| 1. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 2. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 3. |
- Abramowski, A., et al.
(författare)
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A multiwavelength view of the flaring state of PKS 2155-304 in 2006
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539, s. A149-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Multiwavelength (MWL) observations of the blazar PKS 2155-304 during two weeks in July and August 2006, the period when two exceptional flares at very high energies (VHE, E greater than or similar to 100 GeV) occurred, provide a detailed picture of the evolution of its emission. The complete data set from this campaign is presented, including observations in VHE gamma-rays (H.E.S. S.), X-rays (RXTE, Chandra, Swift XRT), optical (Swift UVOT, Bronberg, Watcher, ROTSE), and in the radio band (NRT, HartRAO, ATCA). Optical and radio light curves from 2004 to 2008 are compared to the available VHE data from this period, to put the 2006 campaign into the context of the long-term evolution of the source. Aims. The data set offers a close view of the evolution of the source on different time scales and yields new insights into the properties of the emission process. The predictions of synchrotron self-Compton (SSC) scenarios are compared to the MWL data, with the aim of describing the dominant features in the data down to the hour time scale. Methods. The spectral variability in the X-ray and VHE bands is explored and correlations between the integral fluxes at different wavelengths are evaluated. SSC modelling is used to interpret the general trends of the varying spectral energy distribution. Results. The X-ray and VHE gamma-ray emission are correlated during the observed high state of the source, but show no direct connection with longer wavelengths. The long-term flux evolution in the optical and radio bands is found to be correlated and shows that the source reaches a high state at long wavelengths after the occurrence of the VHE flares. Spectral hardening is seen in the Swift XRT data. Conclusions. The nightly averaged high-energy spectra of the non-flaring nights can be reproduced by a stationary one-zone SSC model, with only small variations in the parameters. The spectral and flux evolution in the high-energy band during the night of the second VHE flare is modelled with multi-zone SSC models, which can provide relatively simple interpretations for the hour time-scale evolution of the high-energy emission, even for such a complex data set. For the first time in this type of source, a clear indication is found for a relation between high activity at high energies and a long-term increase in the low frequency fluxes.
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| 4. |
- Abramowski, A., et al.
(författare)
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A new SNR with TeV shell-type morphology : HESS J1731-347
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 531, s. A81-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The recent discovery of the radio shell-type supernova remnant (SNR), G353.6-0.7, in spatial coincidence with the unidentified TeV source HESS J1731-347 has motivated further observations of the source with the High Energy Stereoscopic System (HESS) Cherenkov telescope array to test a possible association of the gamma-ray emission with the SNR. Methods. With a total of 59 h of observation, representing about four times the initial exposure available in the discovery paper of HESS J1731-347, the gamma-ray morphology is investigated and compared with the radio morphology. An estimate of the distance is derived by comparing the interstellar absorption derived from X-rays and the one obtained from (12)CO and HI observations. Results. The deeper gamma-ray observation of the source has revealed a large shell-type structure with similar position and extension (r similar to 0.25 degrees) as the radio SNR, thus confirming their association. By accounting for the HESS angular resolution and projection effects within a simple shell model, the radial profile is compatible with a thin, spatially unresolved, rim. Together with RX J1713.7-3946, RX J0852.0-4622 and SN 1006, HESS J1731-347 is now the fourth SNR with a significant shell morphology at TeV energies. The derived lower limit on the distance of the SNR of 3.2 kpc is used together with radio and X-ray data to discuss the possible origin of the gamma-ray emission, either via inverse Compton scattering of electrons or the decay of neutral pions resulting from proton-proton interaction.
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| 5. |
- Abramowski, A., et al.
