| 1. |
- Alexandrov, Ludmil B., et al.
(författare)
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Signatures of mutational processes in human cancer
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
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Tidskriftsartikel (refereegranskat)abstract
- All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
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| 2. |
- Vandenbussche, B., et al.
(författare)
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The beta Pictoris disk imaged by Herschel PACS and SPIRE
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L133
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Tidskriftsartikel (refereegranskat)abstract
- We obtained Herschel PACS and SPIRE images of the thermal emission of the debris disk around the A5V star beta Pic. The disk is well resolved in the PACS filters at 70, 100, and 160 mu m. The surface brightness profiles between 70 and 160 mu m show no significant asymmetries along the disk, and are compatible with 90% of the emission between 70 and 160 mu m originating in a region closer than 200 AU to the star. Although only marginally resolving the debris disk, the maps obtained in the SPIRE 250-500 mu m filters provide full-disk photometry, completing the SED over a few octaves in wavelength that had been previously inaccessible. The small far-infrared spectral index (beta = 0.34) indicates that the grain size distribution in the inner disk (
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| 3. |
- Acke, B., et al.
(författare)
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Herschel images of Fomalhaut An extrasolar Kuiper belt at the height of its dynamical activity
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 540, s. Article Number: A125 -
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Tidskriftsartikel (refereegranskat)abstract
- Context. Fomalhaut is a young (2 +/- 1 x 10(8) years), nearby (7.7 pc), 2 M-circle dot star that is suspected to harbor an infant planetary system, interspersed with one or more belts of dusty debris. Aims. We present far-infrared images obtained with the Herschel Space Observatory with an angular resolution between 5.7 '' and 36.7 '' at wavelengths between 70 mu m and 500 mu m. The images show the main debris belt in great detail. Even at high spatial resolution, the belt appears smooth. The region in between the belt and the central star is not devoid of material; thermal emission is observed here as well. Also at the location of the star, excess emission is detected. We aim to construct a consistent image of the Fomalhaut system. Methods. We use a dynamical model together with radiative-transfer tools to derive the parameters of the debris disk. We include detailed models of the interaction of the dust grains with radiation, for both the radiation pressure and the temperature determination. Comparing these models to the spatially resolved temperature information contained in the images allows us to place strong constraints on the presence of grains that will be blown out of the system by radiation pressure. We use this to derive the dynamical parameters of the system. Results. The appearance of the belt points toward a remarkably active system in which dust grains are produced at a very high rate by a collisional cascade in a narrow region filled with dynamically excited planetesimals. Dust particles with sizes below the blow-out size are abundantly present. The equivalent of 2000 one-km-sized comets are destroyed every day, out of a cometary reservoir amounting to 110 Earth masses. From comparison of their scattering and thermal properties, we find evidence that the dust grains are fluffy aggregates, which indicates a cometary origin. The excess emission at the location of the star may be produced by hot dust with a range of temperatures, but may also be due to gaseous free-free emission from a stellar wind.
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| 4. |
- Greaves, J. S., et al.
(författare)
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EXTREME CONDITIONS IN A CLOSE ANALOG TO THE YOUNG SOLAR SYSTEM : HERSCHEL OBSERVATIONS OF is an element of ERIDANI
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 791:1, s. L11-
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Tidskriftsartikel (refereegranskat)abstract
- Far-infrared Herschel images of the is an element of Eridani system, seen at a fifth of the Sun's present age, resolve two belts of debris emission. Fits to the 160 mu m PACS image yield radial spans for these belts of 12-16 and 54-68 AU. The south end of the outer belt is approximate to 10% brighter than the north end in the PACS+SPIRE images at 160, 250, and 350 mu m, indicating a pericenter glow attributable to a planet c From this asymmetry and an upper bound on the offset of the belt center, this second planet should be mildly eccentric (e(c) approximate to 0.03-0.3). Compared to the asteroid and Kuiper Belts of the young Sun, the is an element of Eri belts are intermediate in brightness and more similar to each other, with up to 20 km sized collisional fragments in the inner belt totaling approximate to 5% of an Earth mass. This reservoir may feed the hot dust close to the star and could send many impactors through the Habitable Zone, especially if it is being perturbed by the suspected planet is an element of Eri b, at semi-major axis approximate to 3 AU.
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| 5. |
- Sibthorpe, B., et al.
