| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 3. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 4. |
- Actis, M., et al.
(författare)
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Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
- 2011
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Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
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Tidskriftsartikel (refereegranskat)abstract
- Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
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| 5. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 6. |
- Bidola, Pidassa M., et al.
(författare)
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A high-speed X-ray Radiography Setup for in-situ Electron Beam Powder Bed Fusion at PETRA III
- 2023
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Ingår i: Advances in X-Ray/EUV Optics and Components XVIII. - : SPIE-Intl Soc Optical Eng.
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Konferensbidrag (refereegranskat)abstract
- A high-energy white synchrotron X-ray beam enables penetration of relatively thick and highly absorbing samples. At the P61A White Beam Engineering Materials Science Beamline, operated by Helmholtz-Zentrum Hereon at the PETRA III ring of the Deutsches Elektronen-Synchrotron (DESY), a tailored X-ray radiography system has been developed to perform in-situ X-ray imaging experiments at high temporal resolution, taking advantage of the unprecedented X-ray beam flux delivered by ten successive damping wigglers. The imaging system is equipped with an ultrahigh-speed camera (Phantom v2640) enabling acquisition rates up to 25 kHz at maximal resolution and binned mode. The camera is coupled with optical magnification (5x, 10x) and focusing lenses to enable imaging with a pixel size of 1,35 micrometre. The scintillator screens are housed in a special nitrogen gas cooling environment to withstand the heat load induced by the beam, allowing spatial resolution to be optimized down to few micrometres. We present the current state of the system development, implementation and first results of in situ investigations, especially of the electron beam powder bed fusion (PBF-EB) process, where the details of the mechanism of crack and pore formation during processing of different powder materials, e.g. steels and Ni-based alloys, is not yet known.
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| 7. |
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| 8. |
- Galli, Silvia, et al.
(författare)
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Evaluation of the degradation behavior of resorbable metal implants for in vivo osteosynthesis by synchrotron radiation based x-ray tomography and histology
- 2016
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Ingår i: Developments in X-Ray Tomography X. - : SPIE - International Society for Optical Engineering.
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Konferensbidrag (refereegranskat)abstract
- Magnesium(Mg)-alloys are promising candidates as temporary implants for orthopedic and cranio-facial applications. They can sustain tissues during healing, thanks to favorable mechanical properties, and then they slowly degrade into biocompatible products, avoiding the need of a second surgery for implant removal. They have the potential to benefit a vast number of patients, especially children and elderly patients. However, to be able to tailor their degradation to match the speed of tissue regeneration it is crucial to understand how they actually degrade in the living organism. We utilized high-resolution synchrotron-based tomography at the beamline P05 operated by HZG at the storage ring PETRA III at DESY to study the degradation of 3 novel Mg-alloys in rat bone and the consequent bone response. On three-dimensional reconstructions of the bone-implant explants we were able to follow the dynamic transformation that the materials underwent at different healing times and on the basis of absorption coefficients we could distinguish and quantify the amount of remaining implants, the corrosion layers and the new bone. This was a great advantage compared to laboratory CT, for which the limitation in contrast and in resolution made impossible to discriminate between original alloy, degradation products and bone, leading to inaccurate determination of the materials degradation rates. The same samples imaged by tomography were used for non-decalcified histology. The combination of histological and tomographical images provided new insight on the nature of the bone-to-implant interface and of the degradation products, which appeared to have great similarities to the host bone.
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| 9. |
- Glueckert, Rudolf, et al.
(författare)
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Histology and synchrotron radiation-based microtomography of the inner ear in a molecularly confirmed case of CHARGE syndrome
- 2010
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Ingår i: American journal of medical genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 152A:3, s. 665-673
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Tidskriftsartikel (refereegranskat)abstract
- CHARGE (Coloboma of the iris or retina, heart defects, atresia of the choanae, retardation of growth and/or development, genital anomalies, ear anomalies) syndrome (OMIM #214800) affects about 1 in 10,000 children and is most often caused by chromodomain helicase DNA-binding protein-7 (CHD7) mutations. Inner ear defects and vestibular abnormalities are particularly common. Specifically, semicircular canal (SCC) hypoplasia/aplasia and the presence of a Mondini malformation can be considered pathognomonic in the context of congenital malformations of the CHARGE syndrome. We obtained a temporal bone (TB) of a patient with CHARGE syndrome who died from bacteremia at 3 months of age. The clinical diagnosis was confirmed in the patient by direct DNA sequencing and the detection of a de novo, truncating CHD7 mutation, c.6169dup (p.R2057fs). We assessed changes of the TB and the degree of neural preservation, which may influence the potential benefit of cochlear implantation. The TB was analyzed using synchrotron radiation-based micro computed tomography, and by light microscopy. The vestibular partition consisted of a rudimentary vestibule with agenesis of the SCCs. The cochlea was hypoplastic with poor or deficient interscaling and shortened (Mondini dysplasia). The organ of Corti had near normal structure and innervation. Modiolus and Rosenthal's canal were hypoplastic with perikarya displaced along the axon bundles into the internal acoustic meatus, which may be explained by the arrest or limited migration and translocation of the cell nuclei into the cochlear tube during development.
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| 10. |
- König, Hans-Henrik, et al.
(författare)
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MiniMelt : An instrument for real-time tracking of electron beam additive manufacturing using synchrotron x-ray techniques
- 2023
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 94:12
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Tidskriftsartikel (refereegranskat)abstract
- The development of a sample environment for in situ x-ray characterization during metal Electron Beam Powder Bed Fusion (PBF-EB), called MiniMelt, is presented. The design considerations, the features of the equipment, and its implementation at the synchrotron facility PETRA III at Deutsches Elektronen-Synchrotron, Hamburg, Germany, are described. The equipment is based on the commercially available Freemelt ONE PBF-EB system but has been customized with a unique process chamber to enable real-time synchrotron measurements during the additive manufacturing process. Furthermore, a new unconfined powder bed design to replicate the conditions of the full-scale PBF-EB process is introduced. The first radiography (15 kHz) and diffraction (1 kHz) measurements of PBF-EB with a hot-work tool steel and a Ni-base superalloy, as well as bulk metal melting with the CMSX-4 alloy, using the sample environment are presented. MiniMelt enables time-resolved investigations of the dynamic phenomena taking place during multi-layer PBF-EB, facilitating process understanding and development of advanced process strategies and materials for PBF-EB.
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