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OBJECTIVES/GOALS: Smoking is a well-established risk factor for lung cancer, but never smokers account for up to 25% of lung cancer cases. There is mounting evidence that lung cancer in never smokers is biologically distinct. We aim to characterize the genomic and immunologic features of lung adenocarcinoma in never smokers versus smokers. METHODS/STUDY POPULATION: We examined clinical, genomic, and bulk-RNA sequencing data from 499 patients in the TCGA lung adenocarcinoma cohort. Tumor mutation burden was analyzed using maftools (R package). Tumor immune characterization was completed using CIBERSORTx, a digital cytometry tool that uses single cell reference profiles to determine immune cell type frequencies from bulk-RNA sequencing data. Single cell reference profiles for 19 different immune cell types were constructed from sequencing of freshly resected lung tumor tissue from UCSF patients. Partitioning Around Medoids (PAM; R package) was used to identify distinct immune phenotypes based on immune cell composition. Fisher’s exact test was used to evaluate for associations between immune phenotypes and smoking status. RESULTS/ANTICIPATED RESULTS: Of the 499 TCGA lung adenocarcinoma patients, 75 were never smokers, 269 were female, and 246 were over the age of 65. Never smokers had lower tumor mutation burden and lower predicted neoantigen burden compared to smokers (p < 0.001). There was no difference in total tumor immune cell infiltration between never smokers and smokers. PAM yielded 2 distinct clusters/immune phenotypes. The first was enriched in M1 Macrophages, cytotoxic T Cells, helper T Cells, regulatory T Cells, and Plasma Cells. The second was enriched in plasmacytoid Dendritic Cells, M2 Macrophages, and exhausted cytotoxic T Cells. Never smoking status was associated with an increased odds of having the first immune phenotype (OR 1.95, 95% CI: 1.15 - 3.35) and this association was statistically significant (p = 0.0086). DISCUSSION/SIGNIFICANCE: Our findings suggest that never smokers have an immune phenotype that is distinct from that observed in smokers. The distinct immune characteristics we observed could explain clinical trial data suggesting immune checkpoint inhibitors are less effective in never smokers and hold implications for tailoring therapy.
The first positive genome-wide association study on gestational length and preterm delivery showed the involvement of an Se metabolism gene. In the present study, we examine the association between maternal intake of Se and Se status with gestational length and preterm delivery in 72 025 women with singleton live births from the population-based, prospective Norwegian Mother, Father and Child Cohort Study (MoBa). A self-reported, semi-quantitative FFQ answered in pregnancy week 22 was used to estimate Se intake during the first half of pregnancy. Associations were analysed with adjusted linear and Cox regressions. Se status was assessed in whole blood collected in gestational week 17 (n 2637). Median dietary Se intake was 53 (interquartile range (IQR) 44–62) µg/d, supplements provided additionally 50 (IQR 30–75) µg/d for supplement users (n 23 409). Maternal dietary Se intake was significantly associated with prolonged gestational length (β per sd = 0·25, 95 % CI, 0·07, 0·43) and decreased risk of preterm delivery (n 3618, hazard ratio per sd = 0·92, 95 % CI, 0·87, 0·98). Neither Se intake from supplements nor maternal blood Se status was associated with gestational length or preterm delivery. Hence, the present study showed that maternal dietary Se intake but not intake of Se-containing supplements, during the first half of pregnancy was significantly associated with decreased risk of preterm delivery. Further investigations, preferably in the form of a large randomised controlled trial, are needed to elucidate the impact of Se on pregnancy duration.
We examine the metallicity trends in the Milky Way (MW) bulge – using APOGEE DR13 data – and explore their origin by comparing two N-body models of isolated galaxies which develop a bar and a boxy/peanut (b/p) bulge. Both models have been proposed as scenarios for reconciling a disc origin of the MW bulge with a negative vertical metallicity gradient. The first is a superposition of co-spatial disc populations, different scaleheights and metallicities (with flat gradients) where the thick, metal-poor populations contribute significantly to the stellar mass budget in the inner galaxy. The second model is a single disc with an initial steep radial metallicity gradient which gets mapped by the bar into the b/p bulge in such a way that the vertical metallicity gradient of the MW bulge is reproduced – as shown already in previous works in the literature. As we show here, the latter model does not reproduce the positive longitudinal metallicity gradient of the inner disc, nor the metal-poor innermost regions seen in the data. The model with co-spatial thin and thick disc populations reproduces all the aforementioned trends. We therefore see that it is possible to reconcile a (primarily) disc origin for the MW bulge with the observed trends in metallicity by mapping the inner thin and thick discs of the MW into a b/p.
