Observation of Long-Lived Muonic Hydrogen in the 2S State

The kinetic energy distribution of ground state muonic hydrogen atoms mu-p(1S) is determined from time-of-flight spectra measured at 4, 16, and 64 hPa H2 room-temperature gas. A 0.9 keV-component is discovered and attributed to radiationless deexcitation of long-lived mu-p(2S) atoms in collisions with H2 molecules. The analysis reveals a relative population of about 1%, and a pressure-dependent lifetime (e.g. (30.4 +21.4 -9.7) ns at 64 hPa) of the long-lived mu-p(2S) population, equivalent to a 2S-quench rate in mu-p(2S) + H2 collisions of (4.4 +2.1 -1.8) 10^11 s^-1 at liquid hydrogen density.Comment: 4 pages, 2 figures, accepted for publication in Physical Review Letter

Cellular pharmacology of multi-and duplex drugs consisting of ethynylcytidine and 5-fluoro-2′-deoxyuridine

In vivo, ETC-FdUrd and ETC-L-FdURd were orally active. ETC nucleotides accumulated in both tumor and liver tissues. These formulations seem to be effective when a lipophilic linker is used combined with a liposomal formulation

Low density lipoprotein and liposome mediated uptake and cytotoxic effect of N4-octadecyl-1-β-D-arabinofuranosylcytosine in Daudi lymphoma cells

Low density lipoprotein (LDL) receptor-mediated uptake and cytotoxic effects of N4-octadecyl-1-beta-D-arabinofuranosylcytosine (NOAC) were studied in Daudi lymphoma cells. NOAC was either incorporated into LDL or liposomes to compare specific and unspecific uptake mechanisms. Binding of LDL to Daudi cells was not altered after NOAC incorporation (K(D) 60 nM). Binding of liposomal NOAC was not saturable with increasing concentrations. Specific binding of NOAC-LDL to Daudi cells was five times higher than to human lymphocytes. LDL receptor binding could be blocked and up- or down-regulated. Co-incubation with colchicine reduced NOAC-LDL uptake by 36%. These results suggested that NOAC-LDL is taken up via the LDL receptor pathway. In an in vitro cytotoxicity test, the IC50 of NOAC-LDL was about 160 microM, whereas with liposomal NOAC the IC50 was 40 microM. Blocking the LDL receptors with empty LDL protected 50% of the cells from NOAC cytotoxicity. The cellular distribution of NOAC-LDL or NOAC-liposomes differed only in the membrane and nuclei fraction with 13% and 6% respectively. Although it is more convenient to prepare NOAC-liposomes as compared to the loading of LDL particles with the drug, the receptor-mediated uptake of NOAC-LDL provides an interesting rationale for the specific delivery of the drug to tumours that express elevated numbers of LDL receptors

Sea surface temperatures of the western Arabian Sea during the last deglaciation.

In this study we present a sea surface temperature (SST) record from the western Arabian Sea for the last\ud 20,000 years. We produced centennial-scale d18O and Mg/Ca SST time series of core NIOP929 with focus on\ud the glacial-interglacial transition. The western Arabian Sea is influenced by the seasonal NE and SW monsoon\ud wind systems. Lowest SSTs occur during the SW monsoon season because of upwelling of cold water, and\ud highest SSTs can be found in the low-productivity intermonsoon season. The Mg/Ca-based temperature record\ud reflects the integrated SST of the SW and NE monsoon seasons. The results show a glacial-interglacial SST\ud difference of 2C, which is corroborated by findings from other Arabian Sea cores. At 19 ka B.P. a yet\ud undescribed warm event of several hundred years duration is found, which is also reflected in the d18O record. A\ud second centennial-scale high SST/low d18O event is observed at 17 ka B.P. This event forms the onset of the\ud stepwise yet persistent trend toward Holocene temperatures. Highest Mg/Ca-derived SSTs in the NIOP929\ud record occurred between 13 and 10 ka B.P. Interglacial SST is 24C, indicating influence of upwelling. The\ud onset of Arabian Sea warming occurs when the North Atlantic is experiencing minimum temperatures. The rapid\ud temperature variations at 19, 17, and 13 ka B.P. are difficult to explain with monsoon changes alone and are\ud most likely also linked to regional hydrographic changes, such as trade wind induced variations in warm water\ud advection

Cellular pharmacology of multi- and duplex drugsconsisting of ethynylcytidine and 5-fluoro-2′-deoxyuridine

Prodrugs can have the advantage over parent drugs in increased activation and cellular uptake. The multidrug ETC-L-FdUrd and the duplex drug ETC-FdUrd are composed of two different monophosphate-nucleosides, 5-fluoro-2′deoxyuridine (FdUrd) and ethynylcytidine (ETC), coupled via a glycerolipid or phosphodiester, respectively. The aim of the study was to determine cytotoxicity levels and mode of drug cleavage. Moreover, we determined whether a liposomal formulation of ETC-L-FdUrd would improve cytotoxic activity and/or cleavage. Drug effects/cleavage were studied with standard radioactivity assays, HPLC and LC-MS/MS in FM3A/0 mammary cancer cells and their FdUrd resistant variants FM3A/TK−. ETC-FdUrd was active (IC50 of 2.2 and 79 nM) in FM3A/0 and TK− cells, respectively. ETC-L-FdUrd was less active (IC50: 7 nM in FM3A/0 vs 4500 nM in FM3A/TK−). Although the liposomal formulation was less active than ETC-L-FdUrd in FM3A/0 cells (IC50:19.3 nM), resistance due to thymidine kinase (TK) deficiency was greatly reduced. The prodrugs inhibited thymidylate synthase (TS) in FM3A/0 cells (80–90%), but to a lower extent in FM3A/TK− (10–50%). FdUMP was hardly detected in FM3A/TK− cells. Inhibition of the transporters and nucleotidases/phosphatases resulted in a reduction of cytotoxicity of ETC-FdUrd, indicating that this drug was cleaved outside the cells to the monophosphates, which was verified by the presence of FdUrd and ETC in the medium. ETC-L-FdUrd and the liposomal formulation were neither affected by transporter nor nucleotidase/phosphatase inhibition, indicating circumvention of active transporters. In vivo, ETC-FdUrd and ETC-L-FdURd were orally active. ETC nucleotides accumulated in both tumor and liver tissues. These formulations seem to be effective when a lipophilic linker is used combined with a liposomal formulation

Millennial-scale sea surface temperature variability in the western tropical North Atlantic from planktonic foraminiferal census counts

Planktonic foraminiferal census counts are used to construct high-resolution sea surface temperature (SST) and subsurface (thermocline) temperature records at a core site in the Tobago Basin, Lesser Antilles. The record is used to document climatic variability at this tropical site in comparison to middle- and high-latitude sites and to test current concepts of cross-equatorial heat transports as a major player in interhemispheric climate variability. Temperatures are estimated using transfer function and modern analog techniques. Glacial-maximum cooling of 2.5°'3°C is indicated; maximum cooling by 4°C is inferred for isotope stage 3. The SST record displays millennial-scale variability with temperature jumps of up to 3°C and closely tracks the structure of ice-core Dansgaard/Oeschger cycles. SST variations in part of the record run opposite to the SST evolution at high northern latitude sites, pointing to thermohaline circulation and marine heat transport as an important factor driving SST in the tropical and high-latitude Atlantic, both on orbital and suborbital timescales

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured