Blunted Cystine–Glutamate Antiporter Function in the Nucleus Accumbens Promotes Cocaine-induced Drug Seeking

Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine–glutamate exchange via system xc−, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system xc−. First, we examined whether the cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system xc−. Rats were trained to self-administer cocaine (1 mg/kg/200 μl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0–60 mg/kg, i.p.) in the presence or absence of the system xc− inhibitor (S)-4-carboxyphenylglycine (CPG; 0.5 μM; infused into the nucleus accumbens). N-acetylcysteine attenuated cocaine-primed reinstatement, and this effect was reversed by co-administration of CPG. Secondly, we examined whether reduced system xc− activity is necessary for cocaine-primed reinstatement. To do this, we administered N-acetylcysteine (0 or 90 mg/kg, i.p.) prior to 12 daily self-administration sessions (1 mg/kg/200 μl, i.v.; 6 h/day) since this procedure has previously been shown to prevent reduced activity of system xc−. On the reinstatement test day, we then acutely impaired system xc− in some of the rats by infusing CPG (0.5 μM) into the nucleus accumbens. Rats that had received N-acetylcysteine prior to daily self-administration sessions exhibited diminished cocaine-primed reinstatement; this effect was reversed by infusing the cystine–glutamate exchange inhibitor CPG into the nucleus accumbens. Collectively these data establish system xc− in the nucleus accumbens as a key mechanism contributing to cocaine-primed reinstatement

Repeated \u3cem\u3eN\u3c/em\u3e-Acetylcysteine Administration Alters Plasticity-Dependent Effects of Cocaine

Cocaine produces a persistent reduction in cystine–glutamate exchange via system xc− in the nucleus accumbens that may contribute to pathological glutamate signaling linked to addiction. System xc− influences glutamate neurotransmission by maintaining basal, extracellular glutamate in the nucleus accumbens, which, in turn, shapes synaptic activity by stimulating group II metabotropic glutamate autoreceptors. In the present study, we tested the hypothesis that a long-term reduction in system xc− activity is part of the plasticity produced by repeated cocaine that results in the establishment of compulsive drug seeking. To test this, the cysteine prodrug N-acetylcysteine was administered before daily cocaine to determine the impact of increased cystine–glutamate exchange on the development of plasticity-dependent cocaine seeking. Although N-acetylcysteine administered before cocaine did not alter the acute effects of cocaine on self-administration or locomotor activity, it prevented behaviors produced by repeated cocaine including escalation of drug intake, behavioral sensitization, and cocaine-primed reinstatement. Because sensitization or reinstatement was not evident even 2–3 weeks after the last injection of N-acetylcysteine, we examined whether N-acetylcysteine administered before daily cocaine also prevented the persistent reduction in system xc− activity produced by repeated cocaine. Interestingly, N-acetylcysteine pretreatment prevented cocaine-induced changes in [35S]cystine transport via system xc−, basal glutamate, and cocaine-evoked glutamate in the nucleus accumbens when assessed at least 3 weeks after the last N-acetylcysteine pretreatment. These findings indicate that N-acetylcysteine selectively alters plasticity-dependent behaviors and that normal system xc− activity prevents pathological changes in extracellular glutamate that may be necessary for compulsive drug seeking

Early stages of ramified growth in quasi-two-dimensional electrochemical deposition

I have measured the early stages of the growth of branched metal aggregates formed by electrochemical deposition in very thin layers. The growth rate of spatial Fourier modes is described qualitatively by the results of a linear stability analysis [D.P. Barkey, R.H. Muller, and C.W. Tobias, J. Electrochem. Soc. {\bf 136}, 2207 (1989)]. The maximum growth rate is proportional to $(I/c)^\delta$ where $I$ is the current through the electrochemical cell, $c$ the electrolyte concentration, and $\delta = 1.37 \pm 0.08$. Differences between my results and the theoretical predictions suggest that electroconvection in the electrolyte has a large influence on the instability leading to ramified growth.Comment: REVTeX, four ps figure

The Chandra Source Catalog

The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public ACIS imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents <~ 30''. The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports scientific analysis using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1 sigma uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of <~ 1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively.Comment: To appear in The Astrophysical Journal Supplement Series, 53 pages, 27 figure

