Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery

ObjectivesAnti-inflammatory effects of tranexamic acid and aprotinin, used to abate perioperative blood loss, are reported and might be of substantial clinical relevance. The study of messenger ribonucleic acid synthesis provides a valuable asset in evaluating the inflammatory pathways involved.MethodsWhole-blood messenger ribonucleic acid expression of 114 inflammatory genes was compared pre- and postoperatively in 35 patients randomized to receive either placebo, tranexamic acid, or aprotinin. These results were further confirmed by reverse transcription–polymerase chain reaction.ResultsOf the 23 genes exhibiting independently altered postoperative gene expression levels, 8 were restricted to the aprotinin group only (growth differentiation factor 3, interleukin 19, interleukin 1 family member 7, transforming growth factor α, tumor necrosis factor superfamily 10, tumor necrosis factor superfamily 12, tumor necrosis factor superfamily 13B, vascular endothelial growth factor α), whereas both aprotinin and tranexamic acid altered gene expression of 3 genes as compared with placebo (FMS-related tyrosine kinase 3 ligand, growth differentiation factor 5, interferon-α8). In general, less upregulation of pro-inflammatory, and more upregulation of anti-inflammatory, genes was observed for patients treated with antifibrinolytics. Gene expression affected by aprotinin coded mostly for proteins that function through serine proteases.ConclusionsThis study demonstrates that the use of tranexamic acid and aprotinin results in altered inflammatory pathways on the genomic expression level. We further demonstrate that the use of aprotinin leads to significant attenuation of the immune response, with several inhibitory effects restricted to the use of aprotinin only. The results aid in a better understanding of the targets of these drugs, and add to the discussion on which antifibrinolytic can best be used in the cardiac surgical patient

Black Hole Masses and Star Formation Rates of z >1 Dust Obscured Galaxies (DOGs): Results from Keck OSIRIS Integral Field Spectroscopy

We have obtained high spatial resolution Keck OSIRIS integral field spectroscopy of four z~1.5 ultra-luminous infrared galaxies that exhibit broad H-alpha emission lines indicative of strong AGN activity. The observations were made with the Keck laser guide star adaptive optics system giving a spatial resolution of 0.1", or <1 kpc at these redshifts. These high spatial resolution observations help to spatially separate the extended narrow-line regions --- possibly powered by star formation --- from the nuclear regions, which may be powered by both star formation and AGN activity. There is no evidence for extended, rotating gas disks in these four galaxies. Assuming dust correction factors as high as A(H-alpha)=4.8 mag, the observations suggest lower limits on the black hole masses of (1 - 9) x 10^8 solar masses, and star formation rates <100 solar masses per year. The black hole masses and star formation rates of the sample galaxies appear low in comparison to other high-z galaxies with similar host luminosities. We explore possible explanations for these observations including, host galaxy fading, black hole growth, and the shut down of star formation.Comment: Accepted for publication in the Astronomical Journal. 12 pages, 6 figures, 5 table

First Steps towards Underdominant Genetic Transformation of Insect Populations

The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species. Figure

Spectroscopic identifications of Spitzer sources in the SWIRE/XMM-NEWTON/ELAIS-S1 field: a large fraction of Active Galactic Nuclei with high F(24micron)/F(R) ratio

We present a catalog of optical spectroscopic identifications of sources detected by Spitzer at 3.6 or 24 micron down to 10 and 280 microJy, respectively, in the SWIRE/XMM-Newton/ELAIS-S1 field and classified via line width analysis and diagnostic diagrams. A total of 1376 sources down to R~24.2 mag have been identified (1362 detected at 3.6 micron, 419 at 24 micron, and 405 at both) by low-resolution optical spectroscopy carried out with FORS2, VIMOS, and EFOSC2 at the Very Large Telescope and 3.6m ESO telescopes. The spectroscopic campaigns have been carried out over the central 0.6 square degrees area of ELAIS-S1 which, in particular, has also been observed by XMM-Newton and Chandra. We find the first direct optical spectroscopic evidence that the fraction of active galactic nuclei (AGN; mostly AGN2) increases with increasing F(24 micron)/F(R) ratio, reaching values of 70(+/-20)% in the range 316<F(24 micron)F(R)<1000. We present an IRAC-MIPS color-color diagram able to separate AGN1 from obscured AGN2 candidates. After having corrected for the spectroscopic incompleteness of our sample, it results that the AGN fraction at F(24 micron)=0.8 mJy is ~22(+/-7)% and decreases slowly to ~19(+/-5)% down to F(24 micron)=0.3 mJy.Comment: Accepted for publication in the Astrophysical Journal. 15 pages, 17 figures, 2 table

The central energy source of 70micron-selected galaxies: Starburst or AGN?