(författare)
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The Vega debris disc: A view from Herschel
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L130
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Tidskriftsartikel (refereegranskat)abstract
- We present five band imaging of the Vega debris disc obtained using the Herschel Space Observatory. These data span a wavelength range of 70-500 mu m with full-width half-maximum angular resolutions of 5.6-36.9 ''. The disc is well resolved in all bands, with the ring structure visible at 70 and 160 mu m. Radial profiles of the disc surface brightness are produced, and a disc radius of 11 '' (similar to 85AU) is determined. The disc is seen to have a smooth structure thoughout the entire wavelength range, suggesting that the disc is in a steady state, rather than being an ephemeral structure caused by the recent collision of two large planetesimals.
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| 6. |
- Greaves, J. S., et al.
(författare)
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Extreme Conditions in a Close Analog to the Young Solar System: Herschel Observations of ∈ Eridani
- 2014
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 791:1
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Tidskriftsartikel (refereegranskat)abstract
- Far-infrared Herschel images of the is an element of Eridani system, seen at a fifth of the Sun's present age, resolve two belts of debris emission. Fits to the 160 mu m PACS image yield radial spans for these belts of 12-16 and 54-68 AU. The south end of the outer belt is approximate to 10% brighter than the north end in the PACS+SPIRE images at 160, 250, and 350 mu m, indicating a pericenter glow attributable to a planet "c" From this asymmetry and an upper bound on the offset of the belt center, this second planet should be mildly eccentric (e(c) approximate to 0.03-0.3). Compared to the asteroid and Kuiper Belts of the young Sun, the is an element of Eri belts are intermediate in brightness and more similar to each other, with up to 20 km sized collisional fragments in the inner belt totaling approximate to 5% of an Earth mass. This reservoir may feed the hot dust close to the star and could send many impactors through the Habitable Zone, especially if it is being perturbed by the suspected planet is an element of Eri b, at semi-major axis approximate to 3 AU.
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| 7. |
- Ertel, S., et al.
(författare)
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A peculiar class of debris disks from Herschel/DUNES - A steep fall off in the far infrared
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541
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Tidskriftsartikel (refereegranskat)abstract
- Context. The existence of debris disks around old main sequence stars is usually explained by continuous replenishment of small dust grains through collisions from a reservoir of larger objects. Aims. We present photometric data of debris disks around HIP 103389 (HD199260), HIP 107350 (HNPeg, HD206860), and HIP 114948 (HD219482), obtained in the context of our Herschel open time key program DUNES (DUst around NEarby Stars). Methods. We used Herschel/PACS to detect the thermal emission of the three debris disks with a 3 sigma sensitivity of a few mJy at 100 mu m and 160 mu m. In addition, we obtained Herschel/PACS photometric data at 70 mu m for HIP 103389. These observations are complemented by a large variety of optical to far-infrared photometric data. Two different approaches are applied to reduce the Herschel data to investigate the impact of data reduction on the photometry. We fit analytical models to the available spectral energy distribution (SED) data using the fitting method of simulated thermal annealing as well as a classical grid search method. Results. The SEDs of the three disks potentially exhibit an unusually steep decrease at wavelengths >= 70 mu m. We investigate the significance of the peculiar shape of these SEDs and the impact on models of the disks provided it is real. Using grain compositions that have been applied successfully for modeling of many other debris disks, our modeling reveals that such a steep decrease of the SEDs in the long wavelength regime is inconsistent with a power-law exponent of the grain size distribution -3.5 expected from a standard equilibrium collisional cascade. In contrast, a steep grain size distribution or, alternatively an upper grain size in the range of few tens of micrometers are implied. This suggests that a very distinct range of grain sizes would dominate the thermal emission of such disks. However, we demonstrate that the understanding of the data of faint sources obtained with Herschel is still incomplete and that the significance of our results depends on the version of the data reduction pipeline used. Conclusions. A new mechanism to produce the dust in the presented debris disks, deviations from the conditions required for a standard equilibrium collisional cascade (grain size exponent of -3.5), and/or significantly different dust properties would be necessary to explain the potentially steep SED shape of the three debris disks presented.
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| 8. |
- de Vries, B. L., et al.