Uncertainty in United States coastal wetland greenhouse gas inventorying

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Research Letters 13 (2018): 115005, doi:10.1088/1748-9326/aae157.Coastal wetlands store carbon dioxide (CO2) and emit CO2 and methane (CH4) making them an important part of greenhouse gas (GHG) inventorying. In the contiguous United States (CONUS), a coastal wetland inventory was recently calculated by combining maps of wetland type and change with soil, biomass, and CH4 flux data from a literature review. We assess uncertainty in this developing carbon monitoring system to quantify confidence in the inventory process itself and to prioritize future research. We provide a value-added analysis by defining types and scales of uncertainty for assumptions, burial and emissions datasets, and wetland maps, simulating 10 000 iterations of a simplified version of the inventory, and performing a sensitivity analysis. Coastal wetlands were likely a source of net-CO2-equivalent (CO2e) emissions from 2006–2011. Although stable estuarine wetlands were likely a CO2e sink, this effect was counteracted by catastrophic soil losses in the Gulf Coast, and CH4 emissions from tidal freshwater wetlands. The direction and magnitude of total CONUS CO2e flux were most sensitive to uncertainty in emissions and burial data, and assumptions about how to calculate the inventory. Critical data uncertainties included CH4 emissions for stable freshwater wetlands and carbon burial rates for all coastal wetlands. Critical assumptions included the average depth of soil affected by erosion events, the method used to convert CH4 fluxes to CO2e, and the fraction of carbon lost to the atmosphere following an erosion event. The inventory was relatively insensitive to mapping uncertainties. Future versions could be improved by collecting additional data, especially the depth affected by loss events, and by better mapping salinity and inundation gradients relevant to key GHG fluxes. Social Media Abstract: US coastal wetlands were a recent and uncertain source of greenhouse gasses because of CH4 and erosion.Financial support was provided primarily by NASA Carbon Monitoring Systems (NNH14AY67I) and the USGS Land Carbon Program, with additional support from The Smithsonian Institution, The Coastal Carbon Research Coordination Network (DEB-1655622), and NOAA Grant: NA16NMF4630103

Statistical Characterization of the Chandra Source Catalog

The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray sources in a total area of ~0.75% of the entire sky, using data from ~3,900 separate ACIS observations of a multitude of different types of X-ray sources. In order to maximize the scientific benefit of such a large, heterogeneous data-set, careful characterization of the statistical properties of the catalog, i.e., completeness, sensitivity, false source rate, and accuracy of source properties, is required. Characterization efforts of other, large Chandra catalogs, such as the ChaMP Point Source Catalog (Kim et al. 2007) or the 2 Mega-second Deep Field Surveys (Alexander et al. 2003), while informative, cannot serve this purpose, since the CSC analysis procedures are significantly different and the range of allowable data is much less restrictive. We describe here the characterization process for the CSC. This process includes both a comparison of real CSC results with those of other, deeper Chandra catalogs of the same targets and extensive simulations of blank-sky and point source populations.Comment: To be published in the Astrophysical Journal Supplement Series (Fig. 52 replaced with a version which astro-ph can convert to PDF without issues.

Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group

Chemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or radiation therapy constitute the usual approach to localized Ewing sarcoma in North America. We tested whether chemotherapy intensification through interval compression could improve outcome

Interaction effects on common measures of sensitivity:Choice of measure, type I error, and power

Here we use simulation to assess previously unaddressed problems in the assessment of statistical interactions in detection and recognition tasks. The proportion of hits and false-alarms made by an observer on such tasks is affected by both their sensitivity and bias, and numerous measures have been developed to separate out these two factors. Each of these measures makes different assumptions regarding the underlying process and different predictions as to how false-alarm and hit rates should covary. Previous simulations have shown that choice of an inappropriate measure can lead to inflated type I error rates, or reduced power, for main effects, provided there are differences in response bias between the conditions being compared. Interaction effects pose a particular problem in this context. We show that spurious interaction effects in analysis of variance can be produced, or true interactions missed, even in the absence of variation in bias. Additional simulations show that variation in bias complicates patterns of type I error and power further. This under-appreciated fact has the potential to greatly distort the assessment of interactions in detection and recognition experiments. We discuss steps researchers can take to mitigate their chances of making an error

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected