Deubiquitylating Enzymes and DNA Damage Response Pathways

Covalent post-translational modification of proteins by ubiquitin and ubiquitin-like factors has emerged as a general mechanism to regulate myriad intra-cellular processes. The addition and removal of ubiquitin or ubiquitin-like proteins from factors has recently been demonstrated as a key mechanism to modulate DNA damage response (DDR) pathways. It is thus, timely to evaluate the potential for ubiquitin pathway enzymes as DDR drug targets for therapeutic intervention. The synthetic lethal approach provides exciting opportunities for the development of targeted therapies to treat cancer: most tumours have lost critical DDR pathways, and thus rely more heavily on the remaining pathways, while normal tissues are still equipped with all DDR pathways. Here, we review key deubiquitylating enzymes (DUBs) involved in DDR pathways, and describe how targeting DUBs may lead to selective therapies to treat cancer patients

The Bell Laboratories (13)CO Survey: Longitude-Velocity Maps

A survey is presented of the Galactic plane in the J=1-0 transition of (13)CO. About 73,000 spectra were obtained with the 7 m telescope at Bell Laboratories over a ten-year period. The coverage of survey is (l, b) = (-5 to 117, -1 to +1), or 244 square degrees, with a grid spacing of 3' for |b| < 0.5, and a grid spacing of 6' for |b| > 0.5. The data presented here have been resampled onto a 3' grid. For 0.68 km/s channels, the rms noise level of the survey is 0.1 K on the $T_R^*$ scale. The raw data have been transformed into FITS format, and all the reduction processes, such as correcting for emission in the reference positions, baseline removal and interpolation were conducted within IRAF using the FCRAO task package and additional programs. The reduced data are presented here in the form of longitude-velocity color maps at each latitude. These data allow identification and classification of molecular clouds with masses in excess of ~ 1,000 solar masses throughout the first quadrant of the Galaxy. Spiral structure is manifested by the locations of the largest and brightest molecular clouds.Comment: 23 pages, 7 figures, ApJS submitted (out of 41 frames of Figure4, only one is included becaue of size limit

Discovery of Interstellar Hydrogen Fluoride

We report the first detection of interstellar hydrogen fluoride. Using the Long Wavelength Spectrometer (LWS) of the Infrared Space Observatory (ISO), we have detected the 121.6973 micron J = 2 - 1 line of HF in absorption toward the far-infrared continuum source Sagittarius B2. The detection is statistically significant at the 13 sigma level. On the basis of our model for the excitation of HF in Sgr B2, the observed line equivalent width of 1.0 nm implies a hydrogen fluoride abundance of 3E-10 relative to H2. If the elemental abundance of fluorine in Sgr B2 is the same as that in the solar system, then HF accounts for ~ 2% of the total number of fluorine nuclei. We expect hydrogen fluoride to be the dominant reservoir of gas-phase fluorine in Sgr B2, because it is formed rapidly in exothermic reactions of atomic fluorine with either water or molecular hydrogen; thus the measured HF abundance suggests a substantial depletion of fluorine onto dust grains. Similar conclusions regarding depletion have previously been reached for the case of chlorine in dense interstellar clouds. We also find evidence at a lower level of statistical significance (~ 5 sigma) for an emission feature at the expected position of the 4(3,2)-4(2,3) 121.7219 micron line of water. The emission line equivalent width of 0.5 nm for the water feature is consistent with the water abundance of 5E-6 relative to H2 that has been inferred previously from observations of the hot core of Sgr B2.Comment: 11 pages (AASTeX using aaspp4.sty) plus 2 figures; to appear in ApJ Letter

A Neutral Hydrogen Self-Absorption Cloud in the SGPS

Using data from the Southern Galactic Plane Survey (SGPS) we analyze an HI self-absorption cloud centered on l = 318.0 deg, b = -0.5 deg, and velocity, v = -1.1 km/s. The cloud was observed with the Australia Telescope Compact Array (ATCA) and the Parkes Radio Telescope, and is at a near kinematic distance of less than 400 pc with derived dimensions of less than 5 x 11 pc. We apply two different methods to find the optical depth and spin temperature. In both methods we find upper limit spin temperatures ranging from 20 K to 25 K and lower limit optical depths ~ 1. We look into the nature of the HI emission and find that 60-70% originates behind the cloud. We analyze a second cloud at the same velocity centered on l = 319 deg and b = 0.4 deg with an upper limit spin temperature of 20 K and a lower limit optical depth of 1.6. The similarities in spin temperature, optical depth, velocity, and spatial location are evidence the clouds are associated, possibly as one large cloud consisting of smaller clumps of gas. We compare HI emission data with 12CO emission and find a physical association of the HI self-absorption cloud with molecular gas.Comment: 33 pages, 17 figures, 5 tables; Accepted for publication in ApJ. A version with higher quality images availabe at http://www.astro.umn.edu/~dkavars/ms.p

