| 1. |
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| 2. |
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| 3. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 4. |
- Amole, C., et al.
(författare)
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Experimental and computational study of the injection of antiprotons into a positron plasma for antihydrogen production
- 2013
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 20:4, s. 043510-
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Tidskriftsartikel (refereegranskat)abstract
- One of the goals of synthesizing and trapping antihydrogen is to study the validity of charge-parity-time symmetry through precision spectroscopy on the anti-atoms, but the trapping yield achieved in recent experiments must be significantly improved before this can be realized. Antihydrogen atoms are commonly produced by mixing antiprotons and positrons stored in a nested Penning-Malmberg trap, which was achieved in ALPHA by an autoresonant excitation of the antiprotons, injecting them into the positron plasma. In this work, a hybrid numerical model is developed to simulate antiproton and positron dynamics during the mixing process. The simulation is benchmarked against other numerical and analytic models, as well as experimental measurements. The autoresonant injection scheme and an alternative scheme are compared numerically over a range of plasma parameters which can be reached in current and upcoming antihydrogen experiments, and the latter scheme is seen to offer significant improvement in trapping yield as the number of available antiprotons increases.
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| 5. |
- Amole, C., et al.
(författare)
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Resonant quantum transitions in trapped antihydrogen atoms
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 483:7390, s. 439-U86
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Tidskriftsartikel (refereegranskat)abstract
- The hydrogen atom is one of the most important and influential model systems in modern physics. Attempts to understand its spectrum are inextricably linked to the early history and development of quantum mechanics. The hydrogen atom's stature lies in its simplicity and in the accuracy with which its spectrum can be measured(1) and compared to theory. Today its spectrum remains a valuable tool for determining the values of fundamental constants and for challenging the limits of modern physics, including the validity of quantum electrodynamics and-by comparison with measurements on its antimatter counterpart, antihydrogen-the validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we report spectroscopy of a pure antimatter atom, demonstrating resonant quantum transitions in antihydrogen. We have manipulated the internal spin state(2,3) of antihydrogen atoms so as to induce magnetic resonance transitions between hyperfine levels of the positronic ground state. We used resonant microwave radiation to flip the spin of the positron in antihydrogen atoms that were magnetically trapped(4-6) in the ALPHA apparatus. The spin flip causes trapped anti-atoms to be ejected from the trap. We look for evidence of resonant interaction by comparing the survival rate of trapped atoms irradiated with microwaves on-resonance to that of atoms subjected to microwaves that are off-resonance. In one variant of the experiment, we detect 23 atoms that survive in 110 trapping attempts with microwaves off-resonance (0.21 per attempt), and only two atoms that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We also describe the direct detection of the annihilation of antihydrogen atoms ejected by the microwaves.
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| 6. |
- Amole, C., et al.
(författare)
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Silicon vertex detector upgrade in the ALPHA experiment
- 2013
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 732, s. 134-136
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Tidskriftsartikel (refereegranskat)abstract
- The Silicon Vertex Detector (SVD) is the main diagnostic tool in the ALPHA-experiment. It provides precise spatial and timing information of antiproton (antihydrogen) annihilation events (vertices), and most importantly, the SVD is capable of directly identifying and analysing single annihilation events, thereby forming the basis of ALPHA's analysis. This paper describes the ALPHA SVD and its upgrade, installed in the ALPHA's new neutral atom trap.
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| 7. |
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| 8. |
- Amole, C., et al.
(författare)
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An experimental limit on the charge of antihydrogen
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3955-
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Tidskriftsartikel (refereegranskat)abstract
- The properties of antihydrogen are expected to be identical to those of hydrogen, and any differences would constitute a profound challenge to the fundamental theories of physics. The most commonly discussed antiatom- based tests of these theories are searches for antihydrogen- hydrogen spectral differences (tests of CPT (charge- parity- time) invariance) or gravitational differences (tests of the weak equivalence principle). Here we, the ALPHA Collaboration, report a different and somewhat unusual test of CPT and of quantum anomaly cancellation. A retrospective analysis of the influence of electric fields on antihydrogen atoms released from the ALPHA trap finds a mean axial deflection of 4.1 +/- 3.4mm for an average axial electric field of 0.51Vmm1. Combined with extensive numerical modelling, this measurement leads to a bound on the charge Qe of antihydrogen of Q (+/- 1.3 +/- 1.1 +/- 0.4)10 8. Here, e is the unit charge, and the errors are from statistics and systematic effects.
