Surface morphology and in-plane-epitaxy of SmBa₂Cu₃O₇_-δ films on SrTiO₃ (001) substrates studied by STM and grazing incidence x-ray diffraction

The surface morphology and in-plane epitaxy of thin films of SmBa2Cu3O7−δ (SmBCO) grown on SrTiO3 (001) substrates with various thicknesses have been investigated by scanning tunneling microscopy (STM) and grazing incidence x-ray diffraction (GIXRD). As revealed by GIXRD, SmBCO films as thick as 500 Å grow pseudomorphically on SrTiO3 (001) surfaces, in comparison with a maximum of 130 Å for YBCO. This is probably due to a better lattice match of SmBCO (εa=1.2%, εb=−0.5%) compared to YBCO (εa=2.0%, εb=0.7%) with the SrTiO3 substrate. Three different types of surface morphology were observed by STM with increasing film thickness h: a) 2D growth for h<hc1, b) columnar structures for hc1 <h<hc2, c) spiral growth for h>hc2. With GIXRD, a density modulation is observed in the films with a thickness below hc2. For thicker films above hc2, introduction of screw dislocations leads to spiral growth

Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death

Cells exposed to low-oxygen conditions (hypoxia) alter their metabolism to survive. This response, although vital during development and high-altitude survival, is now known to be a major factor in the selection of cells with a transformed metabolic phenotype during tumorigenesis. It is thought that hypoxia-selected cells have increased invasive capacity and resistance to both chemo-and radiotherapies, and therefore represent an attractive target for antitumor therapy. Hypoxia inducible factors (HIFs) are responsible for the majority of gene expression changes under hypoxia, and are themselves controlled by the oxygen-sensing HIF prolyl hydroxylases (PHDs). It was previously shown that mutations in succinate dehydrogenase lead to the inactivation PHDs under normoxic conditions, which can be overcome by treatment with alpha-ketoglutarate derivatives. Given that solid tumors contain large regions of hypoxia, the reactivation of PHDs in these conditions could induce metabolic catastrophe and therefore prove an effective antitumor therapy. In this report we demonstrate that derivatized alpha-ketoglutarate can be used as a strategy for maintaining PHD activity under hypoxia. By increasing intracellular alpha-ketoglutarate and activating PHDs we trigger PHD-dependent reversal of HIF1 activation, and PHD-dependent hypoxic cell death. We also show that derivatized alpha-ketoglutarate can permeate multiple layers of cells, reducing HIF1 alpha levels and its target genes in vivo