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1.	van Haarlem, M. P., et al. (författare) LOFAR : The LOw-Frequency ARray 2013 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 556, s. 1-53 Tidskriftsartikel (refereegranskat)abstract LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10–240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR’s new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory.
2.	Fresard, Laure, et al. (författare) Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts 2019 Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919 Tidskriftsartikel (refereegranskat)abstract It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
3.	Heald, G. H., et al. (författare) The LOFAR Multifrequency Snapshot Sky Survey (MSSS) : I. Survey description and first results 2015 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 582, s. 1-22 Tidskriftsartikel (refereegranskat)abstract We present the Multifrequency Snapshot Sky Survey (MSSS), the first northern-sky Low Frequency Array (LOFAR) imaging survey. In this introductory paper, we first describe in detail the motivation and design of the survey. Compared to previous radio surveys, MSSS is exceptional due to its intrinsic multifrequency nature providing information about the spectral properties of the detected sources over more than two octaves (from 30 to 160 MHz). The broadband frequency coverage, together with the fast survey speed generated by LOFAR’s multibeaming capabilities, make MSSS the first survey of the sort anticipated to be carried out with the forthcoming Square Kilometre Array (SKA). Two of the sixteen frequency bands included in the survey were chosen to exactly overlap the frequency coverage of large-area Very Large Array (VLA) and Giant Metrewave Radio Telescope (GMRT) surveys at 74 MHz and 151 MHz respectively. The survey performance is illustrated within the MSSS Verification Field (MVF), a region of 100 square degrees centered at (α,δ)J2000 = (15h,69°). The MSSS results from the MVF are compared with previous radio survey catalogs. We assess the flux and astrometric uncertainties in the catalog, as well as the completeness and reliability considering our source finding strategy. We determine the 90% completeness levels within the MVF to be 100 mJy at 135 MHz with 108″ resolution, and 550 mJy at 50 MHz with 166″ resolution. Images and catalogs for the full survey, expected to contain 150 000–200 000 sources, will be released to a public web server. We outline the plans for the ongoing production of the final survey products, and the ultimate public release of images and source catalogs.
4.	Machiela, Mitchell J., et al. (författare) Characterization of Large Structural Genetic Mosaicism in Human Autosomes 2015 Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497 Tidskriftsartikel (refereegranskat)abstract Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
5.	Asgekar, A., et al. (författare) LOFAR detections of low-frequency radio recombination lines towards Cassiopeia A 2013 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 551 Tidskriftsartikel (refereegranskat)abstract Cassiopeia A was observed using the low-band antennas of the LOw Frequency ARray (LOFAR) with high spectral resolution. This allowed a search for radio recombination lines (RRLs) along the line-of-sight to this source. Five carbon alpha RRLs were detected in absorption between 40 and 50 MHz with a signal-to-noise ratio of >5 from two independent LOFAR data sets. The derived line velocities (v(LSR) similar to -50 km s(-1)) and integrated optical depths (similar to 13 s(-1)) of the RRLs in our spectra, extracted over the whole supernova remnant, are consistent within each LOFAR data set and with those previously reported. For the first time, we are able to extract spectra against the brightest hotspot of the remnant at frequencies below 330 MHz. These spectra show significantly higher (15-80 percent) integrated optical depths, indicating that there is small-scale angular structure of the order of similar to 1 pc in the absorbing gas distribution over the face of the remnant. We also place an upper limit of 3 x 10(-4) on the peak optical depths of hydrogen and helium RRLs. These results demonstrate that LOFAR has the desired spectral stability and sensitivity to study faint recombination lines in the decameter band.
6.	Buitink, S., et al. (författare) A large light-mass component of cosmic rays at 1017–1017.5 electronvolts from radio observations 2016 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 531:7592, s. 70-73 Tidskriftsartikel (refereegranskat)abstract Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 1017–1018 electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal1 comes from accelerators capable of producing cosmic rays of these energies2. Cosmic rays initiate air showers—cascades of secondary particles in the atmosphere—and their masses can be inferred from measurements of the atmospheric depth of the shower maximum3 (Xmax; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground4. Current measurements5 have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays6, 7, 8 is a rapidly developing technique9 for determining Xmax (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front6, 12. Here we report radio measurements of Xmax with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 1017–1017.5 electronvolts. This high resolution in Xmax enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 1017.5 electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 1017–1017.5 electronvolt range.
7.	De Gasperin, F., et al. (författare) M 87 at metre wavelengths: the LOFAR picture 2012 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. article no. 56- Tidskriftsartikel (refereegranskat)abstract Context. M87 is a giant elliptical galaxy located in the centre of the Virgo cluster, which harbours a supermassive black hole of mass 6.4x10(9) M-circle dot, whose activity is responsible for the extended (80 kpc) radio lobes that surround the galaxy. The energy generated by matter falling onto the central black hole is ejected and transferred to the intra-cluster medium via a relativistic jet and morphologically complex systems of buoyant bubbles, which rise towards the edges of the extended halo. Aims. To place constraints on past activity cycles of the active nucleus, images of M 87 were produced at low radio frequencies never explored before at these high spatial resolution and dynamic range. To disentangle different synchrotron models and place constraints on source magnetic field, age and energetics, we also performed a detailed spectral analysis of M 87 extended radio-halo. Methods. We present the first observations made with the new Low-Frequency Array (LOFAR) of M 87 at frequencies down to 20 MHz. Three observations were conducted, at 15-30 MHz, 30-77 MHz and 116-162 MHz. We used these observations together with archival data to produce a low-frequency spectral index map and to perform a spectral analysis in the wide frequency range 30 MHz-10 GHz. Results. We do not find any sign of new extended emissions; on the contrary the source appears well confined by the high pressure of the intra-cluster medium. A continuous injection of relativistic electrons is the model that best fits our data, and provides a scenario in which the lobes are still supplied by fresh relativistic particles from the active galactic nuclei. We suggest that the discrepancy between the low-frequency radio-spectral slope in the core and in the halo implies a strong adiabatic expansion of the plasma as soon as it leaves the core area. The extended halo has an equipartition magnetic field strength of similar or equal to 10 mu G, which increases to similar or equal to 13 mu G in the zones where the particle flows are more active. The continuous injection model for synchrotron ageing provides an age for the halo of similar or equal to 40 Myr, which in turn provides a jet kinetic power of 6-10 x 10(44) erg s(-1).
8.	Offringa, A. R., et al. (författare) The LOFAR radio environment 2012 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 549 Tidskriftsartikel (refereegranskat)abstract Aims. This paper discusses the spectral occupancy for performing radio astronomy with the Low-Frequency Array (LOFAR), with a focus on imaging observations.Methods. We have analysed the radio-frequency interference (RFI) situation in two 24-h surveys with Dutch LOFAR stations, covering 30-78 MHz with low-band antennas and 115-163 MHz with high-band antennas. This is a subset of the full frequency range of LOFAR. The surveys have been observed with a 0.76 kHz/1 s resolution.Results. We measured the RFI occupancy in the low and high frequency sets to be 1.8% and 3.2% respectively. These values are found to be representative values for the LOFAR radio environment. Between day and night, there is no significant difference in the radio environment. We find that lowering the current observational time and frequency resolutions of LOFAR results in a slight loss of flagging accuracy. At LOFAR's nominal resolution of 0.76 kHz and 1 s, the false-positives rate is about 0.5%. This rate increases approximately linearly when decreasing the data frequency resolution.Conclusions. Currently, by using an automated RFI detection strategy, the LOFAR radio environment poses no perceivable problems for sensitive observing. It remains to be seen if this is still true for very deep observations that integrate over tens of nights, but the situation looks promising. Reasons for the low impact of RFI are the high spectral and time resolution of LOFAR; accurate detection methods; strong filters and high receiver linearity; and the proximity of the antennas to the ground. We discuss some strategies that can be used once low-level RFI starts to become apparent. It is important that the frequency range of LOFAR remains free of broadband interference, such as DAB stations and windmills.
9.	Orrù, E., et al. (författare) Wide-field LOFAR imaging of the field around the double-double radio galaxy B1834+620 : A fresh view on a restarted AGN and doubeltjes 2015 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 584, s. 1-12 Tidskriftsartikel (refereegranskat)abstract Context. The existence of double-double radio galaxies (DDRGs) is evidence for recurrent jet activity in active galactic nuclei (AGN), as expected from standard accretion models. A detailed study of these rare sources provides new perspectives for investigating the AGN duty cycle, AGN-galaxy feedback, and accretion mechanisms. Large catalogues of radio sources, on the other hand, provide statistical information about the evolution of the radio-loud AGN population out to high redshifts.Aims. Using wide-field imaging with the LOFAR telescope, we study both a well-known DDRG as well as a large number of radio sources in the field of view.Methods. We present a high resolution image of the DDRG B1834+620 obtained at 144 MHz using LOFAR commissioning data. Our image covers about 100 square degrees and contains over 1000 sources.Results. The four components of the DDRG B1834+620 have been resolved for the first time at 144 MHz. Inner lobes were found to point towards the direction of the outer lobes, unlike standard FR II sources. Polarized emission was detected at +60 rad m-2 in the northern outer lobe. The high spatial resolution allows the identification of a large number of small double-lobed radio sources; roughly 10% of all sources in the field are doubles with a separation smaller than 1′.Conclusions. The spectral fit of the four components is consistent with a scenario in which the outer lobes are still active or the jets recently switched off, while emission of the inner lobes is the result of a mix-up of new and old jet activity. From the presence of the newly extended features in the inner lobes of the DDRG, we can infer that the mechanism responsible for their formation is the bow shock that is driven by the newly launched jet. We find that the density of the small doubles exceeds the density of FR II sources with similar properties at 1.4 GHz, but this difference becomes smaller for low flux densities. Finally, we show that the significant challenges of wide-field imaging (e.g., time and frequency variation of the beam, directional dependent calibration errors) can be solved using LOFAR commissioning data, thus demonstrating the potential of the full LOFAR telescope to discover millions of powerful AGN at redshift z ~ 1.