(författare)
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Detection of very-high-energy gamma-ray emission from the vicinity of PSR B1706-44 and G 343.1-2.3 with HESS
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 528, s. A143-
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Tidskriftsartikel (refereegranskat)abstract
- The gamma-ray pulsar PSR B1706-44 and the adjacent supernova remnant (SNR) candidate G 343.1-2.3 were observed by H. E. S. S. during a dedicated observation campaign in 2007. As a result of this observation campaign, a new source of very-high-energy (VHE; E > 100 GeV) gamma-ray emission, H.E.S.S. J1708-443, was detected with a statistical significance of 7 sigma, although no significant point-like emission was detected at the position of the energetic pulsar itself. In this paper, the morphological and spectral analyses of the newly-discovered TeV source are presented. The centroid of H. E. S. S. J1708-443 is considerably offset from the pulsar and located near the apparent center of the SNR, at alpha(J2000) = 17(h)08(m)11(s) +/- 17(s) and delta(J2000) = -44 degrees 20' +/- 4'. The source is found to be significantly more extended than the H. E. S. S. point spread function (similar to 0.1 degrees), with an intrinsic Gaussian width of 0.29 degrees +/- 0.04 degrees. Its integral flux between 1 and 10 TeV is similar to 3.8 x 10(-1)2 ph cm(-2) s(-1), equivalent to 17% of the Crab Nebula flux in the same energy range. The measured energy spectrum is well-fit by a power law with a relatively hard photon index Gamma = 2.0 +/- 0.1(stat) +/-0.2(sys). Additional multi-wavelength data, including 330 MHz VLA observations, were used to investigate the VHE gamma-ray source's possible associations with the pulsar wind nebula of PSR B1706-44 and/or with the complex radio structure of the partial shell-type SNR G 343.1-2.3.
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| 6. |
- Abramowski, A., et al.
(författare)
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Discovery of extended VHE gamma-ray emission from the vicinity of the young massive stellar cluster Westerlund 1
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537, s. A114-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Results obtained in very-high-energy (VHE; E >= 100 GeV) gamma-ray observations performed with the H.E.S.S. telescope array are used to investigate particle acceleration processes in the vicinity of the young massive stellar cluster Westerlund 1 (Wd 1). Methods. Imaging of Cherenkov light from gamma-ray induced particle cascades in the Earth's atmosphere is used to search for VHE gamma rays from the region around Wd 1. Possible catalogued counterparts are searched for and discussed in terms of morphology and energetics of the H.E.S.S. source. Results. The detection of the degree-scale extended VHE gamma-ray source HESS J1646-458 is reported based on 45 h of H.E.S.S. observations performed between 2004 and 2008. The VHE gamma-ray source is centred on the nominal position of Wd 1 and detected with a total statistical significance of similar to 20 sigma. The emission region clearly extends beyond the H.E.S.S. point-spread function (PSF). The differential energy spectrum follows a power law in energy with an index of Gamma = 2.19 +/- 0.08(stat) +/- 0.20(sys) and a flux normalisation at 1 TeV of Phi(0) = (9.0 +/- 1.4(stat) +/- 1.8(sys)) x 10(-12) TeV-1 cm(-2) s(-1). The integral flux above 0.2 TeV amounts to (5.2 +/- 0.9) x 10(-11) cm(-2) s(-1). Conclusions. Four objects coincident with HESS J1646-458 are discussed in the search of a counterpart, namely the magnetar CXOU J164710.2-455216, the X-ray binary 4U 1642-45, the pulsar PSR J1648-4611 and the massive stellar cluster Wd 1. In a single-source scenario, Wd 1 is favoured as site of VHE particle acceleration. Here, a hadronic parent population would be accelerated within the stellar cluster. Beside this, there is evidence for a multi-source origin, where a scenario involving PSR J1648-4611 could be viable to explain parts of the VHE gamma-ray emission of HESS J1646-458.
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| 7. |
- Abramowski, A., et al.
(författare)
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Discovery of gamma-ray emission from the extragalactic pulsar wind nebula N 157B with HESS
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. Article ID: L2-
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Tidskriftsartikel (refereegranskat)abstract
- We present the significant detection of the first extragalactic pulsar wind nebula (PWN) detected in gamma rays, N 157B, located in the large Magellanic Cloud (LMC). Pulsars with high spin-down luminosity are found to power energised nebulae that emit gamma rays up to energies of several tens of TeV. N 157B is associated with PSR J0537-6910, which is the pulsar with the highest known spin-down luminosity. The High Energy Stereoscopic System telescope array observed this nebula on a yearly basis from 2004 to 2009 with a dead-time corrected exposure of 46 h. The gamma-ray spectrum between 600 GeV and 12 TeV is well-described by a pure power-law with a photon index of 2.8 +/- 0.2(stat) +/- 0.3(syst) and a normalisation at 1 TeV of (8.2 +/- 0.8(stat) +/- 2.5(syst)) x 10(-13) cm(-2) s(-1) TeV-1. A leptonic multi-wavelength model shows that an energy of about 4 x 10(49) erg is stored in electrons and positrons. The apparent efficiency, which is the ratio of the TeV gamma-ray luminosity to the pulsar's spin-down luminosity, 0.08% +/- 0.01%, is comparable to those of PWNe found in the Milky Way. The detection of a PWN at such a large distance is possible due to the pulsar's favourable spin-down luminosity and a bright infrared photon-field serving as an inverse-Compton-scattering target for accelerated leptons. By applying a calorimetric technique to these observations, the pulsar's birth period is estimated to be shorter than 10 ms.
