VLBI Imaging of Luminous Infrared Galaxies: AGN Cores in Mrk231, UGC 5101 & NGC 7469

We report 18cm VLBI continuum imaging observations at 5 mas resolution for UGC 5101, NGC 7469, and Mrk 231, all part of a sample of Luminous Infrared Galaxies which have been shown to have strong VLBI radio cores. The radio morphology of these three systems on VLBI scales is AGN-like, with well-defined ridgelines and high-brightness yet spatially resolved components. The structure and flux densities of these VLBI components are not consistent with starburst generated radio supernovae of the type found in Arp 220. On scales of 100pc the radio continuum in all three objects appears to be dominated by an AGN, not a starburst. Radio emission on larger scales may well originate in a less compact circumnuclear star-forming region. Confirming and extending VLBI imaging of Mrk 231 by Ulvestad et al. (1999), our continuum image shows a triple structure, with a core and two lobes, classifying it as a Compact Symmetric Object (CS0). If the southern (primary) lobe/hot-spot in Mrk 231 is confined by ram pressure, we estimate a lobe advance speed, $v_a \sim 10^{-4}c$, and an age for the jet/compact source, $< 10^6 yr$. We have also imaged the 1667 MHz OH maser emission in Mrk 231, which is extended on scales of 50--100 milliarcsec (40--80 pc) and probably coincides with the inner region of the disk which is seen in CO emission and HI absorption. Among OH megamasers studied at high sensitivity with mas resolution, Mrk 231 is unique in the stringent upper limits placed upon the flux density of compact OH structures of the type found in Arp 220 and other LIGs. It is possible that the circumnuclear environment of Mrk 231 has been sufficiently disrupted by the emergent QSO that the cool, dense clouds necessary for such compact masers no longer exist.Comment: 43 pages, 7 figure

WFPC2 Observations of Compact Star Cluster Nuclei in Low Luminosity Spiral Galaxies

We have used the Wide Field Planetary Camera 2 aboard the Hubble Space Telescope to image the compact star cluster nuclei of the nearby, late-type, low-luminosity spiral galaxies NGC 4395, NGC 4242, and ESO 359-029. We also analyze archival WFPC2 observations of the compact star cluster nucleus of M33. A comparative analysis of the structural and photometric properties of these four nuclei is presented. All of the nuclei are very compact, with luminosity densities increasing at small radii to the resolution limit of our data. NGC 4395 contains a Seyfert 1 nucleus with a distinct bipolar structure and bright associated filaments which are likely due to [OIII] emission. The M33 nucleus has a complex structure, with elongated isophotes and possible signatures of weak activity, including a jet-like component. The other two nuclei are not known to be active, but share similar physical size scales and luminosities to the M33 and NGC 4395 nuclei. The circumnuclear environments of all four of our program galaxies are extremely diffuse, have only low-to-moderate star formation, and appear to be devoid of large quantities of dust. The central gravitational potentials of the galaxies are also quite shallow, making the origin of these types of `naked' nuclei problematic.Comment: to appear in the July 1999 Astronomical Journal; 38 pages (Latex), 5 tables (postscript), 21 figures (gif); postscript versions of the figures may be obtained via anonymous ftp at ftp://ftp.cv.nrao.edu/NRAO-staff/lmatthew/lanl-nucle

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD.

BACKGROUND: Germline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers. METHODS: A retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC/SDHD (n=673/43/160). Tumour risks were correlated with in silico structural prediction analyses. RESULTS: Tumour risks analysis provided novel penetrance estimates and genotype-phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD:p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%). CONCLUSIONS: Overall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype-tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB/SDHC/SDHD mutation carriers

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns.

In cancer, the primary tumour's organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA

Widespread retreat of coastal habitat is likely at warming levels above 1.5 °C

Several coastal ecosystems—most notably mangroves and tidal marshes—exhibit biogenic feedbacks that are facilitating adjustment to relative sea-level rise (RSLR), including the sequestration of carbon and the trapping of mineral sediment. The stability of reef-top habitats under RSLR is similarly linked to reef-derived sediment accumulation and the vertical accretion of protective coral reefs. The persistence of these ecosystems under high rates of RSLR is contested. Here we show that the probability of vertical adjustment to RSLR inferred from palaeo-stratigraphic observations aligns with contemporary in situ survey measurements. A defcit between tidal marsh and mangrove adjustment and RSLR is likely at 4 mm yr−1 and highly likely at 7 mm yr−1 of RSLR. As rates of RSLR exceed 7 mm yr−1, the probability that reef islands destabilize through increased shoreline erosion and wave over-topping increases. Increased global warming from 1.5 °C to 2.0 °C would double the area of mapped tidal marsh exposed to 4 mm yr−1 of RSLR by between 2080 and 2100. With 3 °C of warming, nearly all the world’s mangrove forests and coral reef islands and almost 40% of mapped tidal marshes are estimated to be exposed to RSLR of at least 7 mm yr−1. Meeting the Paris agreement targets would minimize disruption to coastal ecosystems