10.	Stappers, B. W., et al. (författare) Observing pulsars and fast transients with LOFAR 2011 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 530 Tidskriftsartikel (refereegranskat)abstract Low frequency radio waves, while challenging to observe, are a rich source of information about pulsars. The LOw Frequency ARray (LOFAR) is a new radio interferometer operating in the lowest 4 octaves of the ionospheric "radio window": 10-240 MHz, that will greatly facilitate observing pulsars at low radio frequencies. Through the huge collecting area, long baselines, and flexible digital hardware, it is expected that LOFAR will revolutionize radio astronomy at the lowest frequencies visible from Earth. LOFAR is a next-generation radio telescope and a pathfinder to the Square Kilometre Array (SKA), in that it incorporates advanced multi-beaming techniques between thousands of individual elements. We discuss the motivation for low-frequency pulsar observations in general and the potential of LOFAR in addressing these science goals. We present LOFAR as it is designed to perform high-time-resolution observations of pulsars and other fast transients, and outline the various relevant observing modes and data reduction pipelines that are already or will soon be implemented to facilitate these observations. A number of results obtained from commissioning observations are presented to demonstrate the exciting potential of the telescope. This paper outlines the case for low frequency pulsar observations and is also intended to serve as a reference for upcoming pulsar/fast transient science papers with LOFAR.
11.	van Weeren, R. J., et al. (författare) First LOFAR observations at very low frequencies of cluster-scale non-thermal emission: the case of Abell 2256 2012 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 543, s. Article Number: A43 - Tidskriftsartikel (refereegranskat)abstract Abell 2256 is one of the best known examples of a galaxy cluster hosting large-scale diffuse radio emission that is unrelated to individual galaxies. It contains both a giant radio halo and a relic, as well as a number of head-tail sources and smaller diffuse steep-spectrum radio sources. The origin of radio halos and relics is still being debated, but over the last years it has become clear that the presence of these radio sources is closely related to galaxy cluster merger events. Here we present the results from the first LOFAR low band antenna (LBA) observations of Abell 2256 between 18 and 67 MHz. To our knowledge, the image presented in this paper at 63 MHz is the deepest ever obtained at frequencies below 100 MHz in general. Both the radio halo and the giant relic are detected in the image at 63 MHz, and the diffuse radio emission remains visible at frequencies as low as 20 MHz. The observations confirm the presence of a previously claimed ultra-steep spectrum source to the west of the cluster center with a spectral index of -2.3 +/- 0.4 between 63 and 153 MHz. The steep spectrum suggests that this source is an old part of a head-tail radio source in the cluster. For the radio relic we find an integrated spectral index of -0.81 +/- 0.03, after removing the flux contribution from the other sources. This is relatively flat which could indicate that the efficiency of particle acceleration at the shock substantially changed in the last similar to 0.1 Gyr due to an increase of the shock Mach number. In an alternative scenario, particles are re-accelerated by some mechanism in the downstream region of the shock, resulting in the relatively flat integrated radio spectrum. In the radio halo region we find indications of low-frequency spectral steepening which may suggest that relativistic particles are accelerated in a rather inhomogeneous turbulent region.
12.	Yatawatta, S., et al. (författare) Initial deep LOFAR observations of epoch of reionization windows I. The north celestial pole 2013 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 550, s. A136- Tidskriftsartikel (refereegranskat)abstract Aims. The aim of the LOFAR epoch of reionization (EoR) project is to detect the spectral fluctuations of the redshifted HI 21 cm signal. This signal is weaker by several orders of magnitude than the astrophysical foreground signals and hence, in order to achieve this, very long integrations, accurate calibration for stations and ionosphere and reliable foreground removal are essential. Methods. One of the prospective observing windows for the LOFAR EoR project will be centered at the north celestial pole (NCP). We present results from observations of the NCP window using the LOFAR highband antenna (HBA) array in the frequency range 115 MHz to 163 MHz. The data were obtained in April 2011 during the commissioning phase of LOFAR. We used baselines up to about 30 km. The data was processed using a dedicated processing pipeline which is an enhanced version of the standard LOFAR processing pipeline. Results. With about 3 nights, of 6 h each, effective integration we have achieved a noise level of about 100 mu Jy/PSF in the NCP window. Close to the NCP, the noise level increases to about 180 mu Jy/PSF, mainly due to additional contamination from unsubtracted nearby sources. We estimate that in our best night, we have reached a noise level only a factor of 1.4 above the thermal limit set by the noise from our Galaxy and the receivers. Our continuum images are several times deeper than have been achieved previously using the WSRT and GMRT arrays. We derive an analytical explanation for the excess noise that we believe to be mainly due to sources at large angular separation from the NCP. We present some details of the data processing challenges and how we solved them. Conclusions. Although many LOFAR stations were, at the time of the observations, in a still poorly calibrated state we have seen no artefacts in our images which would prevent us from producing deeper images in much longer integrations on the NCP window which are about to commence. The limitations present in our current results are mainly due to sidelobe noise from the large number of distant sources, as well as errors related to station beam variations and rapid ionospheric phase fluctuations acting on bright sources. We are confident that we can improve our results with refined processing.
13.	Iacobelli, M., et al. (författare) Studying Galactic interstellar turbulence through fluctuations in synchrotron emission: First LOFAR Galactic foreground detection 2013 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 558, s. 721- Tidskriftsartikel (refereegranskat)abstract Aims. The characteristic outer scale of turbulence (i.e. the scale at which the dominant source of turbulence injects energy to the interstellar medium) and the ratio of the random to ordered components of the magnetic field are key parameters to characterise magnetic turbulence in the interstellar gas, which affects the propagation of cosmic rays within the Galaxy. We provide new constraints to those two parameters. Methods. We use the LOw Frequency ARray (LOFAR) to image the diffuse continuum emission in the Fan region at (l,b) ∼ (137.0, +7.0) at 80′′ × 70′′ resolution in the range [146, 174] MHz. We detect multi-scale fluctuations in the Galactic synchrotron emission and compute their power spectrum. Applying theoretical estimates and derivations from the literature for the first time, we derive the outer scale of turbulence and the ratio of random to ordered magnetic field from the characteristics of these fluctuations. Results. We obtain the deepest image of the Fan region to date and find diffuse continuum emission within the primary beam. The power spectrum displays a power law behaviour for scales between 100 and 8 arcmin with a slope α =-1.84 ± 0.19. We find an upper limit of ∼20 pc for the outer scale of the magnetic interstellar turbulence toward the Fan region, which is in agreement with previous estimates in literature. We also find a variation of the ratio of random to ordered field as a function of Galactic coordinates, supporting different turbulent regimes. Conclusions. We present the first LOFAR detection and imaging of the Galactic diffuse synchrotron emission around 160 MHz from the highly polarized Fan region. The power spectrum of the foreground synchrotron fluctuations is approximately a power law with a slope α ≈-1.84 up to angular multipoles of ≤1300, corresponding to an angular scale of ∼8 arcmin. We use power spectra fluctuations from LOFAR as well as earlier GMRT and WSRT observations to constrain the outer scale of turbulence (Lout) of the Galactic synchrotron foreground, finding a range of plausible values of 10-20 pc. Then, we use this information to deduce lower limits of the ratio of ordered to random magnetic field strength. These are found to be 0.3, 0.3, and 0.5 for the LOFAR, WSRT and GMRT fields considered respectively. Both these constraints are in agreement with previous estimates. © 2013 ESO.
14.	Moldón, J., et al. (författare) The LOFAR long baseline snapshot calibrator survey 2015 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 574 Tidskriftsartikel (refereegranskat)abstract Aims. An efficient means of locating calibrator sources for international LOw Frequency ARray (LOFAR) is developed and used to determine the average density of usable calibrator sources on the sky for subarcsecond observations at 140 MHz.Methods. We used the multi-beaming capability of LOFAR to conduct a fast and computationally inexpensive survey with the full international LOFAR array. Sources were preselected on the basis of 325 MHz arcminute-scale flux density using existing catalogues. By observing 30 different sources in each of the 12 sets of pointings per hour, we were able to inspect 630 sources in two hours to determine if they possess a sufficiently bright compact component to be usable as LOFAR delay calibrators.Results. More than 40% of the observed sources are detected on multiple baselines between international stations and 86 are classified as satisfactory calibrators. We show that a flat low-frequency spectrum (from 74 to 325 MHz) is the best predictor of compactness at 140 MHz. We extrapolate from our sample to show that the sky density of calibrators that are sufficiently bright to calibrate dispersive and non-dispersive delays for the international LOFAR using existing methods is 1.0 per square degree.Conclusions. The observed density of satisfactory delay calibrator sources means that observations with international LOFAR should be possible at virtually any point in the sky provided that a fast and efficient search, using the methodology described here, is conducted prior to the observation to identify the best calibrator.
15.	Oonk, J. B. R., et al. (författare) Discovery of carbon radio recombination lines in absorption towards Cygnus A 2014 Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 437:4, s. 3506-3515 Tidskriftsartikel (refereegranskat)abstract We present the first detection of carbon radio recombination line absorption along the line of sight to Cygnus A. The observations were carried out with the Low Frequency Array in the 33–57 MHz range. These low-frequency radio observations provide us with a new line of sight to study the diffuse, neutral gas in our Galaxy. To our knowledge this is the first time that foreground Milky Way recombination line absorption has been observed against a bright extragalactic background source. By stacking 48 carbon α lines in the observed frequency range we detect carbon absorption with a signal-to-noise ratio of about 5. The average carbon absorption has a peak optical depth of 2 × 10−4, a line width of 10 km s−1 and a velocity of +4 km s−1 with respect to the local standard of rest. The associated gas is found to have an electron temperature Te ∼ 110 K and density ne ∼ 0.06 cm−3. These properties imply that the observed carbon α absorption likely arises in the cold neutral medium of the Orion arm of the Milky Way. Hydrogen and helium lines were not detected to a 3σ peak optical depth limit of 1.5 × 10−4 for a 4 km s−1 channel width. Radio recombination lines associated with Cygnus A itself were also searched for, but are not detected. We set a 3σ upper limit of 1.5 × 10−4 for the peak optical depth of these lines for a 4 km s−1 channel width.
