1. |
- Schael, S., et al.
(author)
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Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
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Research review (peer-reviewed)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.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)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. |
- Swayne,, et al.
(author)
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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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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 506:1, s. 306-322
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Journal article (peer-reviewed)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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4. |
- Nascimbeni, V., et al.
(author)
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A new dynamical modeling of the WASP-47 system with CHEOPS observations
- 2023
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In: Astronomy & Astrophysics. - : EDP Sciences. - 1432-0746 .- 0004-6361. ; 673
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Journal article (peer-reviewed)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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5. |
- Bonfanti, A., et al.
(author)
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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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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
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Journal article (peer-reviewed)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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6. |
- Ehrenreich, D., et al.
(author)
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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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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Journal article (peer-reviewed)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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7. |
- Sulis, S., et al.
(author)
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Connecting photometric and spectroscopic granulation signals with CHEOPS and ESPRESSO
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 670
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Journal article (peer-reviewed)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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8. |
- Sulis, S., et al.
(author)
-
HIP 41378 observed by CHEOPS: Where is planet d?
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 686
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Journal article (peer-reviewed)abstract
- HIP 41378 d is a long-period planet that has only been observed to transit twice, three years apart, with K2. According to stability considerations and a partial detection of the Rossiter- McLaughlin effect, Pd = 278.36 d has been determined to be the most likely orbital period. We targeted HIP 41378 d with CHEOPS at the predicted transit timing based on Pd = 278.36 d, but the observations show no transit. We find that large (> 22.4 h) transit timing variations (TTVs) could explain this non-detection during the CHEOPS observation window. We also investigated the possibility of an incorrect orbital solution, which would have major implications for our knowledge of this system. If Pd ≠ 278.36 d, the periods that minimize the eccentricity would be 101.22 d and 371.14 d. The shortest orbital period will be tested by TESS, which will observe HIP 41378 in Sector 88 starting in January 2025. Our study shows the importance of a mission like CHEOPS, which today is the only mission able to make long observations (i.e., from space) to track the ephemeris of long-period planets possibly affected by large TTVs.
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9. |
- Maxted, P. F. L., et al.
(author)
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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
-
In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 6042-6057
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Journal article (peer-reviewed)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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10. |
- Singh, V., et al.
(author)
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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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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
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Journal article (peer-reviewed)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. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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12. |
- Roth, D., et al.
(author)
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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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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 118:10
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Journal article (peer-reviewed)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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13. |
- Hu, H., et al.
(author)
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X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes
- 2016
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:1, s. 133-148
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Journal article (peer-reviewed)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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14. |
- Schneider, A., et al.
(author)
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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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In: Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 28:4, s. 892-910
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Journal article (peer-reviewed)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. |
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16. |
- Steffen, L M, et al.
(author)
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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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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 32:8, s. 1297-1304
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Journal article (peer-reviewed)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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17. |
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18. |
- Tobias, J., et al.
(author)
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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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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Journal article (peer-reviewed)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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19. |
- van der Wouden, C. H., et al.
(author)
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Implementing Pharmacogenomics in Europe : Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium
- 2017
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In: Clinical Pharmacology and Therapeutics. - : WILEY. - 0009-9236 .- 1532-6535. ; 101:3, s. 341-358
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Journal article (peer-reviewed)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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