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1.
Nanotechnology ; 28(12): 124003, 2017 Mar 24.
Article in English | MEDLINE | ID: mdl-28229953

ABSTRACT

We report on the low-temperature fabrication of field-effect transistors by bridging pre-patterned electrodes using ZnO nanowires grown in situ, which operate without requiring post-growth processing or annealing. The devices show good performance using as-grown nanowires, with on-off ratios of 105 and threshold voltages of 2 V. Electron microscopy shows the field-dependent nanowires hierarchically nucleate from larger ZnO nanorods, and both are oriented along a common c-axis. A high nanowire surface-to-volume ratio allows depleting electron traps on the nanowire surface to compensate intrinsic electron donors present throughout the nanowire bulk. This eliminates the need to reduce the electron concentration through high-temperature annealing, making the nanowires naturally field-dependent in their as-grown state.

2.
Pharmacol Res ; 114: 13-26, 2016 12.
Article in English | MEDLINE | ID: mdl-27751876

ABSTRACT

A set of histamine H1 receptor (H1R) agonists and antagonists was characterized in functional assays, using dynamic mass redistribution (DMR), electric cell-substrate impedance sensing (ECIS) and various signaling pathway specific readouts (Fura-2 and aequorin calcium assays, arrestin recruitment (luciferase fragment complementation) assay, luciferase gene reporter assay). Data were gained from genetically engineered HEK293T cells and compared with reference data from GTPase assays and radioligand binding. Histamine and the other H1R agonists gave different assay-related pEC50 values, however, the order of potency was maintained. In the luciferase fragment complementation assay, the H1R preferred ß-arrestin2 over ß-arrestin1. The calcium and the impedimetric assay depended on Gq coupling of the H1R, as demonstrated by complete inhibition of the histamine-induced signals in the presence of the Gq inhibitor FR900359 (UBO-QIC). Whereas partial inhibition by FR900359 was observed in DMR and the gene reporter assay, pertussis toxin substantially decreased the response in DMR, but increased the luciferase signal, reflecting the contribution of both, Gq and Gi, to signaling in these assays. For antagonists, the results from DMR were essentially compatible with those from conventional readouts, whereas the impedance-based data revealed a trend towards higher pKb values. ECIS and calcium assays apparently only reflect Gq signaling, whereas DMR and gene reporter assays appear to integrate both, Gq and Gi mediated signaling. The results confirm the value of the label-free methods, DMR and ECIS, for the characterization of H1R ligands. Both noninvasive techniques are complementary to each other, but cannot fully replace reductionist signaling pathway focused assays.


Subject(s)
Histamine Agonists/pharmacology , Histamine H1 Antagonists/pharmacology , Receptors, Histamine H1/metabolism , Calcium/metabolism , Drug Evaluation, Preclinical , Electric Impedance , GTP-Binding Proteins/metabolism , Genes, Reporter , HEK293 Cells , Histamine/pharmacology , Humans , Ligands , Radioligand Assay , Signal Transduction/drug effects , beta-Arrestins/metabolism
3.
Pharmacol Res ; 108: 65-74, 2016 06.
Article in English | MEDLINE | ID: mdl-27133553

ABSTRACT

Label-free cell-based assays have been attracting growing attention in drug research. Optical approaches based on evanescent electric fields (e.g. EPIC, RWG/DMR, SPR) and electrochemical impedance analysis (ECIS, xCELLigence) are by far the most widespread techniques for such purposes. We compared three label-free approaches (ECIS, RWG/DMR and SPR) with respect to the activation of the human histamine H1 receptor (H1R) expressed by U-373 MG glioblastoma and genetically engineered HEK 293T cells. HEK 293T cells were either expressing the hH1R alone or in combination with the adhesion protein hMSR1. The ß2-adrenergic receptor (ß2-AR) expressed by bovine aortic endothelial cells (BAEC) served as a second cell model. Reduced cell adhesion to the surface of the sensing devices affected both, the optical and the impedance-based readout, but became much more obvious in case of RWG- or SPR-based assays. By contrast, the co-expression of hH1R and hMSR1 in HEK 293T cells strongly enhanced the signal compared to hH1R expression alone. As the sensitivity of the optical readouts is confined to a distance of 100-200nm from the surface, depending on the wavelength of the incident light, this observation is in accordance with tighter adhesion of the co-transfectants, inducing a shorter distance between the cell membrane and the substrate. Combining ECIS and SPR, allowing for simultaneous registration of both signals for a single cell population, provided a direct correlation of both readouts, when H1R or ß2-AR stimulation was investigated for the same cell populations. Cell adhesion was found to have a critical impact on the results of label-free cell monitoring, in particular when techniques based on evanescent electric fields are applied.


Subject(s)
Cell Adhesion , Receptors, G-Protein-Coupled/metabolism , Animals , Cattle , Cell Line, Tumor , Electrochemical Techniques/instrumentation , Equipment Design , HEK293 Cells , Humans , Light , Refractometry , Signal Transduction , Surface Plasmon Resonance/instrumentation
4.
Nanotechnology ; 19(46): 465603, 2008 Nov 19.
Article in English | MEDLINE | ID: mdl-21836250

ABSTRACT

We report a hydrothermal synthesis method for MgO shell coatings directly onto the surface of ZnO nanowire arrays. The entire process can be carried out below 100 °C. The MgO shells are produced by the addition of 10 mM magnesium nitrate with 0.2 M sodium hydroxide in water, resulting in a shell thickness of up to 8 nm, verified by high resolution transmission electron microscopy. The viability of the MgO layer as a functional element of optoelectronic devices was tested on solid-state organic hole-transporter based dye-sensitized solar cells. Incorporation of the MgO shell into the solar cell resulted in substantive efficiency improvements of over 400% in comparison to the pristine ZnO nanowire based photovoltaics, indicating that electrons can efficiently tunnel through the 'insulating' MgO shell.

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