Ground-based passive measurements of downwelling atmospheric radiation at ~110.836 GHz allow extracting the spectra of ozone self-radiation (rotational transition J = 6sub.1,5 –6sub.0,6 ) coming from ...the low stratosphere–mesosphere and retrieving vertical profiles of ozone concentration at these altitudes. There is a notable (several hundred kHz) ambiguity in the determination of the resonance frequency of this important ozone line. We carried out long-term ground-based measurements of atmospheric microwave radiation in this range using upgraded apparatus with high technical accuracy and spectral resolution (~12 kHz). The obtained brightness temperature spectra allowed us to determine the frequency of this ozone line to be 110,835.909 ± 0.016 MHz. We verified that the Doppler frequency shift by horizontal wind as well as the variations of the tropospheric absorption had little effect on the obtained result. The found value was 131 ± 16 kHz less than that measured in the laboratory and differed from modern model calculations. At the same time, it was close to the results of early semiempirical calculations made more than 40 years ago. The applications where precise knowledge about the resonance frequency of this ozone line can be important were discussed in this paper.
Ground-based microwave radiometers are increasingly used in operational meteorology and nowcasting. These instruments continuously measure the spectra of downwelling atmospheric radiation in the ...range 20–60 GHz used for the retrieval of tropospheric temperature and water vapor profiles. Spectroscopic uncertainty is an important part of the retrieval error budget, as it leads to systematic bias. In this study, we analyze the difference between observed and simulated microwave spectra obtained from more than four years of microwave and radiosonde observations over Nizhny Novgorod (56.2° N, 44° E). We focus on zenith-measured and elevation-scanning data in clear-sky conditions. The simulated spectra are calculated by a radiative transfer model with the use of radiosonde profiles and different absorption models, corresponding to the latest spectroscopy research. In the case of zenith-measurements, we found a systematic bias (up to ~2 K) of simulated spectra at 51–54 GHz. The sign of bias depends on the absorption model. A thorough investigation of the error budget points to a spectroscopic nature of the observed differences. The dependence of the results on the elevation angle and absorption model can be explained by the basic properties of radiative transfer and by cloud contamination at elevation angles.
In this work, we compare the values of 15 convective indices obtained from radiosonde and microwave temperature and water vapor profiles simultaneously measured over Nizhny Novgorod (56.2°N, 44°E) ...during 5 convective seasons of 2014–2018. A good or moderate correlation (with coefficients of ~0.7–0.85) is found for most indices. We assess the thunderstorm prediction skills with a lead time of 12 h for each radiosonde and microwave index. It is revealed that the effectiveness of thunderstorm prediction by microwave indices is much better than by radiosonde ones. Moreover, a good correlation between radiosonde and microwave values of a certain index does not necessarily correspond to similar prediction skills. Eight indices (Showalter Index, Maximum Unstable Convective Available Potential Energy (CAPE), Total Totals index, TQ index, Jefferson Index, S index, K index, and Thompson index) are regarded to be the best predictors from both the true skill statistics (TSS) maximum and Heidke skill score (HSS) maximum points of view. In the case of radiosonde data, the best indices are the Jefferson Index, K index, S index, and Thompson index. Only TSS and HSS maxima for these indices are close to the microwave ones, whereas the prediction skills of other radiosonde indices are essentially worse than in the case of microwave data. The analysis suggests that the main possible reason of this discrepancy is an unexpectedly low quality of radiosonde data.
Ground-based passive measurements of downwelling atmospheric radiation at ~110.836 GHz allow extracting the spectra of ozone self-radiation (rotational transition J = 61,5–60,6) coming from the low ...stratosphere–mesosphere and retrieving vertical profiles of ozone concentration at these altitudes. There is a notable (several hundred kHz) ambiguity in the determination of the resonance frequency of this important ozone line. We carried out long-term ground-based measurements of atmospheric microwave radiation in this range using upgraded apparatus with high technical accuracy and spectral resolution (~12 kHz). The obtained brightness temperature spectra allowed us to determine the frequency of this ozone line to be 110,835.909 ± 0.016 MHz. We verified that the Doppler frequency shift by horizontal wind as well as the variations of the tropospheric absorption had little effect on the obtained result. The found value was 131 ± 16 kHz less than that measured in the laboratory and differed from modern model calculations. At the same time, it was close to the results of early semiempirical calculations made more than 40 years ago. The applications where precise knowledge about the resonance frequency of this ozone line can be important were discussed in this paper.
