Effects of D-amino acid oxidase inhibition on memory performance and long-term potentiation in vivo

N-methyl-d-aspartate receptor (NMDAR) activation can initiate changes in synaptic strength, evident as long-term potentiation (LTP), and is a key molecular correlate of memory formation. Inhibition of d-amino acid oxidase (DAAO) may increase NMDAR activity by regulating d-serine concentrations, but which neuronal and behavioral effects are influenced by DAAO inhibition remain elusive. In anesthetized rats, extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded before and after a theta frequency burst stimulation (TBS) of the Schaffer collateral pathway of the CA1 region in the hippocampus. Memory performance was assessed after training with tests of contextual fear conditioning (FC, mice) and novel object recognition (NOR, rats). Oral administration of 3, 10, and 30 mg/kg 4H-furo[3,2-b]pyrrole-5-carboxylic acid (SUN) produced dose-related and steady increases of cerebellum d-serine in rats and mice, indicative of lasting inhibition of central DAAO. SUN administered 2 h prior to training improved contextual fear conditioning in mice and novel object recognition memory in rats when tested 24 h after training. In anesthetized rats, LTP was established proportional to the number of TBS trains. d-cycloserine (DCS) was used to identify a submaximal level of LTP (5× TBS) that responded to NMDA receptor activation; SUN administered at 10 mg/kg 3–4 h prior to testing similarly increased in vivo LTP levels compared to vehicle control animals. Interestingly, in vivo administration of DCS also increased brain d-serine concentrations. These results indicate that DAAO inhibition increased NMDAR-related synaptic plasticity during phases of post training memory consolidation to improve memory performance in hippocampal-dependent behavioral tests

Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study

Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptors agonist, has demonstrated efficacy in the treatment of patients with an acute exacerbation of schizophrenia in a 4-week, double-blind, placebo-controlled study. The aim of this 26-week open-label extension study was to evaluate the safety and effectiveness of ulotaront (25/50/75 mg/d) in patients who completed the initial 4-week study. Of the 193 4-week completers, 157 patients (81.3%) continued into the open-label extension study; 66.9% were completers. Among all extension phase patients, treatment with ulotaront was associated with minimal changes in body weight (mean [SD] change from double-blind baseline: -0.3 [3.7] kg), cholesterol (median change, -2.0 mg/dL), triglycerides (median, -5.0 mg/dL), and prolactin (female, median, -3.4 ng/mL; male, median, -2.7 ng/mL). Movement disorder scales showed no extrapyramidal effects. Twenty-six weeks of extension phase treatment was associated with a mean (95% CI) observed change from open-label baseline in the PANSS total score of -22.6 (-25.6, -19.6; effect size, 1.46), and a mean (95% CI) change in the CGI-Severity score of -1.0 (-1.2, -0.8; effect size, 1.07). Long-term treatment with the TAAR1 agonist ulotaront, in the daily dose range of 25-75 mg, was characterized by a relatively high completion rate, an adverse event profile notable for the absence of extrapyramidal-related adverse effects, a low liability for adverse weight and metabolic effects, and no effect on prolactin levels. Additional studies are needed to further confirm the long-term efficacy and safety of ulotaront

Discovery of an active supermassive black hole in the bulge-less galaxy NGC 4561

We present XMM-Newton observations of the Chandra-detected nuclear X-ray source in NGC 4561. The hard X-ray spectrum can be described by a model composed of an absorbed power-law with Gamma= 2.5^{+0.4}_{-0.3}, and column density N_H=1.9^{+0.1}_{-0.2} times 10^{22} atoms cm^{-2}. The absorption corrected luminosity of the source is L(0.2 - 10.0 keV) = 2.5 times 10^{41} ergs s^{-1}, with bolometric luminosity over 3 \times 10^{42} ergs s^{-1}. Based on the spectrum and the luminosity, we identify the nuclear X-ray source in NGC 4561 to be an AGN, with a black hole of mass M_BH > 20,000 solar masses. The presence of a supermassive black hole at the center of this bulge-less galaxy shows that black hole masses are not necessarily related to bulge properties, contrary to the general belief. Observations such as these call into question several theoretical models of BH--galaxy co-evolution that are based on merger-driven BH growth; secular processes clearly play an important role. Several emission lines are detected in the soft X-ray spectrum of the source which can be well parametrized by an absorbed diffuse thermal plasma with non-solar abundances of some heavy elements. Similar soft X-ray emission is observed in spectra of Seyfert 2 galaxies and low luminosity AGNs, suggesting an origin in the circumnuclear plasma.Comment: To appear in Ap

Local Lyman Break Galaxy Analogs: The Impact of Massive Star-forming Clumps on the Interstellar Medium and the Global Structure of Young, Forming Galaxies

We present HST UV/optical imaging, Spitzer mid-IR photometry, and optical spectroscopy of a sample of 30 low-redshift (z=0.1-0.3) galaxies chosen from SDSS/GALEX to be accurate local analogs of the high-z Lyman Break Galaxies. The Lyman Break Analogs (LBAs) are similar in mass, metallicity, dust, SFR, size and gas velocity dispersion, thus enabling a detailed investigation of processes that are important at high-z. The optical emission line properties of LBAs are also similar to those of LBGs, indicating comparable conditions in their ISM. In the UV, LBAs are characterized by complexes of massive star-forming "clumps", while in the optical they most often show evidence for (post-)mergers/interactions. In 6 cases, we find an extremely massive (>10^9 Msun) compact (R~100 pc) dominant central object (DCO). The DCOs are preferentially found in LBAs with the highest mid-IR luminosities and correspondingly high SFRs (15-100 Msun/yr). We show that the massive SF clumps (including the DCOs) have masses much larger than the nuclear super star clusters seen in normal late type galaxies. However, the DCOs have masses, sizes, and densities similar to the excess-light/central-cusps seen in typical elliptical galaxies with masses similar to the LBA galaxies. We suggest that the DCOs form in present-day examples of the dissipative mergers at high redshift that are believed to have produced the central-cusps in local ellipticals. More generally, the properties of the LBAs are consistent with the idea that instabilities in a gas-rich disk lead to very massive star-forming clumps that eventually coalesce to form a spheroid. We speculate that the DCOs are too young at present to be growing a supermassive black hole because they are still in a supernova-dominated outflow phase.Comment: The Astrophysical Journal, In Press (22 pages, 16 figures). For the full version with high-resolution colour figures, see: http://www.mpa-garching.mpg.de/~overzier/Overzier_LBApaper09.pd

The Hubble Space Telescope Wide Field Camera 3 Early Release Science data: Panchromatic Faint Object Counts for 0.2-2 microns wavelength

We describe the Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) Early Release Science (ERS) observations in the Great Observatories Origins Deep Survey (GOODS) South field. The new WFC3 ERS data provide calibrated, drizzled mosaics in the UV filters F225W, F275W, and F336W, as well as in the near-IR filters F098M (Ys), F125W (J), and F160W (H) with 1-2 HST orbits per filter. Together with the existing HST Advanced Camera for Surveys (ACS) GOODS-South mosaics in the BViz filters, these panchromatic 10-band ERS data cover 40-50 square arcmin at 0.2-1.7 {\mu}m in wavelength at 0.07-0.15" FWHM resolution and 0.090" Multidrizzled pixels to depths of AB\simeq 26.0-27.0 mag (5-{\sigma}) for point sources, and AB\simeq 25.5-26.5 mag for compact galaxies. In this paper, we describe: a) the scientific rationale, and the data taking plus reduction procedures of the panchromatic 10-band ERS mosaics; b) the procedure of generating object catalogs across the 10 different ERS filters, and the specific star-galaxy separation techniques used; and c) the reliability and completeness of the object catalogs from the WFC3 ERS mosaics. The excellent 0.07-0.15" FWHM resolution of HST/WFC3 and ACS makes star- galaxy separation straightforward over a factor of 10 in wavelength to AB\simeq 25-26 mag from the UV to the near-IR, respectively.Comment: 51 pages, 71 figures Accepted to ApJS 2011.01.2

The JCMT Nearby Galaxies Legacy Survey VII: H\alpha{} imaging and massive star formation properties

We present H\alpha{} fluxes, star formation rates (SFRs) and equivalent widths (EWs) for a sample of 156 nearby galaxies observed in the 12CO J=3-2 line as part of the James Clerk Maxwell Telescope Nearby Galaxies Legacy Survey. These are derived from images and values in the literature and from new H\alpha{} images for 72 galaxies which we publish here. We describe the sample, observations and procedures to extract the H\alpha{} fluxes and related quantities. We discuss the SFR properties of our sample and confirm the well-known correlation with galaxy luminosity, albeit with high dispersion. Our SFRs range from 0.1 to 11 Msun yr-1 with a median SFR value for the complete sample of 0.2 Msun yr-1. This median values is somewhat lower than similar published measurements, which we attribute, in part, to our sample being HI-selected and, thus, not biased towards high SFRs as has frequently been the case in previous studies. Additionally, we calculate internal absorptions for the H\alpha{} line, A(H\alpha{}), which are lower than many of those used in previous studies. Our derived EWs, which range from 1 to 880\AA{} with a median value of 27\AA{}, show little dependence with luminosity but rise by a factor of five from early- to late-type galaxies. This paper is the first in a series aimed at comparing SFRs obtained from H\alpha{} imaging of galaxies with information derived from other tracers of star formation and atomic and molecular gas.Comment: Accepted for publication in MNRAS. 47 pages, 18 figure