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| 9. |
- Amole, C., et al.
(författare)
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Autoresonant-spectrometric determination of the residual gas composition in the ALPHA experiment apparatus
- 2013
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 84:6, s. 065110-
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of the residual gas composition in the ALPHA experiment apparatus is important in our studies of antihydrogen and nonneutral plasmas. A technique based on autoresonant ion extraction from an electrostatic potential well has been developed that enables the study of the vacuum in our trap. Computer simulations allow an interpretation of our measurements and provide the residual gas composition under operating conditions typical of those used in experiments to produce, trap, and study antihydrogen. The methods developed may also be applicable in a range of atomic and molecular trap experiments where Penning-Malmberg traps are used and where access is limited.
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| 10. |
- Amole, C., et al.
(författare)
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In situ electromagnetic field diagnostics with an electron plasma in a Penning-Malmberg trap
- 2014
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 16, s. 013037-
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate a novel detection method for the cyclotron resonance frequency of an electron plasma in a Penning-Malmberg trap. With this technique, the electron plasma is used as an in situ diagnostic tool for the measurement of the static magnetic field and the microwave electric field in the trap. The cyclotron motion of the electron plasma is excited by microwave radiation and the temperature change of the plasma is measured non-destructively by monitoring the plasma's quadrupole mode frequency. The spatially resolved microwave electric field strength can be inferred from the plasma temperature change and the magnetic field is found through the cyclotron resonance frequency. These measurements were used extensively in the recently reported demonstration of resonant quantum interactions with antihydrogen.
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| 11. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 12. |
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| 13. |
- Amole, C., et al.
(författare)
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The ALPHA antihydrogen trapping apparatus
- 2014
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 735, s. 319-340
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Tidskriftsartikel (refereegranskat)abstract
- The ALPHA collaboration, based at CERN, has recently succeeded in confining cold antihydrogen atoms in a magnetic minimum neutral atom trap and has performed the first study of a resonant transition of the anti-atoms. The ALPHA apparatus will be described herein, with emphasis on the structural aspects, diagnostic methods and techniques that have enabled antihydrogen trapping and experimentation to be achieved.
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| 14. |
- Andresen, G. B., et al.
(författare)
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Search for trapped antihydrogen
- 2011
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 695:1-4, s. 95-104
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of an experiment to search for trapped antihydrogen atoms with the ALPHA antihydrogen trap at the CERN Antiproton Decelerator. Sensitive diagnostics of the temperatures, sizes, and densities of the trapped antiproton and positron plasmas have been developed, which in turn permitted development of techniques to precisely and reproducibly control the initial experimental parameters. The use of a position-sensitive annihilation vertex detector, together with the capability of controllably quenching the superconducting magnetic minimum trap, enabled us to carry out a high-sensitivity and low-background search for trapped synthesised antihydrogen atoms. We aim to identify the annihilations of antihydrogen atoms held for at least 130 ms in the trap before being released over ~30 ms. After a three-week experimental run in 2009 involving mixing of 107 antiprotons with 1.3ￜ109 positrons to produce 6ￜ105 antihydrogen atoms, we have identified six antiproton annihilation events that are consistent with the release of trapped antihydrogen. The cosmic ray background, estimated to contribute 0.14 counts, is incompatible with this observation at a significance of 5.6 sigma. Extensive simulations predict that an alternative source of annihilations, the escape of mirror-trapped antiprotons, is highly unlikely, though this possibility has not yet been ruled out experimentally.
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| 15. |
- Charlton, M, et al.
