| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Weinstein, John N., et al.
(author)
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The cancer genome atlas pan-cancer analysis project
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 3. |
- Aliu, E., et al.
(author)
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Long-term TeV and X-ray Observations of the Gamma-ray Binary HESS J0632+057
- 2014
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 780:2
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Journal article (peer-reviewed)abstract
- HESS J0632+057 is the only gamma-ray binary known so far whose position in the sky allows observations with ground-based observatories in both thenorthern and southern hemispheres. Here we report on long-term observations of HESS J0632+057 conducted with the Very Energetic Radiation Imaging Telescope Array System and High Energy Stereoscopic System Cherenkov telescopes and the X-ray satellite Swift, spanning a time range from 2004 to 2012 and covering most of the system's orbit. The very-high-energy (VHE) emission is found to be variable and is correlated with that at X-ray energies. An orbital period of 315(-4)(+6) days is derived from the X-ray data set, which is compatible with previous results, P = (321 +/- 5) days. The VHE light curve shows a distinct maximum at orbital phases close to 0.3, or about 100 days after periastron passage, which coincides with the periodic enhancement of the X-rayemission. Furthermore, the analysis of the TeV data shows for the first time a statistically significant (> 6.5 sigma) detection at orbital phases 0.6-0.9. Theobtained gamma-ray and X-ray light curves and the correlation of the source emission at these two energy bands are discussed in the context of the recent ephemeris obtained for the system. Our results are compared to those reported for other gamma-ray binaries.
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| 4. |
- Abramowski, A., et al.
(author)
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Diffuse Galactic gamma-ray emission with HESS
- 2014
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In: Physical Review D. - 1550-7998 .- 1550-2368. ; 90:12, s. Article ID: 122007-
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Journal article (peer-reviewed)abstract
- Diffuse gamma-ray emission is the most prominent observable signature of celestial cosmic-ray interactions at high energies. While already being investigated at GeVenergies over several decades, assessments of diffuse gamma-ray emission at TeVenergies remain sparse. After completion of the systematic survey of the inner Galaxy, the H.E.S.S. experiment is in a prime position to observe large-scale diffuse emission at TeVenergies. Data of the H.E.S.S. Galactic Plane Survey are investigated in regions off known gamma-ray sources. Corresponding gamma-ray flux measurements were made over an extensive grid of celestial locations. Longitudinal and latitudinal profiles of the observed gamma-ray fluxes show characteristic excess emission not attributable to known gamma-ray sources. For the first time large-scale gamma-ray emission along the Galactic plane using imaging atmospheric Cherenkov telescopes has been observed. While the background subtraction technique limits the ability to recover modest variation on the scale of the H.E.S.S. field of view or larger, which is characteristic of the inverse Compton scatter-induced Galactic diffuse emission, contributions of neutral pion decay as well as emission from unresolved gamma-ray sources can be recovered in the observed signal to a large fraction. Calculations show that the minimum gamma-ray emission from pi(0) decay represents a significant contribution to the total signal. This detection is interpreted as a mix of diffuse Galactic gamma-ray emission and unresolved sources.
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| 5. |
- Abramowski, A., et al.
(author)
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Discovery of the Hard Spectrum VHE γ-Ray Source HESS J1641–463
- 2014
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In: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 794:1, s. Article ID: L1-
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Journal article (peer-reviewed)abstract
- This Letter reports the discovery of a remarkably hard spectrum source, HESS J1641-463, by the High Energy Stereoscopic System (H.E.S.S.) in the very high energy (VHE) domain. HESS J1641-463 remained unnoticed by the usual analysis techniques due to confusion with the bright nearby source HESS J1640-465. It emerged at a significance level of 8.5 standard deviations after restricting the analysis to events with energies above 4 TeV. It shows a moderate flux level of phi(E > 1TeV) = (3.64 +/- 0.44(stat)+/- 0.73(sys)) x 10(-13) cm(-2) s(-1), corresponding to 1.8% of the Crab Nebula flux above the same energy, and a hard spectrum with a photon index of Gamma = 2.07 +/- 0.11(stat)+/- 0.20(sys). It is a point-like source, although an extension up to a Gaussian width of sigma = 3 arcmin cannot be discounted due to uncertainties in the H.E.S.S. point-spread function. The VHE gamma-ray flux of HESS J1641-463 is found to be constant over the observed period when checking time binnings from the year-by-year to the 28 minute exposure timescales. HESS J1641-463 is positionally coincident with the radio supernova remnant SNR G338.5+0.1. No X-ray candidate stands out as a clear association; however, Chandra and XMM-Newton data reveal some potential weak counterparts. Various VHE gamma-ray production scenarios are discussed. If the emission from HESS J1641-463 is produced by cosmic ray protons colliding with the ambient gas, then their spectrum must extend close to 1 PeV. This object may represent a source population contributing significantly to the galactic cosmic ray flux around the knee.
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| 6. |
- Abramowski, A., et al.
(author)
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Long-term monitoring of PKS2155-304 with ATOM and HESS:investigation of optical/gamma-ray correlations in different spectral states
- 2014
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 571
-
Journal article (peer-reviewed)abstract
- In this paper we report on the analysis of all the available optical and very high-energy gamma-ray (> 200 GeV) data for the BL Lac object PKS 2155-304, collected simultaneously with the ATOM and H.E.S.S. telescopes from 2007 until 2009. This study also includes X-ray (RXTE, Swift) and high-energy gamma-ray (Fermi-LAT) data. During the period analysed, the source was transitioning from its flaring to quiescent optical states, and was characterized by only moderate flux changes at different wavelengths on the timescales of days and months. A flattening of the optical continuum with an increasing optical flux can be noted in the collected dataset, but only occasionally and only at higher flux levels. We did not find any universal relation between the very high-energy gamma-ray and optical flux changes on the timescales from days and weeks up to several years. On the other hand, we noted that at higher flux levels the source can follow two distinct tracks in the optical flux-colour diagrams, which seem to be related to distinct gamma-ray states of the blazar. The obtained results therefore indicate a complex scaling between the optical and gamma-ray emission of PKS 2155 304, with different correlation patterns holding at different epochs, and a gamma-ray flux depending on the combination of an optical flux and colour rather than a flux alone.
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| 7. |
- Abramowski, A., et al.
(author)
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Search for dark matter annihilation signatures in HESS observations of dwarf spheroidal galaxies
- 2014
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 90:11, s. 112012-
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Journal article (peer-reviewed)abstract
- Dwarf spheroidal galaxies of the Local Group are close satellites of the Milky Way characterized by a large mass-to-light ratio and are not expected to be the site of nonthermal high-energy gamma-ray emission or intense star formation. Therefore they are among the most promising candidates for indirect dark matter searches. During the last years the High Energy Stereoscopic System (H.E.S.S.) of imaging atmospheric Cherenkov telescopes observed five of these dwarf galaxies for more than 140 hours in total, searching for TeV gamma-ray emission from annihilation of dark matter particles. The new results of the deep exposure of the Sagittarius dwarf spheroidal galaxy, the first observations of the Coma Berenices and Fornax dwarves and the reanalysis of two more dwarf spheroidal galaxies already published by the H.E.S.S. Collaboration, Carina and Sculptor, are presented. In the absence of a significant signal new constraints on the annihilation cross section applicable to weakly interacting massive particles (WIMPs) are derived by combining the observations of the five dwarf galaxies. The combined exclusion limit depends on the WIMP mass and the best constraint is reached at 1-2 TeV masses with a cross-section upper bound of similar to 3.9 x 10(-24) cm(3) s(-1) at a 95% confidence level.
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| 8. |
- Blunden, Jessica, et al.
(author)
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State of the Climate in 2012
- 2013
-
In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
-
Journal article (peer-reviewed)abstract
- For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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| 9. |
- Meyer, H., et al.