16.	Shimwell, T. W., et al. (författare) The LOFAR Two-metre Sky Survey: II. First data release 2019 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 622 Forskningsöversikt (refereegranskat)abstract The LOFAR Two-metre Sky Survey (LoTSS) is an ongoing sensitive, high-resolution 120-168 MHz survey of the entire northern sky for which observations are now 20% complete. We present our first full-quality public data release. For this data release 424 square degrees, or 2% of the eventual coverage, in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00′00″ to 57°00′00″) were mapped using a fully automated direction-dependent calibration and imaging pipeline that we developed. A total of 325 694 sources are detected with a signal of at least five times the noise, and the source density is a factor of ∼10 higher than the most sensitive existing very wide-area radio-continuum surveys. The median sensitivity is S144 MHz = 71 μJy beam -1 and the point-source completeness is 90% at an integrated flux density of 0.45 mJy. The resolution of the images is 6″ and the positional accuracy is within 0.2″. This data release consists of a catalogue containing location, flux, and shape estimates together with 58 mosaic images that cover the catalogued area. In this paper we provide an overview of the data release with a focus on the processing of the LOFAR data and the characteristics of the resulting images. In two accompanying papers we provide the radio source associations and deblending and, where possible, the optical identifications of the radio sources together with the photometric redshifts and properties of the host galaxies. These data release papers are published together with a further ∼20 articles that highlight the scientific potential of LoTSS.
17.	Stewart, A. J., et al. (författare) LOFAR MSSS : detection of a low-frequency radio transient in 400 h of monitoring of the North Celestial Pole 2016 Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:3, s. 2321-2342 Tidskriftsartikel (refereegranskat)abstract We present the results of a four-month campaign searching for low-frequency radio transients near the North Celestial Pole with the Low-Frequency Array (LOFAR), as part of the Multifrequency Snapshot Sky Survey (MSSS). The data were recorded between 2011 December and 2012 April and comprised 2149 11-min snapshots, each covering 175 deg2. We have found one convincing candidate astrophysical transient, with a duration of a few minutes and a flux density at 60 MHz of 15–25 Jy. The transient does not repeat and has no obvious optical or high-energy counterpart, as a result of which its nature is unclear. The detection of this event implies a transient rate at 60 MHz of 3.9−3.7+14.7×10−4" style="position: relative;" tabindex="0" id="MathJax-Element-1-Frame" class="MathJax">3.9+14.7−3.7×10−4 d−1 deg−2, and a transient surface density of 1.5 × 10−5 deg−2, at a 7.9-Jy limiting flux density and ∼10-min time-scale. The campaign data were also searched for transients at a range of other time-scales, from 0.5 to 297 min, which allowed us to place a range of limits on transient rates at 60 MHz as a function of observation duration.
18.	Jackson, N., et al. (författare) LBCS: The LOFAR Long-Baseline Calibrator Survey 2016 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595, s. Art no A86- Tidskriftsartikel (refereegranskat)abstract We outline the LOFAR Long-Baseline Calibrator Survey (LBCS), whose aim is to identify sources suitable for calibrating the highest-resolution observations made with the International LOFAR Telescope, which include baselines > 1000 km. Suitable sources must contain significant correlated flux density (greater than or similar to 50 - 100 mJy) at frequencies around 110-190 MHz on scales of a few hundred milliarcseconds. At least for the 200-300-km international baselines, we find around 1 suitable calibrator source per square degree over a large part of the northern sky, in agreement with previous work. This should allow a randomly selected target to be successfully phase calibrated on the international baselines in over 50% of cases. Products of the survey include calibrator source lists and fringe-rate and delay maps of wide areas-typically a few degrees-around each source. The density of sources with significant correlated flux declines noticeably with baseline length over the range 200-600 km, with good calibrators on the longest baselines appearing only at the rate of 0.5 per sq. deg. Coherence times decrease from 1-3 min on 200-km baselines to about 1 min on 600-km baselines, suggesting that ionospheric phase variations contain components with scales of a few hundred kilometres. The longest median coherence time, at just over 3 min, is seen on the DE609 baseline, which at 227 km is close to being the shortest. We see median coherence times of between 80 and 110 s on the four longest baselines (580-600 km), and about 2 min for the other baselines. The success of phase transfer from calibrator to target is shown to be influenced by distance, in a manner that suggests a coherence patch at 150-MHz of the order of 1 deg. Although source structures cannot be measured in these observations, we deduce that phase transfer is affected if the calibrator source structure is not known. We give suggestions for calibration strategies and choice of calibrator sources, and describe the access to the online catalogue and data products.
19.	Shimwell, T. W., et al. (författare) The LOFAR Two-metre Sky Survey: I. Survey description and preliminary data release 2017 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 598, s. Art no A104- Tidskriftsartikel (refereegranskat)abstract The LOFAR Two-metre Sky Survey (LoTSS) is a deep 120-168 MHz imaging survey that will eventually cover the entire northern sky. Each of the 3170 pointings will be observed for 8 h, which, at most declinations, is sufficient to produce ~5? resolution images with a sensitivity of ~100 ?Jy/beam and accomplish the main scientific aims of the survey, which are to explore the formation and evolution of massive black holes, galaxies, clusters of galaxies and large-scale structure. Owing to the compact core and long baselines of LOFAR, the images provide excellent sensitivity to both highly extended and compact emission. For legacy value, the data are archived at high spectral and time resolution to facilitate subarcsecond imaging and spectral line studies. In this paper we provide an overview of the LoTSS. We outline the survey strategy, the observational status, the current calibration techniques, a preliminary data release, and the anticipated scientific impact. The preliminary images that we have released were created using a fully automated but direction-independent calibration strategy and are significantly more sensitive than those produced by any existing large-Area low-frequency survey. In excess of 44 000 sources are detected in the images that have a resolution of 25?, typical noise levels of less than 0.5 mJy/beam, and cover an area of over 350 square degrees in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00?00? to 57°00?00?).