(författare)
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Antiparticle sources for antihydrogen production and trapping
- 2011
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596. ; 262, s. 012001-
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Tidskriftsartikel (refereegranskat)abstract
- Sources of positrons and antiprotons that are currently used for the formation of antihydrogen with low kinetic energies are reviewed, mostly in the context of the ALPHA collaboration and its predecessor ATHENA. The experiments were undertaken at the Antiproton Decelerator facility, which is located at CERN. Operations performed on the clouds of antiparticles to facilitate their mixing to produce antihydrogen are described. These include accumulation, cooling and manipulation. The formation of antihydrogen and some of the characteristics of the anti-atoms that are created are discussed. Prospects for trapping antihydrogen in a magnetic minimum trap, as envisaged by the ALPHA collaboration, are reviewed.
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| 16. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 17. |
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| 18. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 19. |
- Madsen, N, et al.
(författare)
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Search for trapped antihydrogen in ALPHA
- 2011
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Ingår i: Canadian journal of physics (Print). - 0008-4204 .- 1208-6045. ; 89:1, s. 7-16
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Tidskriftsartikel (refereegranskat)abstract
- Antihydrogen spectroscopy promises precise tests of the symmetry of matter and antimatter, and can possibly offer new insights into the baryon asymmetry of the universe. Antihydrogen is, however, difficult to synthesize and is produced only in small quantities. The ALPHA collaboration is therefore pursuing a path towards trapping cold antihydrogen to permit the use of precision atomic physics tools to carry out comparisons of antihydrogen and hydrogen. ALPHA has addressed these challenges. Control of the plasma sizes has helped to lower the influence of the multipole field used in the neutral atom trap, and thus lowered the temperature of the created atoms. Finally, the first systematic attempt to identify trapped antihydrogen in our system is discussed. This discussion includes special techniques for fast release of the trapped anti-atoms, as well as a silicon vertex detector to identify antiproton annihilations. The silicon detector reduces the background of annihilations, including background from antiprotons that can be mirror trapped in the fields of the neutral atom trap. A description of how to differentiate between these events and those resulting from trapped antihydrogen atoms is also included.
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| 20. |
- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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| 21. |
- Van Der Werf, D. P., et al.
(författare)
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Antimatter transport processes
- 2010
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Ingår i: AAPS Journal. - : IOP Publishing. - 1550-7416. ; 257:1
-
Tidskriftsartikel (refereegranskat)abstract
- A comparison of the 1S-2S transitions of hydrogen and antihydrogen will yield a stringent test of CPT conservation. Necessarily, the antihydrogen atoms need to be trapped to perform high precision spectroscopy measurements. Therefore, an approximately 0.75 T deep neutral atom trap, equivalent to about 0.5 K for ground state (anti)hydrogen atoms, has been superimposed on a Penning-Malmberg trap in which the anti-atoms are formed. The antihydrogen atoms are produced following a number of steps. A bunch of antiprotons from the CERN Antiproton Decelerator is caught in a Penning-Malmberg trap and subsequently sympathetically cooled and then compressed using rotating wall electric fields. A positron plasma, formed in a separate accumulator, is transported to the main system and also compressed. Antihydrogen atoms are then formed by mixing the antiprotons and positrons. The velocity of the anti-atoms, and their binding energies, will strongly depend on the initial conditions of the constituent particles, for example their temperatures and densities, and on the details of the mixing process. In this paper the complete lifecycle of antihydrogen atoms will be presented, starting with the production of the constituent antiparticles and the description of the manipulations necessary to prepare them appropriately for antihydrogen formation. The latter will also be described, as will the possible fates of the anti-atoms.
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| 22. |
- Amole, C., et al.
