On the Interpretation of the broad-band millimeter-wave flux from Orion

Spectral observations of the core of Orion A at wavelengths around 1.3 mm show a high density of strong, broad emission lines. The combined flux in lines with peak antenna temperatures stronger than 0.2 K accounts for approximately 40 percent of the broad-band millimeter-wave flux from the region. Thus the broad-band flux from Orion A is in large part due to sources other than dust emission

Molecular abundances in OMC-1: The chemical composition of interstellar molecular clouds and the influence of massive star formation

We present here an investigation of the chemical composition of the various regions in the core of the Orion molecular cloud (OMC-1) based on results from the Caltech Owens Valley Radio Observatory (OVRO) millimeter-wave spectral line survey (Sutton et al.; Blake et al.). This survey covered a 55 GHz interval in the 1.3 mm (230 GHz) atmospheric window and contained emission from over 800 resolved spectral features. Of the 29 identified species 14 have a sufficient number of detected transitions to be investigated with an LTE "rotation diagram" technique, in which large numbers of lines are used to estimate both the rotational excitation and the overall abundance. The rotational temperatures and column densities resulting from these fits have then been used to model the emission from those remaining species which either have too few lines or which are too weak to be so analyzed. When different kinematic sources of emission are blended to produce a single feature, Gaussian fits have been used to derive the individual contributions to the total line profile. The uniformly calibrated data in the unique and extensive Caltech spectral line survey lead to accurate estimates of the chemical and physical parameters of the Orion molecular cloud, and place significant constraints on models of interstellar chemistry. A global analysis of the observed abundances shows that the markedly different chemical compositions of the kinematically and spatially distinct Orion subsources may be interpreted in the framework of an evolving, initially quiescent, gas-phase chemistry influenced by the process of massive star formation. The chemical composition of the extended Orion cloud complex is similar to that found in a number of other objects, but the central regions of OMC-1 have had their chemistry selectively altered by the radiation and high-velocity outflow from the young stars embedded deep within the interior of the molecular cloud. Specifically, the extended ridge clouds are inferred to have a low (subsolar) gas-phase oxygen content from the prevalence of reactive carbon-rich species like CN, CCH, and C_3H_2 also found in more truly quiescent objects such as TMC-1. The similar abundances of these and other simple species in clouds like OMC-1, Sgr B2, and TMC-1 lend support to gas-phase ion-molecule models of interstellar chemistry, but grain processes may also play a significant role in maintaining the overall chemical balance in such regions through selective depletion mechanisms and grain mantle processing. In contrast, the chemical compositions of the more turbulent plateau and hot core components of OMC-1 are dominated by high-temperature, shock-induced gas and grain surface neutral-neutral reaction processes. The high silicon/sulfur oxide and water content of the plateau gas is best modeled by fast shock disruption of smaller grain cores to release the more refractory elements followed by a predominantly neutral chemistry in the cooling postshock regions, while a more passive release of grain mantle products driven toward kinetic equilibrium most naturally explains the prominence of fully hydrogenated N-containing species like HCN, NH_3 , CH_3CN, and C_2H_5CN in the hot core. The clumpy nature of the outflow is illustrated by the high-velocity emission observed from easily decomposed molecules such as H_2CO. Areas immediately adjacent to the shocked core in which the cooler, ion-rich gas of the surrounding molecular cloud is mixed with water/oxygen rich gas from the plateau source are proposed to give rise to the enhanced abundances of complex internal rotors such as CH_30H, HCOOCH_3 , and CH_30CH_3 whose line widths are similar to carbon-rich species such as CN and CCH found in the extended ridge, but whose rotational temperatures are somewhat higher and whose spatial extents are much more compact

The rotational emission-line spectrum of Orion A between 247 and 263 GHz

Results are presented from a molecular line survey of the core of the Orion molecular cloud between 247 and 263 GHz. The spectrum contains a total of 243 resolvable lines from 23 different chemical species. When combined with the earlier survey of Orion from 215 to 247 GHz by Sutton et al. (1985), the complete data set includes over 780 emission features from 29 distinct molecules. Of the 23 molecules detected in this survey, only NO, CCH, and HCO^+ were not identified in the lower frequency data. As a result of the supporting laboratory spectroscopy performed to supplement existing millimeter-wave spectral line catalogs, only 33 of the more than 780 lines remain unidentified, of which 16 occur in the upper frequency band. A significant chance remains that a number of these unidentified lines are due to transitions between states of either isotopically substituted or highly excited abundant and complex molecules such as CH_3OH, CH_3OCH_3, and HCOOCH_3, whose rotational spectra are poorly known at present. The very small percentage and weak strength of the unidentified lines implies that the dominant chemical constituents visible at millimeter wavelengths have been identified in the Orion molecular cloud

