Chronic l-Alpha Acetylmethadol in Rhesus Monkeys: Discriminative Stimulus and Other Behavioral Measures of Dependence and Withdrawal 1

ABSTRACT This study characterized discriminative stimulus and other effects of naltrexone in rhesus monkeys treated daily with the long-acting opioid l-alpha acetylmethadol (LAAM). An initial dose-finding study assessed the rate-decreasing effects of naltrexone in three monkeys receiving LAAM daily (0.32-1.78 mg/ kg); subsequently, these monkeys and a fourth received 1.0 mg/kg/12 hr of LAAM although discriminating between naltrexone and saline. Responding occurred on the saline lever after the administration of LAAM, whereas Ͼ90% drug-lever responding occurred after the administration of 0.1 mg/kg of naltrexone that also elicited signs of withdrawal. Naloxone and quadazocine, but not morphine, nalbuphine or ketamine, substituted for naltrexone. Morphine and nalbuphine shifted the naltrexone dose-effect curve to the right. Compared to precipitated withdrawal, deprivation-induced withdrawal occasioned less naltrexone-lever responding and fewer observable signs of withdrawal. Maximal naltrexone-level responding occurred 24 to 48 hr after the discontinuation of LAAM treatment; the frequency of other withdrawal signs also peaked 24 to 48 hr after the discontinuation of LAAM. Partial naltrexone-lever responding occurred for up to 10 days after discontinuation of LAAM treatment; 4 and 8 days after the discontinuation of LAAM treatment, 0.1 mg/kg of naltrexone did no further increase naltrexone-lever responding or withdrawal signs suggesting that less-then-maximal naltrexone-lever responding was not due to long-lasting effects of LAAM or its metabolites. The discriminative stimuli that are associated with LAAM deprivation might be different from the stimuli associated with either training condition. This study is the first antagonist discrimination in non-humans primates treated chronically with LAAM and the results indicate that the naltrexone stimulus is related to opioid withdrawal. The frequent administration of some drugs often results in the development of dependence that can be quantified by the severity of withdrawal that occurs after either the discontinuation of drug treatment or the administration of a pharmacologic antagonist. Of particular clinical relevance are the adverse signs and symptoms (i.e., withdrawal) that often emerge on the discontinuation of drug use and that can contribute to the continued drug use. Moreover, individuals often report an increased motivation to obtain and use drugs during periods of withdrawal LAAM is a mu opioid agonist that is used as a maintenance therapy in opioid-dependent patients. In huma

A Long, Hard Look at the Low-Hard State in Accreting Black Holes

We present the first results of coordinated multi-wavelength observations of the Galactic black hole GX 339-4 in a canonical low-hard state, obtained during its 2004 outburst. XMM-Newton observed the source for 2 revolutions, or approximately 280 ksec; RXTE monitored the source throughout this long stare. The resulting data offer the best view yet obtained of the inner accretion flow geometry in the low-hard state, which is thought to be analogous to the geometry in low-luminosity active galactic nuclei. The XMM-Newton spectra clearly reveal the presence of a cool accretion disk component, and a relativistic Fe K emission line. The results of fits made to both components strongly suggest that a standard thin disk remains at or near to the innermost stable circular orbit, at least in bright phases of the low-hard state. These findings indicate that potential links between the inner disk radius and the onset of a steady compact jet, and the paradigm of a radially-recessed disk in the low-hard state, do not hold universally. The results of our observations can best be explained if a standard thin accretion disk fuels a corona which is closely related to, or consistent with, the base of a compact jet. In a brief examination of archival data, we show that Cygnus X-1 supports this picture of the low/hard state. We discuss our results within the context of disk-jet connections and prevailing models for accretion onto black holes.Comment: 13 pages, 10 figures (6 in color), ApJ, in pres

X-ray behaviour of Circinus X-1 - I: X-ray Dips as a diagnostic of periodic behaviour

We examine the periodic nature of detailed structure (particularly dips) in the RXTE/ASM lightcurve of Circinus X-1. The significant phase wandering of the X-ray maxima suggests their identification with the response on a viscous timescale of the accretion disk to perturbation. We find that the X-ray dips provide a more accurate system clock than the maxima, and thus use these as indicators of the times of periastron passage. We fit a quadratic ephemeris to these dips, and find its predictive power for the X-ray lightcurve to be superior to ephemerides based on the radio flares and the full archival X-ray lightcurve. Under the hypothesis that the dips are tracers of the mass transfer rate from the donor, we use their occurrence rate as a function of orbital phase to explore the (as yet unconstrained) nature of the donor. The high $\dot{P}$ term in the ephemeris provides another piece of evidence that Cir X-1 is in a state of dynamical evolution, and thus is a very young post-supernova system. We further suggest that the radio ``synchrotron nebula'' immediately surrounding Cir X-1 is in fact the remnant of the event that created the compact object, and discuss briefly the evidence for and against such an interpretation.Comment: 11 pages, 11 figures, accepted for publication in MNRA

