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- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Lacour, S., et al.
(författare)
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The mass of β Pictoris c from β Pictoris b orbital motion
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We aim to demonstrate that the presence and mass of an exoplanet can now be effectively derived from the astrometry of another exoplanet.Methods. We combined previous astrometry of β Pictoris b with a new set of observations from the GRAVITY interferometer. The orbital motion of β Pictoris b is fit using Markov chain Monte Carlo simulations in Jacobi coordinates. The inner planet, β Pictoris c, was also reobserved at a separation of 96 mas, confirming the previous orbital estimations.Results. From the astrometry of planet b only, we can (i) detect the presence of β Pictoris c and (ii) constrain its mass to 10.04(-3.10)(+4.53) M-Jup. If one adds the astrometry of β Pictoris c, the mass is narrowed down to 9.15(-1.06)(+1.08) M-Jup. The inclusion of radial velocity measurements does not affect the orbital parameters significantly, but it does slightly decrease the mass estimate to 8.89(-0.75)(+0.75) M-Jup. With a semimajor axis of 2.68 +/- 0.02 au, a period of 1221 +/- 15 days, and an eccentricity of 0.32 +/- 0.02, the orbital parameters of β Pictoris c are now constrained as precisely as those of β Pictoris b. The orbital configuration is compatible with a high-order mean-motion resonance (7:1). The impact of the resonance on the planets' dynamics would then be negligible with respect to the secular perturbations, which might have played an important role in the eccentricity excitation of the outer planet.
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- Lagrange, A. M., et al.
(författare)
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Unveiling the beta Pictoris system, coupling high contrast imaging, interferometric, and radial velocity data
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
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Tidskriftsartikel (refereegranskat)abstract
- Context. The nearby and young beta Pictoris system hosts a well resolved disk, a directly imaged massive giant planet orbiting at similar or equal to 9 au, as well as an inner planet orbiting at similar or equal to 2.7 au, which was recently detected through radial velocity (RV). As such, it offers several unique opportunities for detailed studies of planetary system formation and early evolution.Aims. We aim to further constrain the orbital and physical properties of beta Pictoris b and c using a combination of high contrast imaging, long base-line interferometry, and RV data. We also predict the closest approaches or the transit times of both planets, and we constrain the presence of additional planets in the system.Methods. We obtained six additional epochs of SPHERE data, six additional epochs of GRAVITY data, and five additional epochs of RV data. We combined these various types of data in a single Markov-chain Monte Carlo analysis to constrain the orbital parameters and masses of the two planets simultaneously. The analysis takes into account the gravitational influence of both planets on the star and hence their relative astrometry. Secondly, we used the RV and high contrast imaging data to derive the probabilities of presence of additional planets throughout the disk, and we tested the impact of absolute astrometry.Results. The orbital properties of both planets are constrained with a semi-major axis of 9.8 0.4 au and 2.7 +/- 0.02 au for b and c, respectively, and eccentricities of 0.09 +/- 0.1 and 0.27 +/- 0.07, assuming the HIPPARCOS distance. We note that despite these low fitting error bars, the eccentricity of beta Pictoris c might still be over-estimated. If no prior is provided on the mass of beta Pictoris b, we obtain a very low value that is inconsistent with what is derived from brightness-mass models. When we set an evolutionary model motivated prior to the mass of beta Pictoris b, we find a solution in the 10-11 M-Jup range. Conversely, beta Pictoris c's mass is well constrained, at 7.8 +/- 0.4 M-Jup, assuming both planets are on coplanar orbits. These values depend on the assumptions on the distance of the beta Pictoris system. The absolute astrometry HIPPARCOS-Gaia data are consistent with the solutions presented here at the 2 sigma level, but these solutions are fully driven by the relative astrometry plus RV data. Finally, we derive unprecedented limits on the presence of additional planets in the disk. We can now exclude the presence of planets that are more massive than about 2.5 M-Jup closer than 3 au, and more massive than 3.5 M-Jup between 3 and 7.5 au. Beyond 7.5 au, we exclude the presence of planets that are more massive than 1-2 M-Jup.Conclusions. Combining relative astrometry and RVs allows one to precisely constrain the orbital parameters of both planets and to give lower limits to potential additional planets throughout the disk. The mass of beta Pictoris c is also well constrained, while additional RV data with appropriate observing strategies are required to properly constrain the mass of beta Pictoris b.
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- Desgrange, C., et al.