(författare)
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Comet-like mineralogy of olivine crystals in an extrasolar proto-Kuiper belt
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7418, s. 74-76
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Tidskriftsartikel (refereegranskat)abstract
- Some planetary systems harbour debris disks containing planetesimals such as asteroids and comets(1). Collisions between such bodies produce small dust particles(2), the spectral features of which reveal their composition and, hence, that of their parent bodies. A measurement of the composition of olivine crystals (Mg2-2xFe2xSiO4) has been done for the protoplanetary disk HD 100546 (refs 3, 4) and for olivine crystals in the warm inner parts of planetary systems. The latter compares well with the iron-rich olivine in asteroids(5,6) (x approximate to 0.29). In the cold outskirts of the beta Pictoris system, an analogue to the young Solar System, olivine crystals were detected(7) but their composition remained undetermined, leaving unknown how the composition of the bulk of Solar System cometary olivine grains compares with that of extrasolar comets(8,9). Here we report the detection of the 69-micrometre-wavelength band of olivine crystals in the spectrum of beta Pictoris. Because the disk is optically thin, we can associate the crystals with an extrasolar proto-Kuiper belt a distance of 15-45 astronomical units from the star (one astronomical unit is the Sun-Earth distance), determine their magnesium-rich composition (x = 0.01 +/- 0.001) and show that they make up 3.6 +/- 1.0 per cent of the total dust mass. These values are strikingly similar to those for the dust emitted by the most primitive comets in the Solar System(8-10), even though beta Pictoris is more massive and more luminous and has a different planetary system architecture.
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| 9. |
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| 10. |
- Digby, Janet E, et al.
(författare)
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Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin.
- 2010
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 209:1, s. 89-95
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A major site of action for the atheroprotective drug nicotinic acid (NA) is adipose tissue, via the G-protein-coupled receptor, GPR109A. Since, adipose tissue is an active secretory organ that contributes both positively and negatively to systemic inflammatory processes associated with cardiovascular disease, we hypothesized that NA would act directly upon adipocytes to alter the expression of pro-inflammatory chemokines, and the anti-inflammatory adipokine adiponectin.METHODS AND RESULTS: TNF-alpha treatment (1.0ng/mL) of 3T3-L1 adipocytes resulted in an increase in gene expression of fractalkine (9+/-3.3-fold, P<0.01); monocyte chemoattractant protein-1 (MCP-1) (24+/-1.2-fold, P<0.001), 'regulated upon activation, normal T cell expressed and secreted' (RANTES) (500+/-55-fold, P<0.001) and inducible nitric oxide synthase (iNOS) (200+/-70-fold, P<0.05). The addition of NA (10(-4)M) to TNF-alpha-treated adipocytes attenuated expression of fractalkine (50+/-12%, P<0.01); MCP-1 (50+/-6%, P<0.01), RANTES (70+/-3%, P<0.01) and iNOS (60+/-16%). This pattern was mirrored in protein released from the adipocytes into the surrounding media. The effect on gene expression was neutralised by pre-treatment with pertussis toxin. NA attenuated macrophage chemotaxis (by 27+/-3.5%, P<0.001) towards adipocyte conditioned media. By contrast, NA, (10(-6)-10(-3)M) increased, in a dose-dependent manner, mRNA of the atheroprotective hormone adiponectin (3-5-fold n=6, P<0.01).CONCLUSIONS: NA suppresses pro-atherogenic chemokines and upregulates the atheroprotective adiponectin through a G-protein-coupled pathway. Since adipose tissue has the potential to contribute to both systemic and local (perivascular) inflammation associated with atherosclerosis our results suggest a new "pleiotropic" role for NA.
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| 11. |
- Euser, Anja S, et al.
(författare)
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The P300 event-related brain potential as a neurobiological endophenotype for substance use disorders : a meta-analytic investigation
- 2012
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 36:1, s. 572-603
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Forskningsöversikt (refereegranskat)abstract
- Endophenotypes are intermediate phenotypes on the putative causal pathway from genotype to phenotype and can aid in discovering the genetic etiology of a disorder. There are currently very few suitable endophenotypes available for substance use disorders (SUD). The amplitude of the P300 event-related brain potential is a possible candidate. The present study determined whether the P300 amplitude fulfils two fundamental criteria for an endophenotype: (1) an association with the disorder (disease marker), and (2) presence in unaffected biological relatives of those who have the disorder (vulnerability marker). For this purpose, two separate meta-analyses were performed. Meta-analysis 1 investigated the P300 amplitude in relation to SUD in 39 studies and Meta-analysis 2 investigated P300 amplitude in relation to a family history (FH+) of SUD in 35 studies. The findings indicate that a reduced P300 amplitude is significantly associated with SUD (d=0.51) and, though to a lesser extent, with a FH+ of SUD (d=0.28). As a disease maker, the association between reduced P300 amplitude and SUD is significantly larger for participants that were exclusively recruited from treatment facilities (d=0.67) than by other methods (i.e., community samples and family studies; d=0.45 and 0.32, respectively), and larger for abstinent SUD patients (d=0.71) than for current substance users (d=0.37). Furthermore, in contrast to FH+ males, a P300 amplitude reduction seems not to be present in FH+ females (d=-0.07). Taken together, these results suggest that P300 amplitude reduction can be both a useful disease and vulnerability marker and is a promising neurobiological endophenotype for SUD, though only in males. Implications and future directions are discussed.