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| 8. |
- Abramowski, A., et al.
(författare)
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Discovery of hard-spectrum gamma- ray emission from the BL Lacertae object 1ES 0414+009
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 538, s. A103-
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Tidskriftsartikel (refereegranskat)abstract
- Context. 1ES 0414+009 (z = 0.287) is a distant high-frequency- peaked BL Lac object, and has long been considered a likely emitter of very-highenergy (VHE, E > 100 GeV) gamma-rays due to its high X-ray and radio flux. Aims. Observations in the VHE gamma-ray band and across the electromagnetic spectrum can provide insights into the origin of highly energetic particles present in the source and the radiation processes at work. Because of the distance of the source, the gamma-ray spectrum might provide further limits on the level of the extragalactic background light (EBL). Methods. We report observations made between October 2005 and December 2009 with H. E. S. S., an array of four imaging atmospheric Cherenkov telescopes. Observations at high energies (HE, 100 MeV-100 GeV) with the Fermi-LAT instrument in the first 20 months of its operation are also reported. To complete the multi-wavelength picture, archival UV and X-ray observations with the Swift satellite and optical observations with the ATOM telescope are also used. Results. Based on the observations with H.E.S.S., 1ES 0414+009 is detected for the first time in the VHE band. An excess of 224 events is measured, corresponding to a significance of 7.8 sigma. The photon spectrum of the source is well described by a power law, with photon index of Gamma(VHE) = 3.45 +/- 0.25(stat) +/- 0.20(syst). The integral flux above 200 GeV is (1.88 +/- 0.20(stat) +/- 0.38(syst)) x10(-12) cm(-2) s(-1). Observations with the Fermi-LAT in the first 20 months of operation show a flux between 200 MeV and 100 GeV of (2.3 +/- 0.2(stat)) x 10(-9) erg cm(-2) s(-1), and a spectrum well described by a power-law function with a photon index Gamma(HE) = 1.85 +/- 0.18. Swift/XRT observations show an X-ray flux between 2 and 10 keV of (0.8-1) x 10(-11) erg cm(-2) s(-1), and a steep spectrum Gamma(X) = (2.2-2.3). Combining X-ray with optical-UV data, a fit with a log-parabolic function locates the synchrotron peak around 0.1 keV. Conclusions. Although the GeV-TeV observations do not provide better constraints on the EBL than previously obtained, they confirm a low density of the EBL, close to the lower limits from galaxy counts. The absorption-corrected HE and VHE gamma-ray spectra are both hard and have similar spectral indices (approximate to 1.86), indicating no significant change of slope between the HE and VHE gamma-ray bands, and locating the gamma-ray peak in the SED above 1-2 TeV. As for other TeV BL Lac objects with the gamma-ray peak at such high energies and a large separation between the two SED humps, this average broad-band SED represents a challenge for simple one-zone synchrotron self-Compton models, requiring a high Doppler factor and very low B-field.
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| 9. |
- Abramowski, A., et al.