(författare)
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In-depth direct imaging and spectroscopic characterization of the young Solar System analog HD 95086
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 664
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Tidskriftsartikel (refereegranskat)abstract
- Context. HD 95086 is a young nearby Solar System analog hosting a giant exoplanet orbiting at 57 au from the star between an inner and outer debris belt. The existence of additional planets has been suggested as the mechanism that maintains the broad cavity between the two belts.Aims. We present a dedicated monitoring of HD 95086 with the VLT/SPHERE instrument to refine the orbital and atmospheric properties of HD 95086 b, and to search for additional planets in this system.Methods. SPHERE observations, spread over ten epochs from 2015 to 2019 and including five new datasets, were used. Combined with archival observations, from VLT/NaCo (2012-2013) and Gemini/GPI (2013-2016), the extended set of astrometric measurements allowed us to refine the orbital properties of HD 95086 b. We also investigated the spectral properties and the presence of a circumplanetary disk around HD 95086 b by using the special fitting tool exploring the diversity of several atmospheric models. In addition, we improved our detection limits in order to search for a putative planet c via the K-Stacker algorithm.Results. We extracted for the first time the JH low-resolution spectrum of HD 95086 b by stacking the six best epochs, and confirm its very red spectral energy distribution. Combined with additional datasets from GPI and NaCo, our analysis indicates that this very red color can be explained by the presence of a circumplanetary disk around planet b, with a range of high-temperature solutions (1400–1600 K) and significant extinction (Av ≳ 10 mag), or by a super-solar metallicity atmosphere with lower temperatures (800–300 K), and small to medium amount of extinction (Av ≲ 10 mag). We do not find any robust candidates for planet c, but give updated constraints on its potential mass and location.
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- Liu, JJ, et al.
(författare)
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Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 9688-
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Tidskriftsartikel (refereegranskat)abstract
- In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859–1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482–1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
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- Perotti, G., et al.
(författare)
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Water in the terrestrial planet-forming zone of the PDS 70 disk
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 620:7974, s. 516-520
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Tidskriftsartikel (refereegranskat)abstract
- Terrestrial and sub-Neptune planets are expected to form in the inner (less than 10 AU) regions of protoplanetary disks1. Water plays a key role in their formation2,3,4, although it is yet unclear whether water molecules are formed in situ or transported from the outer disk5,6. So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks7, similar to PDS 70, the first system with direct confirmation of protoplanet presence8,9. Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large (approximately 54 AU) planet-carved gap separating an inner and outer disk10,11. Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H2 and/or OH, and survival through water self-shielding5. This is also supported by the presence of CO2 emission, another molecule sensitive to ultraviolet photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir12. Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry.
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- Tabone, B., et al.
(författare)
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A rich hydrocarbon chemistry and high C to O ratio in the inner disk around a very low-mass star
- 2023
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Ingår i: Nature Astronomy. - 2397-3366. ; 7:7, s. 805-814
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Tidskriftsartikel (refereegranskat)abstract
- Carbon is an essential element for life but how much can be delivered to young planets is still an open question. The chemical characterization of planet-forming disks is a crucial step in our understanding of the diversity and habitability of exoplanets. Very low-mass stars (less than 0.2 M⊙) are interesting targets because they host a rich population of terrestrial planets. Here we present the James Webb Space Telescope detection of abundant hydrocarbons in the disk of a very low-mass star obtained as part of the Mid-InfraRed Instrument mid-INfrared Disk Survey (MINDS). In addition to very strong and broad emission from C2H2 and its 13C12CH2 isotopologue, C4H2, benzene and possibly CH4 are identified, but water, polycyclic aromatic hydrocarbons and silicate features are weak or absent. The lack of small silicate grains indicates that we can look deep down into this disk. These detections testify to an active warm hydrocarbon chemistry with a high C/O ratio larger than unity in the inner 0.1 astronomical units (AU) of this disk, perhaps due to destruction of carbonaceous grains. The exceptionally high C2H2/CO2 and C2H2/H2O column density ratios indicate that oxygen is locked up in icy pebbles and planetesimals outside the water iceline. This, in turn, will have important consequences for the composition of forming exoplanets.
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- Grant, Sierra L., et al.
(författare)
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MINDS. The Detection of 13 CO 2 with JWST-MIRI Indicates Abundant CO 2 in a Protoplanetary Disk
- 2023
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Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 947:1
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Tidskriftsartikel (refereegranskat)abstract
- We present JWST-MIRI Medium Resolution Spectrometer (MRS) spectra of the protoplanetary disk around the low-mass T Tauri star GW Lup from the MIRI mid-INfrared Disk Survey Guaranteed Time Observations program. Emission from 12CO213CO2, H2O, HCN, C2H2, and OH is identified with 13CO2 being detected for the first time in a protoplanetary disk. We characterize the chemical and physical conditions in the inner few astronomical units of the GW Lup disk using these molecules as probes. The spectral resolution of JWST-MIRI MRS paired with high signal-to-noise data is essential to identify these species and determine their column densities and temperatures. The Q branches of these molecules, including those of hot bands, are particularly sensitive to temperature and column density. We find that the 12CO2 emission in the GW Lup disk is coming from optically thick emission at a temperature of ∼400 K. 13CO2 is optically thinner and based on a lower temperature of ∼325 K, and thus may be tracing deeper into the disk and/or a larger emitting radius than 12CO2. The derived N CO 2 / N H 2 O ratio is orders of magnitude higher than previously derived for GW Lup and other targets based on Spitzer-InfraRed-Spectrograph data. This high column density ratio may be due to an inner cavity with a radius in between the H2O and CO2 snowlines and/or an overall lower disk temperature. This paper demonstrates the unique ability of JWST to probe inner disk structures and chemistry through weak, previously unseen molecular features.