Chandra Observations of SDSS J1004+4112: Constraints on the Lensing Cluster and Anomalous X-Ray Flux Ratios of the Quadruply Imaged Quasar

We present results from Chandra observations of SDSS J1004+4112, a strongly lensed quasar system with a maximum image separation of 15". All four bright images of the quasar, as well as resolved X-ray emission originating from the lensing cluster, are clearly detected. The emission from the lensing cluster extends out to approximately 1.5 arcmin. We measure the bolometric X-ray luminosity and temperature of the lensing cluster to be 4.7e44 erg s^-1 and 6.4 keV, consistent with the luminosity-temperature relation for distant clusters. The mass estimated from the X-ray observation shows excellent agreement with the mass derived from gravitational lensing. The X-ray flux ratios of the quasar images differ markedly from the optical flux ratios, and the combined X-ray spectrum of the images possesses an unusually strong Fe Kalpha emission line, both of which are indicative of microlensing.Comment: 9 pages, 5 figures. Accepted for publication in ApJ. Version with high-quality color figures at http://cosmic.riken.jp/ota/publications/index.htm

Can a combination of the conformal thin-sandwich and puncture methods yield binary black hole solutions in quasi-equilibrium?

We consider combining two important methods for constructing quasi-equilibrium initial data for binary black holes: the conformal thin-sandwich formalism and the puncture method. The former seeks to enforce stationarity in the conformal three-metric and the latter attempts to avoid internal boundaries, like minimal surfaces or apparent horizons. We show that these two methods make partially conflicting requirements on the boundary conditions that determine the time slices. In particular, it does not seem possible to construct slices that are quasi-stationary and avoid physical singularities and simultaneously are connected by an everywhere positive lapse function, a condition which must obtain if internal boundaries are to be avoided. Some relaxation of these conflicting requirements may yield a soluble system, but some of the advantages that were sought in combining these approaches will be lost.Comment: 8 pages, LaTeX2e, 2 postscript figure

Chandra localisation and optical/NIR follow-up of Galactic X-ray sources

We investigate a sample of eleven Galactic X-ray sources recently discovered with INTEGRAL or RXTE with the goal of identifying their optical and/or near-infrared (NIR) counterpart. For this purpose new Chandra positions of nine objects are presented together with follow-up observations of all the targets in the optical and NIR. For the four sources IGR J16194-2810, IGRJ 16479-4514, IGR J16500-3307 and IGR J19308+530, the Chandra position confirms an existing association with an optical/NIR object, while for two sources (XTE J1716-389 and 18490-0000) it rules out previously proposed counterparts indicating new ones. In the case of IGR J17597-220, a counterpart is selected out of the several possibilities proposed in the literature and we present the first association with an optical/NIR source for J16293-4603 and XTE J1743-363. Moreover, optical/NIR observations are reported for XTE J1710-281 and IGR J17254-3257: we investigate the counterpart to the X-ray sources based on their XMM-Newton positions. We discuss the nature of each system considering its optical/NIR and X-ray properties.Comment: 15 pages,14 figures. Accepted for publication on MNRA

GRS 1915+105: The first three months with INTEGRAL

GRS 1915+105 is being observed as part of an Open Time monitoring program with INTEGRAL. Three out of six observations from the monitoring program are presented here, in addition to data obtained through an exchange with other observers. We also present simultaneous RXTE observations of GRS 1915+105. During INTEGRAL Revolution 48 (2003 March 6) the source was observed to be in a highly variable state, characterized by 5-minute quasi-periodic oscillations. During these oscillations, the rise is faster than the decline, and is harder. This particular type of variability has never been observed before. During subsequent INTEGRAL revolutions (2003 March-May), the source was in a steady or ''plateau'' state (also known as class $\chi$ according to Belloni et al. 2000). Here we discuss both the temporal and spectral characteristics of the source during the first three months of observations. The source was clearly detected with all three gamma-ray and X-ray instruments onboard INTEGRAL.Comment: 7 pages, 12 figures. Proceedings of the 5th INTEGRAL Workshop, Munich 16-20 February 2004. ESA SP-552. High resolution version of Fig. 6 can be obtained from http://www.astro.helsinki.fi/~diana/Figure6.p

Search for Early Gamma-ray Production in Supernovae Located in a Dense Circumstellar Medium with the Fermi LAT