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| 12. |
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| 13. |
- Lawler, S. M., et al.
(författare)
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The debris disc of solar analogue tau Ceti : Herschel observations and dynamical simulations of the proposed multiplanet system
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 444:3, s. 2665-2675
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Tidskriftsartikel (refereegranskat)abstract
- tau Ceti is a nearby, mature G-type star very similar to our Sun, with a massive Kuiper Belt analogue and possible multiplanet system that has been compared to our Solar system. We present Herschel Space Observatory images of the debris disc, finding the disc is resolved at 70 mu m and 160 mu m, and marginally resolved at 250 mu m. The Herschel images and infrared photometry from the literature are best modelled using a wide dust annulus with an inner edge between 1 and 10 au and an outer edge at similar to 55 au, inclined from face-on by 35 degrees +/- 10 degrees, and with no significant azimuthal structure. We model the proposed tightly packed planetary system of five super-Earths and find that the innermost dynamically stable disc orbits are consistent with the inner edge found by the observations. The photometric modelling, however, cannot rule out a disc inner edge as close to the star as 1 au, though larger distances produce a better fit to the data. Dynamical modelling shows that the five-planet system is stable with the addition of a Neptune or smaller mass planet on an orbit outside 5 au, where the radial velocity data analysis would not have detected a planet of this mass.
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| 14. |
- Levin, Malin, 1973, et al.
(författare)
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Evaluation of macrophage-specific promoters using lentiviral delivery in mice.
- 2012
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Ingår i: Gene therapy. - : Springer Science and Business Media LLC. - 1476-5462 .- 0969-7128. ; 19:11, s. 1041-7
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Tidskriftsartikel (refereegranskat)abstract
- In gene therapy, tissue-specific promoters are useful tools to direct transgene expression and improve efficiency and safety. Macrophage-specific promoters (MSPs) have previously been published using different delivery systems. In this study, we evaluated five different MSPs fused with green fluorescent protein (GFP) to delineate the one with highest specificity using lentiviral delivery. We compared three variants of the CD68 promoter (full length, the 343-bp proximal part and the 150-bp proximal part) and two variants (in forward and reverse orientation) of a previously characterized synthetic promoter derived from elements of transcription factor genes. We transduced a number of cell lines and primary cells in vitro. In addition, hematopoietic stem cells were transduced with MSPs and transferred into lethally irradiated recipient mice. Fluorescence activated cell sorting analysis was performed to determine the GFP expression in different cell populations both in vitro and in vivo. We showed that MSPs can efficiently be used for lentiviral gene delivery and that the 150-bp proximal part of the CD68 promoter provides primarily macrophage-specific expression of GFP. We propose that this is the best currently available MSP to use for directing transgene expression to macrophage populations in vivo using lentiviral vectors.
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| 15. |
- Marshall, J. P., et al.
(författare)
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Correlations between the stellar, planetary, and debris components of exoplanet systems observed by Herschel
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 565, s. A15-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Stars form surrounded by gas- and dust-rich protoplanetary discs. Generally, these discs dissipate over a few (3-10) Myr, leaving a faint tenuous debris disc composed of second-generation dust produced by the attrition of larger bodies formed in the protoplanetary disc. Giant planets detected in radial velocity and transit surveys of main-sequence stars also form within the protoplanetary disc, whilst super-Earths now detectable may form once the gas has dissipated. Our own solar system, with its eight planets and two debris belts, is a prime example of an end state of this process. Aims. The Herschel DEBRIS, DUNES, and GI' programmes observed 37 exoplanet host stars within 25 pc at 70, 100, and 160 mu m with the sensitivity to detect far-infrared excess emission at flux density levels only an order of magnitude greater than that of the solar system's Edgeworth-Kuiper belt. Here we present an analysis of that sample, using it to more accurately determine the (possible) level of dust emission from these exoplanet host stars and thereafter determine the links between the various components of these exoplanetary systems through statistical analysis. Methods. We have fitted the flux densities measured from recent Herschel observations with a simple two parameter (T-d, L-IR/L-*) black-body model (or to the 3 sigma upper limits at 100 mu m). From this uniform approach we calculated the fractional luminosity, radial extent and dust temperature. We then plotted the calculated dust luminosity or upper limits against the stellar properties, e.g. effective temperature, metallicity, and age, and identified correlations between these parameters. Results. A total of eleven debris discs are identified around the 37 stars in the sample. An incidence of ten cool debris discs around the Sun-like exoplanet host stars (29 +/- 9%) is consistent with the detection rate found by DUNES (20.2 +/- 2.0%). For the debris disc systems, the dust temperatures range from 20 to 80 K, and fractional luminosities (L-IR/L-*) between 2.4 x10(-6) and 4.1 x10(-4). In the case of non-detections, we calculated typical 3 sigma upper limits to the dust fractional luminosities of a few x10(-6). Conclusions. We recover the previously identified correlation between stellar metallicity and hot-Jupiter planets in our data set. We find a correlation between the increased presence of dust, lower planet masses, and lower stellar metallicities. This confirms the recently identified correlation between cold debris discs and low-mass planets in the context of planet formation by core accretion.