We explore morphological, kinematic and chemical trends of boxy/peanut (b/p) bulges of Milky Way (MW)-type galaxies, to better understand the formation history of the MW’s bulge. We show, using N-body simulations with both a kinematically cold and a kinematically hot disc, that colder populations develop a more prominent bar and X-shaped peanut as compared to their hotter counterpart. Colder discs also exhibit lower line-of-sight velocities (when viewed edge-on) at the edges of the b/p compared to hot discs, in agreement with what is seen for the MW bulge. Furthermore, we explore an N-body model which has three co-spatial discs with metallicities which correspond to the stellar populations of the inner Milky Way, where the α-enhanced thick disc populations are massive and centrally concentrated. The metallicity trends seen in observations of the Bulge can be reproduced in the model without the need of adding any additional components, which hints to the disc origin of the MW’s bulge.
To explore the relation between bar formation and star formation in Milky Way-type galaxies quantitatively, we simulated gas-rich disk isolated galaxies. We find that the action of the stellar bar efficiently quenches star formation, reducing the star-formation rate by a factor of 10 in less than 1 Gyr. Analytical and self-consistent galaxy simulations with bars suggest that the action of the stellar bar increases the gas random motions within the co-rotation radius of the bar. Indeed, we detect an increase in the gas velocity dispersion at the end of the bar formation phase. The star formation efficiency decreases rapidly, and in all of our models, the bar quenches the star formation in the galaxy. The star-formation efficiency is much lower in simulated barred compared to unbarred galaxies and more rapid bar formation implies more rapid quenching.
We have recently discovered evidence for a population of radio-loud quasars that is reddened by dust. The dust is either along the line of sight to the quasars or is associated with the quasars. In the latter case the dust may be in molecular clouds in the quasar’s host galaxy, or in a molecular torus around the nucleus. We are planning to use 3 mm observations to search for molecular absorption lines (CO and HCO+) associated with dust at the redshift of these quasars. If any absorption systems are detected we will be able to deduce detailed information about the physical state of the molecular gas, hopefully showing which of the proposed locations of the dust is most likely.
We found with ALMA 3D spectroscopy two bipolar molecular outflows in the luminous infrared galaxy NGC 3256. Each of the two merger nuclei has its own bipolar outflow.
For the first time in any ram pressure stripped galaxy, we detect large amounts of cold molecular gas in the X-ray bright, and star forming tail of ESO 137-001 in the Norma cluster. We find very low star formation efficiency in the stripped gas, similar to values found in the outer spiral disks where however molecular gas is mostly undetected. The results were recently published in Jáchym et al. (2014).
Star formation is evolving very fast in the second half of the Universe, and it is as yet unclear whether this is due to evolving gas content, or evolving star formation efficiency (SFE). We have carried out a survey of ultra-luminous galaxies (ULIRG) between z = 0.2 and 1, to check the gas fraction in this domain of redshift which is still poorly known. Our survey with the IRAM-30m detected 33 galaxies out of 69, and we derive a significant evolution of both the gas fraction and SFE of ULIRGs over the whole period, and in particular a turning point around z = 0.35. The result is sensitive to the CO-to-H2 conversion factor adopted, and both gas fraction and SFE have comparable evolution, when we adopt the low starburst conversion factor of α = 0.8 M⊙ (K km s−1 pc2)−1. Adopting a higher α will increase the role of the gas fraction. Using α = 0.8, the SFE and the gas fraction for z∼0.2-1.0 ULIRGs are found to be significantly higher, by a factor 3, than for local ULIRGs, and are comparable to high redshift ones. We compare this evolution to the expected cosmic H2 abundance and the cosmic star formation history.
In this talk, I will present the result of high resolution numerical simulations of disk galaxies with various bulge/disk ratios evolving isolated, showing that:
• Most of migration takes place when the bar strength is high and decreases in the phases of low activity (in agreement with the results by Brunetti et el. 2011, Minchev et al. 2011).
• Most of the stars inside the corotation radius (CR) do not migrate in the outer regions, but stay confined in the inner disk, while stars outside CR can migrate either inwards or outwards, diffusing over the whole disk.
• Migration is accompanied by significative azimuthal variations in the metallicity distribution, of the order of 0.1 dex for an initial gradient of ~-0.07 dex/kpc.
• Boxy bulges are an example of stellar structures whose properties (stellar content, vertical metallicity, [α/Fe] and age gradients, ..) are affected by radial migration (see also Fig. 1).
We have carried out 1mm/3mm continuum and 12CO(2−1) line high resolution observations to identify the footprints of AGN feedback on 3C 236. The CO emission comes from a spatially resolved disk characterized by a regular rotating pattern. Within the limits imposed by the sensitivity and velocity coverage of our data, we do not detect any outflow signatures in the cold molecular gas. Re-inspection of optical and IR spectra, shows the presence of a previously unknown ionized gas outflow. The star-formation efficiency in 3C 236, is consistent with the value measured in normal galaxies, which follow the canonical Kennicutt-Schmidt law. This result, confirmed to hold in other young radio sources examined in this work, is in stark contrast with the factor of 10–50 lower SFE that has been claimed to characterize evolved powerful radio galaxies. The recent reactivation of the AGN in 3C 236 is a likely explanation for the early evolutionary status of its molecular disk.
