A spectroscopic study of the cycling transition 4s[3/2]_2-4p[5/2]_3 at 811.8 nm in Ar-39: Hyperfine structure and isotope shift

Doppler-free saturated absorption spectroscopy is performed on an enriched radioactive Ar-39 sample. The spectrum of the 3s^2 3p^5 4s [3/2]_2 - 3s^2 3p^5 4p [5/2]_3 cycling transition at 811.8 nm is recorded, and its isotope shift between Ar-39 and Ar-40 is derived. The hyperfine coupling constants A and B for both the 4s [3/2]_2 and 4p [5/2]_3 energy levels in Ar-39 are also determined. The results partially disagree with a recently published measurement of the same transition. Based on earlier measurements as well as the current work, the isotope shift and hyperfine structure of the corresponding transition in Ar-37 are also calculated. These spectroscopic data are essential for the realization of laser trapping and cooling of Ar-37 and Ar-39

Spectroscopic study of the cycling transition 4s[3/2]2-4p[5/2] 3 at 811.8 nm in Ar39: Hyperfine structure and isotope shift

Doppler-free saturated absorption spectroscopy is performed on an enriched radioactive Ar39 sample. The spectrum of the 3s23p54s[3/2]2- 3s23p54p[5/2]3 cycling transition at 811.8 nm is recorded, and its isotope shift between Ar39 and Ar40 is derived. The hyperfine coupling constants A and B for both the 4s[3/2]2 and 4p[5/2]3 energy levels in Ar39 are also determined. The results partially disagree with a recently published measurement of the same transition. Based on earlier measurements as well as the current work, the isotope shift and hyperfine structure of the corresponding transition in Ar37 are also calculated. These spectroscopic data are essential for the realization of laser trapping and cooling of Ar37,39. © 2011 American Physical Society

Tracer Applications of Noble Gas Radionuclides in the Geosciences

The noble gas radionuclides, including 81Kr (half-life = 229,000 yr), 85Kr (11 yr), and 39Ar (269 yr), possess nearly ideal chemical and physical properties for studies of earth and environmental processes. Recent advances in Atom Trap Trace Analysis (ATTA), a laser-based atom counting method, have enabled routine measurements of the radiokrypton isotopes, as well as the demonstration of the ability to measure 39Ar in environmental samples. Here we provide an overview of the ATTA technique, and a survey of recent progress made in several laboratories worldwide. We review the application of noble gas radionuclides in the geosciences and discuss how ATTA can help advance these fields, specifically determination of groundwater residence times using 81Kr, 85Kr, and 39Ar; dating old glacial ice using 81Kr; and an 39Ar survey of the main water masses of the oceans, to study circulation pathways and estimate mean residence times. Other scientific questions involving deeper circulation of fluids in the Earth's crust and mantle also are within the scope of future applications. We conclude that the geoscience community would greatly benefit from an ATTA facility dedicated to this field, with instrumentation for routine measurements, as well as for research on further development of ATTA methods

An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe

A nuclear magnetic resonance-based ligand screening strategy utilizing a paramagnetic lanthanide probe is presented. By fixing a paramagnetic lanthanide ion to a target protein, a pseudo-contact shift (PCS) and a paramagnetic relaxation enhancement (PRE) can be observed for both the target protein and its bound ligand. Based on PRE and PCS information, the bound ligand is then screened from the compound library and the structure of the ligand–protein complex is determined. PRE is an isotropic paramagnetic effect observed within 30 Å from the lanthanide ion, and is utilized for the ligand screening in the present study. PCS is an anisotropic paramagnetic effect providing long-range (~40 Å) distance and angular information on the observed nuclei relative to the paramagnetic lanthanide ion, and utilized for the structure determination of the ligand–protein complex. Since a two-point anchored lanthanide-binding peptide tag is utilized for fixing the lanthanide ion to the target protein, this screening method can be generally applied to non-metal-binding proteins. The usefulness of this strategy was demonstrated in the case of the growth factor receptor-bound protein 2 (Grb2) Src homology 2 (SH2) domain and its low- and high-affinity ligands