(author)
-
Overview of physics results from MAST towards ITER/DEMO and the MAST Upgrade
- 2013
-
In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:10, s. 104008-
-
Journal article (peer-reviewed)abstract
- New diagnostic, modelling and plant capability on the Mega Ampere Spherical Tokamak (MAST) have delivered important results in key areas for ITER/DEMO and the upcoming MAST Upgrade, a step towards future ST devices on the path to fusion currently under procurement. Micro-stability analysis of the pedestal highlights the potential roles of micro-tearing modes and kinetic ballooning modes for the pedestal formation. Mitigation of edge localized modes (ELM) using resonant magnetic perturbation has been demonstrated for toroidal mode numbers n = 3, 4, 6 with an ELM frequency increase by up to a factor of 9, compatible with pellet fuelling. The peak heat flux of mitigated and natural ELMs follows the same linear trend with ELM energy loss and the first ELM-resolved T-i measurements in the divertor region are shown. Measurements of flow shear and turbulence dynamics during L-H transitions show filaments erupting from the plasma edge whilst the full flow shear is still present. Off-axis neutral beam injection helps to strongly reduce the redistribution of fast-ions due to fishbone modes when compared to on-axis injection. Low-k ion-scale turbulence has been measured in L-mode and compared to global gyro-kinetic simulations. A statistical analysis of principal turbulence time scales shows them to be of comparable magnitude and reasonably correlated with turbulence decorrelation time. T-e inside the island of a neoclassical tearing mode allow the analysis of the island evolution without assuming specific models for the heat flux. Other results include the discrepancy of the current profile evolution during the current ramp-up with solutions of the poloidal field diffusion equation, studies of the anomalous Doppler resonance compressional Alfven eigenmodes, disruption mitigation studies and modelling of the new divertor design for MAST Upgrade. The novel 3D electron Bernstein synthetic imaging shows promising first data sensitive to the edge current profile and flows.
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| 10. |
- Lloyd, B., et al.
(author)
-
Overview of physics results from MAST
- 2011
-
In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9, s. 094013 (paper no.)-
-
Journal article (peer-reviewed)abstract
- Major developments on the Mega Amp Spherical Tokamak (MAST) have enabled important advances in support of ITER and the physics basis of a spherical tokamak (ST) based component test facility (CTF), as well as providing new insight into underlying tokamak physics. For example, L-H transition studies benefit from high spatial and temporal resolution measurements of pedestal profile evolution (temperature, density and radial electric field) and in support of pedestal stability studies the edge current density profile has been inferred from motional Stark effect measurements. The influence of the q-profile and E x B flow shear on transport has been studied in MAST and equilibrium flow shear has been included in gyro-kinetic codes, improving comparisons with the experimental data. H-modes exhibit a weaker q and stronger collisionality dependence of heat diffusivity than implied by IPB98(gamma, 2) scaling, which may have important implications for the design of an ST-based CTF. ELM mitigation, an important issue for ITER, has been demonstrated by applying resonant magnetic perturbations (RMPs) using both internal and external coils, but full stabilization of type-I ELMs has not been observed. Modelling shows the importance of including the plasma response to the RMP fields. MAST plasmas with q > 1 and weak central magnetic shear regularly exhibit a long-lived saturated ideal internal mode. Measured plasma braking in the presence of this mode compares well with neo-classical toroidal viscosity theory. In support of basic physics understanding, high resolution Thomson scattering measurements are providing new insight into sawtooth crash dynamics and neo-classical tearing mode critical island widths. Retarding field analyser measurements show elevated ion temperatures in the scrape-off layer of L-mode plasmas and, in the presence of type-I ELMs, ions with energy greater than 500 eV are detected 20 cm outside the separatrix. Disruption mitigation by massive gas injection has reduced divertor heat loads by up to 70%.
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| 11. |
- Hudson, Thomas J., et al.
(author)
-
International network of cancer genome projects
- 2010
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Journal article (peer-reviewed)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 12. |
- Jacobs, Kevin B, et al.
