Thermo-responsive self-immolative nanoassemblies: Direct and indirect triggering

A thermo-responsive end-cap based on a retro-Diels-Alder and subsequent furan elimination reaction was developed. It was used to cap poly(ethyl glyoxylate), allowing end-to-end depolymerization upon thermal triggering. Using block copolymers, thermo-responsive micelles and vesicles were prepared and shown to disassemble upon heating. Thermal degradation could also be triggered indirectly by magnetic field hyperthermia after incorporation of iron oxide nanoparticles into the assemblies

Gain properties of dye-doped polymer thin films

Hybrid pumping appears as a promising compromise in order to reach the much coveted goal of an electrically pumped organic laser. In such configuration the organic material is optically pumped by an electrically pumped inorganic device on chip. This engineering solution requires therefore an optimization of the organic gain medium under optical pumping. Here, we report a detailed study of the gain features of dye-doped polymer thin films. In particular we introduce the gain efficiency $K$, in order to facilitate comparison between different materials and experimental conditions. The gain efficiency was measured with various setups (pump-probe amplification, variable stripe length method, laser thresholds) in order to study several factors which modify the actual gain of a layer, namely the confinement factor, the pump polarization, the molecular anisotropy, and the re-absorption. For instance, for a 600 nm thick 5 wt\% DCM doped PMMA layer, the different experimental approaches give a consistent value $K\simeq$ 80 cm.MW$^{-1}$. On the contrary, the usual model predicting the gain from the characteristics of the material leads to an overestimation by two orders of magnitude, which raises a serious problem in the design of actual devices. In this context, we demonstrate the feasibility to infer the gain efficiency from the laser threshold of well-calibrated devices. Besides, temporal measurements at the picosecond scale were carried out to support the analysis.Comment: 15 pages, 17 figure

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors.

PurposeThis study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition.MethodsThis was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD.ResultsAdverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses).ConclusionsContinuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested

Influence of the substrate-induced strain and irradiation disorder on the Peierls transition in TTF-TCNQ microdomains

The influence of the combined effects of substrate-induced strain, finite size and electron irradiation-induced defects have been studied on individual micron-sized domains of the organic charge transfer compound tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ) by temperature-dependent conductivity and current-voltage measurements. The individual domains have been isolated by focused ion beam etching and electrically contacted by focused ion and electron beam induced deposition of metallic contacts. The temperature-dependent conductivity follows a variable range hopping behavior which shows a crossover of the exponent as the Peierls transition is approached. The low temperature behavior is analyzed within the segmented rod model of Fogler, Teber and Shklowskii, as originally developed for a charge-ordered quasi one-dimensional electron crystal. The results are compared with data obtained on as-grown and electron irradiated epitaxial TTF-TCNQ thin films of the two-domain type