Pigment epithelium-derived factor (PEDF) is a potent multifunctional protein that inhibits angiogenesis and has neurogenic and neuroprotective properties. Since the wet form of age-related macular degeneration is characterized by choroidal neovascularization (CNV), PEDF would be an ideal candidate to inhibit CNV and support retinal pigment epithelial (RPE) cells. However, its short half-life has precluded its clinical use. To deliver PEDF to the subretinal space, we transfected RPE cells with the PEDF gene using the Sleeping Beauty transposon system. Transfected cells expressed and secreted biologically active recombinant PEDF (rPEDF). In cultures of human umbilical vein endothelial cells, rPEDF reduced VEGF-induced cumulative sprouting by ≥47%, decreased migration by 77%, and increased rate of apoptosis at least 3.4 times. rPEDF induced neurite outgrowth in neuroblastoma cells and protected ganglion and photoreceptor cells in organotypic retinal cultures. In a rat model of CNV, subretinal transplantation of PEDF-transfected cells led to a reduction of the CNV area by 48% 14 days after transplantation and decreased clinical significant lesions by 55% and 40% after 7 and 14 days, respectively. We showed that transplantation of pigment epithelial cells overexpressing PEDF can restore a permissive subretinal environment for RPE and photoreceptor maintenance, while inhibiting choroidal blood vessel growth.
In-situ specific-heat measurements between 0.3 K and 2 K of quench-condensed amorphous Ge1-xAux films for x = 0.18 and x = 0.14 are reported. These concentrations are close to xc=0.12 for the metal-insulator transition. The samples exhibit bulk superconductivity at 1.6 and 0.6 K respectively, as determined from the discontinuity in the specific heat. The observed strong decrease of the normal-state electronic specific-heat coefficient from x = 0.18 to 0.14 gives evidence that the density of states at the Fermi energy vanishes upon approaching xc, as previously inferred from tunneling measurements.
The following article outlines the essential clauses within agreements about the funding of German Universities or German clinical trial sites in order for them to conduct a non-commercial clinical trial on their own, a so-called Investigator-Initiated-Trials or Investigator-Sponsored-Trials. The authors explain the basic legal principles and clauses for such an agreement and clarify certain German Law specialities, which any funder should be aware of, if they were to fund an Investigator-Initiated-Trial in Germany. It becomes clear, that it is very important for the funding pharmaceutical company or foundation, not to be confused with the regulatory sponsor of the given clinical trial. Unclear wording in the funding agreement could lead to the actual transfer of a sponsor’s responsibilities from the University or clinical trial site to the funding pharmaceutical company or foundation, with all legal and monetary risks. In order to avoid unwanted penalties and costs, it is imperative for the funding entity to draft the essential clauses carefully. This article aims to help with that.
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