(author)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
-
In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
-
Journal article (peer-reviewed)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 13. |
- Abramowski, A., et al.
(author)
-
Flux upper limits for 47 AGN observed with HESS in 2004-2011
- 2014
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 564, s. A9-
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Journal article (peer-reviewed)abstract
- Context. About 40% of the observation time of the High Energy Stereoscopic System (H.E.S.S.) is dedicated to studying active galactic nuclei (AGN), with the aim of increasing the sample of known extragalactic very-high-energy (VHE, E > 100 GeV) sources and constraining the physical processes at play in potential emitters. Aims. H.E.S.S. observations of AGN, spanning a period from April 2004 to December 2011, are investigated to constrain their gamma-ray fluxes. Only the 47 sources without significant excess detected at the position of the targets are presented. Methods. Upper limits on VHE fluxes of the targets were computed and a search for variability was performed on the nightly time scale. Results. For 41 objects, the flux upper limits we derived are the most constraining reported to date. These constraints at VHE are compared with the flux level expected from extrapolations of Fermi-LAT measurements in the two-year catalog of AGN. The H.E.S.S. upper limits are at least a factor of two lower than the extrapolated Fermi-LAT fluxes for 11 objects Taking into account the attenuation by the extragalactic background light reduces the tension for all but two of them, suggesting intrinsic curvature in the high-energy spectra of these two AGN. Conclusions. Compilation efforts led by current VHE instruments are of critical importance for target-selection strategies before the advent of the Cherenkov Telescope Array (CTA).
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| 14. |
- Abramowski, A., et al.
(author)
-
HESS J1640-465-an exceptionally luminous TeV gamma-ray supernova remnant
- 2014
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 439:3, s. 2828-2836
-
Journal article (peer-reviewed)abstract
- The results of follow-up observations of the TeV gamma-ray source HESS J1640-465 from 2004 to 2011 with the High Energy Stereoscopic System (HESS) are reported in this work. The spectrum is well described by an exponential cut-off power law with photon index Gamma = 2.11 +/- 0.09(stat) +/- 0.10(sys), and a cut-off energy of E-2 = 6.0(-1.2)(+2.0) TeV. The TeV emission is significantly extended and overlaps with the northwestern part of the shell of the SNR G338.3-0.0. The new HESS results, a re-analysis of archival XMM-Newton data and multiwavelength observations suggest that a significant part of the gamma-ray emission from HESS J1640-465 originates in the supernova remnant shell. In a hadronic scenario, as suggested by the smooth connection of the GeV and TeV spectra, the product of total proton energy and mean target density could be as high as W(p)n(H) similar to 4 x 10(52)(d/10kpc)(2) erg cm(-3).
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| 15. |
- Abramowski, A., et al.
(author)
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HESS J1818-154, a new composite supernova remnant discovered in TeV gamma rays and X-rays
- 2014
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 562, s. 562-
-
Journal article (peer-reviewed)abstract
- Composite supernova remnants (SNRs) constitute a small subclass of the remnants of massive stellar explosions where non-thermal radiation is observed from both the expanding shell-like shock front and from a pulsar wind nebula (PWN) located inside of the SNR. These systems represent a unique evolutionary phase of SNRs where observations in the radio, X-ray, and gamma-ray regimes allow the study of the co-evolution of both these energetic phenomena. In this article, we report results from observations of the shell-type SNR G15.4+0.1 performed with the High Energy Stereoscopic System (H. E. S. S.) and XMM-Newton. A compact TeV gamma-ray source, HESS J1818-154, located in the center and contained within the shell of G15.4+0.1 is detected by H. E. S. S. and featurs a spectrum best represented by a power-law model with a spectral index of -2.3 +/- 0.3(stat) +/- 0.2(sys) and an integral flux of F(>0.42 TeV) = (0.9 +/- 0.3(stat) +/- 0.2(sys)) x 10(-12) cm(-2) s(-1). Furthermore, a recent observation with XMM-Newton reveals extended X-ray emission strongly peaked in the center of G15.4+0.1. The X-ray source shows indications of an energy-dependent morphology featuring a compact core at energies above 4 keV and more extended emission that fills the entire region within the SNR at lower energies. Together, the X-ray and VHE gamma-ray emission provide strong evidence of a PWN located inside the shell of G15.4+0.1 and this SNR can therefore be classified as a composite based on these observations. The radio, X-ray, and gamma-ray emission from the PWN is compatible with a one-zone leptonic model that requires a low average magnetic field inside the emission region. An unambiguous counterpart to the putative pulsar, which is thought to power the PWN, has been detected neither in radio nor in X-ray observations of G15.4+0.1.
