ASCA Observations of OAO 1657-415 and its Dust-Scattered X-Ray Halo

We report on two ASCA observations of the high-mass X-ray binary pulsar OAO 1657-415. A short observation near mid-eclipse caught the source in a low-intensity state, with a weak continuum and iron emission dominated by the 6.4-keV fluorescent line. A later, longer observation found the source in a high-intensity state and covered the uneclipsed through mid-eclipse phases. In the high-intensity state, the non-eclipse spectrum has an absorbed continuum component due to scattering by material near the pulsar and 80 per cent of the fluorescent iron emission comes from less than 19 lt-sec away from the pulsar. We find a dust-scattered X-ray halo whose intensity decays through the eclipse. We use this halo to estimate the distance to the source as 7.1 +/- 1.3 kpc.Comment: Accepted for publication in MNRA

Study of the Intracluster and Intergalactic Medium in the Sculptor Supercluster with Suzaku

We studied the high temperature plasma in the direction of the Sculptor supercluster at z=0.108 with Suzaku. Suzaku carried out four observations in the supercluster: namely, A2811, A2811 offset, A2804, A2801 regions in 2005 Nov.--Dec., including the regions beyond the virial radii of these clusters. The study needed precise background estimation because the measured intensity of the redshifted lines, especially those from oxygen, were strongly affected by the the Galactic emission. The spectra taken in the regions outside of the virial radii of the member clusters were used as the background which included both the Galactic and Cosmic X-ray Background (CXB) components. We also used the background data which were taken near the Sculptor supercluster. Temperature and metal abundance profiles were determined to the virial radii of the member clusters, and then we searched for the oxygen line emission in the region outside of the virial radii of the clusters. As a result, the temperature of the clusters decreased toward the virial radii, and the spectral fits for the filament region did not require extra component other than the Galactic and CXB components. We constrained the intensities of O VII and O VIII lines to be less than 8.1 and 5.1 photons cm^-2 s^-1 arcmin^-2, respectively, as 2-sigma upper limits. The intensity of O VII indicates n_H < 1.6e-5 cm^-3 (Z/0.1 Z_solar)^-1/2 (L/25 Mpc)^-1/2, which corresponds to an over density, delta < 60 (Z/0.1 Z_solar)^-1/2 (L/25 Mpc)^-1/2.Comment: 11 pages, 8 figures, accepted for publication in PAS

Search for X-Ray Emission Associated with the Shapley Supercluster with Suzaku

Suzaku performed observations of 3 regions in and around the Shapley supercluster: a region located between A3558 and A3556, at ~0.9 times the virial radii of both clusters, and two other regions at 1{\deg}and 4{\deg}away from the first pointing. The 4{\deg}-offset observation was used to evaluate the Galactic foreground emission. We did not detect significant redshifted Oxygen emission lines (O VII and O VIII) in the spectra of all three pointings, after subtracting the contribution of foreground and background emission. An upper limit for the redshifted O VIII Ka line intensity of the warm-hot intergalactic medium (WHIM) is 1.5 \times 10^-7 photons s^-1 cm^-2 arcmin^-2, which corresponds to an overdensity of ~380 (Z/0.1 Z_solar)^{-1/2} (L/3 Mpc)^{-1/2}, assuming T=3\times10^6 K. We found excess continuum emission in the 1{\deg}-offset and on-filament regions, represented by thermal models with kT ~1 keV and ~2 keV, respectively. The redshifts of both 0 and that of the supercluster (0.048) are consistent with the observed spectra. The ~1 keV emission can be also fitted with Ne-rich Galactic (zero redshift) thin thermal emission. Radial intensity profile of 2 keV component suggests contribution from A3558 and A3556, but with significant steepening of the intensity slope in the outer region of A3558. Finally, we summarized the previous Suzaku search for the WHIM and discussed the feasibility of constraining the WHIM. An overdensity of < 400 can be detectable using O VII and O VIII emission lines in a range of 1.4\times10^6 K < T < 5\times10^6 K or a continuum emission in a relatively high temperature range T > 5\times10^6 K with the Suzaku XIS. The non detection with Suzaku suggests that typical line-of-sight average overdensity is < 400

