Phosphorothioate Anti-sense Oligonucleotides: The Kinetics and Mechanism of the Generation of the Sulfurising Agent from Phenylacetyl Disulfide (PADS)

The synthesis of phosphorothioate oligonucleotides is often accomplished in the pharmaceutical industry by the sulfurisation of the nucleotide-phosphite using phenylacetyl disulfide (PADS) which has an optimal combination of properties. This is best achieved by an initial ‘ageing’ of PADS for 48 hrs in acetonitrile with 3-picoline to generate polysulfides. The initial base-catalysed degradation of PADS occurs by an E1cB-type elimination to generate a ketene and acyldisulfide anion. Proton abstraction to reversibly generate a carbanion is demonstrated by H/D exchange, the rate of which is greatly increased by electron-withdrawing substituents in the aromatic ring of PADS. The ketene can be trapped intramolecularly by an o-allyl group. The disulfide anion generated subsequently attacks unreacted PADS on sulfur to give polysulfides, the active sulfurising agent. The rate of degradation of PADS is decreased by less basic substituted pyridines and is only first order in PADS indicating that the rate-limiting step is formation of the disulfide anion from the carbanion

Systematic Blueshift of Line Profiles in the Type IIn Supernova 2010jl: Evidence for Post-Shock Dust Formation?

Type IIn SNe show spectral evidence for strong interaction between their blast wave and dense circumstellar material (CSM) around the progenitor star. SN2010jl was the brightest core-collapse SN in 2010, and it was a Type IIn explosion with strong CSM interaction. Andrews et al. recently reported evidence for an IR excess in SN2010jl, indicating either new dust formation or the heating of CSM dust in an IR echo. Here we report multi-epoch spectra of SN2010jl that reveal the tell-tale signature of new dust formation: emission-line profiles becoming systematically more blueshifted as the red side of the line is blocked by increasing extinction. The effect is seen clearly in the intermediate-width (400--4000 km/s) component of H$\alpha$ beginning roughly 30d after explosion. Moreover, we present near-IR spectra demonstrating that the asymmetry in the hydrogen-line profiles is wavelength dependent, appearing more pronounced at shorter wavelengths. This evidence suggests that new dust grains had formed quickly in the post-shock shell of SN 2010jl arising from CSM interaction. Since the observed dust temperature has been attributed to an IR echo and not to new dust, either (1) IR excess emission at $\lambda < 5 \mu$m is not a particularly sensitive tracer of new dust formation in SNe, or (2) some assumptions about expected dust temperatures might require further study. Lastly, we discuss one possible mechanism other than dust that might lead to increasingly blueshifted line profiles in SNeIIn, although the wavelength dependence of the asymmetry argues against this hypothesis in the case of SN2010jl.Comment: 6 pages, 4 figures, submitted to A

The Architecture of the GW Ori Young Triple Star System and Its Disk: Dynamical Masses, Mutual Inclinations, and Recurrent Eclipses

We present spatially and spectrally resolved Atacama Large Millimeter/submillimeter Array (ALMA) observations of gas and dust orbiting the pre-main sequence hierarchical triple star system GW Ori. A forward-modeling of the ${}^{13}$CO and C${}^{18}$O $J$=2-1 transitions permits a measurement of the total stellar mass in this system, $5.29 \pm 0.09\,M_\odot$, and the circum-triple disk inclination, $137.6 \pm 2.0^\circ$. Optical spectra spanning a 35 year period were used to derive new radial velocities and, coupled with a spectroscopic disentangling technique, revealed that the A and B components of GW Ori form a double-lined spectroscopic binary with a $241.50\pm0.05$ day period; a tertiary companion orbits that inner pair with a $4218\pm50$ day period. Combining the results from the ALMA data and the optical spectra with three epochs of astrometry in the literature, we constrain the individual stellar masses in the system ($M_\mathrm{A} \approx 2.7\,M_\odot$, $M_\mathrm{B} \approx 1.7\,M_\odot$, $M_\mathrm{C} \approx 0.9\,M_\odot$) and find strong evidence that at least one (and likely both) stellar orbital planes are misaligned with the disk plane by as much as $45^\circ$. A $V$-band light curve spanning 30 years reveals several new $\sim$30 day eclipse events 0.1-0.7~mag in depth and a 0.2 mag sinusoidal oscillation that is clearly phased with the AB-C orbital period. Taken together, these features suggest that the A-B pair may be partially obscured by material in the inner disk as the pair approaches apoastron in the hierarchical orbit. Lastly, we conclude that stellar evolutionary models are consistent with our measurements of the masses and basic photospheric properties if the GW Ori system is $\sim$1 Myr old.Comment: 26 pages, 15 figures, accepted to Ap