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| 16. |
- Abramowski, A., et al.
(author)
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Search for TeV Gamma-ray Emission from GRB 100621A, an extremely bright GRB in X-rays, with HESS
- 2014
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 565, s. 1-6
-
Journal article (peer-reviewed)abstract
- The long gamma-ray burst (GRB) 100621A, at the time the brightest X-ray transient ever detected by Swift-XRT in the 0.3-10 keV range, has been observed with the H.E.S.S. imaging air Cherenkov telescope array, sensitive to gamma radiation in the very-high-energy (VHE, >100 GeV) regime. Due to its relatively small redshift of z similar to 0.5, the favourable position in the southern sky and the relatively short follow-up time (<700 s after the satellite trigger) of the H.E.S.S. observations, this GRB could be within the sensitivity reach of the HESS. instrument. The analysis of the HESS. data shows no indication of emission and yields an integral flux upper limit above similar to 380 GeV of 4.2 x 10(-12) cm(-2) s(-1) s (95% confidence level), assuming a simple Band function extension model. A comparison to a spectral-temporal model, normalised to the prompt flux at sub-MeV energies, constraints the existence of a temporally extended and strong additional hard power law, as has been observed in the other bright X-ray GRB 130427A. A comparison between the HESS. upper limit and the contemporaneous energy output in X-rays constrains the ratio between the X-ray and VHE gamma-ray fluxes to be greater than 0.4. This value is an important quantity for modelling the afterglow and can constrain leptonic emission scenarios, where leptons are responsible for the X-ray emission and might produce VHE gamma rays.
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| 17. |
- Abramowski, A., et al.
(author)
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TeV gamma-ray observations of the young synchrotron-dominated SNRs G1.9+0.3 and G330.2+1.0 with HESS
- 2014
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 441:1, s. 790-799
-
Journal article (peer-reviewed)abstract
- The non-thermal nature of the X-ray emission from the shell-type supernova remnants (SNRs) G1.9+0.3 and G330.2+1.0 is an indication of intense particle acceleration in the shock fronts of both objects. This suggests that the SNRs are prime candidates for very-high-energy (VHE; E > 0.1 TeV) gamma-ray observations. G1.9+0.3, recently established as the youngest known SNR in the Galaxy, also offers a unique opportunity to study the earliest stages of SNR evolution in the VHE domain. The purpose of this work is to probe the level of VHE gamma-ray emission from both SNRs and use this to constrain their physical properties. Observations were conducted with the H. E. S. S. (High Energy Stereoscopic System) Cherenkov Telescope Array over a more than six-year period spanning 2004-2010. The obtained data have effective livetimes of 67 h for G1.9+0.3 and 16 h for G330.2+1.0. The data are analysed in the context of the multiwavelength observations currently available and in the framework of both leptonic and hadronic particle acceleration scenarios. No significant gamma-ray signal from G1.9+0.3 or G330.2+1.0 was detected. Upper limits (99 per cent confidence level) to the TeV flux from G1.9+0.3 and G330.2+1.0 for the assumed spectral index Gamma = 2.5 were set at 5.6 x 10(-1)3 cm(-2) s(-1) above 0.26 TeV and 3.2 x 10(-12) cm(-2) s(-1) above 0.38 TeV, respectively. In a one-zone leptonic scenario, these upper limits imply lower limits on the interior magnetic field to B-G1.9 greater than or similar to 12 mu G for G1.9+0.3 and to B-G330 greater than or similar to 8 mu G for G330.2+1.0. In a hadronic scenario, the low ambient densities and the large distances to the SNRs result in very low predicted fluxes, for which the H.E.S.S. upper limits are not constraining.