Supernovae (SNe) exploding in a dense circumstellar medium (CSM) are hypothesized to accelerate cosmic rays in collisionless shocks and emit GeV gamma rays and TeV neutrinos on a time scale of several months. We perform the first systematic search for gamma-ray emission in Fermi LAT data in the energy range from 100 MeV to 300 GeV from the ensemble of 147 SNe Type IIn exploding in dense CSM. We search for a gamma-ray excess at each SNe location in a one year time window. In order to enhance a possible weak signal, we simultaneously study the closest and optically brightest sources of our sample in a joint-likelihood analysis in three different time windows (1 year, 6 months and 3 months). For the most promising source of the sample, SN 2010jl (PTF10aaxf), we repeat the analysis with an extended time window lasting 4.5 years. We do not find a significant excess in gamma rays for any individual source nor for the combined sources and provide model-independent flux upper limits for both cases. In addition, we derive limits on the gamma-ray luminosity and the ratio of gamma-ray-to-optical luminosity ratio as a function of the index of the proton injection spectrum assuming a generic gamma-ray production model. Furthermore, we present detailed flux predictions based on multi-wavelength observations and the corresponding flux upper limit at 95% confidence level (CL) for the source SN 2010jl (PTF10aaxf).Comment: Accepted for publication in ApJ. Corresponding author: A. Franckowiak ([email protected]), updated author list and acknowledgement

Global optical/infrared - X-ray correlations in X-ray binaries: quantifying disc and jet contributions

The optical/near-infrared (OIR) region of the spectra of low-mass X-ray binaries appears to lie at the intersection of a variety of different emission processes. In this paper we present quasi-simultaneous OIR - X-ray observations of 33 XBs in an attempt to estimate the contributions of various emission processes in these sources, as a function of X-ray state and luminosity. A global correlation is found between OIR and X-ray luminosity for low-mass black hole candidate XBs (BHXBs) in the hard X-ray state, of the form L_OIR is proportional to Lx^0.6. This correlation holds over 8 orders of magnitude in Lx and includes data from BHXBs in quiescence and at large distances (LMC and M31). A similar correlation is found in low-mass neutron star XBs (NSXBs) in the hard state. For BHXBs in the soft state, all the near-infrared (NIR) and some of the optical emission is suppressed below the correlation, a behaviour indicative of the jet switching off/on in transition to/from the soft state. We compare these relations to theoretical models of a number of emission processes. We find that X-ray reprocessing in the disc and emission from the jets both predict a slope close to 0.6 for BHXBs, and both contribute to the OIR in BHXBs in the hard state, the jets producing ~90 percent of the NIR emission at high luminosities. X-ray reprocessing dominates the OIR in NSXBs in the hard state, with possible contributions from the jets (only at high luminosity) and the viscously heated disc. We also show that the optically thick jet spectrum of BHXBs extends to near the K-band. (abridged)Comment: Accepted for publication in MNRAS; 19 pages, 7 figure

Constraints on the Cosmic-Ray Density Gradient beyond the Solar Circle from Fermi gamma-ray Observations of the Third Galactic Quadrant

We report an analysis of the interstellar $\gamma$-ray emission in the third Galactic quadrant measured by the {Fermi} Large Area Telescope. The window encompassing the Galactic plane from longitude 210\arcdeg to 250\arcdeg has kinematically well-defined segments of the Local and the Perseus arms, suitable to study the cosmic-ray densities across the outer Galaxy. We measure no large gradient with Galactocentric distance of the $\gamma$-ray emissivities per interstellar H atom over the regions sampled in this study. The gradient depends, however, on the optical depth correction applied to derive the \HI\ column densities. No significant variations are found in the interstellar spectra in the outer Galaxy, indicating similar shapes of the cosmic-ray spectrum up to the Perseus arm for particles with GeV to tens of GeV energies. The emissivity as a function of Galactocentric radius does not show a large enhancement in the spiral arms with respect to the interarm region. The measured emissivity gradient is flatter than expectations based on a cosmic-ray propagation model using the radial distribution of supernova remnants and uniform diffusion properties. In this context, observations require a larger halo size and/or a flatter CR source distribution than usually assumed. The molecular mass calibrating ratio, $X_{\rm CO} = N({\rm H_{2}})/W_{\rm CO}$, is found to be $(2.08 \pm 0.11) \times 10^{20} {\rm cm^{-2} (K km s^{-1})^{-1}}$ in the Local-arm clouds and is not significantly sensitive to the choice of \HI\ spin temperature. No significant variations are found for clouds in the interarm region.Comment: Corresponding authors: I. A. Grenier ([email protected]); T. Mizuno ([email protected]); L. Tibaldo ([email protected]) accepted for publication in Ap