The Gender-GAP Pipeline: A Gender-Aware Polyglot Pipeline for Gender Characterisation in 55 Languages

Gender biases in language generation systems are challenging to mitigate. One possible source for these biases is gender representation disparities in the training and evaluation data. Despite recent progress in documenting this problem and many attempts at mitigating it, we still lack shared methodology and tooling to report gender representation in large datasets. Such quantitative reporting will enable further mitigation, e.g., via data augmentation. This paper describes the Gender-GAP Pipeline (for Gender-Aware Polyglot Pipeline), an automatic pipeline to characterize gender representation in large-scale datasets for 55 languages. The pipeline uses a multilingual lexicon of gendered person-nouns to quantify the gender representation in text. We showcase it to report gender representation in WMT training data and development data for the News task, confirming that current data is skewed towards masculine representation. Having unbalanced datasets may indirectly optimize our systems towards outperforming one gender over the others. We suggest introducing our gender quantification pipeline in current datasets and, ideally, modifying them toward a balanced representation.Comment: 15 page

Leptin and Insulin Act on POMC Neurons to Promote the Browning of White Fat

SummaryThe primary task of white adipose tissue (WAT) is the storage of lipids. However, “beige” adipocytes also exist in WAT. Beige adipocytes burn fat and dissipate the energy as heat, but their abundance is diminished in obesity. Stimulating beige adipocyte development, or WAT browning, increases energy expenditure and holds potential for combating metabolic disease and obesity. Here, we report that insulin and leptin act together on hypothalamic neurons to promote WAT browning and weight loss. Deletion of the phosphatases PTP1B and TCPTP enhanced insulin and leptin signaling in proopiomelanocortin neurons and prevented diet-induced obesity by increasing WAT browning and energy expenditure. The coinfusion of insulin plus leptin into the CNS or the activation of proopiomelanocortin neurons also increased WAT browning and decreased adiposity. Our findings identify a homeostatic mechanism for coordinating the status of energy stores, as relayed by insulin and leptin, with the central control of WAT browning

The architecture of the GW Ori Young triple-star system and its disk : dynamical masses, mutual inclinations, and recurrent eclipses

We present spatially and spectrally resolved Atacama Large Millimeter/submillimeter Array (ALMA) observations of gas and dust orbiting the pre-main-sequence hierarchical triple-star system GW Ori. A forward modeling of the 13CO and C18O J = 2-1 transitions permits a measurement of the total stellar mass in this system, 5.29+/- 0.09 M⊙ , and the circumtriple disk inclination, 137 o. 6+/- 2 o.  0. Optical spectra spanning a 35 yr period were used to derive new radial velocities and, coupled with a spectroscopic disentangling technique, revealed that the A and B components of GW Ori form a double-lined spectroscopic binary with a period of 241.50 ± 0.05 days; a tertiary companion orbits that inner pair with a period of 4218 ± 50 days. Combining the results from the ALMA data and the optical spectra with three epochs of astrometry in the literature, we constrain the individual stellar masses in the system (MA ≈ 2.7 M⊙ , MB ≈ 1.7 M⊙ , MC ≈ 0.9 M⊙) and find strong evidence that at least one of the stellar orbital planes (and likely both) is misaligned with the disk plane by as much as 45°. A V-band light curve spanning 30 yr reveals several new ∼30-day eclipse events 0.1-0.7 mag in depth and a 0.2 mag sinusoidal oscillation that is clearly phased with the AB-C orbital period. Taken together, these features suggest that the A-B pair may be partially obscured by material in the inner disk as the pair approaches apoastron in the hierarchical orbit. Lastly, we conclude that stellar evolutionary models are consistent with our measurements of the masses and basic photospheric properties if the GW Ori system is ∼1 Myr old.Peer reviewe

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol

Introduction: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. Methods and analysis: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2–5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. Ethics and dissemination: Ethical approval has been obtained from the Children’s Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners.Trial registration numberThe trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as ‘Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study – A Multicentre Prospective Trial’. Trial registration: ACTRN12621000904875

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