Cell cycle-dependent cytotoxicity and induction of apoptosis by liposomal N4-hexadecyl-1-beta-D-arabinofuranosylcytosine.

The clonogenic growth inhibition, the cell cycle dependence of N4-hexadecyl-1-beta-D-arabinofuranosylcytosine (NHAC) cytotoxicity and the capability to induce apoptosis in ara-C-sensitive and -resistant HL-60 cells were investigated and compared with arabinofuranosylcytosine (ara-C). In the clonogenic assay with sensitive HL-60 cells, ara-C was slightly more effective than a liposomal preparation of NHAC, whereas in the resistant cells, NHAC revealed its potency to overcome ara-C resistance, resulting in a 23-fold lower 50% inhibitory concentration compared with ara-C. Cell cycle dependent cytotoxicity and induction of apoptosis were studied by flow cytometry, using the bromodeoxyuridine-propidium iodide and terminal transferase method respectively. In contrast to ara-C, NHAC exerted no phase-specific toxicity at low concentrations (< 40 microM). At higher concentrations the S-phase-specific toxicity increased, probably resulting from ara-C formed from NHAC. NHAC induced apoptosis at higher drug concentrations than ara-C, however apoptosis appeared not to be limited to the S-phase cells. Apoptosis occurred in both cell lines within 2-4 h after drug exposure. These results give further evidence that NHAC exerts its cytotoxicity by different mechanisms of action than ara-C and might therefore be active in ara-C-resistant tumours

The sky distribution of 511 keV positron annihilation line emission as measured with INTEGRAL/SPI

The imaging spectrometer SPI on board ESA's INTEGRAL observatory provides us with an unprecedented view of positron annihilation in our Galaxy. The first sky maps in the 511 keV annihilation line and in the positronium continuum from SPI showed a puzzling concentration of annihilation radiation in the Galactic bulge region. By now, more than twice as many INTEGRAL observations are available, offering new clues to the origin of Galactic positrons. We present the current status of our analyses of this augmented data set. We now detect significant emission from outside the Galactic bulge region. The 511 keV line is clearly detected from the Galactic disk; in addition, there is a tantalizing hint at possible halo-like emission. The available data do not yet permit to discern whether the emission around the bulge region originates from a halo-like component or from a disk component that is very extended in latitude.Comment: to be published in the proceedings of the 6th INTEGRAL Workshop "The Obscured Universe" (3-7 July 2006, Moscow

The Dynamic X-Ray Sky of the Local Universe

Over the next decade, we can expect time domain astronomy to flourish at optical and radio wavelengths. In parallel with these efforts, a dedicated transient machine operating at higher energies (X-ray band through soft gamma-rays) is required to reveal the unique subset of events with variable emission predominantly visible above 100 eV. Here we focus on the transient phase space never yet sampled due to the lack of a sensitive, wide-field and triggering facility dedicated exclusively to catching high energy transients and enabling rapid coordinated multi-wavelength follow-up. We first describe the advancements in our understanding of known X-ray transients that can only be enabled through such a facility and then focus on the classes of transients theoretically predicted to be out of reach of current detection capabilities. Finally there is the exciting opportunity of revealing new classes of X-ray transients and unveiling their nature through coordinated follow-up observations at longer wavelengths

Elevated preoperative Galectin-3 is associated with acute kidney injury after cardiac surgery

Abstract Background Previous research suggests that novel biomarkers may be used to identify patients at increased risk of acute kidney injury following cardiac surgery. The purpose of this study was to evaluate the relationship between preoperative levels of circulating Galectin-3 (Gal-3) and acute kidney injury after cardiac surgery. Methods Preoperative serum Gal-3 was measured in 1498 patients who underwent coronary artery bypass graft (CABG) surgery and/or valve surgery as part of the Northern New England Biomarker Study between 2004 and 2007. Preoperative Gal-3 levels were measured using multiplex assays and grouped into terciles. Univariate and multinomial logistic regression was used to assess the predictive ability of Gal-3 terciles and AKI occurrence and severity. Results Before adjustment, patients in the highest tercile of Gal-3 had a 2.86-greater odds of developing postoperative KDIGO Stage 2 or 3 (p < 0.001) and 1.70-greater odds of developing KDIGO Stage 1 (p = < 0.001), compared to the first tercile. After adjustment, patients in the highest tercile had 2.95-greater odds of developing KDIGO Stage 2 or 3 (p < 0.001) and 1.71-increased odds of developing KDIGO Stage 1 (p = 0.001), compared to the first tercile. Compared to the base model, the addition of Gal-3 terciles improved discriminatory power compared to without Gal-3 terciles (test of equality = 0.042). Conclusion Elevated preoperative Gal-3 levels significantly improves predictive ability over existing clinical models for postoperative AKI and may be used to augment risk information for patients at the highest risk of developing AKI and AKI severity after cardiac surgery.https://deepblue.lib.umich.edu/bitstream/2027.42/145735/1/12882_2018_Article_1093.pd

