New developments in detection technologies are providing a variety of biomolecular screening strategies from which to choose. Consequently, we performed a detailed analysis of both separation-based and non-separation-based formats for screening nuclear receptor ligands. In this study, time-resolved fluorescence resonance energy transfer (TR-FRET), ALPHAScreen, and time-resolved fluorescence (TRF) assays were optimized and compared with respect to sensitivity, reproducibility, and miniaturization capability. The results showed that the ALPHAScreen system had the best sensitivity and dynamic range. The TRF assay was more time consuming because of the number of wash steps necessary. The TR-FRET assay had less interwell variation, most likely because of ratiometric measurement. Both the ALPHAScreen and the TR-FRET assays were miniaturized to 8-μl volumes. Of the photomultiplier tube-based readers, the ALPHAScreen reader (ALPHAQuest) presented the advantage of faster reading times through simultaneous reading with four photomultiplier tubes.
This retrospective analysis of two double-blind, placebo-controlled studies in patients with mild to moderately severe AD investigated the efficacy of rivastigmine 6-12 mg/day on cognitive outcomes in patients with or without the apolipoprotein (APOE) e4 allele. APOE data were collected from patients who consented to pharmacogenetic testing. Treatment differences within each subgroup were compared, using the Observed Case (OC) population. The APOE e4 and non-APOE e4 subgroups comprised 246 and 121 patients, respectively. Overall, APOE e4 noncarriers showed greater decline than carriers (Po0.05). However, at 26 weeks, placebo-treated APOE e4 patients declined 3.04 points below baseline on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), and rivastigmine-treated patients improved by 1.67 points. Non-APOE e4 placebo-treated patients declined by 4.59 points and rivastigmine-treated patients declined by 0.48 points. Thus, non-APOE e4 carriers showed a less favorable course under either placebo or rivastigmine, but both genotype-defined subgroups showed quantitatively similar responses to therapy (both Po0.05 vs placebo).
The use of different Sn valence states (such as Sn4+ and Sn2+) in the Cu2ZnSn(S,Se)4 (CZTSSe) precursor solution is especially important for the quality of the subsequent growth of the CZTSSe films. The latest study has found that replacing SnCl2·2H2O with anhydrous SnCl4 can remarkably improve the performance of CZTSSe solar cells, but it needs to be operated in the glovebox. Herein, for the precursor solution, SnCl4·5H2O powder is used instead of anhydrous SnCl4 in air environment, and the proportion of Sn4+ and Sn2+ precursor solutions is further systematically studied. When the ratio of Sn4+ to Sn2+ is 1:1, a uniform, compact, and noncracking CZTSSe thin film is obtained, effectively alleviating the interface recombination and reducing the concentration of deep‐level defects. In particular, the concentration of CuZn antisite defects is decreased by an order of magnitude, and the carrier recombination and band tail effect are alleviated. When JSC is maintained, VOC and FF are considerably improved. Finally, CZTSSe thin‐film solar cells are fabricated with an efficiency of over 11%. Herein, the feasibility of controlling the ratio of Sn4+ to Sn2+ in the CZTSSe precursor solution for higher efficiency of CZTSSe thin‐film solar cells is demonstrated.
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