(författare)
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Discriminating between antihydrogen and mirror-trapped antiprotons in a minimum-B trap
- 2012
-
Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 14, s. 015010-
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Tidskriftsartikel (refereegranskat)abstract
- Recently, antihydrogen atoms were trapped at CERN in a magnetic minimum (minimum-B) trap formed by superconducting octupole and mirror magnet coils. The trapped antiatoms were detected by rapidly turning off these magnets, thereby eliminating the magnetic minimum and releasing any antiatoms contained in the trap. Once released, these antiatoms quickly hit the trap wall, whereupon the positrons and antiprotons in the antiatoms annihilate. The antiproton annihilations produce easily detected signals; we used these signals to prove that we trapped antihydrogen. However, our technique could be confounded by mirror-trapped antiprotons, which would produce seemingly identical annihilation signals upon hitting the trap wall. In this paper, we discuss possible sources of mirror-trapped antiprotons and show that antihydrogen and antiprotons can be readily distinguished, often with the aid of applied electric fields, by analyzing the annihilation locations and times. We further discuss the general properties of antiproton and antihydrogen trajectories in this magnetic geometry, and reconstruct the antihydrogen energy distribution from the measured annihilation time history.
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| 23. |
- Andresen, G. B., et al.
(författare)
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Confinement of antihydrogen for 1,000 seconds
- 2011
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Ingår i: Nature Physics. - 1745-2473 .- 1745-2481. ; 7:7, s. 558-564
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Tidskriftsartikel (refereegranskat)abstract
- Atoms made of a particle and an antiparticle are unstable, usually surviving less than a microsecond. Antihydrogen, made entirely of antiparticles, is believed to be stable, and it is this longevity that holds the promise of precision studies of matter-antimatter symmetry. We have recently demonstrated trapping of antihydrogen atoms by releasing them after a confinement time of 172 ms. A critical question for future studies is: how long can anti-atoms be trapped? Here, we report the observation of anti-atom confinement for 1,000 s, extending our earlier results by nearly four orders of magnitude. Our calculations indicate that most of the trapped anti-atoms reach the ground state. Further, we report the first measurement of the energy distribution of trapped antihydrogen, which, coupled with detailed comparisons with simulations, provides a key tool for the systematic investigation of trapping dynamics. These advances open up a range of experimental possibilities, including precision studies of charge-parity-time reversal symmetry and cooling to temperatures where gravitational effects could become apparent.
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| 24. |
- Andresen, G. B., et al.
(författare)
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Antihydrogen annihilation reconstruction with the ALPHA silicon detector
- 2012
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 684, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- The ALPHA experiment has succeeded in trapping antihydrogen, a major milestone on the road to spectroscopic comparisons of antihydrogen with hydrogen. An annihilation vertex detector, which determines the time and position of antiproton annihilations, has been central to this achievement. This detector, an array of double-sided silicon microstrip detector modules arranged in three concentric cylindrical tiers, is sensitive to the passage of charged particles resulting from antiproton annihilation. This article describes the method used to reconstruct the annihilation location and to distinguish the annihilation signal from the cosmic ray background. Recent experimental results using this detector are outlined.
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| 25. |
- Andresen, G. B., et al.
(författare)
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Autoresonant Excitation of Antiproton Plasmas
- 2011
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 106:2, s. 025002-
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate controllable excitation of the center-of-mass longitudinal motion of a thermal antiproton plasma using a swept-frequency autoresonant drive. When the plasma is cold, dense, and highly collective in nature, we observe that the entire system behaves as a single-particle nonlinear oscillator, as predicted by a recent theory. In contrast, only a fraction of the antiprotons in a warm plasma can be similarly excited. Antihydrogen was produced and trapped by using this technique to drive antiprotons into a positron plasma, thereby initiating atomic recombination
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| 26. |
- Andresen, G. B., et al.
(författare)
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Evaporative Cooling of Antiprotons to Cryogenic Temperatures
- 2010
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 105:1, s. 013003-
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Tidskriftsartikel (refereegranskat)abstract
- We report the application of evaporative cooling to clouds of trapped antiprotons, resulting in plasmas with measured temperature as low as 9 K. We have modeled the evaporation process for charged particles using appropriate rate equations. Good agreement between experiment and theory is observed, permitting prediction of cooling efficiency in future experiments. The technique opens up new possibilities for cooling of trapped ions and is of particular interest in antiproton physics, where a precise CPT test on trapped antihydrogen is a long-standing goal.