The Radio Evolution of SN 2001gd

We present the results of observations of the radio emission from Supernova 2001gd in NGC 5033 from 2002 February 8 through 2006 September 25. The data were obtained using the Very Large Array at wavelengths of 1.3 cm (22.4 GHz), 2 cm (14.9 GHz), 3.6 cm (8.4 GHz), 6 cm (4.9 GHz), and 20 cm (1.5 GHz), with one upper limit at 90 cm (0.3 GHz). In addition, one detection has been provided by the Giant Metrewave Radio Telescope at 21 cm (1.4 GHz). SN 2001gd was discovered in the optical well past maximum light, so that it was not possible to obtain many of the early radio "turn-on" measurements which are important for estimating the local circumstellar medium (CSM) properties. Only at 20 cm were turn-on data available. However, our analysis and fitting of the radio light curves, and the assumption that the Type IIb SN 2001gd resembles the much better studied Type IIb SN 1993J, enables us to describe the radio evolution as being very regular through day ~550 and consistent with a nonthermal-emitting model with a thermal absorbing CSM. The presence of synchrotron-self absorption (SSA) at early times is implied by the data, but determination of the exact relationship between the SSA component from the emitting region and the free-free absorption component from the CSM is not possible as there are insufficient early measurements to distinguish between models. After day ~550, the radio emission exhibits a dramatically steeper decline rate which, assuming similarity to SN 1993J, can be described as an exponential decrease with an e-folding time of 500 days. We interpret this abrupt change in the radio flux density decline rate as implying a transition of the shock front into a more tenuous region of circumstellar material. A similar change in radio evolution has been seen earlier in other SNe such as SN 1988Z, SN 1980K, and SN 1993J.Comment: 3 tables, 2 figures, To appear in the Astrophysical Journa

Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)

The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Ape1/ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Ape1 can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Ape1 redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Ape1. Benzoquinone and naphthoquinone analogues of the Ape1-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Ape1 redox activity, and the most potent analogues inhibited tumor cell growth with IC50 values in the 10−20 μM range

Longitudinal, Diet-induced Weight Gain is Associated with Increased Blood Monocytes and Reduced TLR4 Expression

Excessive weight gain increases systemic inflammation resulting in increased disease risk. Toll-like receptor 4 (TLR4) reportedly mediates increases in inflammation; however, its role has not been fully evaluated. Objective. The purpose of this study was to determine the longitudinal effect of diet-induced weight gain on blood monocyte concentration and cell-surface TLR4 expression. Research Methods & Procedures. Male CD-1 mice were randomly assigned to high-fat (HF, n = 12) or low-fat (LF, n = 13) groups. Non-lethal, saphenous vein blood samples were collected at 0, 4, 8 and 12 weeks of treatment. Three-color flow cytometry was used to measure monocyte (CD11b+/CD14+) concentration and TLR4 cells-surface expression. Data were analyzed with a repeated measures ANOVA; significance was set at P\u3c0.05. Results. Body weight at week 12 was 21% greater in HF than LF (P\u3c0.05). At week 12 HF had 155% more monocytes (P\u3c0.05) with 24% less TLR4; Monocyte concentration and body weight at week 12 was negatively correlated with TLR4 gMFI (P\u3c0.05). Conclusions. The observed effects of high-fat feeding on blood monocytes are consistent with a phenotype, which may be associated with premature morbidity. The observed monocyte responses may be associated with immune dysfunction and diminished response to infection

Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic

Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung and leukemias, leading to increased aggressiveness. Transcription factors downstream of Ref-1/APE1 are key contributors to many cancers, and Ref-1/APE1 redox signaling inhibition slows growth and progression in a number of tumor types. Ref-1/APE1 inhibition is also highly effective when paired with other drugs, including standard-of-care therapies and therapies targeting pathways affected by Ref-1/APE1 redox signaling. Additionally, Ref-1/APE1 plays a role in a variety of other indications, such as retinopathy, inflammation, and neuropathy. In this review, we discuss the functional consequences of activation of the Ref-1/APE1 node in cancer and other diseases, as well as potential therapies targeting Ref-1/APE1 and related pathways in relevant diseases. APX3330, a novel oral anticancer agent and the first drug to target Ref-1/APE1 for cancer is entering clinical trials and will be explored in various cancers and other diseases bringing bench discoveries to the clinic