Rapid processing of ⁸⁵5 Kr/Kr ratios using Atom Trap Trace Analysis

We report a methodology for measuring ⁸⁵ Kr/Kr isotopic abundances using Atom Trap Trace Analysis (ATTA) that increases sample measurement throughput by over an order of magnitude to six samples per 24 h. The noble gas isotope ⁸⁵ Kr (half-life 510.7 years) is a useful tracer for young groundwater in the age range of 5–50 years. ATTA, an efficient and selective laser-based atom counting method, has recently been applied to ⁸⁵ Kr/Kr isotopic abundance measurements, requiring 5–10 μL of krypton gas at STP extracted from 50 to 100 L of water. Previously, a single such measurement required 48 h. Our new method demonstrates that we can measure 85Kr/Kr ratios with 3–5% relative uncertainty every 4 h, on average, with the same sample requirements

Intracellular expression of toll-like receptor 4 in neuroblastoma cells and their unresponsiveness to lipopolysaccharide

BACKGROUND: Recently it has been reported that, toll-like receptors (TLRs) are expressed on a series of tumor cells, such as colon cancer, breast cancer, prostate cancer, melanoma and lung cancer. Although some cancer cells like melanoma cells are known to respond to lipopolysaccharide (LPS) via TLR4, not all cancer cells are positive for TLR4. There is little information on the expression and function of TLR4 in neuroblastoma cells. In this study, we investigated the expression of TLR4 in human neuroblastoma NB-1 cell line. METHODS: Expression and localization of TLR4 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis, respectively. Activation of nuclear factor (NF)-κB by LPS was detected by degradation of IκB-α and NF-κB luciferase assay. Activation and expression of mitogen-activated protein (MAP) kinase and interferon regulatory factor (IRF)-3 was detected by immunoblot analysis. RESULTS: Human NB-1 neuroblastoma cells expressed intracellular form of TLR4, but not the cell surface form. Further, NB-1 cells express CD14, MD2 and MyD88, which are required for LPS response. However, LPS did not significantly induce NF-κB activation in NB-1 cells although it slightly degraded IκB-α. NB-1 cells expressed no IRF-3, which plays a pivotal role on the MyD88-independent pathway of LPS signaling. Collectively, NB-1 cells are capable to avoid their response to LPS. CONCLUSION: Although human NB-1 neuroblastoma cells possessed all the molecules required for LPS response, they did not respond to LPS. It might be responsible for intracellular expression of TLR4 or lack of IRF-3

Disruption of Dnmt1/PCNA/UHRF1 Interactions Promotes Tumorigenesis from Human and Mice Glial Cells

Global DNA hypomethylation is a hallmark of cancer cells, but its molecular mechanisms have not been elucidated. Here, we show that the disruption of Dnmt1/PCNA/UHRF1 interactions promotes a global DNA hypomethylation in human gliomas. We then demonstrate that the Dnmt1 phosphorylations by Akt and/or PKC abrogate the interactions of Dnmt1 with PCNA and UHRF1 in cellular and acelluar studies including mass spectrometric analyses and the use of primary cultured patient-derived glioma. By using methylated DNA immunoprecipitation, methylation and CGH arrays, we show that global DNA hypomethylation is associated with genes hypomethylation, hypomethylation of DNA repeat element and chromosomal instability. Our results reveal that the disruption of Dnmt1/PCNA/UHRF1 interactions acts as an oncogenic event and that one of its signatures (i.e. the low level of mMTase activity) is a molecular biomarker associated with a poor prognosis in GBM patients. We identify the genetic and epigenetic alterations which collectively promote the acquisition of tumor/glioma traits by human astrocytes and glial progenitor cells as that promoting high proliferation and apoptosis evasion