Chandra observations of the recurrent nova CI Aql after its April 2000 outburst

We report the results of two Chandra observations of the recurrent nova CI Aql at 14 and 16 months after its outburst in April 2000, respectively. The X-ray emission is faint in both cases, without any noticeable change in spectrum or intensity. Although the emission is very soft, it is not luminous enough to be due to late-time H-burning. This implies that the luminous supersoft phase ended even before the time predicted by the most recent calculations. The details of the X-ray spectrum, together with the fact that the observed X-ray intensity is brighter than pre-outburst (1992/1993), suggest that the observed X-ray emission is either due to ionization of the circumstellar material or due to the shocks within the wind and/or with the surrounding medium.Comment: 10 pages ApJ style with 5 figures; accepted for publication in Ap

The 2000 outburst of the recurrent nova CI Aquilae: optical spectroscopy

We present low- and medium resolution spectra of the recurrent nova CI Aquilae taken at 14 epochs in May and June, 2000. The overall appearance is similar to other U Sco-type recurrent novae (U Sco, V394 CrA). Medium resolution (R=7000-10000) hydrogen and iron profiles suggest an early expansion velocity of 2000-2500 km/s. The H\alpha evolution is followed from Dt = -0.6 d to +53 d, starting from a nearly Gaussian shape to a double peaked profile through strong P-Cyg profiles. The interstellar component of the sodium D line and two diffuse interstellar bands put constraints on the interstellar reddening which is estimated to be E(B-V)=0.85\pm0.3. The available visual and CCD-V observations are used to determine t0,t2 and t3. The resulting parameters are: t0=2451669.5\pm0.1, t2=30\pm1 d, t3=36\pm1 d. The recent lightcurve is found to be generally similar to that observed in 1917 with departures as large as 1-2 mag in certain phases. This behaviour is also typical for the U Sco subclass.Comment: 8 pages, 7 figures, accepted for publication in A&

Oligomerization and Nitration of the Grass Pollen Allergen Phl p 5 by Ozone, Nitrogen Dioxide, and Peroxynitrite: Reaction Products, Kinetics, and Health Effects

The allergenic and inflammatory potential of proteins can be enhanced by chemical modification upon exposure to atmospheric or physiological oxidants. The molecular mechanisms and kinetics of such modifications, however, have not yet been fully resolved. We investigated the oligomerization and nitration of the grass pollen allergen Phl p 5 by ozone (O(3)), nitrogen dioxide (NO(2)), and peroxynitrite (ONOO(–)). Within several hours of exposure to atmospherically relevant concentration levels of O(3) and NO(2), up to 50% of Phl p 5 were converted into protein oligomers, likely by formation of dityrosine cross-links. Assuming that tyrosine residues are the preferential site of nitration, up to 10% of the 12 tyrosine residues per protein monomer were nitrated. For the reaction with peroxynitrite, the largest oligomer mass fractions (up to 50%) were found for equimolar concentrations of peroxynitrite over tyrosine residues. With excess peroxynitrite, the nitration degrees increased up to 40% whereas the oligomer mass fractions decreased to 20%. Our results suggest that protein oligomerization and nitration are competing processes, which is consistent with a two-step mechanism involving a reactive oxygen intermediate (ROI), as observed for other proteins. The modified proteins can promote pro-inflammatory cellular signaling that may contribute to chronic inflammation and allergies in response to air pollution

Revised analysis of the supersoft X-ray phase, helium enrichment, and turn-off time in the 2000 outburst of recurrent nova CI Aquilae

Recurrent nova CI Aquilae has entered the final decline phase a bit before May of 2001, about 300 days after the optical maximum, showing the slowest evolution among recurrent novae. Based on the optically thick wind mass-loss theory of the thermonuclear runaway model, we have estimated the turn-off time of the CI Aql 2000 outburst. It is in late March of 2001 after a luminous supersoft X-ray source phase lasts 150 days (from November of 2000 until March of 2001). We have also obtained, by fitting our theoretical light curves with the 1917 and 2000 outbursts, the white dwarf (WD) mass to be M_{WD}= 1.2 \pm 0.05 M_\sun, the helium enrichment of the envelope is He/H = 0.5 by number, the mass of the hydrogen-rich envelope on the WD at the optical maximum is \Delta M_{max} = 8.0 x 10^{-6} M_\sun, and the average mass accretion rate is \dot M_{acc}= 1.0 x 10^{-7} M_\sun/yr during the quiescent phase between the 1917 and 2000 outbursts. Using these obtained values, we have consistently reproduced the light curve in quiescence as well as of the two outbursts. We have also discussed the possibility whether or not CI Aql will explode as a Type Ia supernova in a future.Comment: 16 pages including 9 figures, to appear in the Astrophysical Journa

