Far-Ultraviolet Absorption Lines in the Remnant of SN 1006

We have obtained a far-ultraviolet spectrum (1150-1600 Å) of a hot subdwarf star behind the remnant of supernova 1006 with the Faint Object Spectrograph (FOS) on the Hubble Space Telescope. The high-quality spectrum is used to test previous identifications of the strong absorption features discovered with the International Ultraviolet Explorer. These features have FWHM = 4000 (±300) km s-1 and are not at the rest wavelengths of known interstellar lines, as opposed to the broader (~8000 km s-1 FWHM) Fe II lines from the remnant centered at 0 km s-1 in near-UV FOS spectra. We confirm that the broad absorption features are principally due to redshifted Si II, Si III, and Si IV lines, which are centered at a radial velocity of 5100 (±200) km s-1. The Si II λ1260.4 profile is asymmetric, with a nearly flat core and sharp red wing, unlike the Si II λ1526.7 and Si IV λλ1393.8, 1402.8 profiles. One possible explanation is additional absorption from another species. Previous work has suggested that S II λλ1250.6, 1253.8, 1259.5 at a radial velocity of ~6000 km s-1 is responsible, but this would require a sulfur-to-silicon abundance ratio that is at least a factor of 10 higher than expected. Another possible explanation is that the Si II and Si IV profiles are intrinsically different, but this does not explain the symmetric (albeit weaker) Si II λ1526.7 profile

Far-UV Absorption Lines in the Remnant of SN 1006

We have obtained a far-ultraviolet spectrum (1150 - 1600 Ang.) of a hot subdwarf star behind the remnant of SN 1006 with the Faint Object Spectrograph (FOS) on the Hubble Space Telescope. The high-quality spectrum is used to test previous identifications of the strong absorption features discovered with the International Ultraviolet Explorer. These features have FWHM = 4000 (+/- 300) km/sec and are not at the rest wavelengths of known interstellar lines, as opposed to the broader (8000 km/sec FWHM) Fe II lines from the remnant centered at zero km/sec in near-UV FOS spectra. We confirm that the broad absorption features are principally due to redshifted Si II, Si III, and Si IV lines, which are centered at a radial velocity of 5100 (+/- 200) km/sec. The Si II 1260.4 profile is asymmetric, with a nearly flat core and sharp red wing, unlike the Si II 1526.7 and Si IV 1393.8, 1402.8 profiles. One possible explanation is additional absorption from another species. Previous work has suggested that S II 1250.6, 1253.8, 1259.5 at a radial velocity of 6000 km/sec is responsible, but this would require a sulfur to silicon abundance ratio that is at least a factor of ten higher than expected. Another possible explanation is that the Si II and Si IV profiles are intrinsically different, but this does not explain the symmetric (albeit weaker) Si II 1526.7 profile.Comment: 17 pages, Latex, 2 postscript figures; to appear in ApJ (Letters

Diversity in the Glucose Transporter-4 Gene (SLC2A4) in Humans Reflects the Action of Natural Selection along the Old-World Primates Evolution

BACKGROUND: Glucose is an important source of energy for living organisms. In vertebrates it is ingested with the diet and transported into the cells by conserved mechanisms and molecules, such as the trans-membrane Glucose Transporters (GLUTs). Members of this family have tissue specific expression, biochemical properties and physiologic functions that together regulate glucose levels and distribution. GLUT4 -coded by SLC2A4 (17p13) is an insulin-sensitive transporter with a critical role in glucose homeostasis and diabetes pathogenesis, preferentially expressed in the adipose tissue, heart muscle and skeletal muscle. We tested the hypothesis that natural selection acted on SLC2A4. METHODOLOGY/PRINCIPAL FINDINGS: We re-sequenced SLC2A4 and genotyped 104 SNPs along a approximately 1 Mb region flanking this gene in 102 ethnically diverse individuals. Across the studied populations (African, European, Asian and Latin-American), all the eight common SNPs are concentrated in the N-terminal region upstream of exon 7 ( approximately 3700 bp), while the C-terminal region downstream of intron 6 ( approximately 2600 bp) harbors only 6 singletons, a pattern that is not compatible with neutrality for this part of the gene. Tests of neutrality based on comparative genomics suggest that: (1) episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity downstream of intron 6 and, (2) the target of natural selection may not be in the SLC2A4 coding sequence. CONCLUSIONS: We propose that the contrast in the pattern of genetic variation between the N-terminal and C-terminal regions are signatures of the action of natural selection and thus follow-up studies should investigate the functional importance of different regions of the SLC2A4 gene

