Torsion–rotation global analysis of the first three torsional states (νt = 0, 1, 2) and terahertz database for methanol

Stimulated by recent THz measurements of the methanol spectrum in one of our laboratories, undertaken in support of NASA programs related to the Herschel Space Observatory (HSO) and the Atacama Large Millimeter Array (ALMA), we have carried out a global analysis of available microwave and high-resolution infrared data for the first three torsional states (νt = 0, 1, 2), and for J values up to 30. This global fit of approximately 5600 frequency measurements and 19 000 Fourier transform far infrared (FTFIR) wavenumber measurements to 119 parameters reaches the estimated experimental measurement accuracy for the FTFIR transitions, and about twice the estimated experimental measurement accuracy for the microwave, submillimeter-wave, and terahertz transitions. The present fit is essentially a continuation of our earlier work, but we have greatly expanded our previous data set and have added a large number of new torsion–rotation interaction terms to the Hamiltonian in our previously used computer program. The results, together with a number of calculated (but unmeasured) transitions, including their line strength, estimated uncertainty, and lower state energy, are made available in the supplementary material as a database formatted to be useful for astronomical searches. Some discussion of several open spectroscopic problems, e.g., (i) an improved notation for the numerous parameters in the torsion–rotation Hamiltonian, (ii) possible causes of the failure to fit frequency measurements to the estimated measurement uncertainty, and (iii) pitfalls to be avoided when intercomparing apparently identical parameters from the internal axis method and the rho axis method are also given

Laboratory Characterization and Astrophysical Detection of Vibrationally Excited States of Vinyl Cyanide in Orion-KL

New laboratory data of CH$_2$CHCN (vinyl cyanide) in its ground and vibrationally excited states at the microwave to THz domain allow searching for these excited state transitions in the Orion-KL line survey. Frequency-modulated spectrometers combined into a single broadband 50-1900 GHz spectrum provided measurements of CH$_2$CHCN covering a spectral range of 18-1893 GHz, whose assignments was confirmed by Stark modulation spectra in the 18-40 GHz region and by ab-initio anharmonic force field calculations. For analyzing the emission lines of CH$_2$CHCN species detected in Orion-KL we used the excitation and radiative transfer code (MADEX) at LTE conditions. The rotational transitions of the ground state of this molecule emerge from four cloud components of hot core nature which trace the physical and chemical conditions of high mass star forming regions in the Orion-KL Nebula. The total column density of CH$_2$CHCN in the ground state is (3.0$\pm$0.9)x10$^{15}$ cm$^{-2}$. We report on the first interstellar detection of transitions in the v10=1/(v11=1,v15=1) dyad in space, and in the v11=2 and v11=3 states in Orion-KL. The lowest energy vibrationally excited states of vinyl cyanide such as v11=1 (at 328.5 K), v15=1 (at 478.6 K), v11=2 (at 657.8 K), the v10=1/(v11=1,v15=1) dyad (at 806.4/809.9 K), and v11=3 (at 987.9 K) are populated under warm and dense conditions, so they probe the hottest parts of the Orion-KL source. Column density and rotational and vibrational temperatures for CH$_2$CHCN in their ground and excited states, as well as for the isotopologues, have been constrained by means of a sample of more than 1000 lines in this survey. Moreover, we present the detection of methyl isocyanide (CH$_3$NC) for the first time in Orion-KL and a tentative detection of vinyl isocyanide (CH$_2$CHNC) and give column density ratios between the cyanide and isocyanide isomers.Comment: 46 pages, 22 figures, 14 tables, 9 online table

THz extended spectrum of the monodeuterated methyl formate (DCOOCH3)

Context. Laboratory spectral recordings and an accurate molecular spectral analysis of any potential interstellar molecule are essential for generating a complete spectroscopic line list. This permits predicting the frequencies and intensities of any transition so that subsequently, it can be identified in the interstellar medium. Aims. Our analysis of DCOOCH3 aims to provide a comprehensive spectral catalog that encompasses as much as possible the frequency coverage of the new-generation far-IR and submillimeter wave observation facilities. Methods. We newly measured the rotational spectrum of DCOOCH3 in the laboratory of the Jet Propulsion Laboratory in the frequency range of 0.85 to 1.5 THz. We jointly analyzed the new data with literature data using the rho axis method, which is a tool developed for the spectral analysis of molecules with large-amplitude internal CH3 rotors. Results. We fit 27 spectroscopic constants of DCOOCH3 to 3763 transitions with highest values of J = 69 and Ka = 36 of the ground torsional state with a standard (unitless) deviation of 0.97. With respect to previous work, this is a significantly better result that was obtained with 2060 more transitions, and we also achieved a better accuracy for the new parameter values.This research was supported by the FIS2011-28738-C02-02 project (MINECO, Spain), the French PCMI (Programme National de Physique Chimie du Milieu Interstellaire), and the National Natural Science Foundation of China (Grant No. 11174098). M.C. acknowledges the research stay at the Universite Paris Diderot under the Guest Faculty programme in May 2014. Portions of this paper present research carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. Government sponsorship is acknowledged

Defining Midbrain Dopaminergic Neuron Diversity by Single-Cell Gene Expression Profiling

SummaryEffective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously evaluate the expression of 96 genes in single neurons. With this approach, we successfully identified multiple molecularly distinct dopamine neuron subtypes and localized them in the adult mouse brain. To validate the anatomical and functional correlates of molecular diversity, we provide evidence that one Vip+ subtype, located in the periaqueductal region, has a discrete projection field within the extended amygdala. Another Aldh1a1+ subtype, located in the substantia nigra, is especially vulnerable in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson’s disease. Overall, this rapid, cost-effective approach enables the identification and classification of multiple dopamine neuron subtypes, with distinct molecular, anatomical, and functional properties

Incidence of Opportunistic Infections and the Impact of Antiretroviral Therapy Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.