We present the first AGN census in a sample of 61 galaxies selected at 70microns, a wavelength which should strongly favour the detection of star-forming systems. For the purpose of this study we take advantage of deep Chandra X-ray and Spitzer infrared (3.6-160micron) data, as well as optical spectroscopy and photometry from the Deep Extragalactic Evolutionary Probe 2 (DEEP2) survey for the Extended Groth Strip (EGS) field. We investigate spectral line diagnostics ([OIII]/Hbeta and [NeIII]/[OII] ratios, Hdelta Balmer absorption line equivalent widths and the strength of the 4000Ang break), X-ray luminosities and spectral energy distributions (SEDs). We find that the 70micron sources are undergoing starburst episodes and are therefore characterised by a predominance of young stars. In addition, 13 per cent of the sources show AGN signatures and hence potentially host an AGN. When the sample is split into starbursts (SBs, 10^10<L_IR<10^11 L_solar), Luminous InfraRed Galaxies (LIRGs, 10^11<L_IR<10^12 L_solar) and UltraLuminous InfraRed Galaxies (ULIRGs,10^12<L_IR<10^13 L_solar), the AGN fraction becomes 0, 11 and 23 per cent respectively, showing an increase with total infrared luminosity. However, by examining the sources' panchromatic SEDs, we conclude that although the AGN is energetically important in 1 out of 61 objects, all 70micron-selected galaxies are primarily powered by star-formation.Comment: 20 pages, 14 figures, accepted for publication in MNRA

History of Galaxy Interactions and their Impact on Star Formation over the Last 7 Gyr from GEMS

We perform a comprehensive estimate of the frequency of galaxy mergers and their impact on star formation over z~0.24--0.80 (lookback time T_b~3--7 Gyr) using 3698 (M*>=1e9 Msun) galaxies with GEMS HST, COMBO-17, and Spitzer data. Our results are: (1) Among 790 high mass (M*>=2.5e10 Msun) galaxies, the visually-based merger fraction over z~0.24--0.80, ranges from 9%+-5% to 8%+-2%. Lower limits on the major and minor merger fractions over this interval range from 1.1% to 3.5%, and 3.6% to 7.5%, respectively. This is the first approximate empirical estimate of the frequency of minor mergers at z<1. For a visibility timescale of ~0.5 Gyr, it follows that over T_b~3--7 Gyr, ~68% of high mass systems have undergone a merger of mass ratio >1/10, with ~16%, 45%, and 7% of these corresponding respectively to major, minor, and ambiguous `major or minor' mergers. The mean merger rate is a few x 1e-4 Gyr-1 Mpc-3. (2) We compare the empirical merger fraction and rate for high mass galaxies to a suite of Lambda CDM-based models: halo occupation distribution models, semi-analytic models, and hydrodynamic SPH simulations. We find qualitative agreement between observations and models such that the (major+minor) merger fraction or rate from different models bracket the observations, and show a factor of five dispersion. Near-future improvements can now start to rule out certain merger scenarios. (3) Among ~3698 M*>=1e9 Msun galaxies, we find that the mean SFR of visibly merging systems is only modestly enhanced compared to non-interacting galaxies over z~0.24--0.80. Visibly merging systems only account for less than 30% of the cosmic SFR density over T_b~3--7 Gyr. This suggests that the behavior of the cosmic SFR density over the last 7 Gyr is predominantly shaped by non-interacting galaxies.Comment: Accepted for Publication in the Astrophysical Journal. 17 pages of text, 21 figures, 3 tables. Uses emulateapj5.st

PCCR: Pancreatic Cancer Collaborative Registry

The Pancreatic Cancer Collaborative Registry (PCCR) is a multi-institutional web-based system aimed to collect a variety of data on pancreatic cancer patients and high-risk subjects in a standard and efficient way. The PCCR was initiated by a group of experts in medical oncology, gastroenterology, genetics, pathology, epidemiology, nutrition, and computer science with the goal of facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention and treatment strategies against pancreatic cancer. The PCCR is a multi-tier web application that utilizes Java/JSP technology and has Oracle 10 g database as a back-end. The PCCR uses a “confederation model” that encourages participation of any interested center, irrespective of its size or location. The PCCR utilizes a standardized approach to data collection and reporting, and uses extensive validation procedures to prevent entering erroneous data. The PCCR controlled vocabulary is harmonized with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). The PCCR questionnaire has accommodated standards accepted in cancer research and healthcare. Currently, seven cancer centers in the USA, as well as one center in Italy are participating in the PCCR. At present, the PCCR database contains data on more than 2,700 subjects (PC patients and individuals at high risk of getting this disease). The PCCR has been certified by the NCI Center for Biomedical Informatics and Information Technology as a cancer Biomedical Informatics Grid (caBIG®) Bronze Compatible product. The PCCR provides a foundation for collaborative PC research. It has all the necessary prerequisites for subsequent evolution of the developed infrastructure from simply gathering PC-related data into a biomedical computing platform vital for successful PC studies, care and treatment. Studies utilizing data collected in the PCCR may engender new approaches to disease prognosis, risk factor assessment, and therapeutic interventions

