The proton analysing power in p→p elastic scattering has been measured at small angles at COSY-ANKE at 796 MeV and five other beam energies between 1.6 and 2.4 GeV using a polarised proton beam. The ...asymmetries obtained by detecting the fast proton in the ANKE forward detector or the slow recoil proton in a silicon tracking telescope are completely consistent. Although the analysing power results agree well with the many published data at 796 MeV, and also with the most recent partial wave solution at this energy, the ANKE data at the higher energies lie well above the predictions of this solution at small angles. An updated phase shift analysis that uses the ANKE results together with the World data leads to a much better description of these new measurements.
A new energy-dependent fit strategy, independent of any specific microscopic theory, is applied to kaon photoproduction data with center-of-mass energies ranging from 1625 MeV to 2296 MeV. ...Experimental data are fitted in terms of a modified Laurent expansion (Laurent+Pietarinen expansion) which previously has been successfully applied to multipoles. The present aim is to extract resonance pole parameters directly from the data, rather than from sets of multipoles. A constrained single-energy fit is then used to search for missing structures. In this proof-of-principle study, the data are well-described by the initial L+P fit, and it is shown that only a moderate amount of structure, mostly in higher multipoles, is missing from the original fit. Problems due to an unmeasurable overall phase, plaguing single-channel multipole analyses, are mitigated by implementing a form of phase limitation, fixing the initial values of fit parameters using a multi-channel analysis.
Neutron radiography was used to measure water concentrations through the cross-sections of sprayed gas diffusion electrodes (GDE) and electrospun perfluorosulfonic acid-platinum nanofiber (NF) ...electrodes during fuel cell operation. The performance of Generation 1 poly(acrylic acid)-based NF electrodes is improved at high current densities compared to the baseline given by a GDE cell. Through-thickness water profiles reveal that at high current densities, the water concentrations within the membrane electrode assembly (MEA) and gas diffusion layers are around 2x lower in the nanofiber-containing MEA compared to the baseline GDE, commensurate with the observed polarization performance. In Generation 2 electrospun nanofiber electrodes, poly(ethylene oxide)-based electrodes show higher performance than poly(acrylic acid) electrodes, while retaining less water in the MEA. These results imply that the electrospun nanofiber electrodes have an improved ability to maintain hydration without flooding, which leads to improved performance over a range of relative humidities.
Purpose: To investigate pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors
olomoucine, bohemine, and CYC202 ( R -roscovitine; ...seliciclib) in the HCT116 human colon carcinoma model.
Experimental Design: The in vitro activity of the agents was determined in a human tumor panel using the sulforhodamine B assay. The concentration and time
dependence was established in HCT116 cells. Molecular biomarkers, including RB phosphorylation and cyclin expression, were
assessed by Western blotting. Pharmacokinetic properties were characterized in mice following analysis by liquid chromatography-tandem
mass spectrometry. Based on these studies, a dosing regimen was developed for CYC202 that allowed therapeutic exposures in
the HCT116 tumor xenograft.
Results: The antitumor potency of the agents in vitro was in the order olomoucine (IC 50 , 56 μmol/L) < bohemine (IC 50 , 27 μmol/L) < CYC202 (IC 50 , 15 μmol/L), corresponding to their activities as cyclin-dependent kinase inhibitors. Antitumor activity increased with exposure
time up to 16 hours. The agents caused inhibition of RB and RNA polymerase II phosphorylation and depletion of cyclins. They
exhibited relatively rapid clearance following administration to mice. CYC202 displayed the slowest clearance from plasma
and the highest tumor uptake, with oral bioavailability of 86%. Oral dosing of CYC202 gave active concentrations in the tumor,
modulation of pharmacodynamic markers, and inhibition of tumor growth.
Conclusions: CYC202 showed therapeutic activity on human cancer cell lines in vitro and on xenografts. Pharmacodynamic markers are altered in vitro and in vivo , consistent with the inhibition of cyclin-dependent kinases. Such markers may be potentially useful in the clinical development
of CYC202 and other cyclin-dependent kinase inhibitors.
An experimental study of the η′→π0π0η→6γ decay has been conducted with the best up-to-date statistical accuracy, by measuring η′ mesons produced in the γp→η′p reaction with the A2 tagged-photon ...facility at the Mainz Microtron, MAMI. The results obtained for the standard parametrization of the η′→π0π0η matrix element are consistent with the most recent results for η′→ππη decays, but have smaller uncertainties. The available statistics and experimental resolution allowed, for the first time, an observation of a structure below the π+π− mass threshold, the magnitude and sign of which, checked within the framework of the nonrelativistic effective-field theory, demonstrated good agreement with the cusp that was predicted based on the ππ scattering length combination, a0−a2, extracted from K→3π decays.
Absolute total cross sections for np and pp scattering below 1000 MeV are determined based on partial-wave analyses (PWAs) of nucleon-nucleon scattering data. These cross sections are compared with ...most recent ENDF/B and JENDL data files, and the Nijmegen PWA. Systematic deviations from the ENDF/B and JENDL evaluations are found to exist in the low-energy region.
Many tumors overexpress the NQO1 gene, which encodes DT-diaphorase (NADPH:quinone oxidoreductase; EC 1.6.99.2). This obligate two-electron reductase deactivates toxins and activates bioreductive ...anticancer drugs. We describe the establishment of an isogenic human tumor cell model for DT-diaphorase expression. An expression vector was used in which the human elongation factor 1alpha promoter produces a bicistronic message containing the genes for human NQO1 and puromycin resistance. This was transfected into the human colon BE tumor line, which has a disabling point mutation in NQO1. Two clones, BE2 and BE5, were selected that were shown by immunoblotting and enzyme activity to stably express high levels of DT-diaphorase. Drug response was determined using 96-h exposures compared with the BE vector control. Functional validation of the isogenic model was provided by the much greater sensitivity of the NQO1-transfected cells to the known DT-diaphorase substrates and bioreductive agents streptonigrin (113- to 132-fold) and indoloquinone EO9 (17- to 25-fold) and the inhibition of this potentiation by the DT-diaphorase inhibitor dicoumarol. A lower degree of potentiation was seen with the clinically used agent mitomycin C (6- to 7-fold) and the EO9 analogs, EO7 and EO2, that are poorer substrates for DT-diaphorase (5- to 8-fold and 2- to 3-fold potentiation, respectively), and there was no potentiation or protection with menadione and tirapazamine. Exposure time-dependent potentiation was seen with the diaziquone analogs methyl-diaziquone and RH1 2, 5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone, the latter being an agent in preclinical development. In contrast to the in vitro potentiation, there was no difference in the response to mitomycin C when BE2 and BE vector control were treated as tumor xenografts in vivo. This isogenic model should be valuable for mechanistic studies and bioreductive drug development.
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