Deducing signaling pathways from parallel actions of arsenite and antimonite in human epidermal keratinocytes.

Inorganic arsenic oxides have been identified as carcinogens in several human tissues, including epidermis. Due to the chemical similarity between trivalent inorganic arsenic (arsenite) and antimony (antimonite), we hypothesized that common intracellular targets lead to similarities in cellular responses. Indeed, transcriptional and proteomic profiling revealed remarkable similarities in differentially expressed genes and proteins resulting from exposure of cultured human epidermal keratinocytes to arsenite and antimonite in contrast to comparisons of arsenite with other metal compounds. These data were analyzed to predict upstream regulators and affected signaling pathways following arsenite and antimonite treatments. A majority of the top findings in each category were identical after treatment with either compound. Inspection of the predicted upstream regulators led to previously unsuspected roles for oncostatin M, corticosteroids and ephrins in mediating cellular response. The influence of these predicted mediators was then experimentally verified. Together with predictions of transcription factor effects more generally, the analysis has led to model signaling networks largely accounting for arsenite and antimonite action. The striking parallels between responses to arsenite and antimonite indicate the skin carcinogenic risk of exposure to antimonite merits close scrutiny

Superhumps in Cataclysmic Binaries. XXII. 1RXS J232953.9+062814

We report photometry of 1RXS J232953.9+062814, a recently discovered dwarf nova with a remarkably short 64.2-minute orbital period. In quiescence, the star's light curve is that of a double sinusoid, arising from the "ellipsoidal" distortion of the Roche-lobe-filling secondary. During superoutburst, common superhumps develop with a period 3-4% longer than P_orb. This indicates a mass ratio M_2/M_1=0.19+-0.02, a surprisingly large value in so compact a binary. This implies that the secondary star has a density 2-3 times higher than that of other short-period dwarf novae, suggesting a secondary enriched by H-burning prior to the common-envelope phase of evolution. We estimate i=50+-5 deg, M_1=0.63 (+0.12, -0.09) M_sol, M_2=0.12 (+0.03, -0.02) M_sol, R_2=0.121 (+0.010, -0.007) R_sol, and a distance to the binary of 180+-40 pc.Comment: PDF, 17 pages, 3 tables, 5 figures; accepted, in press, to appear June 2002, PASP; more info at http://cba.phys.columbia.edu

The COSPIX mission: focusing on the energetic and obscured Universe

Tracing the formation and evolution of all supermassive black holes, including the obscured ones, understanding how black holes influence their surroundings and how matter behaves under extreme conditions, are recognized as key science objectives to be addressed by the next generation of instruments. These are the main goals of the COSPIX proposal, made to ESA in December 2010 in the context of its call for selection of the M3 mission. In addition, COSPIX, will also provide key measurements on the non thermal Universe, particularly in relation to the question of the acceleration of particles, as well as on many other fundamental questions as for example the energetic particle content of clusters of galaxies. COSPIX is proposed as an observatory operating from 0.3 to more than 100 keV. The payload features a single long focal length focusing telescope offering an effective area close to ten times larger than any scheduled focusing mission at 30 keV, an angular resolution better than 20 arcseconds in hard X-rays, and polarimetric capabilities within the same focal plane instrumentation. In this paper, we describe the science objectives of the mission, its baseline design, and its performances, as proposed to ESA.Comment: 7 pages, accepted for publication in Proceedings of Science, for the 25th Texas Symposium on Relativistic Astrophysics (eds. F. Rieger & C. van Eldik), PoS(Texas 2010)25

