Search

Epoxy acrylate based solder mask formulations were conditioned by different printed circuit board (PCB) manufacturing and PCB assembly process stages. Depending on these different influences the chemistry of the solder mask surface was investigated regarding adhesion to possible adhesion partners. The combination of X-ray photoelectron spectrometry (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS) and the contact angle method, for surface energy determination, provided a detailed understanding of the surface near region up to the topmost monolayer, which forms the contact zone in which adhesion takes place. The combination of ToF-SIMS and XPS provided molecular information of surface components comprising quantitative information. The influences of all process steps, like UV, chemical and thermal treatment, on the chemical surface composition and appearance were identified. Based on the results a chemical surface model could be created regarding the different adhesion mechanisms. It has been shown that an enrichment of siloxanes at the surface is generated by different mechanisms that were distinguished based on ToF-SIMS. Even though an oxidation process in the surface near region (10 nm) was indicated by XPS, no increase of the surface polar groups and thus no polarity increase could be observed within the first monolayer. A surface model derived from the analysis results shows generation and occupation of free sites at the surface through all stages of the process. An occupation of free sites by siloxanes from additives in the solder mask formulation results in a siloxane dominated topmost monolayer.

We have investigated electron transfer and transport processes in several molecular systems adsorbed at metal surfaces using a methodology that combines first-principles electronic structure methods with quantum dynamics and transport approaches. Specifically, we have analysed the molecular factors that control electron transfer in a series of nitrile-substituted alkanethiolate self-assembled monolayer models adsorbed at the Au(111) surface that differ in the size of the aliphatic spacer chain. In addition, we have analysed the possibility of using a proton transfer reaction triggered by an external electrostatic field as a novel mechanism for switching a molecular junction. To demonstrate the feasibility of the process, we have investigated electron transport in a junction containing a molecular bridge that can exist in two tautomeric forms, [2,5-(4-hydroxypyridine)] and 2,5-[4(1H)-pyridone], that exhibit very different conductance properties.

Purpose: To evaluate the source of an apparent clinical pharmacokinetic interaction between lenalidomide (an Immunomodulatory Drug, IMiD) and temsirolimus (mTOR inhibitor). Background: The combination of lenalidomide with temsirolimus demonstrated a synergistic effect in in vitro models of Multiple Myeloma (MM), thus providing rationale for this combination in patients with relapsed MM. However pharmacokinetic interactions between these two agents have not been reported. In the current study, clinical pharmacokinetic interactions of lenalidomide with temsirolimus and the underlying mechanisms were investigated. Methods: A phase I clinical trial was completed for patients with relapsed multiple myeloma with oral lenalidomide (15-25 mg) days 1-21 of a 28 day cycle and weekly × 4 intravenous temsirolimus (15-20 mg). Pharmacokinetic data for both agents were obtained and potential drug-drug interactions were further evaluated using in vitro transport and uptake studies. An apparent clinical interaction was observed between lenalidomide and temsirolimus as demonstrated by statistically significant changes in clearance, maximum concentrations (Cmax), and area under the concentration-time curves (AUCs) for constant doses of lenalidomide with increased doses of temsirolimus. Similar and significant changes for temsirolimus pharmacokinetics at a fixed dose were also observed when lenalidomide doses were increased. In vitro studies indicated a higher basolateral-to-apical (BL-to-AP) flux compared to AP-to-BL flux for lenalidomide in MDCKII monolayers, suggesting an apically directed active transport of lenalidomide. Further evaluation of intracellular lenalidomide uptake showed an approximately 2-fold higher accumulation of lenalidomide in HL-60 than in P-glycoprotein (P-gp, ABCB1, MDR-1)-overexpressing HL-60/VCR cells (38.4 ± 13.2 vs. 19.2 ± 9.6 pmol/mg protein, respectively, P=0.005). Co-incubation with temsirolimus, a known P-gp substrate and inhibitor, resulted in increased lenalidomide accumulation (37.2 ± 6.0 vs. 19.2 ± 9.6 pmol/mg protein, respectively, P=0.002) in HL-60/VCR cells, which was equivalent to that in HL-60 cells. Clinical significance of this pharmacokinetic interaction in terms of either toxicity or response has also been evaluated. Conclusions: These results suggest that lenalidomide is a P-gp substrate, explaining the pharmacokinetic interaction between lenalidomide and temsirolimus. Quantifying the interaction of lenalidomide with other P-gp substrates, e.g. dexamethasone, is warranted to optimize dose administration of IMiD-based therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5473. doi:10.1158/1538-7445.AM2011-5473