Innovations in the Analysis of Chandra-ACIS Observations

As members of the instrument team for the Advanced CCD Imaging Spectrometer (ACIS) on NASA's Chandra X-ray Observatory and as Chandra General Observers, we have developed a wide variety of data analysis methods that we believe are useful to the Chandra community, and have constructed a significant body of publicly-available software (the ACIS Extract package) addressing important ACIS data and science analysis tasks. This paper seeks to describe these data analysis methods for two purposes: to document the data analysis work performed in our own science projects, and to help other ACIS observers judge whether these methods may be useful in their own projects (regardless of what tools and procedures they choose to implement those methods). The ACIS data analysis recommendations we offer here address much of the workflow in a typical ACIS project, including data preparation, point source detection via both wavelet decomposition and image reconstruction, masking point sources, identification of diffuse structures, event extraction for both point and diffuse sources, merging extractions from multiple observations, nonparametric broad-band photometry, analysis of low-count spectra, and automation of these tasks. Many of the innovations presented here arise from several, often interwoven, complications that are found in many Chandra projects: large numbers of point sources (hundreds to several thousand), faint point sources, misaligned multiple observations of an astronomical field, point source crowding, and scientifically relevant diffuse emission.Comment: Accepted by the ApJ, 2010 Mar 10 (\#343576) 39 pages, 16 figure

Optical identification of XMM sources in the CFHTLS

We present optical spectroscopic identifications of X-ray sources in ~3 square degrees of the XMM-Large Scale Structure survey (XMM-LSS), also covered by the Canada France Hawaii Telescope Legacy Survey (CFHTLS), obtained with the AAOmega instrument at the Anglo Australian Telescope. In a flux limited sample of 829 point like sources in the optical band with g' <~22 mag and the 0.5-2 keV flux > 1x10^{-15}erg/cm^2/s, we observed 695 objects and obtained reliable spectroscopic identification for 489 sources, ~59% of the overall sample. We therefore increase the number of identifications in this field by a factor close to five. Galactic stellar sources represent about 15% of the total (74/489). About 55% (267/489) are broad-line Active Galactic Nuclei (AGNs) spanning redshifts between 0.15 and 3.87 with a median value of 1.68. The optical-to-X-ray spectral index of the broad-line AGNs is 1.47, typical of optically-selected Type I quasars and is found to correlate with the rest frame X-ray and optical monochromatic luminosities at 2 keV and 2500 angstroms respectively. Consistent with previous studies, we find alpha_ox not to be correlated with z. In addition, 32 and 116 X-ray sources are, respectively absorption and emission-line galaxies at z<0.76. From a line ratio diagnostic diagram it is found that in about 50% of these emission line galaxies, the emission lines are powered significantly by the AGN. Thirty of the XMM sources are detected at one or more radio frequencies. In addition, 24 sources have ambiguous identification: in 8 cases, two XMM sources have a single optical source within 6 arcsecs of each of them, whereas, 2 and 14 XMM sources have, respectively, 3 and 2 possible optical sources within 6 arcsecs of each of them.Comment: 15 pages, 14 figures, 5 tables, accepted for publication in MNRA

Disk, merger, or outflow ? Molecular gas kinematics in two powerful obscured QSOs at z>3.4

We report on the detection of bright CO(4-3) line emission in two powerful, obscured quasars discovered in the SWIRE survey, SW022513 and SW022550 at z>3.4. We analyze the line strength and profile to determine the gas mass, dynamical mass and the gas dynamics for both galaxies. In SW022513 we may have found the first evidence for a molecular, AGN-driven wind in the early Universe. The line profile in SW022513 is broad (FWHM = 1000 km/s) and blueshifted by -200 km/s relative to systemic (where the systemic velocity is estimated from the narrow components of ionized gas lines, as is commonly done for AGN at low and high redshifts). SW022550 has a more regular, double-peaked profile, which is marginally spatially resolved in our data, consistent with either a merger or an extended disk. The molecular gas masses, 4x10^10 Msun, are large and account for <30% of the stellar mass, making these obscured QSOs as gas rich as other powerful CO emitting galaxies at high redshift, i.e., submillimeter galaxies. Our sources exhibit relatively lower star-formation efficiencies compared to other dusty, powerful starburst galaxies at high redshift. We speculate that this could be a consequence of the AGN perturbing the molecular gas.Comment: Accepted for publication in A&