| 1. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 2. |
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| 3. |
- Akiba, K., et al.
(författare)
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The LHCb VELO Upgrade module construction
- 2024
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 19:6
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Tidskriftsartikel (refereegranskat)abstract
- The LHCb detector has undergone a major upgrade for LHC Run 3. This Upgrade I detector facilitates operation at higher luminosity and utilises full-detector information at the LHC collision rate, critically including the use of vertex information. A new vertex locator system, the VELO Upgrade, has been constructed. The core element of the new VELO are the double-sided pixelated hybrid silicon detector modules which operate in vacuum close to the LHC beam in a high radiation environment. The construction and quality assurance tests of these modules are described in this paper. The modules incorporate 200 mu m thick, n -on -p silicon sensors bump-bonded to 130 nm technology ASICs. These are attached with high precision to a silicon microchannel substrate that uses evaporative CO 2 cooling. The ASICs are controlled and read out with flexible printed circuits that are glued to the substrate and wire -bonded to the chips. The mechanical support of the module is given by a carbon fibre plate, two carbon fibre rods and an aluminium plate. The sensor attachment was achieved with an average precision of 21 mu m, more than 99.5% of all pixels are fully functional, and a thermal figure of merit of 3 Kcm 2 W - 1 was achieved. The production of the modules was successfully completed in 2021, with the final assembly and installation completed in time for data taking in 2022.
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| 4. |
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| 5. |
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| 6. |
- Jacobson, H. R., et al.
(författare)
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The Gaia-ESO Survey : Probes of the inner disk abundance gradient
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 591
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Tidskriftsartikel (refereegranskat)abstract
- Context. The nature of the metallicity gradient inside the solar circle (R-GC < 8 kpc) is poorly understood, but studies of Cepheids and a small sample of open clusters suggest that it steepens in the inner disk. Aims. We investigate the metallicity gradient of the inner disk using a sample of inner disk open clusters that is three times larger than has previously been studied in the literature to better characterize the gradient in this part of the disk. Methods. We used the Gaia-ESO Survey (GES) [Fe/H] values and stellar parameters for stars in 12 open clusters in the inner disk from GES-UVES data. Cluster mean [Fe/H] values were determined based on a membership analysis for each cluster. Where necessary, distances and ages to clusters were determined via comparison to theoretical isochrones. Results. The GES open clusters exhibit a radial metallicity gradient of -0.10 +/- 0.02 dex kpc(-1), consistent with the gradient measured by other literature studies of field red giant stars and open clusters in the range R-GC similar to 6-12 kpc. We also measure a trend of increasing [Fe/H] with increasing cluster age, as has also been found in the literature. Conclusions. We find no evidence for a steepening of the inner disk metallicity gradient inside the solar circle as earlier studies indicated. The age-metallicity relation shown by the clusters is consistent with that predicted by chemical evolution models that include the effects of radial migration, but a more detailed comparison between cluster observations and models would be premature.
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| 7. |
- Cornelissen, M. J., et al.
(författare)
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Perinatal complications in patients with unisutural craniosynostosis: An international multicentre retrospective cohort study
- 2017
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Ingår i: Journal of Cranio-Maxillofacial Surgery. - : Elsevier BV. - 1010-5182. ; 45:11, s. 1809-1814
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Craniosynostosis may lead to hampered fetal head molding and birth complications. To study the interaction between single suture craniosynostosis and delivery complications, an international, multicentre, retrospective cohort study was performed. Materials and methods: All infants born between 2006 and 2012 in the Netherlands and Sweden with sagittal or metopic suture synostosis were included. All births were included as a reference population. The primary outcome measure was rate of medically assisted labor. The secondary outcomes included method of conception, term of birth and fetal position. Results: We included 152 trigonocephaly patients, 272 scaphocephaly patients and 1.954.141 controls. A higher rate of assisted reproductive technology (ART) was found in patients with trigonocephaly (13%) and scaphocephaly (7%) compared to controls (3%, p < 0.001). Scaphocephaly resulted in more postterm births (8% vs 4%, p < 0.001). Trigonocephaly patients showed more preterm births (11% vs 6%, p < 0.001), breech position was more frequent (10% vs 4%, p = 0.003) and labor was more often induced. Rate of assisted delivery, including cesarean section, was significantly higher in both patient groups. Conclusions: Scaphocephaly leads to more postterm births and an increased rate of cesarean sections. Trigonocephaly is related to ART, and in addition higher rates of breech position and cesarean section are found. Prenatal detection of single suture craniosynostosis could improve perinatal care. (C) 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
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| 8. |
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| 9. |
- Costa, H., et al.