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| 16. |
- Migliorini, Gabriele, et al.
(författare)
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Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 122:19, s. 3298-3307
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Tidskriftsartikel (refereegranskat)abstract
- Acute lymphoblastic leukemia (ALL) is the major pediatric cancer diagnosed in economically developed countries with B-cell precursor (BCP)-ALL, accounting for approximately 70% of ALL. Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence for common inherited susceptibility to BCP-ALL, identifying susceptibility loci at 7p12.2, 9p21.3, 10q21.2, and 14q11.2. To identify additional BCP-ALL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1658 cases and 4723 controls, with validation in 1449 cases and 1488 controls. Combined analysis identified novel loci mapping to 10p12.2 (rs10828317, odds ratio [OR] = 1.23; P = 2.30 x 10(-9)) and 10p14marked by rs3824662(OR = 1.31; P = 8.62 x 10(-12)). The single nucleotide polymorphism rs10828317 is responsible for the N215S polymorphism in exon 7 of PIP4K2A, and rs3824662 localizes to intron 3 of the transcription factor and putative tumor suppressor gene GATA3. The rs10828317 association was shown to be specifically associated with hyperdiploid ALL, whereas the rs3824662-associated risk was confined to nonhyperdiploid non-TEL-AML1 + ALL. The risk allele of rs3824662 was correlated with older age at diagnosis (P < .001) and significantly worse event-free survivorship (P < .0001). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to BCP-ALL and the influence of constitutional genotype on disease development.
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| 17. |
- van der Wiel, M. H. D., et al.
(författare)
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Signatures of warm carbon monoxide in protoplanetary discs observed with Herschel SPIRE
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 444:4, s. 3911-3925
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Tidskriftsartikel (refereegranskat)abstract
- Molecular gas constitutes the dominant mass component of protoplanetary discs. To date, these sources have not been studied comprehensively at the longest far-infrared and shortest submillimetre wavelengths. This paper presents Herschel SPIRE FTS spectroscopic observations towards 18 protoplanetary discs, covering the entire 450-1540 GHz (666-195 mu m) range at upsilon/Delta upsilon approximate to 400-1300. The spectra reveal clear detections of the dust continuum and, in six targets, a significant amount of spectral line emission primarily attributable to (CO)-C-12 rotational lines. Other targets exhibit little to no detectable spectral lines. Low signal-to-noise detections also include signatures from (CO)-C-13, [C I] and HCN. For completeness, we present upper limits of non-detected lines in all targets, including low-energy transitions of H2O and CH+ molecules. The 10 (CO)-C-12 lines that fall within the SPIRE FTS bands trace energy levels of similar to 50-500 K. Combined with lower and higher energy lines from the literature, we compare the CO rotational line energy distribution with detailed physical-chemical models, for sources where these are available and published. Our (CO)-C-13 line detections in the disc around Herbig Be star HD 100546 exceed, by factors of similar to 10-30, the values predicted by a model that matches a wealth of other observational constraints, including the SPIRE (CO)-C-12 ladder. To explain the observed (CO)-C-12/(CO)-C-13 ratio, it may be necessary to consider the combined effects of optical depth and isotope selective (photo) chemical processes. Considering the full sample of 18 objects, we find that the strongest line emission is observed in discs around Herbig Ae/Be stars, although not all show line emission. In addition, two of the six T Tauri objects exhibit detectable (CO)-C-12 lines in the SPIRE range.
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