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| 27. |
- Andresen, G. B., et al.
(författare)
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The ALPHA-detector : Module Production and Assembly
- 2012
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 7, s. C01051-
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Tidskriftsartikel (refereegranskat)abstract
- ALPHA is one of the experiments situated at CERN's Antiproton Decelerator (AD). A Silicon Vertex Detector (SVD) is placed to surround the ALPHA atom trap. The main purpose of the SVD is to detect and locate antiproton annihilation events by means of the emitted charged pions. The SVD system is presented with special focus given to the design, fabrication and performance of the modules.
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| 28. |
- Andresen, G. B., et al.
(författare)
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Trapped antihydrogen
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 468:7324, s. 673-676
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Tidskriftsartikel (refereegranskat)abstract
- Antimatter was first predicted1 in 1931, by Dirac. Work with high-energy antiparticles is now commonplace, and anti-electrons are used regularly in the medical technique of positron emission tomography scanning. Antihydrogen, the bound state of an antiproton and a positron, has been produced2, 3 at low energies at CERN (the European Organization for Nuclear Research) since 2002. Antihydrogen is of interest for use in a precision test of nature’s fundamental symmetries. The charge conjugation/parity/time reversal (CPT) theorem, a crucial part of the foundation of the standard model of elementary particles and interactions, demands that hydrogen and antihydrogen have the same spectrum. Given the current experimental precision of measurements on the hydrogen atom (about two parts in 1014 for the frequency of the 1s-to-2s transition4), subjecting antihydrogen to rigorous spectroscopic examination would constitute a compelling, model-independent test of CPT. Antihydrogen could also be used to study the gravitational behaviour of antimatter5. However, so far experiments have produced antihydrogen that is not confined, precluding detailed study of its structure. Here we demonstrate trapping of antihydrogen atoms. From the interaction of about 107 antiprotons and 7 × 108 positrons, we observed 38 annihilation events consistent with the controlled release of trapped antihydrogen from our magnetic trap; the measured background is 1.4 ± 1.4 events. This result opens the door to precision measurements on anti-atoms, which can soon be subjected to the same techniques as developed for hydrogen.
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| 29. |
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| 30. |
- Butler, E., et al.
(författare)
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Towards antihydrogen trapping and spectroscopy at ALPHA
- 2011
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Ingår i: Hyperfine Interactions. - : Springer Science and Business Media LLC. - 0304-3843 .- 1572-9540. ; 199:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Spectroscopy of antihydrogen has the potential to yield high-precision tests of the CPT theorem and shed light on the matter-antimatter imbalance in the Universe. The ALPHA antihydrogen trap at CERN’s Antiproton Decelerator aims to prepare a sample of antihydrogen atoms confined in an octupole-based Ioffe trap and to measure the frequency of several atomic transitions. We describe our techniques to directly measure the antiproton temperature and a new technique to cool them to below 10 K. We also show how our unique position-sensitive annihilation detector provides us with a highly sensitive method of identifying antiproton annihilations and effectively rejecting the cosmic-ray background.
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| 31. |
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| 32. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 33. |
- Kleinberger, G., et al.
(författare)
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TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:243
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to Nasu-Hakola disease, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and FTD-like syndrome without bone involvement. TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis. Whether and how TREM2 missense mutations affect TREM2 function is unclear. We report that missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells. As a consequence of reduced shedding, TREM2 is virtually absent in the cerebrospinal fluid (CSF) and plasma of a patient with FTD-like syndrome. A decrease in soluble TREM2 was also observed in the CSF of patients with AD and FTD, further suggesting that reduced TREM2 function may contribute to increased risk for two neurodegenerative disorders.
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| 34. |
- Majounie, Elisa, et al.