Deuterated Ammonia in Galactic Protostellar Cores

We report on a survey of \nh2d towards protostellar cores in low-mass star formation and quiescent regions in the Galaxy. Twenty-three out of thirty-two observed sources have significant (\gsim 5\sigma) \nh2d emission. Ion-molecule chemistry, which preferentially enhances deuterium in molecules above its cosmological value of \scnot{1.6}{-5} sufficiently explains these abundances. NH2D/NH3 ratios towards Class 0 sources yields information about the ``fossil remnants'' from the era prior to the onset of core collapse and star formation. We compare our observations with predictions of gas-phase chemical networks.Comment: 16 Pages, 7 Figures, Accepted to Ap.J., to appear in the June 20, 2001 editio

Probing the Early Stages of Low-Mass Star Formation in LDN 1689N: Dust and Water in IRAS 16293-2422A, B, and E

We present deep images of dust continuum emission at 450, 800, and 850 micron of the dark cloud LDN 1689N which harbors the low-mass young stellar objects (YSOs) IRAS 16293-2422A and B (I16293A and I16293B) and the cold prestellar object I16293E. Toward the positions of I16293A and E we also obtained spectra of CO-isotopomers and deep submillimeter observations of chemically related molecules with high critical densities. To I16293A we report the detection of the HDO 1_01 - 0_00 and H2O 1_10 - 1_01 ground-state transitions as broad self-reversed emission profiles with narrow absorption, and a tentative detection of H2D+ 1_10 - 1_11. To I16293E we detect weak emission of subthermally excited HDO 1_01 - 0_00. Based on this set of submillimeter continuum and line data we model the envelopes around I16293A and E. The density and velocity structure of I16293A is fit by an inside-out collapse model, yielding a sound speed of a=0.7 km/s, an age of t=(0.6--2.5)e4 yr, and a mass of 6.1 Msun. The density in the envelope of I16293E is fit by a radial power law with index -1.0+/-0.2, a mass of 4.4 Msun, and a constant temperature of 16K. These respective models are used to study the chemistry of the envelopes of these pre- and protostellar objects. The [HDO]/[H2O] abundance ratio in the warm inner envelope of I16293A of a few times 1e-4 is comparable to that measured in comets. This supports the idea that the [HDO]/[H2O] ratio is determined in the cold prestellar core phase and conserved throughout the formation process of low-mass stars and planets.Comment: 61 pages, 17 figures. Accepted for publication in ApJ. To get Fig. 13: send email to [email protected]

Copernicus Cal/Val Solution - D4.1 - Roadmap and Sustainability Analysis

This document analyses funding and schedule aspects of the Copernicus Cal/Val Solution

Water in massive star-forming regions: HIFI observations of W3 IRS5

We present Herschel observations of the water molecule in the massive star-forming region W3 IRS5. The o-H17O 110-101, p-H18O 111-000, p-H2O 22 202-111, p-H2O 111-000, o-H2O 221-212, and o-H2O 212-101 lines, covering a frequency range from 552 up to 1669 GHz, have been detected at high spectral resolution with HIFI. The water lines in W3 IRS5 show well-defined high-velocity wings that indicate a clear contribution by outflows. Moreover, the systematically blue-shifted absorption in the H2O lines suggests expansion, presumably driven by the outflow. No infall signatures are detected. The p-H2O 111-000 and o-H2O 212-101 lines show absorption from the cold material (T ~ 10 K) in which the high-mass protostellar envelope is embedded. One-dimensional radiative transfer models are used to estimate water abundances and to further study the kinematics of the region. We show that the emission in the rare isotopologues comes directly from the inner parts of the envelope (T > 100 K) where water ices in the dust mantles evaporate and the gas-phase abundance increases. The resulting jump in the water abundance (with a constant inner abundance of 10^{-4}) is needed to reproduce the o-H17O 110-101 and p-H18O 111-000 spectra in our models. We estimate water abundances of 10^{-8} to 10^{-9} in the outer parts of the envelope (T < 100 K). The possibility of two protostellar objects contributing to the emission is discussed.Comment: Accepted for publication in the A&A HIFI special issu

Nitrogen hydrides in the cold envelope of IRAS16293-2422

Nitrogen is the fifth most abundant element in the Universe, yet the gas-phase chemistry of N-bearing species remains poorly understood. Nitrogen hydrides are key molecules of nitrogen chemistry. Their abundance ratios place strong constraints on the production pathways and reaction rates of nitrogen-bearing molecules. We observed the class 0 protostar IRAS16293-2422 with the heterodyne instrument HIFI, covering most of the frequency range from 0.48 to 1.78~THz at high spectral resolution. The hyperfine structure of the amidogen radical o-NH2 is resolved and seen in absorption against the continuum of the protostar. Several transitions of ammonia from 1.2 to 1.8~THz are also seen in absorption. These lines trace the low-density envelope of the protostar. Column densities and abundances are estimated for each hydride. We find that NH:NH2:NH3=5:1:300. {Dark clouds chemical models predict steady-state abundances of NH2 and NH3 in reasonable agreement with the present observations, whilst that of NH is underpredicted by more than one order of magnitude, even using updated kinetic rates. Additional modelling of the nitrogen gas-phase chemistry in dark-cloud conditions is necessary before having recourse to heterogen processes