Exosomes are small vesicles which are produced by the cells and released into the surrounding space. They can transfer biomolecules into recipient cells. The main goal of the work was to study the ...exosome involvement in the cell transfer of hormonal resistance. The experiments were performed on in vitro cultured estrogen-dependent MCF-7 breast cancer cells and MCF-7 sublines resistant to SERM tamoxifen and/or biguanide metformin, which exerts its anti-proliferative effect, at least in a part, via the suppression of estrogen machinery. The exosomes were purified by differential ultracentrifugation, cell response to tamoxifen was determined by MTT test, and the level and activity of signaling proteins were determined by Western blot and reporter analysis. We found that the treatment of the parent MCF-7 cells with exosomes from the resistant cells within 14 days lead to the partial resistance of the MCF-7 cells to antiestrogen drugs. The primary resistant cells and the cells with the exosome-induced resistance were characterized with these common features: decrease in ERα activity and parallel activation of Akt and AP-1, NF-κB, and SNAIL1 transcriptional factors. In general, we evaluate the established results as the evidence of the possible exosome involvement in the transferring of the hormone/metformin resistance in breast cancer cells.
Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of ...hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.
Exosomes are the small vesicles that are secreted by different types of normal and tumour cells and can incorporate and transfer their cargo to the recipient cells. The main goal of the present work ...was to study the tumour exosomes' ability to accumulate the parent mutant DNA or RNA transcripts with their following transfer to the surrounding cells. The experiments were performed on the MCF7 breast cancer cells that are characterized by the unique coding mutation in the
gene. Using two independent methods, Sanger sequencing and allele-specific real-time PCR, we revealed the presence of the fragments of the mutant DNA and RNA transcripts in the exosomes secreted by the MCF7 cells. Furthermore, we demonstrated the MCF7 exosomes' ability to incorporate into the heterologous MDA-MB-231 breast cancer cells supporting the possible transferring of the exosomal cargo into the recipient cells. Sanger sequencing of the DNA from MDA-MB-231 cells (originally bearing a wild type of
) treated with MCF7 exosomes showed no detectable amount of mutant DNA or RNA; however, using allele-specific real-time PCR, we revealed a minor signal from amplification of a mutant allele, showing a slight increase of mutant DNA in the exosome-treated MDA-MB-231 cells. The results demonstrate the exosome-mediated secretion of the fragments of mutant DNA and mRNA by the cancer cells and the exosomes' ability to transfer their cargo into the heterologous cells.
Energy imbalance is one of the key properties of tumour cells, which in certain cases supports fast cancer progression and resistance to therapy.
The simultaneous blocking of glycolytic processes and ...oxidative phosphorylation pathways seems to be a promising strategy for antitumor therapies. The study aimed to evaluate the effect of glucose starvation on the antiproliferative and antiestrogenic potency of oligomycin A against hormone-dependent breast cancer cells.
Cell viability was assessed by the MTT test. Estrogen receptor alpha (ERα) activity was evaluated by reporter assay. mTOR, AMPK, Akt, and S6 kinase expression was assessed by immunoblotting.
Glucose starvation caused multiple increases in the antiproliferative potency of oligomycin A in the hormone-dependent breast cancer MCF-7 cells, while its effect on the sensitivity of the second hormone-dependent cancer cell line, named T47D, was weak and limited. Glycolytic inhibitors, 3-bromopyruvate and 2-deoxyglucose, greatly enhanced the antiproliferative potency of oligomycin A in MCF-7 cells. Glucose starvation leads to remarkable activation of Akt in MCF-7 cells, whereas oligomycin A enhances its effect. The mTOR, S6 kinase, and AMPK signalling pathways are significantly modulated by oligomycin A under glucose starvation. Oligomycin A demonstrates more pronounced antiestrogenic effects under glucose starvation. Thus, glucose starvation and pharmacological inhibition of glycolysis are of interest for revealing the antitumor potential of macrolide oligomycin A against hormone-dependent breast cancers.
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•Glucose starvation is a potent sensitizer to oligomycin A anti-cancer effects.•Oligomycin A enhances Akt activation under glucose starvation.•mTOR, S6 kinase, and AMPK pathways are modulated by low-dose oligomycin A under glucose starvation.•Oligomycin A is a promising nanomolar ERα modulator.
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