STE20/SPS1‐related proline/alanine‐rich kinase (SPAK) and oxidative‐stress‐responsive kinase 1 (OSR1) are two serine/threonine protein kinases that play key roles in regulating ion homeostasis. Various SPAK and OSR1 mouse models exhibited reduced blood pressure. Herein, the discovery of verteporfin, a photosensitising agent used in photodynamic therapy, as a potent inhibitor of SPAK and OSR1 kinases is reported. It is shown that verteporfin binds the kinase domains of SPAK and OSR1 and inhibits their catalytic activity in an adenosine triphosphate (ATP)‐independent manner. In cells, verteporfin was able to suppress the phosphorylation of the ion co‐transporter NKCC1; a downstream physiological substrate of SPAK and OSR1 kinases. Kinase panel screening indicated that verteporfin inhibited a further eight protein kinases more potently than that of SPAK and OSR1. Although verteporfin has largely been studied as a modifier of the Hippo signalling pathway, this work indicates that the WNK‐SPAK/OSR1 signalling cascade is also a target of this clinical agent. This finding could explain the fluctuation in blood pressure noted in patients and animals treated with this drug. 相似文献
Low-temperature wet chemical bath deposition (CBD) method is one of the most efficient and least hazardous solution-based techniques which is widely employed to grow ZnO NRs. In CBD method, a seed layer is usually deposited on the substrate. In this paper, high quality ZnO and aluminum doped ZnO (AZO) seed layers are sputtered on the indium tin oxide (ITO) coated glass. In continue, aligned ZnO NRs are grown on the AZO and ZnO seed layers via CBD technique. The effect of the growth time and seed layer on the physical properties of as-grown ZnO NRs are investigated. According to the results, the seed layer plays an essential role on the growth orientation and growth rate of the ZnO NRs. The ZnO NRs grown on AZO seed layer are more aligned rather than ZnO seed layer due to their higher texture coefficients. The relative photoluminescence (PL) intensity ratio of near band emission (NBE) to deep level emission (DLE) (INBE/IDLE) for the ZnO NRs grown on AZO and ZnO seed layers are calculated as 7.45 and 2.62, respectively. To investigate the performance of the as-grown ZnO NRs, near ultraviolet organic light-emitting diodes (UV-OLEDs) using ZnO NRs array as n-type material and poly [2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylene-vinylene] (MEH-PPV) conjugated polymer as p-type material have been fabricated. The total concentration of traps (), the characteristic energies () and the turn-on voltages for the devices with the structures of ITO/AZO/ZnO NRs/MEH-PPV/Al (device A) and ITO/ZnO/ZnO NRs/MEH-PPV/Al (device B) are attained 7.65 × 1016 and 7.75 × 1016 cm?3, 0.232 and 0.206 eV, 23 and 21 V, respectively. Moreover, based on the electroluminescence (EL) spectra, the NBE peaks for device A and B are obtained nearly in the wavelengths of 382 and 388 nm, respectively. Finally, various charge carrier transportation processes of prepared UV-OLEDs have been studied, systematically. 相似文献
Nanosized ZrO2 clusters were prepared by electrospinning a poly(vinylpyrrodine) (PVP)/ZrO2 mixture for calcination to remove PVP template and sizing. The morphological, chemical, structural, and thermal resistance changes during preparation stages were investigated using scanning electron microscope, energy-dispersive X-ray spectroscopy, transmission electron microscope, X-ray diffraction, and thermogravimetric analysis. The obtained ZrO2 clusters were used for preparation of nanocomposite membranes by dispersion in 2,6-pyridine polybenzimidazole (2,6-Py-PBI) matrix at 5?wt% content followed by phosphoric acid (PA) doping. The ZrO2 nanoclusters were found to be uniformly distributed in 2,6-Py-PBI/PA matrix leading to a remarkable increase in the PA doping level and proton conductivity of the obtained composite membrane. 相似文献
Analytical methods for molecular characterization of diagnostic or therapeutic targets have recently gained high interest. This review summarizes the combination of mass spectrometry and surface plasmon resonance (SPR) biosensor analysis for identification and affinity determination of protein interactions with antibodies and DNA-aptamers. The binding constant (KD) of a protein–antibody complex is first determined by immobilizing an antibody or DNA-aptamer on an SPR chip. A proteolytic peptide mixture is then applied to the chip, and following removal of unbound material by washing, the epitope(s) peptide(s) are eluted and identified by MALDI-MS. The SPR-MS combination was applied to a wide range of affinity pairs. Distinct epitope peptides were identified for the cardiac biomarker myoglobin (MG) both from monoclonal and polyclonal antibodies, and binding constants determined for equine and human MG provided molecular assessment of cross immunoreactivities. Mass spectrometric epitope identifications were obtained for linear, as well as for assembled (“conformational”) antibody epitopes, e.g., for the polypeptide chemokine Interleukin-8. Immobilization using protein G substantially improved surface fixation and antibody stabilities for epitope identification and affinity determination. Moreover, epitopes were successfully determined for polyclonal antibodies from biological material, such as from patient antisera upon enzyme replacement therapy of lysosomal diseases. The SPR-MS combination was also successfully applied to identify linear and assembled epitopes for DNA–aptamer interaction complexes of the tumor diagnostic protein C-Met. In summary, the SPR-MS combination has been established as a powerful molecular tool for identification of protein interaction epitopes. 相似文献
Toughness is an important property for being used in steels in engineering applications. In this research, tensile toughness of 45WCrV7 steel was measured and calculated in 10 different processing conditions. The results of tensile test showed that two samples had maximum tensile toughness. Microstructural studies demonstrated that the required condition for high tensile toughness was simultaneous increase in two microstructural factors named content and population density of the secondary carbides because a matrix which was poor of carbon and alloying elements was softened and thus increased total tensile toughness. 相似文献
Designing a spectrally efficient wireless channel requires a comprehensive understanding of its time and frequency varying characteristics, making it a stochastic medium of communication. These characteristics become more challenging to cater at the receiving terminal in a multipath transmission. This is because of the fading effect and Doppler shift of the transmitted frequency, specifically in cellular mobile radio systems and vehicle to vehicle communications. This paper presents the modeling, simulation, and then characterization of a cellular mobile radio multipath channel over its time and frequency varying fading gain. For this purpose, a discrete-time Finite Impulse Response (FIR) type filter of such a channel is designed, modeled, and simulated using time and frequency varying characteristics of the received signal. The simulated channel response is further analyzed in terms of coherence bandwidth, coherence time, delay spread, Doppler spread, and symbol time.