| 1. |
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| 2. |
- Pollard, R. B., et al.
(författare)
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Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x : A phase 2 randomised, double-blind, placebo-controlled trial
- 2014
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Ingår i: The Lancet - Infectious diseases. - 1473-3099 .- 1474-4457. ; 14:4, s. 291-300
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Tidskriftsartikel (refereegranskat)abstract
- Background: Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24Gag, in adults infected with HIV-1. Methods: Between July, 2008, and June, 2010, we did a multinational double-blind, randomised, phase 2 study comparing Vacc-4x with placebo. Participants were adults infected with HIV-1 who were aged 18-55 years and virologically suppressed on cART (viral load <50 copies per mL) with CD4 cell counts of 400 × 106 cells per L or greater. The trial was done at 18 sites in Germany, Italy, Spain, the UK, and the USA. Participants were randomly assigned (2:1) to Vacc-4x or placebo. Group allocation was masked from participants and investigators. Four primary immunisations, weekly for 4 weeks, containing Vacc-4x (or placebo) were given intradermally after administration of adjuvant. Booster immunisations were given at weeks 16 and 18. At week 28, cART was interrupted for up to 24 weeks. The coprimary endpoints were cART resumption and changes in CD4 counts during treatment interruption. Analyses were by modified intention to treat: all participants who received one intervention. Furthermore, safety, viral load, and immunogenicity (as measured by ELISPOT and proliferation assays) were assessed. The 52 week follow-up period was completed in June, 2011. For the coprimary endpoints the proportion of participants who met the criteria for cART resumption was analysed with a logistic regression model with the treatment effect being assessed in a model including country as a covariate. This study is registered with ClinicalTrials.gov, number NCT00659789. Findings: 174 individuals were screened; because of slow recruitment, enrolment stopped with 136 of a planned 345 participants and 93 were randomly assigned to receive Vacc-4x and 43 to receive placebo. There were no differences between the two groups for the primary efficacy endpoints in those participants who stopped cART at week 28. Of the participants who resumed cART, 30 (34%) were in the Vacc-4x group and 11 (29%) in the placebo group, and percentage changes in CD4 counts were not significant (mean treatment difference -5·71, 95% CI -13·01 to 1·59). However, a significant difference in viral load was noted for the Vacc-4x group both at week 48 (median 23 100 copies per mL Vacc-4x vs 71 800 copies per mL placebo; p=0·025) and week 52 (median 19 550 copies per mL vs 51 000 copies per mL; p=0·041). One serious adverse event, exacerbation of multiple sclerosis, was reported as possibly related to study treatment. Vacc-4x was immunogenic, inducing proliferative responses in both CD4 and CD8 T-cell populations. Interpretation: The proportion of participants resuming cART before end of study and change in CD4 counts during the treatment interruption showed no benefit of vaccination. Vacc-4x was safe, well tolerated, immunogenic, seemed to contribute to a viral-load setpoint reduction after cART interruption, and might be worth consideration in future HIV-cure investigative strategies. Funding: Norwegian Research Council GLOBVAC Program and Bionor Pharma ASA.
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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. |
- 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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| 5. |
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| 6. |
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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
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| 11. |
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| 12. |
- 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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| 13. |
- 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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| 14. |
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| 15. |
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| 16. |
- Amole, C., et al.
(författare)
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Discriminating between antihydrogen and mirror-trapped antiprotons in a minimum-B trap
- 2012
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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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| 17. |
- 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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| 18. |
- 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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| 19. |
- 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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| 20. |
- 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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| 21. |
- 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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| 22. |
- 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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| 23. |
- 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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| 24. |
- Andresen, G. B., et al.
(författare)
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Trapped antihydrogen
- 2010
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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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| 25. |
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| 26. |
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| 27. |
- 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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| 28. |
- Hardy, J., et al.
(författare)
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Pathways to Alzheimer's disease
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 275:3, s. 296-303
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Tidskriftsartikel (refereegranskat)abstract
- Recent trials of anti-amyloid agents have not produced convincing improvements in clinical outcome in Alzheimer's disease; however, the reason for these poor or inconclusive results remains unclear. Recent genetic data continue to support the amyloid hypothesis of Alzheimer's disease with protective variants being found in the amyloid gene and both common low-risk and rare high-risk variants for disease being discovered in genes that are part of the amyloid response pathways. These data support the view that genetic variability in how the brain responds to amyloid deposition is a potential therapeutic target for the disease, and are consistent with the notion that anti-amyloid therapies should be initiated early in the disease process. © 2014 The Association for the Publication of the Journal of Internal Medicine.
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| 29. |
- 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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| 30. |
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| 31. |
- 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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| 32. |
- 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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| 33. |
- 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
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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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| 34. |
- van Vliet-Ostaptchouk, J. V., et al.
(författare)
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Pleiotropic effects of obesity-susceptibility loci on metabolic traits : a meta-analysis of up to 37,874 individuals
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:10, s. 2134-2146
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Tidskriftsartikel (refereegranskat)abstract
- Genetic pleiotropy may contribute to the clustering of obesity and metabolic conditions. We assessed whether genetic variants that are robustly associated with BMI and waist-to-hip ratio (WHR) also influence metabolic and cardiovascular traits, independently of obesity-related traits, in meta-analyses of up to 37,874 individuals from six European population-based studies. We examined associations of 32 BMI and 14 WHR loci, individually and combined in two genetic predisposition scores (GPSs), with glycaemic traits, blood lipids and BP, with and without adjusting for BMI and/or WHR. We observed significant associations of BMI-increasing alleles at five BMI loci with lower levels of 2 h glucose (RBJ [also known as DNAJC27], QPTCL: effect sizes -0.068 and -0.107 SD, respectively), HDL-cholesterol (SLC39A8: -0.065 SD, MTCH2: -0.039 SD), and diastolic BP (SLC39A8: -0.069 SD), and higher and lower levels of LDL- and total cholesterol (QPTCL: 0.041 and 0.042 SDs, respectively, FLJ35779 [also known as POC5]: -0.042 and -0.041 SDs, respectively) (all p < 2.4 x 10(-4)), independent of BMI. The WHR-increasing alleles at two WHR loci were significantly associated with higher proinsulin (GRB14: 0.069 SD) and lower fasting glucose levels (CPEB4: -0.049 SD), independent of BMI and WHR. A higher GPS-BMI was associated with lower systolic BP (-0.005 SD), diastolic BP (-0.006 SD) and 2 h glucose (-0.013 SD), while a higher GPS-WHR was associated with lower HDL-cholesterol (-0.015 SD) and higher triacylglycerol levels (0.014 SD) (all p < 2.9 x 10(-3)), independent of BMI and/or WHR. These pleiotropic effects of obesity-susceptibility loci provide novel insights into mechanisms that link obesity with metabolic abnormalities.
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| 36. |
- 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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| 37. |
- Wang, Z.A., et al.
(författare)
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Comparing spatial maps of human population-genetic variation using Procrustes analysis
- 2010
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Ingår i: Statistical Applications in Genetics and Molecular Biology. - : Walter de Gruyter GmbH. - 1544-6115 .- 1544-6115. ; 9:1, s. e13-
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Tidskriftsartikel (refereegranskat)abstract
- Recent applications of principal components analysis (PCA) and multidimensional scaling (MDS) in human population genetics have found that "statistical maps" based on the genotypes in population-genetic samples often resemble geographic maps of the underlying sampling locations. To provide formal tests of these qualitative observations, we describe a Procrustes analysis approach for quantitatively assessing the similarity of population-genetic and geographic maps. We confirm in two scenarios, one using single-nucleotide polymorphism (SNP) data from Europe and one using SNP data worldwide, that a measurably high level of concordance exists between statistical maps of population-genetic variation and geographic maps of sampling locations. Two other examples illustrate the versatility of the Procrustes approach in population-genetic applications, verifying the concordance of SNP analyses using PCA and MDS, and showing that statistical maps of worldwide copy-number variants (CNVs) accord with statistical maps of SNP variation, especially when CNV analysis is limited to samples with the highest-quality data. As statistical maps with PCA and MDS have become increasingly common for use in summarizing population relationships, our examples highlight the potential of Procrustes-based quantitative comparisons for interpreting the results in these maps.
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