| 1. |
- Schael, S., et al.
(författare)
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Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
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Forskningsöversikt (refereegranskat)abstract
- Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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| 2. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 3. |
- Hu, H., et al.
(författare)
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X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:1, s. 133-148
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Tidskriftsartikel (refereegranskat)abstract
- X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.
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| 4. |
- Swayne,, et al.
(författare)
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The EBLM project - VIII. First results for M-dwarf mass, radius, and effective temperature measurements using CHEOPS light curves
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 506:1, s. 306-322
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Tidskriftsartikel (refereegranskat)abstract
- The accuracy of theoretical mass, radius, and effective temperature values for M-dwarf stars is an active topic of debate. Differences between observed and theoretical values have raised the possibility that current theoretical stellar structure and evolution models are inaccurate towards the low-mass end of the main sequence. To explore this issue, we use the CHEOPS satellite to obtain high-precision light curves of eclipsing binaries with low-mass stellar companions. We use these light curves combined with the spectroscopic orbit for the solar-type companion to measure the mass, radius, and effective temperature of the M-dwarf star. Here, we present the analysis of three eclipsing binaries. We use the pycheops data analysis software to fit the observed transit and eclipse events of each system. Two of our systems were also observed by the TESS satellite - we similarly analyse these light curves for comparison. We find consistent results between CHEOPS and TESS, presenting three stellar radii and two stellar effective temperature values of low-mass stellar objects. These initial results from our on-going observing programme with CHEOPS show that we can expect to have similar to 24 new mass, radius, and effective temperature measurements for very low-mass stars within the next few years.
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| 5. |
- Ehrenreich, D., et al.
(författare)
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A full transit of v 2 Lupi d and the search for an exomoon in its Hill sphere with CHEOPS
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Tidskriftsartikel (refereegranskat)abstract
- The planetary system around the naked-eye star v2 Lupi (HD 136352; TOI-2011) is composed of three exoplanets with masses of 4.7, 11.2, and 8.6 Earth masses (M⊕). The TESS and CHEOPS missions revealed that all three planets are transiting and have radii straddling the radius gap separating volatile-rich and volatile-poor super-earths. Only a partial transit of planet d had been covered so we re-observed an inferior conjunction of the long-period 8.6 M⊕ exoplanet v2 Lup d with the CHEOPS space telescope. We confirmed its transiting nature by covering its whole 9.1 h transit for the first time. We refined the planet transit ephemeris to P = 107.13610.0022+0.0019 days and Tc = 2459009.77590.0096+0.0101 BJDTDB, improving by ~40 times on the previously reported transit timing uncertainty. This refined ephemeris will enable further follow-up of this outstanding long-period transiting planet to search for atmospheric signatures or explore the planet s Hill sphere in search for an exomoon. In fact, the CHEOPS observations also cover the transit of a large fraction of the planet s Hill sphere, which is as large as the Earth s, opening the tantalising possibility of catching transiting exomoons. We conducted a search for exomoon signals in this single-epoch light curve but found no conclusive photometric signature of additional transiting bodies larger than Mars. Yet, only a sustained follow-up of v2 Lup d transits will warrant a comprehensive search for a moon around this outstanding exoplanet.
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| 6. |
- Bonfanti, A., et al.
(författare)
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Characterising TOI-732 b and c: New insights into the M-dwarf radius and density valley ★,★★
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
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Tidskriftsartikel (refereegranskat)abstract
- TOI-732 is an M dwarf hosting two transiting planets that are located on the two opposite sides of the radius valley. Inferring a reliable demographics for this type of systems is key to understanding their formation and evolution mechanisms. Aims. By doubling the number of available space-based observations and increasing the number of radial velocity (RV) measurements, we aim at refining the parameters of TOI-732 b and c. We also use the results to study the slope of the radius valley and the density valley for a well-characterised sample of M-dwarf exoplanets. Methods. We performed a global Markov chain Monte Carlo analysis by jointly modelling ground-based light curves and CHEOPS and TESS observations, along with RV time series both taken from the literature and obtained with the MAROON-X spectrograph. The slopes of the M-dwarf valleys were quantified via a support vector machine (SVM) procedure. Results. TOI-732 b is an ultrashort-period planet (P = 0.76837931−+000000004200000039 days) with a radius Rb = 1.325+−00057058 R☉, a mass Mb = 2.46 ± 0.19 M☉, and thus a mean density ρb = 5.8+−1008 g cm−3, while the outer planet at P = 12.252284 ± 0.000013 days has Rc = 2.39+−001011 R☉, Mc = 8.04+−005048 M☉, and thus ρc = 3.24+−005543 g cm−3. Even with respect to the most recently reported values, this work yields uncertainties on the transit depths and on the RV semi-amplitudes that are smaller up to a factor of ∼1.6 and ∼2.4 for TOI-732 b and c, respectively. Our calculations for the interior structure and the location of the planets in the mass-radius diagram lead us to classify TOI-732 b as a super-Earth and TOI-732 c as a mini-Neptune. Following the SVM approach, we quantified d log Rp,valley/d log P = −0.065+−00024013, which is flatter than for Sun-like stars. In line with former analyses, we note that the radius valley for M-dwarf planets is more densely populated, and we further quantify the slope of the density valley as d log ρ̂valley/d log P = −0.02+−001204. Conclusions. Compared to FGK stars, the weaker dependence of the position of the radius valley on the orbital period might indicate that the formation shapes the radius valley around M dwarfs more strongly than the evolution mechanisms.
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| 7. |
- Maxted, P. F. L., et al.
(författare)
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Fundamental effective temperature measurements for eclipsing binary stars - III. SPIRou near-infrared spectroscopy and CHEOPS photometry of the benchmark G0V star EBLM J0113+31
- 2022
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 6042-6057
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Tidskriftsartikel (refereegranskat)abstract
- EBLM J0113+31 is a moderately bright (V = 10.1), metal-poor ([Fe/H] approximate to-0.3) GOV star with a much fainter M dwarf companion on a wide, eccentric orbit (= 14.3 d). We have used near-infrared spectroscopy obtained with the SPIRou spectrograph to measure the semi-amplitude of the M dwarf's spectroscopic orbit, and high-precision photometry of the eclipse and transit from the CHEOPS and TESS space missions to measure the geometry of this binary system. From the combined analysis of these data together with previously published observations, we obtain the following model-independent masses and radii: M-1 = 1.029 +/- 0.025 M-circle dot, M-2 = 0.197 +/- 0.003 M-circle dot, R-1 = 1.417 +/- 0.014 R-circle dot, R-2 = 0.215 +/- 0.002 R-circle dot. Using R-1 and the parallax from Gaia EDR3 we find that this star's angular diameter is theta = 0.0745 +/- 0.0007 mas. The apparent bolometric flux of the GOV star corrected for both extinction and the contribution from the M dwarf (<0.2 per cent) is F-circle plus,F-0 = (2.62 +/- 0.05) x 10(-9) erg cm(-2) S-1. Hence, this G0V star has an effective temperature T-eff(,1) = 6124 K +/- 40 K (rnd.) +/- 10 K (sys.). EBLM J0113+31 is an ideal benchmark star that can be used for 'end-to-end' tests of the stellar parameters measured by large-scale spectroscopic surveys, or stellar parameters derived from asteroseismology with PLATO. The techniques developed here can be applied to many other eclipsing binaries in order to create a network of such benchmark stars.
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| 8. |
- Sulis, S., et al.
(författare)
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Connecting photometric and spectroscopic granulation signals with CHEOPS and ESPRESSO
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 670
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Tidskriftsartikel (refereegranskat)abstract
- Context. Stellar granulation generates fluctuations in photometric and spectroscopic data whose properties depend on the stellar type, composition, and evolutionary state. Characterizing granulation is key for understanding stellar atmospheres and detecting planets. Aims. We aim to detect the signatures of stellar granulation, link spectroscopic and photometric signatures of convection for main-sequence stars, and test predictions from 3D hydrodynamic models. Methods. For the first time, we observed two bright stars (Teff = 5833 and 6205 K) with high-precision observations taken simultaneously with CHEOPS and ESPRESSO. We analyzed the properties of the stellar granulation signal in each individual dataset. We compared them to Kepler observations and 3D hydrodynamic models. While isolating the granulation-induced changes by attenuating and filtering the p-mode oscillation signals, we studied the relationship between photometric and spectroscopic observables. Results. The signature of stellar granulation is detected and precisely characterized for the hotter F star in the CHEOPS and ESPRESSO observations. For the cooler G star, we obtain a clear detection in the CHEOPS dataset only. The TESS observations are blind to this stellar signal. Based on CHEOPS observations, we show that the inferred properties of stellar granulation are in agreement with both Kepler observations and hydrodynamic models. Comparing their periodograms, we observe a strong link between spectroscopic and photometric observables. Correlations of this stellar signal in the time domain (flux versus radial velocities, RV) and with specific spectroscopic observables (shape of the cross-correlation functions) are however difficult to isolate due to S/N dependent variations. Conclusions. In the context of the upcoming PLATO mission and the extreme precision RV surveys, a thorough understanding of the properties of the stellar granulation signal is needed. The CHEOPS and ESPRESSO observations pave the way for detailed analyses of this stellar process.
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| 9. |
- Nascimbeni, V., et al.
(författare)
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A new dynamical modeling of the WASP-47 system with CHEOPS observations
- 2023
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 1432-0746 .- 0004-6361. ; 673
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Tidskriftsartikel (refereegranskat)abstract
- Among the hundreds of known hot Jupiters (HJs), only five have been found to have companions on short-period orbits. Within this rare class of multiple planetary systems, the architecture of WASP-47 is unique, hosting an HJ (planet-b) with both an inner and an outer sub-Neptunian mass companion (-e and -d, respectively) as well as an additional non-transiting, long-period giant (-c). The small period ratio between planets -b and -d boosts the transit time variation (TTV) signal, making it possible to reliably measure the masses of these planets in synergy with the radial velocity (RV) technique. In this paper, we present new space- and ground-based photometric data of WASP-47b and WASP-47-d, including 11 unpublished light curves from the ESA mission CHaracterising ExOPlanet Satellite (CHEOPS). We analyzed the light curves in a homogeneous way together with all the publicly available data to carry out a global N-body dynamical modeling of the TTV and RV signals. We retrieved, among other parameters, a mass and density for planet -d of Md = 15.5 ± 0.8 M⊕ and ρd = 1.69 ± 0.22 g cm−3, which is in good agreement with the literature and consistent with a Neptune-like composition. For the inner planet (-e), we found a mass and density of Me = 9.0 ± 0.5 M⊕ and ρe = 8.1 ± 0.5 g cm−3, suggesting an Earth-like composition close to other ultra-hot planets at similar irradiation levels. Though this result is in agreement with previous RV plus TTV studies, it is not in agreement with the most recent RV analysis (at 2.8σ), which yielded a lower density compatible with a pure silicate composition. This discrepancy highlights the still unresolved issue of suspected systematic offsets between RV and TTV measurements. In this paper, we also significantly improve the orbital ephemerides of all transiting planets, which will be crucial for any future follow-up.
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| 10. |
- Singh, V., et al.
(författare)
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CHEOPS observations of KELT-20 b/MASCARA-2 b: An aligned orbit and signs of variability from a reflective day side
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. Occultations are windows of opportunity to indirectly peek into the dayside atmosphere of exoplanets. High-precision transit events provide information on the spin-orbit alignment of exoplanets around fast-rotating hosts. Aims. We aim to precisely measure the planetary radius and geometric albedo of the ultra-hot Jupiter (UHJ) KELT-20 b along with the spin-orbit alignment of the system. Methods. We obtained optical high-precision transits and occultations of KELT-20 b using CHEOPS observations in conjunction with simultaneous TESS observations. We interpreted the occultation measurements together with archival infrared observations to measure the planetary geometric albedo and dayside temperatures. We further used the host star's gravity-darkened nature to measure the system's obliquity. Results. We present a time-averaged precise occultation depth of 82 ± 6 ppm measured with seven CHEOPS visits and 131-7+8 from the analysis of all available TESS photometry. Using these measurements, we precisely constrain the geometric albedo of KELT-20 b to 0.26 ± 0.04 and the brightness temperature of the dayside hemisphere to 2566-80+77 K. Assuming Lambertian scattering law, we constrain the Bond albedo to 0.36-0.05+0.04 along with a minimal heat transfer to the night side (Ïμ = 0.14-0.10+0.13). Furthermore, using five transit observations we provide stricter constraints of 3 9 ± 1 1 deg on the sky-projected obliquity of the system. Conclusions. The aligned orbit of KELT-20 b is in contrast to previous CHEOPS studies that have found strongly inclined orbits for planets orbiting other A-type stars. The comparably high planetary geometric albedo of KELT-20 b corroborates a known trend of strongly irradiated planets being more reflective. Finally, we tentatively detect signs of temporal variability in the occultation depths, which might indicate variable cloud cover advecting onto the planetary day side.
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| 11. |
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| 12. |
- van der Wouden, C. H., et al.
(författare)
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Implementing Pharmacogenomics in Europe : Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium
- 2017
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY. - 0009-9236 .- 1532-6535. ; 101:3, s. 341-358
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Tidskriftsartikel (refereegranskat)abstract
- Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programs have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs. The Ubiquitous Pharmacogenomics (U-PGx) Consortium, which has been funded by the European Commission's Horizon-2020 program, aims to address this unmet need. In a prospective, block-randomized, controlled clinical study (PREemptive Pharmacogenomic testing for prevention of Adverse drug REactions [PREPARE]), pre-emptive genotyping of a panel of clinically relevant PGx-markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost-effectiveness will be investigated. The program is unique in its multicenter, multigene, multidrug, multi-ethnic, and multi-healthcare system approach.
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| 13. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Schneider, A., et al.
(författare)
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The Evolutionarily Conserved Protein PHOTOSYNTHESIS AFFECTED MUTANT71 Is Required for Efficient Manganese Uptake at the Thylakoid Membrane in Arabidopsis
- 2016
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Ingår i: Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 28:4, s. 892-910
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Tidskriftsartikel (refereegranskat)abstract
- In plants, algae, and cyanobacteria, photosystem II (PSII) catalyzes the light-driven oxidation of water. The oxygen-evolving complex of PSII is a Mn4CaO5 cluster embedded in a well-defined protein environment in the thylakoid membrane. However, transport of manganese and calcium into the thylakoid lumen remains poorly understood. Here, we show that Arabidopsis thaliana PHOTOSYNTHESIS AFFECTED MUTANT71 (PAM71) is an integral thylakoid membrane protein involved in Mn2+ and Ca2+ homeostasis in chloroplasts. This protein is required for normal operation of the oxygen-evolving complex (as evidenced by oxygen evolution rates) and for manganese incorporation. Manganese binding to PSII was severely reduced in pam71 thylakoids, particularly in PSII supercomplexes. In cation partitioning assays with intact chloroplasts, Mn2+ and Ca2+ ions were differently sequestered in pam71, with Ca2+ enriched in pam71 thylakoids relative to the wild type. The changes in Ca2+ homeostasis were accompanied by an increased contribution of the transmembrane electrical potential to the proton motive force across the thylakoid membrane. PSII activity in pam71 plants and the corresponding Chlamydomonas reinhardtii mutant cgld1 was restored by supplementation with Mn2+, but not Ca2+. Furthermore, PAM71 suppressed the Mn2+-sensitive phenotype of the yeast mutant Delta pmr1. Therefore, PAM71 presumably functions in Mn2+ uptake into thylakoids to ensure optimal PSII performance.
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| 15. |
- Tobias, J., et al.
(författare)
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A New Strategy Toward B Cell-Based Cancer Vaccines by Active Immunization With Mimotopes of Immune Checkpoint Inhibitors
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic monoclonal antibodies (mAbs), targeting tumor antigens, or immune checkpoints, have demonstrated a remarkable anti-tumor effect against various malignancies. However, high costs for mono- or combination therapies, associated with adverse effects or possible development of resistance in some patients, warrant further development and modification to gain more flexibility for this immunotherapy approach. An attractive alternative to passive immunization with therapeutic antibodies might be active immunization with mimotopes (B-cell peptides) representing the mAbs' binding epitopes, to activate the patient's own anti-tumor immune response following immunization. Here, we identified and examined the feasibility of inducing anti-tumor effectsin vivofollowing active immunization with a mimotope of the immune checkpoint programmed cell death 1 (PD1), alone or in combination with a Her-2/neu B-cell peptide vaccine. Overlapping peptides spanning the extracellular domains of human PD1 (hPD1) were used to identify hPD1-derived mimotopes, using the therapeutic mAb Nivolumab as a proof of concept. Additionally, forin vivoevaluation in a tumor mouse model, a mouse PD1 (mPD1)-derived mimotope was identified using an anti-mPD1 mAb with mPD1/mPDL-1 blocking capacity. The identified mimotopes were characterized byin vitroassays, including a reporter cell-based assay, and their anti-tumor effects were evaluated in a syngeneic tumor mouse model stably expressing human Her-2/neu. The identified PD1-derived mimotopes were shown to significantly block the mAbs' capacity in inhibiting the respective PD1/PD-L1 interactions. A significant reduction in tumor growthin vivowas observed following active immunization with the mPD1-derived mimotope, associated with a significant reduction in proliferation and increased apoptotic rates in the tumors. Particularly, combined vaccination with the mPD1-derived mimotope and a multiple B-cell epitope Her-2/neu vaccine potentiated the vaccine's anti-tumor effect. Our results suggest active immunization with mimotopes of immune checkpoint inhibitors either as monotherapy or as combination therapy with tumor-specific vaccines, as a new strategy for cancer treatment.
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| 16. |
- Holt, Erica M., et al.
(författare)
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Fruit and Vegetable Consumption and Its Relation to Markers of Inflammation and Oxidative Stress in Adolescents
- 2009
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Ingår i: Journal of the American Dietetic Association. - : Elsevier BV. - 0002-8223 .- 1878-3570. ; 109:3, s. 414-421
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Tidskriftsartikel (refereegranskat)abstract
- Background Fruits and vegetables, foods rich in flavonoids and antioxidants, have been associated with lower risk of stroke, coronary heart disease, and markers of inflammation and oxidative stress in adults. Markers of inflammation and oxidative stress are predictors of coronary heart disease risk; however, it is unknown whether these markers are related to dietary flavonoid and antioxidant intake in youth. Objective To determine whether greater intakes of fruit and vegetables, antioxidants, folate, and total flavonoids were inversely associated with markers of inflammation and oxidative stress in 285 adolescent boys and girls aged 13 to 17 years. Design In this cross-sectional study conducted between February 1996 and January 2000, diet was assessed by a 127-item food frequency questionnaire. Height and weight measurements were obtained and a fasting blood sample drawn. Spearman partial correlation analyses evaluated the relation of intakes of fruit and vegetables, antioxidants, folate, and flavonoids with markers of inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and 15-keto-dihydro-PGF(2 alpha) metabolite and oxidative stress (urinary 8-iso prostaglandin F-2 alpha, an F-2-isoprostane), adjusting for age, sex, race, Tanner stage, energy intake, and body mass index. Results Urinary F-2-isoprostane was inversely correlated with intakes of total fruit and vegetables, vitamin C, beta carotene, and flavonoids. Serum C-reactive protein was significantly inversely associated with intakes of fruit (r=-0.19; P=0.004), vitamin C (r=-0.13, P=0.03), and folate (r=-0.18; P=0.004). Serum interleukin-6 was inversely associated with intakes of legumes, vegetables, beta carotene, and vitamin C. Serum tumor necrosis factor-a was inversely associated with beta carotene (r=-0.14, P=0.02) and luteolin (r=-0.15, P=0.02). Conclusion Study results show that the beneficial effects of fruit and vegetable intake on markers of inflammation and oxidative stress are already present by early adolescence and provide support for the Dietary Guidelines for Americans "to consume five or more servings per day" of fruits and vegetables to promote beneficial cardiovascular health.
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| 17. |
- Mote, Ryan S., et al.
(författare)
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Assessing the Beneficial Effects of the Immunomodulatory Glycan LNFPIII on Gut Microbiota and Health in a Mouse Model of Gulf War Illness
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 17:19
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Tidskriftsartikel (refereegranskat)abstract
- The microbiota’s influence on host (patho) physiology has gained interest in the context of Gulf War Illness (GWI), a chronic disorder featuring dysregulation of the gut–brain–immune axis. This study examined short- and long-term effects of GWI-related chemicals on gut health and fecal microbiota and the potential benefits of Lacto-N-fucopentaose-III (LNFPIII) treatment in a GWI model. Male C57BL/6J mice were administered pyridostigmine bromide (PB; 0.7 mg/kg) and permethrin (PM; 200 mg/kg) for 10 days with concurrent LNFPIII treatment (35 μg/mouse) in a short-term study (12 days total) and delayed LNFPIII treatment (2×/week) beginning 4 months after 10 days of PB/PM exposure in a long-term study (9 months total). Fecal 16S rRNA sequencing was performed on all samples post-LNFPIII treatment to assess microbiota effects of GWI chemicals and acute/delayed LNFPIII administration. Although PB/PM did not affect species composition on a global scale, it affected specific taxa in both short- and long-term settings. PB/PM elicited more prominent long-term effects, notably, on the abundances of bacteria belonging to Lachnospiraceae and Ruminococcaceae families and the genus Allobaculum. LNFPIII improved a marker of gut health (i.e., decreased lipocalin-2) independent of GWI and, importantly, increased butyrate producers (e.g., Butyricoccus, Ruminococcous) in PB/PM-treated mice, indicating a positive selection pressure for these bacteria. Multiple operational taxonomic units correlated with aberrant behavior and lipocalin-2 in PB/PM samples; LNFPIII was modulatory. Overall, significant and lasting GWI effects occurred on specific microbiota and LNFPIII treatment was beneficial.
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| 18. |
- Roth, D., et al.
(författare)
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Electronic Stopping of Slow Protons in Transition and Rare Earth Metals : Breakdown of the Free Electron Gas Concept
- 2017
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 118:10
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Tidskriftsartikel (refereegranskat)abstract
- The electronic stopping cross sections (SCS) of Ta and Gd for slow protons have been investigated experimentally. The data are compared to the results for Pt and Au to learn how electronic stopping in transition and rare earth metals correlates with features of the electronic band structures. The extraordinarily high SCS observed for protons in Ta and Gd cannot be understood in terms of a free electron gas model, but are related to the high densities of both occupied and unoccupied electronic states in these metals.
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| 19. |
- Swen, JesseJ, et al.
(författare)
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A 12-gene pharmacogenetic panel to prevent adverse drug reactions : an open-label, multicentre, controlled, cluster-randomised crossover implementation study
- 2023
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 401:10374, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene-drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed.Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug-gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug-gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug-gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants.Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51.4 % female, 48.6% male; 97.7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1.6%] of the study group and 47 [1.3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11.0%] in the study group and 285 [7.9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21 center dot 0%) of 725 patients in the study group and 231 (27.7%) of 833 patients in the control group (odds ratio [OR] 0 center dot 70 [95% CI 0 center dot 54-0 center dot 91]; p=0.0075), whereas for all patients, the incidence was 628 (21.5%) of 2923 patients in the study group and 934 (28. 6%) of 3270 patients in the control group (OR 0.70 [95% CI 0.61-0.79]; p <0.0001).Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe.
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| 20. |
- van der Wouden, Cathelijne H., et al.
(författare)
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Generating evidence for precision medicine : considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study
- 2020
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 30:6, s. 131-144
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Pharmacogenetic panel-based testing represents a new model for precision medicine. A sufficiently powered prospective study assessing the (cost-)effectiveness of a panel-based pharmacogenomics approach to guide pharmacotherapy is lacking. Therefore, the Ubiquitous Pharmacogenomics Consortium initiated the PREemptive Pharmacogenomic testing for prevention of Adverse drug Reactions (PREPARE) study. Here, we provide an overview of considerations made to mitigate multiple methodological challenges that emerged during the design.Methods An evaluation of considerations made when designing the PREPARE study across six domains: study aims and design, primary endpoint definition and collection of adverse drug events, inclusion and exclusion criteria, target population, pharmacogenomics intervention strategy, and statistical analyses.Results Challenges and respective solutions included: (1) defining and operationalizing a composite primary endpoint enabling measurement of the anticipated effect, by including only severe, causal, and drug genotype-associated adverse drug reactions; (2) avoiding overrepresentation of frequently prescribed drugs within the patient sample while maintaining external validity, by capping drugs of enrolment; (3) designing the pharmacogenomics intervention strategy to be applicable across ethnicities and healthcare settings; and (4) designing a statistical analysis plan to avoid dilution of effect by initially excluding patients without a gene–drug interaction in a gatekeeping analysis.Conclusion Our design considerations will enable quantification of the collective clinical utility of a panel of pharmacogenomics-markers within one trial as a proof-of-concept for pharmacogenomics-guided pharmacotherapy across multiple actionable gene–drug interactions. These considerations may prove useful to other investigators aiming to generate evidence for precision medicine.
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| 21. |
- Seltenhammer, Monika H., et al.
(författare)
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Establishment and characterization of a primary and a metastatic melanoma cell line from Grey horses
- 2014
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Ingår i: In vitro Cellular & Developmental Biology-Animal. - : Springer Science and Business Media LLC. - 1071-2690 .- 1543-706X. ; 50:1, s. 56-65
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Tidskriftsartikel (refereegranskat)abstract
- The Grey horse phenotype, caused by a 4.6 kb duplication in Syntaxin 17, is strongly associated with high incidence of melanoma. In contrast to most human melanomas with an early onset of metastasis, the Grey horse melanomas have an extended period of benign growth, after which 50% or more eventually undergo progression and may metastasize. In efforts to define changes occurring during Grey horse melanoma progression, we established an in vitro model comprised of two cell lines, HoMel-L1 and HoMel-A1, representing a primary and a metastatic stage of the melanoma, respectively. The cell lines were examined for their growth and morphological characteristics, in vitro and in vivo oncogenic potential, chromosome numbers, and expression of melanocytic antigens and tumor suppressors. Both cell lines exhibited malignant characteristics; however, the metastatic HoMel-A1 showed a more aggressive phenotype characterized by higher proliferation rates, invasiveness, and a stronger tumorigenic potential both in vitro and in vivo. HoMel-A1 displayed a near-haploid karyotype, whereas HoMel-L1 was near-diploid. The cell lines expressed melanocytic lineage markers such as TYR, TRP1, MITF, PMEL, ASIP, MC1R, POMC, and KIT. The tumor suppressor p53 was strongly expressed in both cell lines, while the tumor suppressors p16 and PTEN were absent in HoMel-A1, potentially implicating significance of these pathways in the melanoma progression. This in vitro model system will not only aid in understanding of the Grey horse melanoma pathogenesis, but also in unraveling the steps during melanoma progression in general as well as being an invaluable tool for development of new therapeutic strategies.
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| 22. |
- Steffen, L M, et al.
(författare)
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Serum phospholipid and cholesteryl ester fatty acids and estimated desaturase activities are related to overweight and cardiovascular risk factors in adolescents
- 2008
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 32:8, s. 1297-1304
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Tidskriftsartikel (refereegranskat)abstract
- Aim/hypothesis: The objective of this study was to describe the relation of serum fatty acids and desaturase activity (DA) to overweight, insulin sensitivity and cardiovascular disease (CVD) risk factors in adolescents. Methods: The relations of % serum phospholipid (PL) and cholesteryl ester (CE) fatty acids and estimated DA with CVD risk factors were examined in 264 adolescents (average age 15 years). Fatty acids were determined by gas liquid chromotography. Surrogate measures of DA were expressed as ratios of serum fatty acids: Delta 9 DA 16: 0/16: 1, Delta 6 DA 20: 3, n6/18: 2, n6 (PL) or 18: 3, n6/18: 2, n6 (CE), and Delta 5 DA 20: 4, n6/20: 3, n6. Spearman partial correlations of fatty acids (%) and DA ratios with CVD risk factors were reported, adjusting for age, sex, race, Tanner stage, energy intake and physical activity. Results: Overweight adolescents compared to normal weight had more adverse levels of CVD risk factors, composition of PL and CE fatty acids in serum, and D6 DA and D5 DA ratios. Linoleic acid was inversely related to body mass index (BMI), waist circumference and triglycerides (P < ;= 0.01). Dihomo-gamma-linolenic acid was positively related to BMI, waist, insulin, and triglycerides, and inversely related to high-density lipoprotein-cholesterol levels (P < ;= 0.01). D6 DA was adversely associated with most of the risk factors (P < ;= 0.01), whereas triglycerides and fasting insulin were beneficially related to D5 DA (P < ;= 0.01). Conclusion: These findings support those observed in adults, that factors, such as type of dietary fat, physical activity, and obesity, may influence fatty acid metabolism and are important in the development of adverse CVD risk factors as early as adolescence.
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| 23. |
- Wang, Huifen, et al.
(författare)
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Obesity Modifies the Relations Between Serum Markers of Dairy Fats and Inflammation and Oxidative Stress Among Adolescents
- 2011
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 19:12, s. 2404-2410
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Tidskriftsartikel (refereegranskat)abstract
- Pentadecanoic acid (15: 0) and heptadecanoic acid (17: 0), the dairy-specific saturated fatty acids have been inversely, while inflammation and oxidative stress have been positively related to the risk of cardiovascular disease (CVD). Both fatty acid metabolism and inflammation and oxidative stress may be influenced by adiposity. In the current cross-sectional analyses among adolescents (mean age 15 years), we determined whether overweight status modified the associations between dairy fatty acids (pentadecanoic acid (15: 0) and heptadecanoic acid (17: 0)) represented in serum phospholipids (PL) and markers of inflammation and oxidative stress. Six biomarkers for inflammation and oxidative stress were analyzed, including circulating adiponectin, C-reactive protein (CRP), cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and urinary 15-keto-dihydro-PGF2 alpha (15-keto) and 8-iso-PGF2 alpha (F2-iso). Generalized linear regression analyses, adjusted for age, gender, race, tanner score, total energy intake and physical activity, revealed that PL dairy fatty acids were inversely associated with CRP, F2-iso and 15-keto in overweight, but not in normal weight adolescents (all P(interaction) < 0.05). However, higher level of PL dairy fatty acids was associated with lower IL-6 among all adolescents. Further adjustment for dietary intake of calcium, vitamin D, protein, total flavonoids, and omega-3 fatty acids did not materially change the findings. Dairy-specific saturated fats, i.e., 15: 0 and 17: 0 fatty acids, may contribute to the potential health benefits of dairy products, especially for overweight adolescents.
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