High Spectral Resolution Observations of the Massive Stars in the Galactic Center

We present high-resolution near-infrared spectra, obtained with the NIRSPEC spectrograph on the W. M. Keck II Telescope, of a collection of hot, massive stars within the central 25 arcseconds of the Galactic center. We have identified a total of twenty-one emission-line stars, seven of which are new radial velocity detections with five of those being classified as He I emission-line stars for the first time. These stars fall into two categories based on their spectral properties: 1) those with narrow 2.112, 2.113 micron He I doublet absorption lines, and 2) those with broad 2.058 micron He I emission lines. These data have the highest spectral resolution ever obtained for these sources and, as a result, both components of the absorption doublet are separately resolved for the first time. We use these spectral features to measure radial velocities. The majority of the measured radial velocities have relative errors of 20 kms, smaller than those previously obtained with proper-motion or radial velocity measurements for similar stellar samples in the Galactic center. The radial velocities estimated from the He I absorption doublet are more robust than those previously estimated from the 2.058 micron emission line, since they do not suffer from confusion due to emission from the surrounding ISM. Using this velocity information, we agree that the stars are orbiting in a somewhat coherent manner but are not as defined into a disk or disks as previously thought. Finally, multi-epoch radial velocity measurements for IRS 16NE show a change in its velocity presumably due to an unseen stellar companion.Comment: ApJ accepted, 42 pages, 16 figure

High Precision Stellar Radial Velocities in the Galactic Center

We present radial velocities for 85 cool stars projected onto the central parsec of the Galaxy. The majority of these velocities have relative errors of $\sim$1 km/s, or a factor of $\sim$30-100 smaller than those previously obtained with proper motion or other radial velocity measurements for a similar stellar sample. The error in a typical individual stellar velocity, including all sources of uncertainty, is 1.7 km/s. Two similar data sets were obtained one month apart, and the total error in the relative velocities is 0.80 km/s\ in the case where an object is common to both data sets. The data are used to characterize the velocity distribution of the old population in the Galctic Center. We find that the stars have a Gaussian velocity distribution with a mean heliocentric velocity of $-10.1\pm$11.0 km/s (blueshifted) and a standard deviation of 100.9$\pm7.7$ km/s; the mean velocity of the sample is consistent with no bulk line-of-sight motion with respect to the Local Standard of Rest. At the 1 sigma level, the data are consistent with a symmetric velocity distribution about any arbitrary axis in the plane of the sky. We find evidence for a flattening in the distribution of late-type stars within a radius of $\sim$0.4 \pc, and infer a volume density distribution of r$^{-1/4}$ in this region. Finally, we establish a first epoch of radial velocity measurements which can be compared to subsequent epochs to measure small accelerations (1 km/s/yr), corresponding to the magnitude expected over a timespan of several years for stars nearest to Sgr A*.Comment: retrieve full version at http://www-int.stsci.edu/$\sim$figer/papers/nirspec/vel

High spatial resolution ToF-SIMS imaging and image analysis strategies to monitor and quantify early phase separation in amorphous solid dispersions

Amorphous solid dispersions (ASDs) are formulations with enhanced drug solubility and dissolution rate compared to their crystalline counterparts, however, they can be inherently thermodynamically unstable. This can lead to amorphous phase separation and drug re-crystallisation, phenomena that are typically faster and more dominant at the product’s surfaces. This study investigates the use of high-resolution time of flight-secondary ion mass spectrometry (ToF-SIMS) imaging as a surface analysis technique combined with image-analysis for the early detection, monitoring and quantification of surface amorphous phase separation in ASDs. Its capabilities are demonstrated for two pharmaceutically relevant ASD systems with distinct re-crystallisation behaviours, prepared using hot melt extrusion (HME) followed by pelletisation or grinding: (1) paracetamol-hydroxypropyl methylcellulose (PCM-HPMC) pellets with drug loadings of 10–50% w/w and (2) indomethacin-polyvinylpyrrolidone (IND-PVP) ground material with drug loadings of 20–85% w/w. PCM-HPMC pellets showed intense phase separation, reaching 100% surface coverage within 1-5 months. In direct comparison, IND-PVP HME ground material was more stable with only a moderate formation of isolated IND-rich clusters. Image analysis allowed the reliable detection and quantification of local drug-rich clusters. An Avrami model was applied to determine and compare phase separation kinetics. The combination of chemical sensitivity and high spatial resolution afforded by SIMS was crucial to enable the study of early phase separation and re-crystallisation at the surface. Compared with traditional methods used to detect crystalline material, such as XRPD, we show that ToF-SIMS enabled detection of surface physical instability already at early stages of drug cluster formation in the first days of storage

Recent advances in alcohol-related liver disease (ALD): summary of a Gut roundtable meeting

Alcohol-related liver disease (ALD), which includes a range of disorders of different severity and is one of the most prevalent types of liver disease worldwide, has recently regained increased attention. Among other reasons, the realisation that any alcohol intake, regardless of type of beverage represents a health risk, and the new therapeutic strategies tested in recently published or undergoing clinical trials spur scientific interest in this area. In April 2019, Gut convened a round table panel of experts during the European Association for the Study of the Liver (EASL) International Liver Congress (ILC) in Vienna to discuss critical and up-to-date issues and clinical trial data regarding ALD, its epidemiology, diagnosis, management, pathomechanisms, possible future treatments and prevention. This paper summarises the discussion and its conclusions

Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging

Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral resolution and 3D imaging capabilities of SIMS combined with the multiplex capabilities of ToF mass spectrometric detection allows for the visualization of pharmaceutical compound and metabolites in single cells. The intact, unlabeled drug compound was successfully detected at therapeutic dosages in macrophages (cell line: NR8383). Chemical information from endogenous biomolecules was used to correlate drug distributions with morphological features. From this spatial analysis, amiodarone was detected throughout the cell with the majority of the compound found in the membrane and subsurface regions and absent in the nuclear regions. Similar results were obtained when the macrophages were doped with amiodarone metabolite, desethylamiodarone. The FWHM lateral resolution measured across an intracellular interface in a high lateral resolution ion images was approximately 550 nm. Overall, this approach provides the basis for studying cellular uptake of pharmaceutical compounds and their metabolites on the single cell level

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

Erratum: “The eighth data release of the Sloan Digital Sky Survey: first data from SDSS-III” (2011, ApJS, 193, 29)

Section 3.5 of Aihara et al. (2011) described various sources of systematic error in the astrometry of the imaging data of the Sloan Digital Sky Survey (SDSS). In addition to these sources of error, there is an additional and more serious error, which introduces a large systematic shift in the astrometry over a large area around the north celestial pole. The region has irregular boundaries but in places extends as far south as declination δ ≈ 41◦. The sense of the shift is that the positions of all sources in the affected area are offset by roughly 250 mas in a northwest direction. We have updated the SDSS online documentation to reflect these errors, and to provide detailed quality information for each SDSS field

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine