Challenges and barriers for a sustainable transport system – exploring the potential to enact change

This report is divided into three parts; the first part summarizes the results from a workshopconducted within the TRANSFORuMproject. The second part presents the results of interviewscarried out with different experts discussing the different goals and their perceptionsof what might prevent or delay appropriate implementation. The third part is based on a literature reviewdiscussing how to overcome or remove the various barriersand challenges. The overall aim ofthe studies presented in this report is to identify barriers but also to present necessary steps which need to be takenin order to help achieving the goals.The term "Barrier" relates to something which prevents some form of progress or movement, while "Challenge" can be something difficult but also something which is regarded as stimulating; or an opportunity

The Effect of Nitrogen Ion Implantation on the Surface Properties of Ti6Al4V Alloy Coated by a Carbon Nanolayer

The ion beam assisted deposition (IBAD) method was chosen for preparing a carbon thin film with a mixing area on a substrate of Ti6Al4V titanium alloy. Nitrogen ions with energy 90 keV were used. These form a broad ion beam mixing area at the interface between the carbon film and the substrate. We investigated the chemical composition by the glow discharge optical emission spectroscopy (GD-OES) method and the phases by the X-ray diffraction (XRD) method. The measured concentration profiles indicate the mixing of the carbon film into the substrate, which may have an effect on increasing the adhesion of the deposited film. The nanohardness and the coefficient of friction were measured. We found that the modified samples had a markedly lower coefficient of friction even after damage to the carbon film, and they also had higher nanohardness than the unmodified samples. The increased nanohardness is attributed to the newly created phases that arose with ion implantation of nitrogen ions

Interaction Potential of the Multitargeted Receptor Tyrosine Kinase Inhibitor Dovitinib with Drug Transporters and Drug Metabolising Enzymes Assessed in Vitro

Dovitinib (TKI-258) is under development for the treatment of diverse cancer entities. No published information on its pharmacokinetic drug interaction potential is available. Thus, we assessed its interaction with important drug metabolising enzymes and drug transporters and its efficacy in multidrug resistant cells in vitro. P-glycoprotein (P-gp, MDR1, ABCB1) inhibition was evaluated by calcein assay, inhibition of breast cancer resistance protein (BCRP, ABCG2) by pheophorbide A efflux, and inhibition of organic anion transporting polypeptides (OATPs) by 8-fluorescein-cAMP uptake. Inhibition of cytochrome P450 3A4, 2C19, and 2D6 was assessed by using commercial kits. Induction of transporters and enzymes was quantified by real-time RT-PCR. Possible aryl hydrocarbon receptor (AhR) activating properties were assessed by a reporter gene assay. Substrate characteristics were evaluated by growth inhibition assays in cells over-expressing P-gp or BCRP. Dovitinib weakly inhibited CYP2C19, CYP3A4, P-gp and OATPs. The strongest inhibition was observed for BCRP (IC50 = 10.3 ± 4.5 μM). Among the genes investigated, dovitinib only induced mRNA expression of CYP1A1, CYP1A2, ABCC3 (coding for multidrug resistance-associated protein 3), and ABCG2 and suppressed mRNA expression of some transporters and drug metabolising enzymes. AhR reporter gene assay demonstrated that dovitinib is an activator of this nuclear receptor. Dovitinib retained its efficacy in cell lines over-expressing P-gp or BCRP. Our analysis indicates that dovitinib will most likely retain its efficacy in tumours over-expressing P-gp or BCRP and gives first evidence that dovitinib might act as a perpetrator drug in pharmacokinetic drug–drug interactions

Challenges and barriers for a sustainable transport system : exploring the potential to enact change

This report is divided into three parts; the first part summarizes the results from a workshopconducted within the TRANSFORuMproject. The second part presents the results of interviewscarried out with different experts discussing the different goals and their perceptionsof what might prevent or delay appropriate implementation. The third part is based on a literature reviewdiscussing how to overcome or remove the various barriersand challenges. The overall aim ofthe studies presented in this report is to identify barriers but also to present necessary steps which need to be takenin order to help achieving the goals.The term "Barrier" relates to something which prevents some form of progress or movement, while "Challenge" can be something difficult but also something which is regarded as stimulating; or an opportunity