20.	Gisela, Lilja, et al. (författare) Return to Work and Participation in Society After Out-of-Hospital Cardiac Arrest 2018 Ingår i: Circulation-Cardiovascular Quality and Outcomes. - : Ovid Technologies (Wolters Kluwer Health). - 1941-7705 .- 1941-7713. ; 11:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The aim of this study was to describe out-of-hospital cardiac arrest (OHCA) survivors' ability to participate in activities of everyday life and society, including return to work. The specific aim was to evaluate potential effects of cognitive impairment. METHODS AND RESULTS: Two hundred eighty-seven OHCA survivors included in the TTM trial (Target Temperature Management) and 119 matched control patients with ST-segment-elevation myocardial infarction participated in a follow-up 180 days post-event that included assessments of participation, return to work, emotional problems, and cognitive impairment. On the Mayo-Portland Adaptability Inventory-4 Participation Index, OHCA survivors (n=270) reported more restricted participation In everyday life and in society (47% versus 30%; P<0.001) compared with ST-segment-elevation myocardial infarction controls (n=118). Furthermore, 27% (n=36) of pre-event working OHCA survivors (n=135) compared with 7% (n=3) of pre-event working ST-segment-elevation myocardial infarction controls (n=45) were on sick leave (odds ratio, 4.9; 95% confidence interval, 1.4-16.8; P=0.01). Among the OHCA survivors assumed to return to work (n=135), those with cognitive impairment (n=55) were 3x more likely (odds ratio, 3.3; 95% confidence interval, 1.2-9.3; P=0.02) to be on sick leave compared with those without cognitive impairment (n=40; 36%, n=20, versus 15%, n=6). For OHCA survivors, the variables that were found most predictive for a lower participation were depression, restricted mobility, memory impairment, novel problem-solving difficulties, fatigue, and slower processing speed. CONCLUSIONS: OHCA survivors reported a more restricted societal participation 6 months post-arrest, and their return to work was lower compared with ST-segment-elevation myocardial infarction controls. Cognitive impairment was significantly associated with lower participation, together with the closely related symptoms of fatigue, depression, and restricted mobility. These predictive variables may be used during follow-up to identify OHCA survivors at risk of a less successful recovery that may benefit from further support and rehabilitation.
21.	Williams, W. L., et al. (författare) LOFAR 150-MHz observations of the Bootes field: catalogue and source counts 2016 Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 460:3, s. 2385-2412 Tidskriftsartikel (refereegranskat)abstract We present the first wide area (19 deg(2)), deep (a parts per thousand 120-150 mu Jy beam(-1)), high-resolution (5.6 x 7.4 arcsec) LOFAR High Band Antenna image of the Bootes field made at 130-169 MHz. This image is at least an order of magnitude deeper and 3-5 times higher in angular resolution than previously achieved for this field at low frequencies. The observations and data reduction, which includes full direction-dependent calibration, are described here. We present a radio source catalogue containing 6 276 sources detected over an area of 19 deg(2), with a peak flux density threshold of 5 sigma. As the first thorough test of the facet calibration strategy, introduced by van Weeren et al., we investigate the flux and positional accuracy of the catalogue. We present differential source counts that reach an order of magnitude deeper in flux density than previously achieved at these low frequencies, and show flattening at 150-MHz flux densities below 10 mJy associated with the rise of the low flux density star-forming galaxies and radio-quiet AGN.
22.	Frydland, Martin, et al. (författare) Usefulness of Serum B-Type Natriuretic Peptide Levels in Comatose Patients Resuscitated from Out-of-Hospital Cardiac Arrest to Predict Outcome 2016 Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 118:7, s. 998-1005 Tidskriftsartikel (refereegranskat)abstract N-terminal pro-B-type natriuretic (NT-proBNP) is expressed in the heart and brain, and serum levels are elevated in acute heart and brain diseases. We aimed to assess the possible association between serum levels and neurological outcome and death in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Of the 939 comatose OHCA patients enrolled and randomized in the Targeted Temperature Management (TTM) trial to TTM at 33°C or 36°C for 24 hours, 700 were included in the biomarker substudy. Of these, 647 (92%) had serum levels of NT-proBNP measured 24, 48, and 72 hours after return of spontaneous circulation (ROSC). Neurological outcome was evaluated by the Cerebral Performance Category (CPC) score and modified Rankin Scale (mRS) at 6 months. Six hundred thirty-eight patients (99%) had serum NT-proBNP levels ≥125 pg/ml. Patients with TTM at 33°C had significantly lower NT-proBNP serum levels (median 1,472 pg/ml) than those in the 36°C group (1,914 pg/ml) at 24 hours after ROSC, p <0.01 but not at 48 and 72 hours. At 24 hours, an increase in NT-proBNP quartile was associated with death (Plogrank <0.0001). In addition, NT-proBNP serum levels > median were independently associated with poor neurological outcome (odds ratio, ORCPC 2.02, CI 1.34 to 3.05, p <0.001; ORmRS 2.28, CI 1.50 to 3.46, p <0.001) adjusted for potential confounders. The association was diminished at 48 and 72 hours after ROSC. In conclusion, NT-proBNP serum levels are increased in comatose OHCA patients. Furthermore, serum NT-proBNP levels are affected by level of TTM and are associated with death and poor neurological outcome.