(författare)
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Discovery of the source HESS J1356-645 associated with the young and energetic PSR J1357-6429
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533, s. A103-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Several newly discovered very-high-energy (VHE; E > 100 GeV) gamma-ray sources in the Galaxy are thought to be associated with energetic pulsars. Among them, middle-aged (greater than or similar to 10(4) yr) systems exhibit large centre-filled VHE nebulae, offset from the pulsar position, which result from the complex relationship between the pulsar wind and the surrounding medium, and reflect the past evolution of the pulsar. Aims. Imaging Atmospheric Cherenkov Telescopes (IACTs) have been successful in revealing extended emission from these sources in the VHE regime. Together with radio and X-ray observations, this observational window allows one to probe the energetics and magnetic field inside these large-scale nebulae. Methods. H.E.S.S., with its large field of view, angular resolution of less than or similar to 0.1 degrees and unprecedented sensitivity, has been used to discover a large population of such VHE sources. In this paper, the H. E. S. S. data from the continuation of the Galactic Plane Survey (-80 degrees < l < 60 degrees, vertical bar b vertical bar < 3 degrees), together with the existing multi-wavelength observations, are used. Results. A new VHE gamma-ray source was discovered at RA (J2000) = 13(h)56(m)00(s), Dec (J2000) = -64 degrees 30'00 '' with a 2' statistical error in each coordinate, namely HESS J1356-645. The source is extended, with an intrinsic Gaussian width of (0.20 +/- 0.02)degrees. Its integrated energy flux between 1 and 10 TeV of 8 x 10(-12) erg cm(-2) s(-1) represents similar to 11% of the Crab Nebula flux in the same energy band. The energy spectrum between 1 and 20 TeV is well described by a power law dN/dE proportional to E-Gamma with photon index Gamma = 2.2 +/- 0.2(stat) +/- 0.2(sys). The inspection of archival radio images at three frequencies and the analysis of X-ray data from ROSAT/PSPC and XMM-Newton/MOS reveal the presence of faint non-thermal diffuse emission coincident with HESS J1356-645. Conclusions. HESS J1356-645 is most likely associated with the young and energetic pulsar PSR J1357-6429 (d = 2.4 kpc, tau(c) = 7.3 kyr and (E) over dot = 3.1 x 10(36) erg s(-1)), located at a projected distance of similar to 5 pc from the centroid of the VHE emission. HESS J1356-645 and its radio and X-ray counterparts would thus represent the nebula resulting from the past history of the PSR J1357-6429 wind. In a simple one-zone model, constraints on the magnetic field strength in the nebula are obtained from the flux of the faint and extended X-ray emission detected with ROSAT and XMM-Newton. Fermi-LAT upper limits in the high-energy ( HE; 0.1-100 GeV) domain are also used to constrain the parent electron spectrum. From the low magnetic field value inferred from this approach (similar to 3-4 mu G), HESS J1356-645 is thought to share many similarities with other known gamma-ray emitting nebulae, such as Vela X, as it exhibits a large-scale nebula seen in radio, X-rays and VHE gamma-rays.
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| 10. |
- Abramowski, A., et al.
(författare)
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Discovery of VHE emission towards the Carina arm region with the HESS telescope array : HESSJ1018-589
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541, s. A5-
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Tidskriftsartikel (refereegranskat)abstract
- The Carina arm region, containing the supernova remnant SNRG284.3-1.8, the high-energy (HE; E > 100 MeV) binary 1FGL J1018.6-5856 and the energetic pulsar PSRJ1016-5857 and its nebula, has been observed with the H. E. S. S. telescope array. The observational coverage of the region in very-high-energy (VHE; E > 0.1TeV) gamma-rays benefits from deep exposure (40 h) of the neighboring open cluster Westerlund 2. The observations have revealed a new extended region of VHE gamma-ray emission. The new VHE source HESS J1018-589 shows a bright, point-like emission region positionally coincident with SNRG284.3-1.8 and 1FGL J1018.6-5856 and a diffuse extension towards the direction of PSRJ1016-5857. A soft (Gamma = 2.7 +/- 0.5(stat)) photon index, with a differential flux at 1 TeV of N-0 = (4.2 +/- 1.1) x 10(-13) TeV-1 cm(-2) s(-1) is found for the point-like source, whereas the total emission region including the diffuse emission region is well fit by a power-law function with spectral index Gamma = 2.9 +/- 0.4(stat) and differential flux at 1 TeV of N-0 = (6.8 +/- 1.6) x 10(-1)3 TeV-1 cm(-2) s(-1). This H. E. S. S. detection motivated follow-up X-ray observations with the XMM-Newton satellite to investigate the origin of the VHE emission. The analysis of the XMM-Newton data resulted in the discovery of a bright, non-thermal point-like source (XMMU J101855.4-58564) with a photon index of Gamma = 1.65 +/- 0.08 in the center of SNRG284.3-1.8, and a thermal, extended emission region coincident with its bright northern filament. The characteristics of this thermal emission are used to estimate the plasma density in the region as n approximate to 0.5 cm(-3) (2.9 kpc/d)(2). The position of XMMUJ101855.4-58564 is compatible with the position reported by the Fermi-LAT collaboration for the binary system 1FGL J1018.6-5856 and the variable Swift XRT source identified with it. The new X-ray data are used alongside archival multi-wavelength data to investigate the relationship between the VHE gamma-ray emission from HESS J1018-589 and the various potential counterparts in the Carina arm region.
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