| 61. |
- Bausch, Birke, et al.
(författare)
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Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention
- 2017
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Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 3:9, s. 1204-1212
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P amp;lt; .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.
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| 62. |
- Bergamaschi, Peter, et al.
(författare)
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High-resolution inverse modelling of European CH4emissions using the novel FLEXPART-COSMO TM5 4DVAR inverse modelling system
- 2022
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:20, s. 13243-13268
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Tidskriftsartikel (refereegranskat)abstract
- We present a novel high-resolution inverse modelling system ("FLEXVAR") based on FLEXPARTCOSMO back trajectories driven by COSMO meteorological fields at 7 km×7 km resolution over the European COSMO-7 domain and the four-dimensional variational (4DVAR) data assimilation technique. FLEXVAR is coupled offline with the global inverse modelling system TM5-4DVAR to provide background mole fractions ("baselines") consistent with the global observations assimilated in TM5-4DVAR. We have applied the FLEXVAR system for the inverse modelling of European CH4 emissions in 2018 using 24 stations with in situ measurements, complemented with data from five stations with discrete air sampling (and additional stations outside the European COSMO-7 domain used for the global TM5-4DVAR inversions). The sensitivity of the FLEXVAR inversions to different approaches to calculate the baselines, different parameterizations of the model representation error, different settings of the prior error covariance parameters, different prior inventories, and different observation data sets are investigated in detail. Furthermore, the FLEXVAR inversions are compared to inversions with the FLEXPART extended Kalman filter ("FLExKF") system and with TM5-4DVAR inversions at 1° × 1° resolution over Europe. The three inverse modelling systems show overall good consistency of the major spatial patterns of the derived inversion increments and in general only relatively small differences in the derived annual total emissions of larger country regions. At the same time, the FLEXVAR inversions at 7 km × 7 km resolution allow the observations to be better reproduced than the TM5-4DVAR simulations at 1° × 1°. The three inverse models derive higher annual total CH4 emissions in 2018 for Germany, France, and BENELUX compared to the sum of anthropogenic emissions reported to UNFCCC and natural emissions estimated from the Global Carbon Project CH4 inventory, but the uncertainty ranges of top-down and bottom-up total emission estimates overlap for all three country regions. In contrast, the top-down estimates for the sum of emissions from the UK and Ireland agree relatively well with the total of anthropogenic and natural bottom-up inventories.
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| 63. |
- Bernardo, J., et al.
(författare)
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Ion temperature and toroidal rotation in JET's low torque plasmas
- 2016
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 87:11
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports on the procedure developed as the best method to provide an accurate and reliable estimation of the ion temperature T-i and the toroidal velocity v(phi) from Charge-eXchange Recombination Spectroscopy (CXRS) data from intrinsic rotation experiments at the Joint European Torus with the carbon wall. The low impurity content observed in such plasmas, resulting in low active CXRS signal, alongside low Doppler shifts makes the determination of Ti and v(phi) particularly difficult. The beam modulation method will be discussed along with the measures taken to increase photon statistics and minimise errors from the absolute calibration and magneto-hydro-dynamics effects that may impact the CXRS passive emission.
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| 64. |
- Bernert, M., et al.
(författare)
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Power exhaust by SOL and pedestal radiation at ASDEX Upgrade and JET
- 2017
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Ingår i: Nuclear Materials and Energy. - : Elsevier. - 2352-1791. ; 12, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- Future fusion reactors require a safe, steady state divertor operation. A possible solution for the power exhaust challenge is the detached divertor operation in scenarios with high radiated power fractions. The radiation can be increased by seeding impurities, such as N for dominant scrape-off-layer radiation, Ne or Ar for SOL and pedestal radiation and Kr for dominant core radiation. Recent experiments on two of the all-metal tokamaks, ASDEX Upgrade (AUG) and JET, demonstrate operation with high radiated power fractions and a fully-detached divertor by N, Ne or Kr seeding with a conventional divertor in a vertical target geometry. For both devices similar observations can be made. In the scenarios with the highest radiated power fraction, the dominant radiation originates from the confined region, in the case of N and Ne seeding concentrated in a region close to the X-point. Applying these seed impurities for highly radiative scenarios impacts local plasma parameters and alters the impurity transport in the pedestal region. Thus, plasma confinement and stability can be affected. A proper understanding of the effects by these impurities is required in order to predict the applicability of such scenarios for future devices.
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| 65. |
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| 66. |
- Biechele, Gloria, et al.
(författare)
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Associations between sex, body mass index and the individual microglial response in Alzheimer's disease
- 2024
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Ingår i: JOURNAL OF NEUROINFLAMMATION. - 1742-2094. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives18-kDa translocator protein position-emission-tomography (TSPO-PET) imaging emerged for in vivo assessment of neuroinflammation in Alzheimer's disease (AD) research. Sex and obesity effects on TSPO-PET binding have been reported for cognitively normal humans (CN), but such effects have not yet been systematically evaluated in patients with AD. Thus, we aimed to investigate the impact of sex and obesity on the relationship between beta-amyloid-accumulation and microglial activation in AD.Methods49 patients with AD (29 females, all A beta-positive) and 15 A beta-negative CN (8 female) underwent TSPO-PET ([18F]GE-180) and beta-amyloid-PET ([18F]flutemetamol) imaging. In 24 patients with AD (14 females), tau-PET ([18F]PI-2620) was additionally available. The brain was parcellated into 218 cortical regions and standardized-uptake-value-ratios (SUVr, cerebellar reference) were calculated. Per region and tracer, the regional increase of PET SUVr (z-score) was calculated for AD against CN. The regression derived linear effect of regional A beta-PET on TSPO-PET was used to determine the A beta-plaque-dependent microglial response (slope) and the A beta-plaque-independent microglial response (intercept) at the individual patient level. All read-outs were compared between sexes and tested for a moderation effect of sex on associations with body mass index (BMI).ResultsIn AD, females showed higher mean cortical TSPO-PET z-scores (0.91 +/- 0.49; males 0.30 +/- 0.75; p = 0.002), while A beta-PET z-scores were similar. The A beta-plaque-independent microglial response was stronger in females with AD (+ 0.37 +/- 0.38; males with AD - 0.33 +/- 0.87; p = 0.006), pronounced at the prodromal stage. On the contrary, the A beta-plaque-dependent microglial response was not different between sexes. The A beta-plaque-independent microglial response was significantly associated with tau-PET in females (Braak-II regions: r = 0.757, p = 0.003), but not in males. BMI and the A beta-plaque-independent microglial response were significantly associated in females (r = 0.44, p = 0.018) but not in males (BMI*sex interaction: F(3,52) = 3.077, p = 0.005).ConclusionWhile microglia response to fibrillar A beta is similar between sexes, women with AD show a stronger A beta-plaque-independent microglia response. This sex difference in A beta-independent microglial activation may be associated with tau accumulation. BMI is positively associated with the A beta-plaque-independent microglia response in females with AD but not in males, indicating that sex and obesity need to be considered when studying neuroinflammation in AD.
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| 67. |
- Bisoffi, Andrea, et al.
(författare)
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Hybrid cancellation of ripple disturbances arising in AC/DC converters
- 2017
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Ingår i: Automatica. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0005-1098 .- 1873-2836. ; 77, s. 344-352
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Tidskriftsartikel (refereegranskat)abstract
- In AC/DC converters, a peculiar periodic nonsmooth waveform arises, the so-called ripple. In this paper we propose a novel model that captures this nonsmoothness by means of a hybrid dynamical system performing state jumps at certain switching instants, and we illustrate its properties with reference to a three phase diode bridge rectifier. As the ripple corrupts an underlying desirable signal, we propound two observer schemes ensuring asymptotic estimation of the ripple, the first with and the second without knowledge of the switching instants. Our theoretical developments are well placed in the context of recent techniques for hybrid regulation and constitute a contribution especially for our second observer, where the switching instants are estimated. Once asymptotic estimation of the ripple is achieved, the ripple can be conveniently canceled from the desirable signal, and thanks to the inherent robustness properties of the proposed hybrid formulation, the two observer schemes require only that the desirable signal is slowly time varying compared to the ripple. Exploiting this fact, we illustrate the effectiveness of our second hybrid observation law on experimental data collected from the Joint European Torus tokamak.
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| 68. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 69. |
- Bolshakova, I., et al.
(författare)
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Experimental evaluation of stable long term operation of semiconductor magnetic sensors at ITER relevant environment
- 2015
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 55:8
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Tidskriftsartikel (refereegranskat)abstract
- The paper deals with radiation resistant sensors and their associated measuring instrumentation developed in the course of R and D activities carried out in the framework of an international collaboration. The first trial tests of three-dimensional (3D) probes with Hall sensors have been performed in European tokamaks TORE SUPRA (2004) and JET (2005). Later in 2009 six sets of 3D probes were installed in JET and now continue to operate. The statistical analysis performed in 2014 on the basis of the JET database have demonstrated stable long term operation of all 18 sensors of 3D probes. The results of measurements conducted at the neutron fluxes of nuclear reactors have demonstrated the operability of the sensors up to high neutron fluences of F > 10(18)n , cm(-2) that exceeds the maximum one for the locations of steady state sensors in ITER over its total lifetime.
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| 70. |
- Boltruczyk, G., et al.
(författare)
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Development of MPPC-based detectors for high count rate DT campaigns at JET
- 2017
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Ingår i: Fusion engineering and design. - : ELSEVIER SCIENCE SA. - 0920-3796 .- 1873-7196. ; 123, s. 940-944
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Tidskriftsartikel (refereegranskat)abstract
- The products of fusion reactions at JET are measured using different diagnostic techniques. One of the methods is based on measurements of gamma-rays, originating from reactions between fast ions and plasma impurities. During the forthcoming deuterium-tritium (DT) campaign a particular attention will be paid to 4.44 MeV gamma-rays emitted in the Be-9(alpha,n gamma)C-12 reaction. Gamma-ray detectors foreseen for measurements in DT campaigns have to be able to register spectra at high count rates, up to approximately 500 kHz. For the Gamma-ray Camera at JET a new setup will be based on scintillators with a short decay time, e.g., CeBr3, and a multi-pixel photon counter (MPPC). We present two methods of output signal shortening in modules based on MPPC. A short detector output signal is necessary in order to minimize the number of pile up events at high count rates. One method uses a passive RC circuit with a pole zero cancellation, whereas an active transimpedance amplifier is used in the other one. Due to the strong dependence of MPPC properties on temperature variation, a special device MTCD@NCBJ was designed and produced to stabilize the gain in MPPC-based scintillation detectors. We show that this device guarantees stable working conditions.
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