The Allen Telescope Array Twenty-centimeter Survey - A 690-Square-Degree, 12-Epoch Radio Dataset - I: Catalog and Long-Duration Transient Statistics

We present the Allen Telescope Array Twenty-centimeter Survey (ATATS), a multi-epoch (12 visits), 690 square degree radio image and catalog at 1.4GHz. The survey is designed to detect rare, very bright transients as well as to verify the capabilities of the ATA to form large mosaics. The combined image using data from all 12 ATATS epochs has RMS noise sigma = 3.94mJy / beam and dynamic range 180, with a circular beam of 150 arcsec FWHM. It contains 4408 sources to a limiting sensitivity of S = 20 mJy / beam. We compare the catalog generated from this 12-epoch combined image to the NRAO VLA Sky Survey (NVSS), a legacy survey at the same frequency, and find that we can measure source positions to better than ~20 arcsec. For sources above the ATATS completeness limit, the median flux density is 97% of the median value for matched NVSS sources, indicative of an accurate overall flux calibration. We examine the effects of source confusion due to the effects of differing resolution between ATATS and NVSS on our ability to compare flux densities. We detect no transients at flux densities greater than 40 mJy in comparison with NVSS, and place a 2-sigma upper limit on the transient rate for such sources of 0.004 per square degree. These results suggest that the > 1 Jy transients reported by Matsumura et al. (2009) may not be true transients, but rather variable sources at their flux density threshold.Comment: 41 pages, 19 figures, ApJ accepted; corrected minor typo in Table

Massive binary black holes in galactic nuclei and their path to coalescence

Massive binary black holes form at the centre of galaxies that experience a merger episode. They are expected to coalesce into a larger black hole, following the emission of gravitational waves. Coalescing massive binary black holes are among the loudest sources of gravitational waves in the Universe, and the detection of these events is at the frontier of contemporary astrophysics. Understanding the black hole binary formation path and dynamics in galaxy mergers is therefore mandatory. A key question poses: during a merger, will the black holes descend over time on closer orbits, form a Keplerian binary and coalesce shortly after? Here we review progress on the fate of black holes in both major and minor mergers of galaxies, either gas-free or gas-rich, in smooth and clumpy circum-nuclear discs after a galactic merger, and in circum-binary discs present on the smallest scales inside the relic nucleus.Comment: Accepted for publication in Space Science Reviews. To appear in hard cover in the Space Sciences Series of ISSI "The Physics of Accretion onto Black Holes" (Springer Publisher

High spatial resolution imaging of methane and other trace gases with the airborne Hyperspectral Thermal Emission Spectrometer (HyTES)

Currently large uncertainties exist associated with the attribution and quantification of fugitive emissions of criteria pollutants and greenhouse gases such as methane across large regions and key economic sectors. In this study, data from the airborne Hyperspectral Thermal Emission Spectrometer (HyTES) have been used to develop robust and reliable techniques for the detection and wide-area mapping of emission plumes of methane and other atmospheric trace gas species over challenging and diverse environmental conditions with high spatial resolution that permits direct attribution to sources. HyTES is a pushbroom imaging spectrometer with high spectral resolution (256 bands from 7.5 to 12 µm), wide swath (1–2 km), and high spatial resolution (∼ 2 m at 1 km altitude) that incorporates new thermal infrared (TIR) remote sensing technologies. In this study we introduce a hybrid clutter matched filter (CMF) and plume dilation algorithm applied to HyTES observations to efficiently detect and characterize the spatial structures of individual plumes of CH_4, H_2S, NH_3, NO_2, and SO_2 emitters. The sensitivity and field of regard of HyTES allows rapid and frequent airborne surveys of large areas including facilities not readily accessible from the surface. The HyTES CMF algorithm produces plume intensity images of methane and other gases from strong emission sources. The combination of high spatial resolution and multi-species imaging capability provides source attribution in complex environments. The CMF-based detection of strong emission sources over large areas is a fast and powerful tool needed to focus on more computationally intensive retrieval algorithms to quantify emissions with error estimates, and is useful for expediting mitigation efforts and addressing critical science questions

The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field

The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5-year campaign, PiGSS will twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on time scales of days to years. We present here observations of a 10 deg^2 region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4-month period and has an rms flux density between 200 and 250 microJy. This represents a deeper image by a factor of 4 to 8 than we will achieve over the entire 10,000 deg^2. We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify ~100$ new flat spectrum radio sources; we project that when completed PiGSS will identify 10^4 flat spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous figure remove