23.	Kim, Ji Hoon, et al. (författare) THE AGORA HIGH-RESOLUTION GALAXY SIMULATIONS COMPARISON PROJECT. II. ISOLATED DISK TEST 2016 Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 833:2 Tidskriftsartikel (refereegranskat)abstract Using an isolated Milky Way-mass galaxy simulation, we compare results from nine state-of-the-art gravito-hydrodynamics codes widely used in the numerical community. We utilize the infrastructure we have built for the AGORA High-resolution Galaxy Simulations Comparison Project. This includes the common disk initial conditions, common physics models (e.g., radiative cooling and UV background by the standardized package Grackle) and common analysis toolkit yt, all of which are publicly available. Subgrid physics models such as Jeans pressure floor, star formation, supernova feedback energy, and metal production are carefully constrained across code platforms. With numerical accuracy that resolves the disk scale height, we find that the codes overall agree well with one another in many dimensions including: gas and stellar surface densities, rotation curves, velocity dispersions, density and temperature distribution functions, disk vertical heights, stellar clumps, star formation rates, and Kennicutt-Schmidt relations. Quantities such as velocity dispersions are very robust (agreement within a few tens of percent at all radii) while measures like newly formed stellar clump mass functions show more significant variation (difference by up to a factor of ∼3). Systematic differences exist, for example, between mesh-based and particle-based codes in the low-density region, and between more diffusive and less diffusive schemes in the high-density tail of the density distribution. Yet intrinsic code differences are generally small compared to the variations in numerical implementations of the common subgrid physics such as supernova feedback. Our experiment reassures that, if adequately designed in accordance with our proposed common parameters, results of a modern high-resolution galaxy formation simulation are more sensitive to input physics than to intrinsic differences in numerical schemes.
24.	Morabito, L. K., et al. (författare) Discovery of Carbon Radio Recombination Lines in M82 2014 Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 795:2, s. Art. no. L33- Forskningsöversikt (refereegranskat)abstract Carbon radio recombination lines (RRLs) at low frequencies (less than or similar to 500 MHz) trace the cold, diffuse phase of the interstellar medium, which is otherwise difficult to observe. We present the detection of carbon RRLs in absorption in M82 with the Low Frequency Array in the frequency range of 48-64 MHz. This is the first extragalactic detection of RRLs from a species other than hydrogen, and below 1 GHz. Since the carbon RRLs are not detected individually, we cross-correlated the observed spectrum with a template spectrum of carbon RRLs to determine a radial velocity of 219 km s(-1). Using this radial velocity, we stack 22 carbon-alpha transitions from quantum levels n = 468-508 to achieve an 8.5 sigma detection. The absorption line profile exhibits a narrow feature with peak optical depth of 3x10(-3) and FWHM of 31 km s(-1). Closer inspection suggests that the narrow feature is superimposed on a broad, shallow component. The total line profile appears to be correlated with the 21 cm Hi line profile reconstructed from Hi absorption in the direction of supernova remnants in the nucleus. The narrow width and centroid velocity of the feature suggests that it is associated with the nuclear starburst region. It is therefore likely that the carbon RRLs are associated with cold atomic gas in the direction of the nucleus of M82.
25.	Rottgering, H., et al. (författare) LOFAR and APERTIF Surveys of the Radio Sky: Probing Shocks and Magnetic Fields in Galaxy Clusters 2011 Ingår i: Journal of Astrophysics and Astronomy. - : Springer Science and Business Media LLC. - 0250-6335 .- 0973-7758. ; 32:4, s. 557-566 Tidskriftsartikel (refereegranskat)abstract At very low frequencies, the new pan-European radio telescope LOFAR is opening the last unexplored window of the electromagnetic spectrum for astrophysical studies. The revolutionary APERTIF-phased arrays that are about to be installed on the Westerbork radio telescope (WSRT) will dramatically increase the survey speed for the WSRT. Combined surveys with these two facilities will deeply chart the northern sky over almost two decades in radio frequency from similar to 15 up to 1400 MHz. Here we briefly describe some of the capabilities of these new facilities and what radio surveys are planned to study fun-damental issues related to the formation and evolution of galaxies and clusters of galaxies. In the second part we briefly review some recent observational results directly showing that diffuse radio emission in clusters traces shocks due to cluster mergers. As these diffuse radio sources are relatively bright at low frequencies, LOFAR should be able to detect thousands of such sources up to the epoch of cluster formation. This will allow addressing many question about the origin and evolution of shocks and magnetic fields in clusters. At the end we briefly review some of the first and very preliminary LOFAR results on clusters.
