50 research outputs found
On inconsistency of experimental data on primary nuclei spectra with sea level muon intensity measurements
For the first time a complete set of the most recent direct data on primary
cosmic ray spectra is used as input into calculations of muon flux at sea level
in wide energy range GeV. Computations have been performed
with the CORSIKA/QGSJET and CORSIKA/VENUS codes. The comparison of the obtained
muon intensity with the data of muon experiments shows, that measurements of
primary nuclei spectra conform to sea level muon data only up to several tens
of GeV and result in essential deficit of muons at higher energies. As it
follows from our examination, uncertainties in muon flux measurements and in
the description of nuclear cascades development are not suitable to explain
this contradiction, and the only remaining factor, leading to this situation,
is underestimation of primary light nuclei fluxes. We have considered
systematic effects, that may distort the results of the primary cosmic ray
measurements with the application of the emulsion chambers. We suggest, that
re-examination of these measurements is required with the employment of
different hadronic interaction models. Also, in our point of view, it is
necessary to perform estimates of possible influence of the fact, that sizable
fraction of events, identified as protons, actually are antiprotons. Study of
these cosmic ray component begins to attract much attention, but today nothing
definite is known for the energies GeV. In any case, to realize whether
the mentioned, or some other reasons are the sources of disagreement of the
data on primaries with the data on muons, the indicated effects should be
thoroughly analyzed
Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation?
BACKGROUND: Sodium/iodide symporter (NIS) is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer. In the majority of thyroid cancers, however, iodide uptake is reduced, probably as a result of decreased NIS protein expression. METHODS: To identify the mechanisms that negatively affect NIS expression in thyroid tumors, we performed electrophoresis mobility shift assays and immunoblot analysis of nuclear protein extracts from normal and tumoral thyroid tissues from 14 unrelated patients. RESULTS: Two proteins closely related to the transcription factors AP2 and Sp1 were identified in the nuclear extracts. Expression of both AP2 and Sp1 in nuclear extracts from thyroid tumors was significantly higher than that observed in corresponding normal tissues. CONCLUSION: These observations raise the possibility that NIS expression, and subsequently iodide transport, are reduced in thyroid tumors at least in part owing to alterations in the binding activity of AP2 and Sp1 transcription factors to NIS promoter
Induction of Sodium/Iodide Symporter (NIS) Expression and Radioiodine Uptake in Non-Thyroid Cancer Cells
Background: This study was designed to explore the therapeutic potential of suppressing MAP kinase and PI3K/Akt pathways and histone deacetylase (HDAC) to induce the expression of sodium/iodide symporter (NIS) and radioiodine uptake in non-thyroid cancer cells. Methods: We tested the effects of the MEK inhibitor RDEA119, the Akt inhibitor perifosine, and the HDAC inhibitor SAHA on NIS expression in thirteen human cancer cell lines derived from melanoma, hepatic carcinoma, gastric carcinoma, colon carcinoma, breast carcinoma, and brain cancers. We also examined radioiodine uptake and histone acetylation at the NIS promoter in selected cells. Results: Overall, the three inhibitors could induce NIS expression, to various extents, in melanoma and all the epithelial carcinoma-derived cells but not in brain cancer-derived cells. SAHA was most effective and its effect could be significantly enhanced by RDEA119 and perifosine. The expression of NIS, at both mRNA and protein levels, was most robust in the melanoma cell M14, hepatic carcinoma cell HepG2, and the gastric carcinoma cell MKN-7 cell. Radioiodine uptake was correspondingly induced, accompanied by robust increase in histone acetylation at the NIS promoter, in these cells when treated with the three inhibitors. Conclusions: This is the first demonstration that simultaneously suppressing the MAP kinase and PI3K/Akt pathways and HDAC could induce robust NIS expression and radioiodine uptake in certain non-thyroid human cancer cells, providing novel therapeutic implications for adjunct radioiodine treatment of these cancers
Synthesis of Highly Substituted Adamantanones from Bicyclo[3.3.1]nonanes
Trifluoromethanesulfonic acid and other electrophiles promote formation of the adamantanone core from the readily accessible 1,5-dimethyl-3,7-dimethylenebicyclo[3.3.1]nonan-9-one 2. Because adamantyl cation 3 can be trapped by a range of nucleophiles, including aromatic and heteroaromatic rings, alcohol, nitriles, and halides, access to a wide variety of functionality at the newly formed tertiary position is provided