Current perspectives on bone metastases in castrate-resistant prostate cancer

Prostate cancer is the most frequent noncutaneous cancer occurring in men. On average, men with localized prostate cancer have a high 10-year survival rate, and many can be cured. However, men with metastatic castrate-resistant prostate cancer have incurable disease with poor survival despite intensive therapy. This unmet need has led to recent advances in therapy aimed at treating bone metastases resulting from prostate cancer. The bone microenvironment lends itself to metastases in castrate-resistant prostate cancer, as a result of complex interactions between the microenvironment and tumor cells. The development of 223radium dichloride (Ra-223) to treat symptomatic bone metastases has improved survival in men with metastatic castrate-resistant prostate cancer. Moreover, Ra-223 may have effects on the tumor microenvironment that enhance its activity. Ra-223 treatment has been shown to prolong survival, and its effects on the immune system are under investigation. Because prostate cancer affects a sizable portion of the adult male population, understanding how it metastasizes to bone is an important step in advancing therapy. Clinical trials that are underway should yield new information on whether Ra-223 synergizes effectively with immunotherapy agents and whether Ra-223 has enhancing effects on the immune system in patients with prostate cancer

Eclipses During the 2010 Eruption of the Recurrent Nova U Scorpii

The eruption of the recurrent nova U Scorpii on 28 January 2010 is now the all-time best observed nova event. We report 36,776 magnitudes throughout its 67 day eruption, for an average of one measure every 2.6 minutes. This unique and unprecedented coverage is the first time that a nova has any substantial amount of fast photometry. With this, two new phenomena have been discovered: the fast flares in the early light curve seen from days 9-15 (which have no proposed explanation) and the optical dips seen out of eclipse from days 41-61 (likely caused by raised rims of the accretion disk occulting the bright inner regions of the disk as seen over specific orbital phases). The expanding shell and wind cleared enough from days 12-15 so that the inner binary system became visible, resulting in the sudden onset of eclipses and the turn-on of the supersoft X-ray source. On day 15, a strong asymmetry in the out-of-eclipse light points to the existence of the accretion stream. The normal optical flickering restarts on day 24.5. For days 15-26, eclipse mapping shows that the optical source is spherically symmetric with a radius of 4.1 R_sun. For days 26-41, the optical light is coming from a rim-bright disk of radius 3.4 R_sun. For days 41-67, the optical source is a center-bright disk of radius 2.2 R_sun. Throughout the eruption, the colors remain essentially constant. We present 12 eclipse times during eruption plus five just after the eruption.Comment: ApJ in press. 60 pages, 17 figure

The 2001 Superoutburst of WZ Sagittae

We report the results of a worldwide campaign to observe WZ Sagittae during its 2001 superoutburst. After a 23-year slumber at V=15.5, the star rose within 2 days to a peak brightness of 8.2, and showed a main eruption lasting 25 days. The return to quiescence was punctuated by 12 small eruptions, of ~1 mag amplitude and 2 day recurrence time; these "echo outbursts" are of uncertain origin, but somewhat resemble the normal outbursts of dwarf novae. After 52 days, the star began a slow decline to quiescence. Periodic waves in the light curve closely followed the pattern seen in the 1978 superoutburst: a strong orbital signal dominated the first 12 days, followed by a powerful /common superhump/ at 0.05721(5) d, 0.92(8)% longer than P_orb. The latter endured for at least 90 days, although probably mutating into a "late" superhump with a slightly longer mean period [0.05736(5) d]. The superhump appeared to follow familiar rules for such phenomena in dwarf novae, with components given by linear combinations of two basic frequencies: the orbital frequency omega_o and an unseen low frequency Omega, believed to represent the accretion disk's apsidal precession. Long time series reveal an intricate fine structure, with ~20 incommensurate frequencies. Essentially all components occurred at a frequency n(omega_o)-m(Omega), with m=1, ..., n. But during its first week, the common superhump showed primary components at n (omega_o)-Omega, for n=1, 2, 3, 4, 5, 6, 7, 8, 9 (i.e., m=1 consistently); a month later, the dominant power shifted to components with m=n-1. This may arise from a shift in the disk's spiral-arm pattern, likely to be the underlying cause of superhumps. The great majority of frequency components ... . (etc., abstract continues)Comment: PDF, 54 pages, 4 tables, 21 figures, 1 appendix; accepted, in press, to appear July 2002, PASP; more info at http://cba.phys.columbia.edu