(författare)
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Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study
- 2012
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Ingår i: Lancet Neurology. - 1474-4465. ; 11:4, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- Background We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion. Findings In patients with sporadic ALS, we identified the repeat expansion in 236 (7.0%) of 3377 white individuals from the USA, Europe, and Australia, two (4.1%) of 49 black individuals from the USA, and six (8.3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39.3%) of 552 white individuals with familial MS from Europe and the USA. 59 (6.0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24.8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic MS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years. Interpretation A common Mendelian genetic lesion in C9472 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases.
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| 35. |
- Messe, O. M. D. M., et al.
(författare)
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Characterization of Plastic Deformation Induced by Shot-Peening in a Ni-Base Superalloy
- 2014
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Ingår i: JOM. - : Springer Verlag (Germany). - 1047-4838 .- 1543-1851. ; 66:12, s. 2502-2515
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Tidskriftsartikel (refereegranskat)abstract
- The shot-peening process is currently employed in most industries to improve the longevity of components by inhibiting crack initiation as well as crack growth at the surface. The protective effect of shot peening has been mainly attributed to compressive stresses within the deformed layer. Intensive research has been carried out to quantify the near-surface residual stresses on entry into service and evolution throughout life. In nickel-base superalloys, the focus of research on the effects of shot-peening has performed using x-rays from either laboratory or synchrotron-based sources. However, this approach cannot evaluate in detail the deformation mechanisms nor the role of the gamma precipitates in a nickel-base superalloy; the latter is responsible for its unique properties. Our study uses a complementary range of techniques to investigate in detail the microstructure and deformation mechanisms associated with shot-peening in a coarse-grained nickel-based superalloy strengthened with coherent gamma precipitates. These include scanning electron microscopy and transmission electron microscopy, nanoindentation and micropillar compression. Accurate mapping of the dislocation structure produced throughout the deformed layers have been performed. Using an unconventional specimen preparation technique, it provides the basis for a more complete interpretation of how shot-peening inhibits fatigue cracking.
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| 36. |
- Ofer, O., et al.
(författare)
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Absolute value and temperature dependence of the magnetic penetration depth in Ba(Co 0.074Fe 0.926) 2As 2
- 2012
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 85:6, s. 060506-
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Tidskriftsartikel (refereegranskat)abstract
- The absolute value and temperature dependence of the in-plane magnetic penetration depth lambda have been measured on a single crystal of Ba(Co0.074Fe0.926)(2)As-2 using low-energy muon-spin rotation and microwave cavity perturbation. The magnetic field profiles in the Meissner state are consistent with a local London model beyond a depth of 15 nm. We determine the gap symmetry through measurements of the temperature dependence of the superfluid density which follows a two-gap s-wave model over the entire temperature range below T-c. While the intermediate to high temperature data is well fit by an energy gap model in the BCS-like (weak-coupling) limit, a second smaller gap becomes apparent at low temperatures.
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| 37. |
- Vimaleswaran, Karani S, et al.
(författare)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Tidskriftsartikel (refereegranskat)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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| 38. |
- Andréll, Paulin, 1978, et al.
(författare)
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Long-term effects of spinal cord stimulation on angina symptoms and quality of life in patients with refractory angina pectoris--results from the European Angina Registry Link Study (EARL)
- 2010
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Ingår i: Heart. - 1355-6037. ; 96:14, s. 1132-1136
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the long-term effect of spinal cord stimulation (SCS) on angina symptoms and quality of life in patients with refractory angina pectoris defined as severe angina due to coronary artery disease resistant to conventional pharmacological therapy and/or revascularisation. METHODS: During 2003-2005, all patients with refractory angina referred for SCS treatment at 10 European centres were consecutively included in the European registry for refractory angina (European Angina Registry Link, EARL), a prospective, 3-year follow-up study. In the present study, the SCS-treated patients were followed-up regarding angina symptoms and quality of life assessed was with a generic (Short Form 36, SF-36) and a disease-specific (Seattle Angina Questionnaire, SAQ) quality of life questionnaire. RESULTS: In total, 235 patients were included in the study. After screening, 121 patients were implanted and followed up 12.1 months after implantation. The implanted patients reported fewer angina attacks (p<0.0001), reduced short-acting nitrate consumption (p<0.0001) and improved Canadian Cardiovascular Society class (p<0.0001). Furthermore, quality of life was significantly improved in all dimensions of the SF-36 and the SAQ. Seven (5.8%) of the implanted patients died within 1 year of follow up. CONCLUSIONS: SCS treatment is associated with symptom relief and improved quality of life in patients with refractory angina pectoris suffering from severe coronary artery disease.