Observations of SN2011fe with INTEGRAL

SN2011fe was detected by the Palomar Transient Factory on August 24th 2011 in M101 few hours after the explosion. From the early spectra it was immediately realized that it was a Type Ia supernova thus making this event the brightest one discovered in the last twenty years. In this paper the observations performed with the instruments on board of INTEGRAL (SPI, IBIS/ISGRI, JEM-X and OMC) before and after the maximum of the optical light as well as the interpretation in terms of the existing models of $\gamma$--ray emission from such kind of supernovae are reported. All INTEGRAL high-energy have only been able to provide upper limits to the expected emission due to the decay of $^{56}$Ni. These bounds allow to reject explosions involving a massive white dwarf in the sub--Chandrasekhar scenario. On the other hand, the optical light curve obtained with the OMC camera suggests that the event was produced by a delayed detonation of a CO white dwarf that produced $\sim 0.5$ M$\odot$ of $^{56}$Ni. In this particular case, INTEGRAL would have only been able to detect the early $\gamma$--ray emission if the supernova had occurred at a distance of 2 -3 Mpc, although the brightest event could be visible up to distances larger by a factor two.Comment: Proceedings of "An INTEGRAL view of the high-energy sky (the first 10 years)" the 9th INTEGRAL Workshop, October 15-19, 2012, Paris, France, in Proceedings of Science (INTEGRAL 2012), Eds. A. Goldwurm, F. Lebrun and C. Winkler, http://pos.sissa.it/cgi-bin/reader/conf.cgi?confid=176, id number PoS (INTEGRAL 2012) 103 (2013

Observation of SN2011fe with INTEGRAL. I. Pre--maximum phase

SN2011fe was detected by the Palomar Transient Factory on August 24th 2011 in M101 a few hours after the explosion. From the early optical spectra it was immediately realized that it was a Type Ia supernova thus making this event the brightest one discovered in the last twenty years. The distance of the event offered the rare opportunity to perform a detailed observation with the instruments on board of INTEGRAL to detect the gamma-ray emission expected from the decay chains of $^{56}$Ni. The observations were performed in two runs, one before and around the optical maximum, aimed to detect the early emission from the decay of $^{56}$Ni and another after this maximum aimed to detect the emission of $^{56}$Co. The observations performed with the instruments on board of INTEGRAL (SPI, IBIS/ISGRI, JEMX and OMC) have been analyzed and compared with the existing models of gamma-ray emission from such kind of supernovae. In this paper, the analysis of the gamma-ray emission has been restricted to the first epoch. Both, SPI and IBIS/ISGRI, only provide upper-limits to the expected emission due to the decay of $^{56}$Ni. These upper-limits on the gamma-ray flux are of 7.1 $\times$ 10$^{-5}$ ph/s/cm$^2$ for the 158 keV line and of 2.3 $\times$ 10$^{-4}$ ph/s/cm$^2$ for the 812 keV line. These bounds allow to reject at the $2\sigma$ level explosions involving a massive white dwarf, $\sim 1$ M$\odot$ in the sub--Chandrasekhar scenario and specifically all models that would have substantial amounts of radioactive $^{56}$Ni in the outer layers of the exploding star responsible of the SN2011fe event. The optical light curve obtained with the OMC camera also suggests that SN2011fe was the outcome of the explosion, possibly a delayed detonation although other models are possible, of a CO white dwarf that synthesized $\sim 0.55$ M$_\odot$ of $^{56}$Ni. For this specific model.Comment: Accepted for publication in A&A. 10 pages, 10 figure