(författare)
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Human cytomegalovirus may promote tumour progression by upregulating arginase-2
- 2016
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 7:30, s. 47221-47231
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Tidskriftsartikel (refereegranskat)abstract
- Background: Both arginase (ARG2) and human cytomegalovirus (HCMV) have been implicated in tumorigenesis. However, the role of ARG2 in the pathogenesis of glioblastoma (GBM) and the HCMV effects on ARG2 are unknown. We hypothesize that HCMV may contribute to tumorigenesis by increasing ARG2 expression. Results: ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2-overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA. Methods: The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2- overexpressing cell line and ARG inhibitor, N (omega)-hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA). Conclusions: ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2.
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| 10. |
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| 11. |
- Magrini, L., et al.
(författare)
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The Gaia -ESO Survey : radial distribution of abundances in the Galactic disc from open clusters and young-field stars
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 603
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Tidskriftsartikel (refereegranskat)abstract
- Context. The spatial distribution of elemental abundances in the disc of our Galaxy gives insights both on its assembly process and subsequent evolution, and on the stellar nucleogenesis of the different elements. Gradients can be traced using several types of objects as, for instance, (young and old) stars, open clusters, HII regions, planetary nebulae. Aims. We aim to trace the radial distributions of abundances of elements produced through different nucleosynthetic channels - the α-elements O, Mg, Si, Ca and Ti, and the iron-peak elements Fe, Cr, Ni and Sc - by use of the Gaia-ESO IDR4 results for open clusters and young-field stars. Methods. From the UVES spectra of member stars, we have determined the average composition of clusters with ages > 0.1 Gyr. We derived statistical ages and distances of field stars. We traced the abundance gradients using the cluster and field populations and compared them with a chemo-dynamical Galactic evolutionary model. Results. The adopted chemo-dynamical model, with the new generation of metallicity-dependent stellar yields for massive stars, is able to reproduce the observed spatial distributions of abundance ratios, in particular the abundance ratios of [O/Fe] and [Mg/Fe] in the inner disc (5 kpc
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| 12. |
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| 13. |
- van Hoek, A. H. A. M., et al.
(författare)
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A quantitative approach towards a better understanding of the dynamics of Salmonella spp. in a pork slaughter-line
- 2012
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Ingår i: International Journal of Food Microbiology. - : Elsevier BV. - 0168-1605 .- 1879-3460. ; 153:1-2, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Pork contributes significantly to the public health disease burden caused by Salmonella infections. During the slaughter process pig carcasses can become contaminated with Salmonella. Contamination at the slaughter-line is initiated by pigs carrying Salmonella on their skin or in their faeces. Another contamination route could be resident flora present on the slaughter equipment. To unravel the contribution of these two potential sources of Salmonella a quantitative study was conducted. Process equipment (belly openers and carcass splitters), faeces and carcasses (skin and cutting surfaces) along the slaughter-line were sampled at 11 sampling days spanning a period of 4. months.Most samples taken directly after killing were positive for Salmonella. On 96.6% of the skin samples Salmonella was identified, whereas a lower number of animals tested positive in their rectum (62.5%). The prevalence of Salmonella clearly declined on the carcasses at the re-work station, either on the cut section or on the skin of the carcass or both (35.9%). Throughout the sampling period of the slaughter-line the total number of Salmonella per animal was almost 2log lower at the re-work station in comparison to directly after slaughter.Seven different serovars were identified during the study with S. Derby (41%) and S. Typhimurium (29%) as the most prominent types. A recurring S. Rissen contamination of one of the carcass splitters indicated the presence of an endemic 'house flora' in the slaughterhouse studied. On many instances several serotypes per individual sample were found.The enumeration of Salmonella and the genotyping data gave unique insight in the dynamics of transmission of this pathogen in a slaughter-line. The data of the presented study support the hypothesis that resident flora on slaughter equipment was a relevant source for contamination of pork. © 2011 Elsevier B.V.
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| 14. |
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| 15. |
- Leijten, Patty, et al.
(författare)
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Co-occurring change in children's conduct problems and maternal depression: Latent class individual participant data meta-analysis of the Incredible Years parenting program.
- 2019
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Ingår i: Development and psychopathology. - 1469-2198. ; 31:Special Issue 5, s. 1851-1862
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Tidskriftsartikel (refereegranskat)abstract
- Children vary in the extent to which they benefit from parenting programs for conduct problems. How does parental mental health change if children benefit less or more? We assessed whether changes in conduct problems and maternal depressive symptoms co-occur following participation in the Incredible Years parenting program. We integrated individual participant data from 10 randomized trials (N = 1280; children aged 2-10 years) and distinguished latent classes based on families' baseline and post-test conduct problems and maternal depressive symptoms, using repeated measures latent class analysis (RMLCA) and latent transition analysis (LTA). Classes differed mainly in severity of conduct problems and depression (RMLCA; 4 classes). Conduct problems reduced in all classes. Depressive symptoms did not change in most classes, except in a class of families where conduct problems and depression were particularly severe. Incredible Years led to a greater likelihood of families with particularly severe conduct problems and depression moving to a class with mild problems (LTA; 3 classes). Our findings suggest that for the majority of families, children's conduct problems reduce, but maternal depressive symptoms do not, suggesting relative independence, with the exception of families with severe depression and severe conduct problems where changes for the better do co-occur.
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| 16. |
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| 18. |
- Magrini, L., et al.
(författare)
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The Gaia-ESO Survey: Insights into the inner-disc evolution from open clusters
- 2015
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
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Tidskriftsartikel (refereegranskat)abstract
- Context. The inner disc, which links the thin disc with the bulge, has been somewhat neglected in the past because of the intrinsic difficulties in its study, among which crowding and high extinction. Open clusters located in the inner disc are among the best tracers of its chemistry at different ages and distances. Aims. We analyse the chemical patterns of four open clusters located within 7 kpc of the Galactic centre and of field stars to infer the properties of the inner disc with the Gaia-ESO survey idr2/3 data release. Methods. We derive the parameters of the newly observed cluster, Berkeley 81, finding an age of about 1 Gyr and a Galactocentric distance of similar to 5.4 kpc. We construct the chemical patterns of clusters and we compare them with those of field stars in the solar neighbourhood and in the inner-disc samples. Results. Comparing the three populations we observe that inner-disc clusters and field stars are both, on average, enhanced in [O/Fe], [Mg/Fe], and [Si/Fe]. Using the idr2/3 results of M67, we estimate the non-local thermodynamic equilibrium (NLTE) effect on the abundances of Mg and Si in giant stars. After empirically correcting for NLTE effects, we note that NGC 6705 and Be 81 still have a high [alpha/Fe]. Conclusions. The location of the four open clusters and of the field population reveals that the evolution of the metallicity [Fe/H] and of [alpha/Fe] can be explained within the framework of a simple chemical evolution model: both [Fe/H] and [alpha/Fe] of Trumpler 20 and of NGC 4815 are in agreement with expectations from a simple chemical evolution model. On the other hand, NGC 6705, and to a lesser degree Berkeley 81, have higher [alpha/Fe] than expected for their ages, location in the disc, and metallicity. These differences might originate from local enrichment processes as explained in the inhomogeneous evolution framework.
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| 19. |
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| 20. |
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| 21. |
- van Overbeek, A J M, et al.
(författare)
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On-Line Structure Selection for Multivariable State-Space Models
- 1982
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Ingår i: Automatica. - : Elsevier. - 0005-1098 .- 1873-2836. ; 18:5, s. 529-543
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Tidskriftsartikel (refereegranskat)abstract
- An algorithm is described for the selection of model structure for identifying state-space models of ‘black box’ character. The algorithm receives as ‘input’ a given system in a given parametrization. It is then tested whether this parametrization is suitable (well conditioned) for identification purposes. If not, a better one is selected and the transformation of the system to the new representation is performed. This algorithm can be used as a block both in an iterative, off-line identification procedure, and for recursive, on-line identification. It can be called whenever there is some indication that the model structure is ill-conditioned. It is discussed how the model structure selection algorithm can be interfaced with an off-line identification procedure. A complete procedure is described and tested on real and simulated data.
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| 22. |
- van Overbeek, A J M
(författare)
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On-Line Structure Selection for the Identification of Multivariable Systems
- 1982
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An algorithm is described for the selection of mod el structure for identifying multivariable mode Is of"black box" character. The algorithm receives as "input" a mode I in a given parametrization (= mode I structure). It is then tested whether this parametrization is suitable (well conditioned) for identification purposes. If not, a better one is selected and the transformation of the mode! to the new representation is performed.The test is based upon the properties ofthe Hankel matrix ofthe impulse response ofthe mode I. The relation between the conditioning ofthe Hankel matrix and the conditioning of the identification (minimization) is described.This mode! structure selection algorithm can be used as a block in both an iterative, offline identification procedure, and in recursive, on-line identification. It can be used whenever there is some indication that the parametrization is ill-conditioned. It is discussed how the algorithm can be interfaced with an identification procedure.A complete procedure consisting of an off-line identification algorithm and the model structure selection algorithm is described. Results are given when this com bined algorithm is applied to both simulated and real data.
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| 23. |
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