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| 39. |
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| 40. |
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| 41. |
- Cruchley, S., et al.
(författare)
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Cautionary note on use of focused ion beam sectioning as technique for characterising oxidation damage in Ni based superalloys
- 2014
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Ingår i: Materials at High Temperature. - : Science Reviews 2000 Ltd.. - 0960-3409 .- 1878-6413. ; 31:1, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Previous observations on Ni based superalloys, obtained through the use of focused ion beam (FIB) sample preparation and imaging, have reported the presence of subsurface voids after oxidation. In this present study, oxidised specimens of the Ni based superalloy, RR1000, were subjected to conventional sample preparation as well as both dual and single beam FIB preparation, with the aim of re-examining the previous observations of subsurface void formation. It is clear from FIB preparations that features previously interpreted as networks of voids have been demonstrated to be internal oxides by varying the sample tilt angles and imaging signal using either secondary electrons (SEs) or secondary ions (SIs). Conventional preparation methods illustrate the presence of subsurface alumina intrusions and the absence of voids, supporting previous evidence. The positive identification of voids and oxides by FIB can be complex and prone to misinterpretation and thus, the use of several imaging conditions and tilt angles must be used, along with conventional preparation methods, to confirm or refute the presence of voids underneath oxides.
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| 42. |
- Cruchley, S, et al.
(författare)
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Chromia layer growth on a Ni-based superalloy: Sub-parabolic kinetics and the role of titanium
- 2013
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Ingår i: Corrosion Science. - : Elsevier. - 0010-938X .- 1879-0496. ; 75, s. 58-66
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Tidskriftsartikel (refereegranskat)abstract
- Oxidation of the Ni-based superalloy RR1000 has been undertaken in air over the temperature range 600-900 degrees C for times up to 5000 h. The surface oxide consisted of a protective Ti-doped chromia layer but with rutile forming on its outer surface. Sub-surface oxidation of Al and Ti also occurred. The thickening kinetics of the chromia layer were sub-parabolic with initial rates around two orders of magnitude higher than expected for Ti-free chromia. This enhancement and the sub-parabolic kinetics are accounted for by Ti-doping of the chromia layer. Over time the enhancement reduced because of Ti-depletion in the alloy.
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| 43. |
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| 44. |
- Gardner, Michael, et al.
(författare)
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Gender and telomere length : Systematic review and meta-analysis
- 2014
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Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 51, s. 15-27
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Forskningsöversikt (refereegranskat)abstract
- Background: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. Methods: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Results: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p = 1.00) or cell type (p = 0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Conclusions: Telomere length is longer in females thanmales, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. (C) 2013 Published by Elsevier Inc.
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| 45. |
- Grinberg, Marianna, et al.