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- Mawet, Dimitri, et al.
(författare)
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L '-band AGPM vector vortex coronagraph's first light on VLT/NACO Discovery of a late-type companion at two beamwidths from an F0V star
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 552, s. L13-
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Tidskriftsartikel (refereegranskat)abstract
- Context. High contrast imaging has thoroughly combed through the limited search space accessible with first-generation ground-based adaptive optics instruments and the Hubble Space Telescope. Only a few objects were discovered, and many non-detections reported and statistically interpreted. The field is now in need of a technological breakthrough. Aims. Our aim is to open a new search space with first-generation systems such as NACO at the Very Large Telescope, by providing ground-breaking inner working angle (IWA) capabilities in the L' band. The L' band is a sweet spot for high contrast coronagraphy since the planet-to-star brightness ratio is favorable, while the Strehl ratio is naturally higher. Methods. An annular groove phase mask (AGPM) vector vortex coronagraph optimized for the L' band made from diamond subwavelength gratings was manufactured and qualified in the lab. The AGPM enables high contrast imaging at very small IWA, potentially being the key to unexplored discovery space. Results. Here we present the installation and successful on-sky tests of an L'-band AGPM coronagraph on NACO. Using angular differential imaging, which is well suited to the rotational symmetry of the AGPM, we demonstrated a Delta L' > 7.5 mag contrast from an IWA similar or equal to 0 ''.09 onwards, during average seeing conditions, and for total integration times of a few hundred seconds.
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- Milli, J., et al.
(författare)
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Discovery of a low-mass companion inside the debris ring surrounding the F5V star HD 206893
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 597
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Uncovering the ingredients and the architecture of planetary systems is a very active field of research that has fuelled many new theories on giant planet formation, migration, composition, and interaction with the circumstellar environment. We aim at discovering and studying new such systems, to further expand our knowledge of how low-mass companions form and evolve.Methods. We obtained high-contrast H-band images of the circumstellar environment of the F5V star HD 206893, known to host a debris disc never detected in scattered light. These observations are part of the SPHERE High Angular Resolution Debris Disc Survey (SHARDDS) using the InfraRed Dual-band Imager and Spectrograph (IRDIS) installed on VLT/SPHERE.Results. We report the detection of a source with a contrast of 3.6 × 10−5 in the H-band, orbiting at a projected separation of 270 milliarcsecond or 10 au, corresponding to a mass in the range 24 to 73MJup for an age of the system in the range 0.2 to 2 Gyr. The detection was confirmed ten months later with VLT/NaCo, ruling out a background object with no proper motion. A faint extended emission compatible with the disc scattered light signal is also observed.Conclusions. The detection of a low-mass companion inside a massive debris disc makes this system an analog of other young planetary systems such as β Pictoris, HR 8799 or HD 95086 and requires now further characterisation of both components to understand their interactions.
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- Reggiani, M, et al.
(författare)
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Discovery of a point-like source and a third spiral arm in the transition disk around the Herbig Ae star MWC 758
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 611
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Tidskriftsartikel (refereegranskat)abstract
- Context. Transition disks offer the extraordinary opportunity to look for newly born planets and to investigate the early stages of planet formation. Aims. In this context we observed the Herbig A5 star MWC 758 with the L'-band vector vortex coronagraph installed in the near-infrared camera and spectrograph NIRC2 at the Keck II telescope, with the aim of unveiling the nature of the spiral structure by constraining the presence of planetary companions in the system. Methods. Our high-contrast imaging observations show a bright (Delta L' = 7.0 +/- 0.3 mag) point-like emission south of MWC 758 at a deprojected separation of similar to 20 au (r = 0 ''.111 +/- 0 ''.004) from the central star. We also recover the two spiral arms (southeast and northwest), already imaged by previous studies in polarized light, and discover a third arm to the southwest of the star. No additional companions were detected in the system down to 5 Jupiter masses beyond 0 ''.6 from the star. Results. We propose that the bright L'-band emission could be caused by the presence of an embedded and accreting protoplanet, although the possibility of it being an asymmetric disk feature cannot be excluded. The spiral structure is probably not related to the protoplanet candidate, unless on an inclined and eccentric orbit, and it could be due to one (or more) yet undetected planetary companions at the edge of or outside the spiral pattern. Future observations and additional simulations will be needed to shed light on the true nature of the point-like source and its link with the spiral arms.
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- Richards, Stephen, et al.
(författare)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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- Stevens, Kristen N, et al.
(författare)
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19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
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Tidskriftsartikel (refereegranskat)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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