Neuregulin-1 beta attenuates doxorubicin-induced alterations of excitation-contraction coupling and reduces oxidative stress in adult rat cardiomyocytes

Treatment of metastatic breast cancer with doxorubicin (Doxo) in combination with trastuzumab, an antibody targeting the ErbB2 receptor, results in an increased incidence of heart failure. Doxo therapy induces reactive oxygen species (ROS) and alterations of calcium homeostasis. Therefore, we hypothesized that neuregulin-1 beta (NRG), a ligand of the cardiac ErbB receptors, reduces Doxo-induced alterations of EC coupling by triggering antioxidant mechanisms. Adult rat ventricular cardiomyocytes (ARVM) were isolated and treated for 18-48 h. SERCA protein was analyzed by Western blot, EC coupling parameters by fura-2 and video edge detection, gene expression by RT-PCR, and ROS by DCF-fluorescence microscopy. At clinically relevant doses Doxo reduced cardiomyocytes contractility, SERCA protein and SR calcium content. NRG, similarly as the antioxidant N-acetylcystein (NAC), did not affect EC coupling alone, but protected against Doxo-induced damage. NRG and Doxo showed an opposite modulation of glutathione reductase gene expression. NRG, similarly as NAC, reduced peroxide- or Doxo-induced oxidative stress. Specific inhibitors showed, that the antioxidant action of NRG depended on signaling via the ErbB2 receptor and on the Akt- and not on the MAPK-pathway. Therefore, NRG attenuates Doxo-induced alterations of EC coupling and reduces oxidative stress in ARVM. Inhibition of the ErbB2/NRG signaling pathway by trastuzumab in patients concomitantly treated with Doxo might prevent beneficial effects of NRG in the myocardium.

Stochastic rank correlation: a robust merit function for 2D/3D registration of image data obtained at different energies

In this article, the authors evaluate a merit function for 2D/3D registration called stochastic rank correlation (SRC). SRC is characterized by the fact that differences in image intensity do not influence the registration result; it therefore combines the numerical advantages of cross correlation (CC)-type merit functions with the flexibility of mutual-information-type merit functions. The basic idea is that registration is achieved on a random subset of the image, which allows for an efficient computation of Spearman's rank correlation coefficient. This measure is, by nature, invariant to monotonic intensity transforms in the images under comparison, which renders it an ideal solution for intramodal images acquired at different energy levels as encountered in intrafractional kV imaging in image-guided radiotherapy. Initial evaluation was undertaken using a 2D/3D registration reference image dataset of a cadaver spine. Even with no radiometric calibration, SRC shows a significant improvement in robustness and stability compared to CC. Pattern intensity, another merit function that was evaluated for comparison, gave rather poor results due to its limited convergence range. The time required for SRC with 5% image content compares well to the other merit functions; increasing the image content does not significantly influence the algorithm accuracy. The authors conclude that SRC is a promising measure for 2D/3D registration in IGRT and image-guided therapy in general.

Extrapolated difference technique for the determination of atomization energies of Sm, Eu, and Yb bromides

An approach for the determination of atomization energies based on the extrapolated difference technique in the framework of Knudsen effusion mass spectrometry is proposed. Its essence is the use of thermodynamic data for the determination of the appearance energy of fragment ions of a reference and a special mathematical treatment of the ionization efficiency functions. The advantages of this approach are demonstrated for the cases of incongruently vaporizing lanthanide bromides that suffer from decomposition or disproportionation at high temperatures. The atomization energies for SmBr2 (7.78±0.12 eV), EuBr2 (7.51±0.11 eV), YbBr2 (7.25±0.13 eV), SmBr3 (11.09±0.10 eV), and YbBr3 (10.23±0.09 eV) molecules have been determined for the first time.

Highly Efficient IR to NIR Upconversion in Gd2O2S: Er3+ for Photovoltaic Applications

Upconversion (UC) is a promising option to enhance the efficiency of solar cells by conversion of sub-bandgap infrared photons to higher energy photons that can be utilized by the solar cell. The UC quantum yield is a key parameter for a successful application. Here the UC luminescence properties of Er3+-doped Gd2O2S are investigated by means of luminescence spectroscopy, quantum yield measurements, and excited state dynamics experiments. Excitation into the maximum of the 4I15/2 → 4I13/2 Er3+ absorption band around 1500 nm induces very efficient UC emission from different Er3+ excited states with energies above the silicon bandgap, in particular, the emission originating from the 4I11/2 state around 1000 nm. Concentration dependent studies reveal that the highest UC quantum yield is realized for a 10% Er3+-doping concentration. The UC luminescence is compared to the well-known Er3+-doped β-NaYF4 UC material for which the highest UC quantum yield has been reported for 25% Er3+. The UC internal quantum yields were measured in this work for Gd2O2S: 10%Er3+ and β-NaYF4: 25%Er3+ to be 12 ± 1% and 8.9 ± 0.7%, respectively, under monochromatic excitation around 1500 nm at a power of 700 W/m2. The UC quantum yield reported here for Gd2O2S: 10%Er3+ is the highest value achieved so far under monochromatic excitation into the 4I13/2 Er3+ level. Power dependence and lifetime measurements were performed to understand the mechanisms responsible for the efficient UC luminescence. We show that the main process yielding 4I11/2 UC emission is energy transfer UC.

Watson–Crick and Sugar-Edge Base Pairing of Cytosine in the Gas Phase: UV and Infrared Spectra of Cytosine·2-Pyridone

While keto-amino cytosine is the dominant species in aqueous solution, spectroscopic studies in molecular beams and in noble gas matrices show that other cytosine tautomers prevail in apolar environments. Each of these offers two or three H-bonding sites (Watson–Crick, wobble, sugar-edge). The mass- and isomer-specific S1 ← S0 vibronic spectra of cytosine·2-pyridone (Cyt·2PY) and 1-methylcytosine·2PY are measured using UV laser resonant two-photon ionization (R2PI), UV/UV depletion, and IR depletion spectroscopy. The UV spectra of the Watson–Crick and sugar-edge isomers of Cyt·2PY are separated using UV/UV spectral hole-burning. Five different isomers of Cyt·2PY are observed in a supersonic beam. We show that the Watson–Crick and sugar-edge dimers of keto-amino cytosine with 2PY are the most abundant in the beam, although keto-amino-cytosine is only the third most abundant tautomer in the gas phase. We identify the different isomers by combining three different diagnostic tools: (1) methylation of the cytosine N1–H group prevents formation of both the sugar-edge and wobble isomers and gives the Watson–Crick isomer exclusively. (2) The calculated ground state binding and dissociation energies, relative gas-phase abundances, excitation and the ionization energies are in agreement with the assignment of the dominant Cyt·2PY isomers to the Watson–Crick and sugar-edge complexes of keto-amino cytosine. (3) The comparison of calculated ground state vibrational frequencies to the experimental IR spectra in the carbonyl stretch and NH/OH/CH stretch ranges strengthen this identification.