A year-long intervention trial was conducted to characterise the responses of multiple biomarkers of Se status in healthy American adults to supplemental selenomethionine (SeMet) and to identify factors affecting those responses. A total of 261 men and women were randomised to four doses of Se (0, 50, 100 or 200 μg/d as l-SeMet) for 12 months. Responses of several biomarkers of Se status (plasma Se, serum selenoprotein P (SEPP1), plasma glutathione peroxidase activity (GPX3), buccal cell Se, urinary Se) were determined relative to genotype of four selenoproteins (GPX1, GPX3, SEPP1, selenoprotein 15), dietary Se intake and parameters of single-carbon metabolism. Results showed that supplemental SeMet did not affect GPX3 activity or SEPP1 concentration, but produced significant, dose-dependent increases in the Se contents of plasma, urine and buccal cells, each of which plateaued by 9–12 months and was linearly related to effective Se dose (μg/d per kg0·75). The increase in urinary Se excretion was greater for women than men, and for individuals of the GPX1 679 T/T genotype than for those of the GPX1 679 C/C genotype. It is concluded that the most responsive Se-biomarkers in this non-deficient cohort were those related to body Se pools: plasma, buccal cell and urinary Se concentrations. Changes in plasma Se resulted from increases in its non-specific component and were affected by both sex and GPX1 genotype. In a cohort of relatively high Se status, the Se intake (as SeMet) required to support plasma Se concentration at a target level (Sepl-target) is: .
The molecular gas content of local early-type galaxies is constrained and discussed in relation to their evolution. First, as part of the ATLAS3D survey, we present the first complete, large (260 objects), volume-limited single-dish survey of CO in normal local early-type galaxies. We find a surprisingly high detection rate of 22%, independent of luminosity and at best weakly dependent on environment. Second, the extent of the molecular gas is constrained with CO synthesis imaging, and a variety of morphologies is revealed. The kinematics of the molecular gas and stars are often misaligned, implying an external gas origin in over a third of the systems, although this behaviour is drastically diffferent between field and cluster environments. Third, many objects appear to be in the process of forming regular kpc-size decoupled disks, and a star formation sequence can be sketched by piecing together multi-wavelength information on the molecular gas, current star formation, and young stars. Last, early-type galaxies do not seem to systematically obey all our usual prejudices regarding star formation, following the standard Schmidt-Kennicutt law but not the far infrared-radio correlation. This may suggest a greater diversity in star formation processes than observed in disk galaxies. Using multiple molecular tracers, we are thus starting to probe the physical conditions of the cold gas in early-types.
Molecular hydrogen is the most abundant molecule in the Universe. In recent years, advances in theory and laboratory experiments coupled with breakthrough observations with important new telescopes and satellites have revolutionized our understanding of molecular hydrogen in space. It is now possible to address the question of how molecular hydrogen formed in the early Universe and the role it played in the formation of primordial structures. This timely volume presents articles from a host of experts who reviewed this new understanding at an international conference in Paris. This book provides the first multi-disciplinary synthesis of our new understanding of molecular hydrogen. It covers the theory of the physical processes and laboratory experiments, as well as the latest observations. It will therefore be an invaluable reference for all students and researchers in astrophysics and cosmology.
Epidemiological data from bank voles, Myodes glareolus, naturally infected by the hantavirus Puumala (PUUV) were collected by a capture–mark–recapture protocol from 2000 to 2002 in the French department of Ardennes. Four monitored trapping sites were established in two forests located in two cantons (Flize and Monthermé). We captured 912 bank voles corresponding to 557 different individuals during 8820 trapping nights for an overall trapping success of 10·34%. The average PUUV seroprevalence was 22·4%. Characteristics of the system reported in North European countries are confirmed in France. PUUV seroprevalence and abundance of rodents appeared weakly linked. Adult voles were more frequently antibody-positive, but no difference between sexes was established. Anti-PUUV seropositive voles were captured and high seroprevalence was observed from both forests, without human infection reported in Flize canton during the study. One site among the four exhibited peculiar infection dynamics, where vole weight and infection risk were negatively correlated.
We analyzed the distribution and kinematics of the atomic gas (HI) in 16 nearby spiral galaxies. Our results indicate that the morphology of the atomic gas and dynamically disturbed outer disks correlate with the AGN type present (Seyfert, LINER). From the combined HI and CO data (from the NUGA project), 2-dimensional maps of the gas flow are computed and gas inflow rates are derived as a function of radius within the disks.