26.	Rottgering, H., et al. (författare) The "Sausage" and "Toothbrush" clusters of galaxies and the prospects of LOFAR observations of clusters of galaxies 2013 Ingår i: Astronomische Nachrichten. - : Wiley. - 0004-6337 .- 1521-3994. ; 334:4-5, s. 333-337 Tidskriftsartikel (refereegranskat)abstract LOFAR, the Low Frequency Radio Array, is a new pan-European radio telescope that is almost fully operational. One of its main drivers is to make deep images of the low frequency radio sky. To be able to do this a number of challenges need to be addressed. These include the high data rates, removal of radio frequency interference, calibration of the beams and correcting for the corrupting influence of the ionosphere. One of the key science goals is to study merger shocks, particle acceleration mechanisms and the structure of magnetic fields in nearby and distant merging clusters. Recent studies with the GMRT and WSRT radio telescopes of the "Sausage" and the "Toothbrush" clusters have given a very good demonstration of the power of radio observations to study merging clusters. Recently we discovered that both clusters contain relic and halo sources, large diffuse regions of radio emission not associated with individual galaxies. The 2 Mpc northern relic in the Sausage cluster displays highly aligned magnetic fields and and exhibits a strong spectral index gradient that is a consequence of cooling of the synchrotron emitting particles in the post-shock region. We have argued that these observations provide strong evidence that shocks in merging clusters are capable of accelerating particles. For the Toothbrush cluster we observe a puzzling linear relic that extends over 2 Mpc. The proposed scenario is that a triple-merger can lead to such a structure. With LOFAR's sensitivity it will not only be possible to trace much weaker shocks, but also to study those shocks due to merging clusters up to redshifts of at least one. (C) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
27.	Shulevski, A., et al. (författare) AGN duty cycle estimates for the ultra-steep spectrum radio relic VLSS J1431.8+1331 2015 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 583, s. A89- Tidskriftsartikel (refereegranskat)abstract Context. Steep spectrum radio sources associated with active galactic nuclei (AGN) may contain remnants of past AGN activity episodes. Studying these sources gives us insight into the AGN activity history. Novel instruments like the LOw Frequency ARray (LOFAR) are enabling studies of these fascinating structures to be made at tens to hundreds of MHz with sufficient resolution to analyse their complex morphology. Aims. Our goal is to characterize the integrated and resolved spectral properties of VESS J1431+1331 and estimate source ages based on synchrotron radio emission models, thus putting constraints on the AGN duty cycle. Methods. Using a broad spectral coverage, we have derived spectral and curvature maps, and used synchrotron ageing models to determine the time elapsed from the last time the source plasma was energized. We used LOFAR, Giant Metrewave Radio Telescope (GMRT) and Jansky Very Large Array (VLA) data. Results. We confirm the morphology and the spectral index values found in previous studies of this object. Based on our ageing analysis, we infer that the AGN that created this source currently has very low levels of activity or that it is switched off. The derived ages for the larger source component range from around 60 to 130 Myr, hinting that the AGN activity decreased or stopped around 60 Myr ago. We observe that the area around the faint radio core located in the larger source component is the youngest, while the overall age of the smaller source component shows it to be the oldest part of the source. Conclusions. Our analysis suggests that VLSS J1431.8+1331 is an intriguing, two-component source. The larger component seems to host a faint radio core, suggesting that the source may be an AGN radio relic. The spectral index we observe from the smaller component is distinctly flatter at lower frequencies than the spectral index of the larger component, suggesting the possibility that the smaller component may be a shocked plasma bubble. From. the integrated source spectrum, we deduce that its shape and slope can be used as tracers of the activity history of this type of steep spectrum radio source. We discuss the implications this conclusion has for future studies of radio sources having similar characteristics.
28.	Yu, Hao, et al. (författare) Association of an estrogen-sensitive Pax1-Col11a1-Mmp3 signaling axis with adolescent idiopathic scoliosis. 2023 Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than five-fold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here we sought to define the roles of PAX1 and newly-identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 9,161 individuals with AIS and 80,731 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (α1) XI (rs3753841; NM_080629_c.4004C>T; p.(Pro1335Leu); P=7.07e -11 , OR=1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice ( Pax1 -/- ). In postnatal spines we found that Pax1 and collagen (α1) XI protein both localize within the intervertebral disc (IVD)-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in Pax1 -/- spines compared to wildtype. By genetic targeting we found that wildtype Col11a1 expression in growth plate cells (GPCs) suppresses expression of Pax1 and of Mmp3 , encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, this suppression was abrogated in the presence of the AIS-associated COL11A1 P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2 , or tamoxifen treatment, significantly altered Col11a1 and Mmp3 expression in GPCs. These studies support a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a Pax1 - Col11a1 - Mmp3 signaling axis in the growth plate.
29.	Yu, Hao, et al. (författare) Association of genetic variation in COL11A1 with adolescent idiopathic scoliosis 2024 Ingår i: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 12 Tidskriftsartikel (refereegranskat)abstract Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here, we sought to define the roles of PAX1 and newly identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (α1) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); p=7.07E-11, OR = 1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice (Pax1-/-). In postnatal spines we found that PAX1 and collagen (α1) XI protein both localize within the intervertebral disc-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in Pax1-/- spines compared to wild-type. By genetic targeting we found that wild-type Col11a1 expression in costal chondrocytes suppresses expression of Pax1 and of Mmp3, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, the latter suppression was abrogated in the presence of the AIS-associated COL11A1P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2 or tamoxifen treatment significantly altered Col11a1 and Mmp3 expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a PAX1-COL11a1-MMP3 signaling axis in spinal chondrocytes.

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