(författare)
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Toxicogenomics directory of chemically exposed human hepatocytes
- 2014
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 1432-0738 .- 0340-5761. ; 88:12, s. 2261-2287
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Tidskriftsartikel (refereegranskat)abstract
- A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. However, a systematic directory summarizing key features of chemically influenced genes in human hepatocytes is not yet available. To bridge this gap, we used the Open TG-GATES database with Affymetrix files of cultivated human hepatocytes incubated with chemicals, further sets of gene array data with hepatocytes from human donors generated in this study, and publicly available genome-wide datasets of human liver tissue from patients with non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular cancer (HCC). After a curation procedure, expression data of 143 chemicals were included into a comprehensive biostatistical analysis. The results are summarized in the publicly available toxicotranscriptomics directory (http://wiki.toxbank.net/toxicogenomics-map/) which provides information for all genes whether they are up- or downregulated by chemicals and, if yes, by which compounds. The directory also informs about the following key features of chemically influenced genes: (1) Stereotypical stress response. When chemicals induce strong expression alterations, this usually includes a complex but highly reproducible pattern named 'stereotypical response.' On the other hand, more specific expression responses exist that are induced only by individual compounds or small numbers of compounds. The directory differentiates if the gene is part of the stereotypical stress response or if it represents a more specific reaction. (2) Liver disease-associated genes. Approximately 20 % of the genes influenced by chemicals are up- or downregulated, also in liver disease. Liver disease genes deregulated in cirrhosis, HCC, and NASH that overlap with genes of the aforementioned stereotypical chemical stress response include CYP3A7, normally expressed in fetal liver; the phase II metabolizing enzyme SULT1C2; ALDH8A1, known to generate the ligand of RXR, one of the master regulators of gene expression in the liver; and several genes involved in normal liver functions: CPS1, PCK1, SLC2A2, CYP8B1, CYP4A11, ABCA8, and ADH4. (3) Unstable baseline genes. The process of isolating and the cultivation of hepatocytes was sufficient to induce some stress leading to alterations in the expression of genes, the so-called unstable baseline genes. (4) Biological function. Although more than 2,000 genes are transcriptionally influenced by chemicals, they can be assigned to a relatively small group of biological functions, including energy and lipid metabolism, inflammation and immune response, protein modification, endogenous and xenobiotic metabolism, cytoskeletal organization, stress response, and DNA repair. In conclusion, the introduced toxicotranscriptomics directory offers a basis for a rationale choice of candidate genes for biomarker evaluation studies and represents an easy to use source of background information on chemically influenced genes.
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| 46. |
- Hampel, Harald, et al.
(författare)
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Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives.
- 2010
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Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1784 .- 1474-1776. ; 9:7, s. 560-74
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Forskningsöversikt (refereegranskat)abstract
- Advances in therapeutic strategies for Alzheimer's disease that lead to even small delays in onset and progression of the condition would significantly reduce the global burden of the disease. To effectively test compounds for Alzheimer's disease and bring therapy to individuals as early as possible there is an urgent need for collaboration between academic institutions, industry and regulatory organizations for the establishment of standards and networks for the identification and qualification of biological marker candidates. Biomarkers are needed to monitor drug safety, to identify individuals who are most likely to respond to specific treatments, to stratify presymptomatic patients and to quantify the benefits of treatments. Biomarkers that achieve these characteristics should enable objective business decisions in portfolio management and facilitate regulatory approval of new therapies.
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| 47. |
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| 48. |
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| 49. |
- Johnson, Toby, et al.
(författare)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6, s. 688-700
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Tidskriftsartikel (refereegranskat)abstract
- Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56× 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56× 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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| 50. |
- Khan, Tauseef A., et al.
(författare)
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Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke : Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals
- 2013
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 42:2, s. 475-492
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Tidskriftsartikel (refereegranskat)abstract
- Background At the APOE gene, encoding apolipoprotein E, genotypes of the epsilon 2/epsilon 3/epsilon 4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk. Methods We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61 730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60 883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT). Results The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84-1.43) for epsilon 2/epsilon 2; 0.85 (95% CrI: 0.78-0.92) for epsilon 2/epsilon 3; 1.05 (95% CrI: 0.89-1.24) for epsilon 2/epsilon 4; 1.05 (95% CrI: 0.99-1.12) for epsilon 3/epsilon 4; and 1.12 (95% CrI: 0.94-1.33) for epsilon 4/epsilon 4 using the epsilon 3/epsilon 3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 x 10(-152)), apolipoprotein B (P-trend: 8.7 x 10(-06)) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 x 10(-26)) and HDL-C (P-trend: 1.6 x 10(-12)). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear. Conclusions In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE epsilon 2/epsilon 2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
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