Excitation of methyl cyanide in the hot core of Orion

The excitation of CH_3CN in the hot core of Orion is examined using high-sensitivity observational data at 1.3 mm. Observed line fluxes are analyzed by means of multilevel statistical equilibrium (SE) calculations which incorporate current theoretical values of the collisional excitation rates. The analysis is applied to both optically thin models of the hot core region and models with significant optical depths. Trapping is found to play a critical role in the excitation of CH_3CN. An optically thin analysis yields a kinetic temperature of 275 K and a cloud density of 2 x 10^6 cm^(-3). Unequal column densities are deduced in this case for the two symmetry species: N_A = 1.4 x 10^(14) cm^(-2) and N_E = 2.0 x 10^(14) cm^(-2). The deduced cloud density and temperature are lowered to 1.5 x 10^6 cm^(-3) and 240 K. The model with trapping is favored because of the agreement with measured sizes of the hot core source and the more plausible N_A/N_E ratio. Analysis of radiative excitation in the hot core indicates it is unlikely to significantly affect the ground vibrational state populations of CH_3CN. It most likely is significant for excitation of the V_8 band

Molecular line survey of Orion A from 215 to 247 GHz

Molecular line emission from the core of the Orion molecular cloud has been surveyed from 215 to 247 GHz to an average sensitivity of about 0.2 K. A total of 544 resolvable lines were detected, of which 517 are identified and attributed to 25 distinct chemical species. A large fraction of the lines are partially blended with other identified transitions. Because of the large line width in the Orion core, the spectrum is near the confusion limit for the weakest lines identified (≈ 0.2 K). The most abundant complex molecules present are HCOOCH_3, CH_30CH_3, and C_2H_5CN, with beam-averaged column densities of about 3X10^(15) cm^(-2). Together with the simpler species S0_2, CH_30H, and CH_3CN, they account for approximately 70% of the lines in the spectrum. Relatively few unidentified lines are present. There are 27 lines clearly present in the spectrum which are currently unidentified. However, many of these are thought to be high-lying transitions of complex asymmetric rotors such as CH_30H. Present spectroscopic data are inadequate to predict the frequencies of such transitions with sufficient accuracy

^(13)CH_3OH in OMC-1

We report the identification of several previously unidentified or misidentified lines toward OMC-1 as components the J = 5 → 4 α-type band of ^(13)CH_30H, deduced by combining accurate laboratory spectroscopy with sensitive broad-band astronomical line searches. An LTE fit to the data yields a rotational temperature of T_(rot)~ 120 K and a ^(13)CH_30H column density of ~1.3 x 10^(15) cm^(-2), averaged over a 30" beam. A ^(12)C/^(13)C ratio of ~30 is derived. The assignment of the feature at 236063 MHz to the blended K = ±2 E transitions of ^(13)CH_30H, rather than to CO^+, removes a major discrepancy between observation and the predictions of ion-molecule chemical models of dense interstellar clouds

Validation of the aMAP score to predict hepatocellular carcinoma development in a cohort of alcohol‐related cirrhosis patients

Background and AimsThe aMAP score was recently devised to predict hepatocellular carcinoma (HCC) development. However, its performance was not tested in alcohol-related cirrhosis (ALC). We aimed to validate the aMAP score in a cohort of ALC patients.MethodStudy participants with ALC from a prior genome-wide association study were included. All participants had a history of high alcohol consumption. Cirrhosis was defined clinically, using fibroscan and/or histology. Patients were followed until the last liver imaging, HCC, liver transplantation (LT) or death with the latter two adjusted as competing risks.ResultsA total of 269 ALC patients were included: male (72.5%), Caucasian (98.9%), median age 56 years, and median Child-Pugh score 7. The median aMAP score was 60: 12.3% low-risk, 35.3% medium-risk and 52.4% high-risk. After a median follow-up of 41 months, 14 patients developed HCC, 27 received LT and 104 died. The aMAP score predicted HCC development (hazard ratio 1.12 per point increase, P < .001) with good separation of cumulative incidence function between risk groups. The area under the time-dependent receiver operating characteristics curve for predicting HCC development was 0.83 at 1 year and 0.82 at 5 years which was similar to ADRESS-HCC and Veterans Affairs Healthcare System scores respectively.ConclusionsWe validated the excellent performance of the aMAP score in ALC and affirm its applicability across wider aetiologies

Versatility in phospho-dependent molecular recognition of the XRCC1 and XRCC4 DNA-damage scaffolds by aprataxin-family FHA domains

Aprataxin, aprataxin and PNKP-like factor (APLF) and polynucleotide kinase phosphatase (PNKP) are key DNA-repair proteins with diverse functions but which all contain a homologous forkhead-associated (FHA) domain. Their primary binding targets are casein kinase 2-phosphorylated forms of the XRCC1 and XRCC4 scaffold molecules which respectively coordinate single-stranded and double-stranded DNA break repair pathways. Here, we present the high-resolution X-ray structure of a complex of phosphorylated XRCC4 with APLF, the most divergent of the three FHA domain family members. This, combined with NMR and biochemical analysis of aprataxin and APLF binding to singly and multiply-phosphorylated forms of XRCC1 and XRCC4, and comparison with PNKP reveals a pattern of distinct but overlapping binding specificities that are differentially modulated by multi-site phosphorylation. Together, our data illuminate important differences between activities of the three phospho-binding domains, in spite of a close evolutionary relationship between them

LINE-1 Evasion of Epigenetic Repression in Humans

Epigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3' transduction. The source (donor) L1 for this insertion was slightly 5' truncated, lacked the YY1 binding site, and was highly mobile when tested in\ua0vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body