Electron-correlation effects in appearance-potential spectra of Ni

Spin-resolved and temperature-dependent appearance-potential spectra of ferromagnetic Nickel are measured and analyzed theoretically. The Lander self-convolution model which relates the line shape to the unoccupied part of the local density of states turns out to be insufficient. Electron correlations and orbitally resolved transition-matrix elements are shown to be essential for a quantitative agreement between experiment and theory.Comment: LaTeX, 6 pages, 2 eps figures included, Phys. Rev. B (in press

Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors

Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demonstrated independently that these agents can inhibit tumour growth and induce apoptosis in colon cancer in in vivo and in vitro systems. We hypothesized that simultaneous blockade of the VEGF and EGF receptors would enhance the therapy of colon cancer in a mouse model of peritoneal carcinomatosis. Nude mice were given intraperitoneal injection of KM12L4 human colon cancer cells to generate peritoneal metastases. Mice were then randomized into one of four treatment groups: control, anti-VEGFR (DC101), anti-EGFR (C225), or DC101 and C225. Relative to the control group, treatment with DC101 or with DC101+C225 decreased tumour vascularity, growth, proliferation, formation of ascites and increased apoptosis of both tumour cells and endothelial cells. Although C225 therapy did not change any of the above parameters, C225 combined with DC101 led to a significant decrease in tumour vascularity and increases in tumour cell and endothelial cell apoptosis (vs the DC101 group). These findings suggest that DC101 inhibits angiogenesis, endothelial cell survival, and VEGF-mediated ascites formation in a murine model of colon cancer carcinomatosis. The addition of C225 to DC101 appears to lead to a further decrease in angiogenesis and ascites formation. Combination anti-VEGF and anti-EGFR therapy may represent a novel therapeutic strategy for the management of colon peritoneal carcinomatosis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation?

Background: Several c-MET targeting inhibitory molecules have already shown promising results in the treatment of patients with Non-small Cell Lung Cancer (NSCLC). Combination of EGFR-and c-MET-specific molecules may overcome EGFR tyrosine kinase inhibitor (TKI) resistance. The aim of this study was to allow for the identification of patients who might benefit from TKI treatments targeting MET and to narrow in on the diagnostic assessment of MET. Methods: 222 tumor tissues of patients with NSCLC were analyzed concerning c-MET expression and activation in terms of phosphorylation (Y1234/1235 and Y1349) using a microarray format employing immunohistochemistry (IHC). Furthermore, protein expression and MET activation was correlated with the amplification status by Fluorescence in Situ Hybridization (FISH). Results: Correlation was observed between phosphorylation of c-MET at Y1234/1235 and Y1349 (spearman correlation coefficient r(s) = 0.41;p 0.05). c-MET gene amplification was detected in eight of 214 patients (3.7 %). No significant association was observed between c-MET amplification, c-MET protein expression and phosphorylation. Conclusion: Our data indicate, that neither expression of c-MET nor the gene amplification status might be the best way to select patients for MET targeting therapies, since no correlation with the activation status of MET was observed. We propose to take into account analyzing the phosphorylation status of MET by IHC to select patients for MET targeting therapies. Signaling of the receptor and the activation of downstream molecules might be more crucial for the benefit of therapeutics targeting MET receptor tyrosine kinases than expression levels alone

ARCTIC: Durvalumab + tremelimumab and durvalumab monotherapy vs SoC in ≥ 3L advanced NSCLC treatment

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Randomised study of adjuvant chemotherapy for completely resected p-stage I–IIIA non-small cell lung cancer

We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). We also examined the relation between DNA ploidy pattern and the response to chemotherapy. A total of 267 patients with NSCLC (pathologically documented stage I, II, or IIIA) underwent complete resection, and DNA ploidy pattern was analysed. Patients with stage I disease (n=172) were randomly assigned to receive surgery alone (group A) or surgery followed by adjuvant chemotherapy (UFT (oral anti-cancer drug, a combination of Uracil and Tegaful) 400 mg day−1 for 1 year after surgery; group B). Stage II or IIIA disease patients (n=95) were randomly assigned to surgery alone (group C) or surgery followed by chemotherapy (two 28-day courses of cisplatin 80 mg m−2 on day 1 plus vindesine 3 mg m−2 on days 1 and 8, followed by UFT 400 mg day−1 for at least 1 year; group D). Eight-year overall survival rate in patients with stage I disease was 74.2% (95% confidence interval (CI): 64.4–84.0%) in group B and 57.6% (95% CI: 46.4–68.8%) in group A (P=0.045 by log-rank test). In patients with stage II and IIIA disease, no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups. Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC. No difference was seen in relation to DNA pattern in any treatment group