An outflow in the Seyfert ESO 362-G18 revealed by Gemini-GMOS/IFU Observations

We present two-dimensional stellar and gaseous kinematics of the inner 0.7 $\times$ 1.2 kpc$^{2}$ of the Seyfert galaxy ESO 362-G18, derived from optical spectra obtained with the GMOS/IFU on the Gemini South telescope at a spatial resolution of $\approx$170 pc and spectral resolution of 36 km s$^{-1}$. ESO 362-G18 is a strongly perturbed galaxy of morphological type Sa or S0/a, with a minor merger approaching along the NE direction. Previous studies have shown that the [OIII] emission shows a fan-shaped extension of $\approx$ 10\arcsec\ to the SE. We detect the [OIII] doublet, [NII] and H${\alpha}$ emission lines throughout our field of view. The stellar kinematics is dominated by circular motions in the galaxy plane, with a kinematic position angle of $\approx$137$^{\circ}$. The gas kinematics is also dominated by rotation, with kinematic position angles ranging from 122$^{\circ}$ to 139$^{\circ}$. A double-Gaussian fit to the [OIII]$\lambda$5007 and H${\alpha}$ lines, which have the highest signal to noise ratios of the emission lines, reveal two kinematic components: (1) a component at lower radial velocities which we interpret as gas rotating in the galactic disk; and (2) a component with line of sight velocities 100-250 km s$^{-1}$ higher than the systemic velocity, interpreted as originating in the outflowing gas within the AGN ionization cone. We estimate a mass outflow rate of 7.4 $\times$ 10$^{-2}$ M$_{\odot}$ yr$^{-1}$ in the SE ionization cone (this rate doubles if we assume a biconical configuration), and a mass accretion rate on the supermassive black hole (SMBH) of 2.2 $\times$ 10$^{-2}$ M$_{\odot}$ yr$^{-1}$. The total ionized gas mass within $\sim$84 pc of the nucleus is 3.3 $\times$ 10$^{5}$ M$_{\odot}$; infall velocities of $\sim$34 km s$^{-1}$ in this gas would be required to feed both the outflow and SMBH accretion.Comment: 18 pages, 14 figure

Outflows in the narrow-line region of bright Seyfert galaxies : I. GMOS-IFU data

We present two-dimensional maps of emission-line fluxes and kinematics, as well as of the stellar kinematics of the central few kpc of five bright nearby Seyfert galaxies –Mrk 6, Mrk 79, Mrk 348, Mrk 607, and Mrk 1058 – obtained from observations with the Gemini Multi-Object Spectrograph Integral Field Unit on the Gemini North Telescope. The data cover the inner 3.5 arcsec×5.0 arcsec – corresponding to physical scales in the range 0.6×0.9–1.5×2.2 kpc2 – at a spatial resolution ranging from 110 to 280 pc with a spectral coverage of 4300–7100Å and velocity resolution of ≈90 km s−1. The gas excitation is Seyfert like everywhere but show excitation gradients that are correlated with the gas kinematics, reddening and/or the gas density. The gas kinematics show in all cases two components: a rotation one similar to that observed in the stellar velocity field, and an outflow component. In the case of Mrk607, the gas is counter-rotating relative to the stars. Enhanced gas velocity dispersion is observed in association with the outflows according to two patterns: at the locations of the highest outflow velocities along the ionization axis or perpendicularly to it in a strip centred at the nucleus that we attribute to an equatorial outflow. Bipolar outflows are observed in Mrk 348 and Mrk 79, while in Mrk 1058 only the blueshifted part is clearly observed, while in cases of Mrk 6 and Mrk 607, the geometry of the outflow needs further constraints from modelling to be presented in a forthcoming study, where the mass flow rate and powers will also be obtained

Feasibility of High-Throughput Genome-Wide Genotyping using DNA from Stored Buccal Cell Samples

It is unclear if buccal cell samples contain sufficient human DNA with adequately sized fragments for high throughput genetic bioassays. Yet buccal cell sample collection is an attractive alternative to gathering blood samples for genetic epidemiologists engaged in large-scale genetic biomarker studies. We assessed the genotyping efficiency (GE) and genotyping concordance (GC) of buccal cell DNA samples compared to corresponding blood DNA samples, from 32 Nurses’ Health Study (NHS) participants using the Illumina Infinium 660W-Quad platform. We also assessed how GE and GC accuracy varied as a function of DNA concentration using serial dilutions of buccal DNA samples. Finally we determined the nature and genomic distribution of discordant genotypes in buccal DNA samples. The mean GE of undiluted buccal cell DNA samples was high (99.32%), as was the GC between the paired buccal and blood samples (99.29%). GC between the dilutions versus the undiluted buccal DNA was also very high (greater than 97%), though both GE and GC notably declined at DNA concentrations less than 5 ng/μl. Most (greater than 95%) genotype determinations in buccal cell samples were of the “missing call” variety (as opposed to the “alternative genotype call” variety) across the spectrum of buccal DNA concentrations studied. Finally, for buccal DNA concentration above 1.7 ng/ul, discordant genotyping calls did not cluster in any particular chromosome. Buccal cell-derived DNA represents a viable alternative to blood DNA for genotyping on a high-density platform

Feasibility of High-Throughput Genome-Wide Genotyping using DNA from Stored Buccal Cell Samples

It is unclear if buccal cell samples contain sufficient human DNA with adequately sized fragments for high throughput genetic bioassays. Yet buccal cell sample collection is an attractive alternative to gathering blood samples for genetic epidemiologists engaged in large-scale genetic biomarker studies. We assessed the genotyping efficiency (GE) and genotyping concordance (GC) of buccal cell DNA samples compared to corresponding blood DNA samples, from 32 Nurses’ Health Study (NHS) participants using the Illumina Infinium 660W-Quad platform. We also assessed how GE and GC accuracy varied as a function of DNA concentration using serial dilutions of buccal DNA samples. Finally we determined the nature and genomic distribution of discordant genotypes in buccal DNA samples. The mean GE of undiluted buccal cell DNA samples was high (99.32%), as was the GC between the paired buccal and blood samples (99.29%). GC between the dilutions versus the undiluted buccal DNA was also very high (>97%), though both GE and GC notably declined at DNA concentrations less than 5 ng/μl. Most (>95%) genotype determinations in buccal cell samples were of the “missing call” variety (as opposed to the “alternative genotype call” variety) across the spectrum of buccal DNA concentrations studied. Finally, for buccal DNA concentration above 1.7 ng/ul, discordant genotyping calls did not cluster in any particular chromosome. Buccal cell-derived DNA represents a viable alternative to blood DNA for genotyping on a high-density platform

High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo