| 1. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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| 2. |
- Illana, A., et al.
(författare)
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Coulomb excitation of 74,76Zn
- 2023
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Ingår i: Physical Review C. - 2469-9985. ; 108:4
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Tidskriftsartikel (refereegranskat)abstract
- The first experiment using radioactive beams post-accelerated by the HIE-ISOLDE facility has enabled to obtain a precise set of B(E2) transition probabilities in neutron-rich 74,76Zn isotopes. The resulting B(E2; 2+1→0+1) values are consistent with those determined in earlier REX-ISOLDE measurements. While the B(E2; 4+1→2+1) transition probability in 76Zn is also in agreement with earlier Coulomb-excitation results, the value obtained for 74Zn is considerably lower. For the first time, a spectroscopic quadrupole moment of the 2+1 state was measured for an exotic nucleus in this mass region. A detailed comparison is presented with large-scale shell-model and Monte Carlo shell-model calculations.
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| 3. |
- Jentschel, M., et al.
(författare)
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EXILL - a high-efficiency, high-resolution setup for gamma-spectroscopy at an intense cold neutron beam facility
- 2017
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- In the EXILL campaign a highly efficient array of high purity germanium (HPGe) detectors was operated at the cold neutron beam facility PF1B of the Institut Laue-Langevin (ILL) to carry out nuclear structure studies, via measurements of gamma-rays following neutron-induced capture and fission reactions. The setup consisted of a collimation system producing a pencil beam with a thermal capture equivalent flux of about 10(8) ns(-1)cm(2) at the target position and negligible neutron halo. The targetwas surrounded by an array of eight to ten anti-Compton shielded EXOGAMClover detectors, four to six anti-Compton shielded large coaxial GASP detectors and two standard Clover detectors. For a part of the campaign the array was combined with 16 LaBr3:(Ce) detectors from the FATIMA collaboration. The detectorswere arranged in an array of rhombicuboctahedron geometry, providing the possibility to carry out very precise angular correlation and directional-polarization correlation measurements. The triggerless acquisition system allowed a signal collection rate of up to 6 x 10(5) Hz. The data allowed to set multi-fold coincidences to obtain decay schemes and in combination with the FATIMA array of LaBr3:(Ce) detectors to analyze half-lives of excited levels in the pico-to microsecond range. Precise energy and efficiency calibrations of EXILL were performed using standard calibration sources of Ba-133, Co-60 and Eu-152 as well as data from the reactions Al-27(n, gamma)Al-28 and Cl-35(n,gamma)Cl-36 in the energy range from 30 keV up to 10MeV.
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| 4. |
- Goldkuhle, A., et al.
(författare)
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Lifetime measurements in Ti-52,Ti-54 to study shell evolution toward N=32
- 2019
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 100:5
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Tidskriftsartikel (refereegranskat)abstract
- Lifetimes of the excited states in the neutron-rich Ti-52,Ti-54 nuclei, produced in a multinucleon-transfer reaction, were measured by employing the Cologne plunger device and the recoil-distance Doppler-shift method. The experiment was performed at the Grand Accelerateur National d'Ions Lourds facility by using the Advanced Gamma Tracking Array for the gamma-ray detection, coupled to the large-acceptance variable mode spectrometer for an event-by-event particle identification. A comparison between the transition probabilities obtained from the measured lifetimes of the 2(1)(+) to 8(1)(+) yrast states in Ti-52,Ti-54 and that from the shell-model calculations based on the well-established GXPF1A, GXPF1B, and KB3G fp shell interactions support the N = 32 subshell closure. The B(E2) values for Ti-52 determined in this work are in disagreement with the known data, but are consistent with the predictions of the shell-model calculations and reduce the previously observed pronounced staggering across the even-even titanium isotopes.
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| 5. |
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| 6. |
- Butler, P. A., et al.
(författare)
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Evolution of Octupole Deformation in Radium Nuclei from Coulomb Excitation of Radioactive ^{222}Ra and ^{228}Ra Beams
- 2020
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Ingår i: Physical Review Letters. - 1079-7114. ; 124:4
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Tidskriftsartikel (refereegranskat)abstract
- There is sparse direct experimental evidence that atomic nuclei can exhibit stable "pear" shapes arising from strong octupole correlations. In order to investigate the nature of octupole collectivity in radium isotopes, electric octupole (E3) matrix elements have been determined for transitions in ^{222,228}Ra nuclei using the method of sub-barrier, multistep Coulomb excitation. Beams of the radioactive radium isotopes were provided by the HIE-ISOLDE facility at CERN. The observed pattern of E3 matrix elements for different nuclear transitions is explained by describing ^{222}Ra as pear shaped with stable octupole deformation, while ^{228}Ra behaves like an octupole vibrator.
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| 7. |
- Butler, P. A., et al.
(författare)
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The observation of vibrating pear-shapes in radon nuclei
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, which would indicate CP violation and hence probe physics beyond the Standard Model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we observed the low-lying quantum states in 224Rn and 226Rn by accelerating beams of these radioactive nuclei. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.
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| 8. |
- Gjestvang, D., et al.
(författare)
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Examination of how properties of a fissioning system impact isomeric yield ratios of the fragments
- 2023
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 108:6
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Tidskriftsartikel (refereegranskat)abstract
- The population of isomeric states in the prompt decay of fission fragments-so-called isomeric yield ratios (IYRs)-is known to be sensitive to the angular momentum J that the fragment emerged with, and may therefore contain valuable information on the mechanism behind the fission process. In this work, we investigate how changes in the fissioning system impact the measured IYRs of fission fragments to learn more about what parameters affect angular momentum generation. To enable this, a new technique for measuring IYRs is first demonstrated. It is based on the time of arrival of discrete gamma rays, and has the advantage that it enables the study of the IYR as a function of properties of the partner nucleus. This technique is used to extract the IYR of 134Te, strongly populated in actinide fission, from the three different fissioning systems: 232Th(n, f), 238U(n, f), at two different neutron energies, as well as 252Cf(sf). The impacts of changing the fissioning system, the compound nuclear excitation energy, the minimum J of the binary partner, and the number of neutrons emitted on the IYR of 134Te are determined. The decay code TALYS is used in combination with the fission simulation code FREYA to calculate the primary fragment angular momentum from the IYR. We find that the IYR of 134Te has a slope of 0.004 +/- 0.002 with increase in compound nucleus (CN) mass. When investigating the impact on the IYR of increased CN excitation energy, we find no change with an energy increase similar to the difference between thermal and fast fission. By varying the mass of the partner fragment emerging with 134Te, it is revealed that the IYR of 134Te is independent of the total amount of prompt neutrons emitted from the fragment pair. This indicates that neutrons carry minimal angular momentum away from the fission fragments. Comparisons with the FREYA+TALYS simulations reveal that the average angular momentum in 134Te following 238U(n, f) is 6.0 h over bar . This is not consistent with the value deduced from recent CGMF calculations. Finally, the IYR sensitivity to the angular momentum of the primary fragment is discussed. These results are not only important to help understanding the underlying mechanism in nuclear fission, but can also be used to constrain and benchmark fission models, and are relevant to the gamma -ray heating problem of reactors.
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| 9. |
- Spagnoletti, P., et al.
(författare)
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Coulomb excitation of Rn 222
- 2022
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Ingår i: Physical Review C. - 2469-9985. ; 105:2
-
Tidskriftsartikel (refereegranskat)abstract
- The nature of quadrupole and octupole collectivity in Rn222 was investigated by determining the electric-quadrupole (E2) and octupole (E3) matrix elements using subbarrier, multistep Coulomb excitation. The radioactive Rn222 beam, accelerated to 4.23 MeV/u, was provided by the HIE-ISOLDE facility at CERN. Data were collected in the Miniball γ-ray spectrometer following the bombardment of two targets, Sn120 and Ni60. Transition E2 matrix elements within the ground-state and octupole bands were measured up to 10ℏ and the results were consistent with a constant intrinsic electric-quadrupole moment, 518(11)efm2. The values of the intrinsic electric-octupole moment for the 0+→3- and 2+→5- transitions were found to be respectively 2360-210+300efm3 and 2300-500+300efm3 while a smaller value, 1200-900+500efm3, was found for the 2+→1- transition. In addition, four excited non-yrast states were identified in this work via γ-γ coincidences.
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| 10. |
- Rosiak, D., et al.
(författare)
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Enhanced Quadrupole and Octupole Strength in Doubly Magic Sn 132
- 2018
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Ingår i: Physical Review Letters. - 0031-9007. ; 121:25
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Tidskriftsartikel (refereegranskat)abstract
- The first 2+ and 3- states of the doubly magic nucleus Sn132 are populated via safe Coulomb excitation employing the recently commissioned HIE-ISOLDE accelerator at CERN in conjunction with the highly efficient MINIBALL array. The Sn132 ions are accelerated to an energy of 5.49 MeV/nucleon and impinged on a Pb206 target. Deexciting γ rays from the low-lying excited states of the target and the projectile are recorded in coincidence with scattered particles. The reduced transition strengths are determined for the transitions 0g.s.+→21+, 0g.s.+→31-, and 21+→31- in Sn132. The results on these states provide crucial information on cross-shell configurations which are determined within large-scale shell-model and Monte Carlo shell-model calculations as well as from random-phase approximation and relativistic random-phase approximation. The locally enhanced B(E2;0g.s.+→21+) strength is consistent with the microscopic description of the structure of the respective states within all theoretical approaches. The presented results of experiment and theory can be considered to be the first direct verification of the sphericity and double magicity of Sn132.
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| 11. |
- Henrich, C., et al.
(författare)
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Coulomb excitation of 142Xe
- 2018
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Ingår i: Acta Physica Polonica B. - 0587-4254. ; 49:3, s. 529-533
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Tidskriftsartikel (refereegranskat)abstract
- The even-even nucleus 142Xe lies north-east of the doubly magic 132Sn on the neutron-rich side of the nuclear chart. In order to gain further information on the octupole collectivity and the evolution of quadrupole collectivity in this region, a "safe" Coulomb excitation experiment was carried out at the new HIE-ISOLDE facility (CERN) at the end of 2016. As the gamma-ray detector the Miniball spectrometer was used. Beam and target nuclei were detected using C-REX, i.e. an array of segmented Si detectors, covering forward as well as backward angles in the laboratory frame.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Becker, J., et al.
(författare)
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High speed cameras for X-rays : AGIPD and others
- 2013
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 8:1, s. Art. no. C01042-
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Tidskriftsartikel (refereegranskat)abstract
- Experiments at high pulse rate Free Electron Laser (FEL) facilities require new cameras capable of acquiring 2D images at high rates, handling large signal dynamic ranges and resolving images from individual pulses. The Adaptive Gain Integrated Pixel Detector (AGIPD) will operated with pulse rates and separations of 27000/s and 220 ns, respectively at European XFEL. Si-sensors, ASICs, PCBs, and FPGA logic are developed for a 1 Mega-pixel camera with 200 μm square pixels with per-pulse occupancies 104. Data from 3520 images/s will be transferred with 80 Gbits/s to a DAQ-system. The electronics have been adapted for use in other synchrotron light source detectors.
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| 16. |
- Claeys, Shana, et al.
(författare)
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ALK positively regulates MYCN activity through repression of HBP1 expression
- 2019
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 38:15, s. 2690-2705
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Tidskriftsartikel (refereegranskat)abstract
- ALK mutations occur in 10% of primary neuroblastomas and represent a major target for precision treatment. In combination with MYCN amplification, ALK mutations infer an ultra-high-risk phenotype resulting in very poor patient prognosis. To open up opportunities for future precision drugging, a deeper understanding of the molecular consequences of constitutive ALK signaling and its relationship to MYCN activity in this aggressive pediatric tumor entity will be essential. We show that mutant ALK downregulates the ‘HMG-box transcription factor 1’ (HBP1) through the PI3K-AKT–FOXO3a signaling axis. HBP1 inhibits both the transcriptional activating and repressing activity of MYCN, the latter being mediated through PRC2 activity. HBP1 itself is under negative control of MYCN through miR-17~92. Combined targeting of HBP1 by PI3K antagonists and MYCN signaling by BET- or HDAC-inhibitors blocks MYCN activity and significantly reduces tumor growth, suggesting a novel targeted therapy option for high-risk neuroblastoma.
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| 17. |
- Dumke, Roger, et al.
(författare)
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Multi-center evaluation of one commercial and 12 in-house real-time PCR assays for detection of Mycoplasma pneumoniae
- 2017
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Ingår i: Diagnostic microbiology and infectious disease. - : ELSEVIER SCIENCE INC. - 0732-8893 .- 1879-0070. ; 88:2, s. 111-114
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Tidskriftsartikel (refereegranskat)abstract
- Detection of Mycoplasma pneumoniae by real-time PCR is not yet standardized across laboratories. We have implemented a standardization protocol to compare the performance of thirteen commercial and in-house approaches. Despite differences on threshold values of samples, all assays were able to detect at least 20 M. pneumoniae genomes per reaction.
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| 18. |
- Lee, V., et al.
(författare)
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Imaging high energy photons with PILATUS II at the tagged photon beam at MAX-lab
- 2009
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 603:3, s. 379-383
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Tidskriftsartikel (refereegranskat)abstract
- In photonuclear experiments precise location of the photon beam relative to the experimental sample is critical. Previously used techniques such as using photographic film to identify the position, intensity and centroid of the beam is time-consuming and a faster method is required. PILATUS is a single-photon-counting pixel detector developed at the Paul Scherrer Institute (PSI), Switzerland. It is a silicon-based, two-dimensional detector with a large dynamic range and zero readout noise. Designed as an X-ray detector, its optimal quantum efficiency is between 3 and 30 keV. This paper reports measurements carried out at the MAX-lab tagged photon facility in Lund, Sweden. The beam endpoint energy of approximately 200 MeV is far above the designed optimal energy detection range of PILATUS, and provides a critical test of the use of PILATUS under high energy conditions. The detector was placed in the photon beam and images were taken both downstream of other experiments, and in close range of a 19 mm collimator. The successful measurements demonstrate the versatility and robustness of the detector and provide an effective way of quickly and accurately monitoring beam position and profile in real time. (C) 2009 Elsevier B.V. All rights reserved.
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| 19. |
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| 20. |
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| 21. |
- Allahgholi, A., et al.
(författare)
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The adaptive gain integrating pixel detector
- 2016
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- The adaptive gain integrating pixel detector (AGIPD) is a development of a collaboration between Deustsches Elektronen-Synchrotron (DESY), the Paul-Scherrer-Institute (PSI), the University of Hamburg and the University of Bonn. The detector is designed to cope with the demanding challenges of the European XFEL. Therefore it comes along with an adaptive gain stage allowing a high dynamic range, spanning from single photon sensitivity to 10(4) x 12.4 keV photons and 352 analogue memory cells per pixel. The aim of this report is to briefly explain the concepts of the AGIPD electronics and mechanics and then present recent experiments demonstrating the functionality of its key features.
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| 22. |
- Becker, J., et al.
(författare)
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Architecture and design of the AGIPD detector for the European XFEL
- 2012
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Konferensbidrag (refereegranskat)abstract
- AGIPD is a hybrid pixel detector developed by DESY, PSI, the University of Bonn and the University of Hamburg. The detector is targeted for use at the European XFEL, a source with unique properties: a bunch train of 2700 pulses with > 1012 photons of 12 keV each, only 100 fs long and with a 220 ns spacing, is repeated at a 10Hz rate. This puts up very demanding requirements: dynamic range has to cover the detection of single photons and extend up to > 104 photons/pixel in the same image, and as many images, as possible have to be recorded in the pixel to be read out between pulse trains. The high photon flux impinging on the detector also calls for a very radiation hard design of sensor and ASIC. The detector will consist of 16 Sensor modules arranged around a central hole for the direct beam. Each made of a single sensor bump-bonded to 2 × 8 readout chips of 64 × 64 pixels in a grid of 200 μm pitch. Each pixel of these ASICs contains a charge sensitive preamplifier featuring adaptive gain switching, changing sensitivity in three ranges, and a buffer to provide correlated double sampling (in the highest sensitivity mode). Most of the pixel area, albeit, is used for an analogue memory to record 352 frames. It is operated in random-access mode: data containing bad frames can be overwritten and the memory can be used in the most efficient way. The readout between two bunch trains is arranged via 4 ports: Data from pixels of one row is read in parallel and serialised by 4 multiplexers at the end of the pixel columns and driven off-chip as differential signals. The operation of the ASIC is controlled via a three-line serial interface, using a command based protocol. It is also used to configure the chip's operational parameters and internal timings. © 2012 IEEE.
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| 23. |
- Bianco, L., et al.
(författare)
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The AGIPD System for the European XFEL
- 2013
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Ingår i: ADVANCES IN X-RAY FREE-ELECTRON LASERS II. - : SPIE. - 9780819495808 ; , s. Art. no. UNSP 87780V-
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Konferensbidrag (refereegranskat)abstract
- The European XFEL will generate extremely brilliant pulses of X-rays organized in pulse trains consisting of 2700 pulses <100 fs long, with >10(12) photons, and with a 220 ns spacing. The pulse trains are running at a 10Hz repetition rate. The detector to be used under these conditions will have to face several challenges: the dynamic range has to cover the detection of single photons and extend up to >10(4) photons/pixel/pulse in the same image, framing rates of 4.5 MHz (220 ns) are required in order to record one image per pulse, and as many images as possible have to be recorded during the pulse trains. Due to the high flux, the detector will have to withstand a dose up to 1GGy integrated over 3 years. To meet these challenges a consortium, consisting of Deutsches Elektronensynchrotron (DESY), Paul-Scherrer-Institut (PSI), University of Hamburg and University of Bonn, is developing the Adaptive Gain Integrating Pixel Detector (AGIPD). It is a hybrid-pixel detector, featuring a charge integrating amplifier with dynamic gain switching to cope with the extended dynamic range, and an analogue on-pixel memory for image storage at the required 4.5 MHz frame rate. The readout chip consists of 64x64 pixels of (200 mu m)(2), 8x2 of these readout chips are bump-bonded to a monolithic silicon sensor to form the basic module with 512 x 128 pixels. 4 of these modules are stacked to form a quadrant of the 1k x 1k detector system. Each quadrant is independently moveable in order to adjust a central hole, needed for the direct beam to pass through. Special designs are employed for both the sensor and the readout chip to withstand the integrated dose for 3 years.
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| 24. |
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| 25. |
- Peluso, Michael J, et al.
(författare)
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Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1.
- 2020
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Ingår i: Journal of virus eradication. - 2055-6640. ; 6:1, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess soluble CD30 (sCD30), a protein that colocalises with HIV-1 RNA and DNA in lymphoid cells and tissues, in cerebrospinal fluid (CSF) as a marker of HIV-1 infection in the central nervous system (CNS).This was a cross-sectional study using archived samples from two clinical cohorts. Soluble CD30 concentrations were measured in paired CSF and plasma from untreated viraemic individuals (n=52), individuals on suppressive antiretroviral therapy (ART) (n=33), HIV-1 controllers (n=10), participants with CSF HIV-1 'escape' (n=11) and controls without HIV-1 infection (n=16). Nonparametric tests were used to compare levels across groups and evaluate correlations with HIV-1 RNA, CSF neurofilament light chain protein (NFL) and neopterin.Compared with controls (median 30ng/mL, interquartile range [IRQ] 23-50), plasma sCD30 levels were elevated in viraemic participants (75ng/mL, 52-116; P<0.001), but not in those on suppressive ART (38ng/mL, 32-62). In contrast, CSF sCD30 levels were elevated in ART-suppressed individuals (34ng/mL, 19-46; P=0.001) and in those with CSF 'escape' (33ng/mL, 27-40; P=0.004) compared with controls (18ng/mL, 11-23), but not in untreated viraemic individuals. No association was observed between CSF sCD30 and plasma HIV-1 RNA, concurrent or nadir CD4+ T cell count, duration of infection or plasma sCD30. CSF sCD30 correlated with CSF NFL (r=0.34, P=0.001).In contrast to plasma, sCD30 levels are elevated in the CSF of individuals with HIV-1 infection who are on suppressive ART. Elevated levels of sCD30 in the CSF may be an indicator of persistent CNS HIV-1 infection, although the mechanism underlying this elevation warrants further investigation.
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| 26. |
- Rosilio, M, et al.
(författare)
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Long-term improvement of quality of life during growth hormone (GH) replacement therapy in adults with GH deficiency, as measured by questions on life satisfaction-hypopituitarism (QLS-H)
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 89:4, s. 1684-1693
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Tidskriftsartikel (refereegranskat)abstract
- Questions on Life Satisfaction-Hypopituitarism (QLS-H) is a new quality-of-life (QoL) questionnaire developed for adults with hypopituitarism. To determine the effects of long-term GH treatment on QoL, we evaluated QLS-H Z-scores in 576 adult patients with GH deficiency (GHD) enrolled in HypoCCS, an international observational study, using data from five countries in which comparative QLS-H data from the general population were available. Baseline QLS-H Z-scores were significantly lower in GH-deficient patients than in the general population of the same age, gender, and nationality. Z-scores were also significantly lower in female patients vs. males (P=0.006) and in adult-onset vs. childhood-onset GHD (P=0.002). Multivariate analysis associated female gender, multiple pituitary hormone deficiencies, low serum IGF-I values (<75 μg/liter), and concomitant antidepressant medication with low baseline Z-scores. QLS-H Z-scores increased from -1.02&PLUSMN;1.43 (SD) at baseline to -0.25&PLUSMN;1.34 (SD) after 1 yr of GH treatment (P<0.001) and were no longer significantly different from the general population after 4 yr of treatment. There was no correlation between change in Z-score and GH dose or changes in IGF-I and IGF binding protein-3 during treatment. This study demonstrates that 1) improvements in QoL, as measured by the QLS-H, are maintained during long-term GH replacement therapy of adults with GHD, and 2) the QLS-H is a useful tool for evaluating QoL in hypopituitary patients treated in clinical practice. The authors suggest that evaluation of QoL should be a part of the routine clinical management of adult GH-deficient patients, complementing the measurement of surrogate biological markers or other clinical end points.
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| 27. |
- Ruchkin, Vladislav, et al.
(författare)
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Violence exposure and psychopathology in urban youth : the mediating role of posttraumatic stress.
- 2007
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Ingår i: Journal of Abnormal Child Psychology. - : Springer Science and Business Media LLC. - 0091-0627 .- 1573-2835. ; 35:4, s. 578-93
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the mechanisms underlying the development of violence exposure sequelae is essential to providing effective treatments for traumatized youth. This longitudinal study examined the mediating role of posttraumatic stress in the relationship between violence exposure and psychopathology, and compared the mediated models by gender. Urban adolescents (n=1,358) were surveyed using the Social and Health Assessment. The proposed relationships were examined using Structural Equation Modeling. Posttraumatic stress fully mediated the relationships between victimization and depression and anxiety in girls, and partially so in boys. In addition, posttraumatic stress partially mediated the relationships between violence exposure and commission of violence in boys. Current findings support the longitudinal effects of violence exposure on adolescent mental health. Posttraumatic stress represents a unique mechanism for the development of psychopathology in girls and is also related to negative outcomes in boys. These findings have direct implications for prevention and rehabilitation efforts among violence exposed youth.
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| 28. |
- Sobek, Jens, et al.
(författare)
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Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, tau and alpha-synuclein
- 2024
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089.
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThere is an unmet need for compounds to detect fibrillar forms of alpha-synuclein (alpha Syn) and 4-repeat tau, which are critical in many neurodegenerative diseases. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based assay to facilitate the characterization of small molecules that can bind these fibrils.MethodsSPR measurements were conducted to characterize the binding properties of fluorescent ligands/compounds toward recombinant amyloid-beta (A beta)42, K18-tau, full-length 2N4R-tau and alpha Syn fibrils. In silico modeling was performed to examine the binding pockets of ligands on alpha Syn fibrils. Immunofluorescence staining of postmortem brain tissue slices from Parkinson's disease patients and mouse models was performed with fluorescence ligands and specific antibodies.ResultsWe optimized the protocol for the immobilization of A beta 42, K18-tau, full-length 2N4R-tau and alpha Syn fibrils in a controlled aggregation state on SPR-sensor chips and for assessing their binding to ligands. The SPR results from the analysis of binding kinetics suggested the presence of at least two binding sites for all fibrils, including luminescent conjugated oligothiophenes, benzothiazole derivatives, nonfluorescent methylene blue and lansoprazole. In silico modeling studies for alpha Syn (6H6B) revealed four binding sites with a preference for one site on the surface. Immunofluorescence staining validated the detection of pS129-alpha Syn positivity in the brains of Parkinson's disease patients and alpha Syn preformed-fibril injected mice, 6E10-positive A beta in arcA beta mice, and AT-8/AT-100-positivity in pR5 mice.ConclusionSPR measurements of small molecules binding to A beta 42, K18/full-length 2N4R-tau and alpha Syn fibrils suggested the existence of multiple binding sites. This approach may provide efficient characterization of compounds for neurodegenerative disease-relevant proteinopathies.
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| 29. |
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| 30. |
- Voigt, Ines, et al.
(författare)
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Holocene shifts of the southern westerlies across the South Atlantic
- 2015
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Ingår i: Paleoceanography. - 0883-8305 .- 1944-9186. ; 30:2, s. 39-51
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Tidskriftsartikel (refereegranskat)abstract
- The southern westerly winds (SWW) exert a crucial influence over the world ocean and climate. Nevertheless, a comprehensive understanding of the Holocene temporal and spatial evolution of the SWW remains a significant challenge due to the sparsity of high-resolution marine archives and appropriate SWW proxies. Here we present a north-south transect of high-resolution planktonic foraminiferal oxygen isotope records from the western South Atlantic. Our proxy records reveal Holocene migrations of the Brazil-Malvinas Confluence (BMC), a highly sensitive feature for changes in the position and strength of the northern portion of the SWW. Through the tight coupling of the BMC position to the large-scale wind field, the records allow a quantitative reconstruction of Holocene latitudinal displacements of the SWW across the South Atlantic. Our data reveal a gradual poleward movement of the SWW by about 1-1.5 degrees from the early to the mid-Holocene. Afterward, variability in the SWW is dominated by millennial scale displacements on the order of 1 degrees in latitude with no recognizable longer-term trend. These findings are confronted with results from a state-of-the-art transient Holocene climate simulation using a comprehensive coupled atmosphere-ocean general circulation model. Proxy-inferred and modeled SWW shifts compare qualitatively, but the model underestimates both orbitally forced multimillennial and internal millennial SWW variability by almost an order of magnitude. The underestimated natural variability implies a substantial uncertainty in model projections of future SWW shifts.
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