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| 18. |
- Collaboration, H. E. S. S., et al.
(author)
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HESS observations of the Crab during its March 2013 GeV gamma-ray flare
- 2014
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 562, s. Article ID: UNSP L4-
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Journal article (peer-reviewed)abstract
- Context. On March 4, 2013 the Fermi-EAT and AGILE reported a flare from the direction of the Crab nebula in which the high-energy (HE; E > 100 MeV) flux was six times above its quiescent level. Simultaneous observations in other energy bands give us hints about the emission processes during the flare episode and the physics of pulsar wind nebulae in general. Aims. We search for variability in the emission of the Crab nebula at very-high energies (VHF,; E > 100 GeV), using contemporaneous data taken with the H.E.S.S. array of Cherenkov telescopes. Methods. Observational data taken with the H.E.S.S. instrument on five consecutive days during the flare were analysed for the flux and spectral shape of the emission from the Crab nebula. Night-wise light curves are presented with energy thresholds of 1 TeV and 5 TeV. Results. The observations conducted with H.E.S.S. on March 6 to March 10, 2013 show no significant changes in the flux. They limit the variation in the integral flux above 1 TeV to less than 63% and the integral flux above 5 TeV to less than 78% at a 95% confidence level.
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| 19. |
- Abramowski, A., et al.
(author)
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Search for extended gamma-ray emission around AGN with HESS and Fermi-LAT
- 2014
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 562, s. A145-
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Journal article (peer-reviewed)abstract
- Context. Very-high-energy (VHE; E > 100 GeV) gamma-ray emission from blazars inevitably gives rise to electron-positron pair production through the interaction of these gamma-rays with the extragalactic background light (EBL). Depending on the magnetic fields in the proximity of the source, the cascade initiated from pair production can result in either an isotropic halo around an initially- beamed source or a magnetically- broadened cascade :aux. Aims. Both extended pair-halo (PH) and magnetically broadened cascade (MBC) emission from regions surrounding the blazars 1ES 1101-232, IRS 0229+200, and PKS 2155-304 were searched for using VHE y-ray data taken with the High Energy Stereoscopic System (HESS.) and high-energy (HE; 100 MeV < E < 100 GeV) gamma-ray data with the Fermi Large Area Telescope (LAT). Methods. By comparing the angular distributions of the reconstructed gamma-ray events to the angular profiles calculated from detailed theoretical models, the presence of PH and MBC was investigated. Results. Upper limits on the extended emission around lES 1101-232, lES 0229+200, and PKS 2155-304 are found to be at a level of a few per cent of the Crab nebula flux above 1 TeV, depending on the assumed photon index of the cascade emission. Assuming strong extra-Galactic magnetic field (EGME) values, >10(-12) G, this limits the production of pair haloes developing from electromagnetic cascades. For weaker magnetic fields, in which electromagnetic cascades would result in MBCs. EGMF strengths in the range (0.3-3) x 10(-15) G were excluded for PKS 2155-304 at the 99% confidence level, under the assumption of a 1 Mpc coherence length.
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| 20. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 21. |
- Wormser, David, et al.
(author)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Journal article (peer-reviewed)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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| 22. |
- Peloso, Gina M, et al.
(author)
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Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.
- 2014
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 223-232
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Journal article (peer-reviewed)abstract
- Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121(∗)], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
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| 23. |
- An, Junghwa, et al.
(author)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Journal article (peer-reviewed)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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| 24. |
- Asselbergs, Folkert W., et al.
(author)
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Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
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| 25. |
- Furberg, Helena, et al.
(author)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Journal article (peer-reviewed)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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