduce the number of arrivals to Europe from countries in the Horn of Africa (HoA) (Eritrea, Somalia, Ethiopia, South Sudan and Sudan). These initiatives are underpinned by assumptions about the factors driving migration from the region, including the idea that poverty rather than political oppression and human rights abuse is the principal cause. The paper draws on interview and survey data with 128 people originating from HoA countries and arriving in Europe between March 2011 and October 2016 to show that conflict, insecurity and human rights abuse in countries of origin and neighbouring countries drive decisions to move. This evidence challenges the premises underlying the European Agenda. Moreover, a lack of coherence between the EU’s ambitions to control irregular migration and the rights-violating States with which Europe seeks to engage threatens to create further political destabilisation which may ultimately increase, rather than decrease, outward migration from the region. Agreements between the EU and HoA should be re-centred to focus on compliance with international human rights standards rather than States’ willingness and to prevent irregular migration to Europe

Biological Effects of Antiprotons Are Antiprotons a Candidate for Cancer Therapy?

2009 Status Report of AD-4 Experimen

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

E-Cadherin loss associated with EMT promotes radioresistance in human tumor cells

BACKGROUND AND PURPOSE: Hypoxia is a hallmark of solid cancers and associated with metastases and treatment failure. During tumor progression epithelial cells often acquire mesenchymal features, a phenomenon known as epithelial-to-mesenchymal transition (EMT). Intratumoral hypoxia has been linked to EMT induction. We hypothesized that signals from the tumor microenvironment such as growth factors and tumor oxygenation collaborate to promote EMT and thereby contribute to radioresistance. MATERIALS AND METHODS: Gene expression changes under hypoxia were analyzed using microarray and validated by qRT-PCR. Conversion of epithelial phenotype upon hypoxic exposure, TGFβ addition or oncogene activation was investigated by Western blot and immunofluorescence. Cell survival following ionizing radiation was assayed using clonogenic survival. RESULTS: Upon hypoxia, TGFβ addition or EGFRvIII expression, MCF7, A549 and NMuMG epithelial cells acquired a spindle shape and lost cell–cell contacts. Expression of epithelial markers such as E-cadherin decreased, whereas mesenchymal markers such as vimentin and N-cadherin increased. Combining hypoxia with TGFβ or EGFRvIII expression, lead to more rapid and pronounced EMT-like phenotype. Interestingly, E-cadherin expression and the mesenchymal appearance were reversible upon reoxygenation. Mesenchymal conversion and E-cadherin loss were associated with radioresistance. CONCLUSIONS: Our findings describe a mechanism by which the tumor microenvironment may contribute to tumor radioresistance via E-cadherin loss and EMT

Small-Molecule Activation of p53 Blocks Hypoxia-Inducible Factor 1α and Vascular Endothelial Growth Factor Expression In Vivo and Leads to Tumor Cell Apoptosis in Normoxia and Hypoxia▿

The p53 tumor suppressor protein negatively regulates hypoxia-inducible factor 1α (HIF-1α). Here, we show that induction of p53 by the small-molecule RITA (reactivation of p53 and induction of tumor cell apoptosis) [2,5-bis(5-hydroxymethyl-2-thienyl) furan] (NSC-652287) inhibits HIF-1α and vascular endothelial growth factor expression in vivo and induces significant tumor cell apoptosis in normoxia and hypoxia in p53-positive cells. RITA has been proposed to stabilize p53 by inhibiting the p53-HDM2 interaction. However, induction of p53 alone was insufficient to block HIF-1α induced in hypoxia and has previously been shown to require additional stimuli, such as DNA damage. Here, we identify a new mechanism of action for RITA: RITA activates a DNA damage response, resulting in phosphorylation of p53 and γH2AX in vivo. Unlike other DNA damage response-inducing agents, RITA treatment of cells induced a p53-dependent increase in phosphorylation of the α subunit of eukaryotic initiation factor 2, requiring PKR-like endoplasmic reticulum kinase activity, and led to the subsequent downregulation of HIF-1α and p53 target proteins, including HDM2 and p21. Through the identification of a new mechanism of action for RITA, our study uncovers a novel link between the DNA damage response-p53 pathway and the protein translational machinery