BACKGROUND: To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in human immunodeficiency virus (HIV)-infected adults in low- and middle-income countries (LMICs). METHODS: Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random-effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at a CD4 count ≥200 cells/µL were estimated using Joint United Nations Programme on HIV/AIDS (UNAIDS) country estimates and global average OI treatment cost per case. RESULTS: We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range, 57%-91%) except for tuberculosis, and was largest for oral candidiasis, Pneumocystis pneumonia, and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032-874 853), with cost savings of $46.7 million (95$43.8-$49.4 million). CONCLUSIONS: There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted

Incidence and Prevalence of Opportunistic and Other Infections and the Impact of Antiretroviral Therapy Among HIV-infected Children in Low- and Middle-income Countries: A Systematic Review and Meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the incidence and prevalence of 14 opportunistic infections (OIs) and other infections as well as the impact of antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected children (aged 161 000 OIs (2013 UNAIDS data) with estimated cost savings of at least US$17 million per year. CONCLUSIONS: There is a decrease in the risk of most OIs with ART use in HIV-infected children in LMICs, and estimated large potential cost savings in OIs averted with ART use, although there are greater uncertainties in pediatric data compared with that of adults

Influence of the substrate-induced strain and irradiation disorder on the Peierls transition in TTF-TCNQ microdomains

The influence of the combined effects of substrate-induced strain, finite size and electron irradiation-induced defects have been studied on individual micron-sized domains of the organic charge transfer compound tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ) by temperature-dependent conductivity and current-voltage measurements. The individual domains have been isolated by focused ion beam etching and electrically contacted by focused ion and electron beam induced deposition of metallic contacts. The temperature-dependent conductivity follows a variable range hopping behavior which shows a crossover of the exponent as the Peierls transition is approached. The low temperature behavior is analyzed within the segmented rod model of Fogler, Teber and Shklowskii, as originally developed for a charge-ordered quasi one-dimensional electron crystal. The results are compared with data obtained on as-grown and electron irradiated epitaxial TTF-TCNQ thin films of the two-domain type

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing's disease.

The CABLES1 cell cycle regulator participates in the adrenal-pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of CABLES1 mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing's disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for CABLES1 mutations. CNVs were assessed in 116 pediatric CD patients (87 germline DNA only/29 germline and tumor DNA). Four potentially pathogenic missense variants in CABLES1 were identified, two in young adults (c.532G > A, p.E178K and c.718C > T, p.L240F) and two in children (c.935G > A, p.G312D and c.1388A > G, and p.D463G) with CD; no CNVs were found. The four variants affected residues within or close to the predicted cyclin-dependent kinase-3 (CDK3)-binding region of the CABLES1 protein and impaired its ability to block cell growth in a mouse corticotropinoma cell line (AtT20/D16v-F2). The four patients had macroadenomas. We provide evidence for a role of CABLES1 as a novel pituitary tumor-predisposing gene. Its function might link two of the main molecular mechanisms altered in corticotropinomas: the cyclin-dependent kinase/cyclin group of cell cycle regulators and the epidermal growth factor receptor signaling pathway. Further studies are needed to assess the prevalence of CABLES1 mutations among patients with other types of pituitary adenomas and to elucidate the pituitary-specific functions of this gene

Rotational spectra of isotopic species of methyl cyanide, CH3_3CN, in their ground vibrational states up to terahertz frequencies

Methyl cyanide is an important trace molecule in star-forming regions. It is one of the more common molecules used to derive kinetic temperatures in such sources. As preparatory work for Herschel, SOFIA, and in particular ALMA we want to improve the rest frequencies of the main as well as minor isotopologs of methyl cyanide. The laboratory rotational spectrum of methyl cyanide in natural isotopic composition has been recorded up to 1.63 THz. Transitions with good signal-to-noise ratio could be identified for CH$_3$CN, $^{13}$CH$_3$CN, CH$_3^{13}$CN, CH$_3$C$^{15}$N, CH$_2$DCN, and $^{13}$CH$_3^{13}$CN in their ground vibrational states up to about 1.2 THz. The main isotopic species could be identified even in the highest frequency spectral recordings around 1.6 THz. The highest $J'$ quantum numbers included in the fit are 64 for $^{13}$CH$_3^{13}$CN and 89 for the main isotopic species. Greatly improved spectroscopic parameters have been obtained by fitting the present data together with previously reported transition frequencies. The present data will be helpful to identify isotopologs of methyl cyanide in the higher frequency bands of instruments such as the recently launched Herschel satellite, the upcoming airplane mission SOFIA or the radio telescope array ALMA.Comment: 13 pages, 2 figures, article appeared; CDMS links update