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- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 4. |
- Habs, D., et al.
(författare)
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The REX-ISOLDE project
- 2000
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Ingår i: Hyperfine Interactions. - 0304-3843 .- 1572-9540. ; 129:1-4, s. 43-66
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Tidskriftsartikel (refereegranskat)abstract
- The Radioactive Beam Experiment REX-ISOLDE [1-3] is a pilot experiment at ISOLDE (CERN) testing the new concept of post acceleration of radioactive ion beams by using charge breeding of the ions in a high charge state ion source and the efficient acceleration of the highly charged ions in a short LINAC using modern ion accelerator structures. In order to prepare the ions for the experiments singly charged radioactive ions from the on-line mass separator ISOLDE will be cooled and bunched in a Penning trap, charge bred in an electron beam ion source (EBIS) and finally accelerated in the LINAC. The LINAC consists of a radiofrequency quadrupole (RFQ) accelerator, which accelerates the ions up to 0.3 MeV/u, an interdigital H-type (IH) structure with a final energy between 1.1 and 1.2 MeV/u and three seven gap resonators, which allow the variation of the final energy. With an energy of the radioactive beams between 0.8 MeV/u and 2.2 MeV/u a wide range of experiments in the field of nuclear spectroscopy, astrophysics and solid state physics will be addressed by REX-ISOLDE.
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- Aquila, Andrew, et al.
(författare)
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Time-resolved protein nanocrystallography using an X-ray free-electron laser
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:3, s. 2706-2716
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.
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| 6. |
- Chapman, Henry N, et al.
(författare)
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Femtosecond X-ray protein nanocrystallography.
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7
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Tidskriftsartikel (refereegranskat)abstract
- X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200nm to 2μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
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| 7. |
- Berger, Christian, 1980, et al.
(författare)
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Simulations on Consumer Tests: A Systematic Evaluation Approach in an Industrial Case Study
- 2015
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Ingår i: Ieee Intelligent Transportation Systems Magazine. - : Institute of Electrical and Electronics Engineers (IEEE). - 1939-1390 .- 1941-1197. ; 7:4, s. 24-36
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Tidskriftsartikel (refereegranskat)abstract
- Context: Consumer tests which assess safety features of modern vehicles have a tradition in Europe. Recently, such test protocols have been substantially extended to also cover active safety systems like Volkswagen's Front Assist. Objective: Simulations for passive safety systems are already a widely adopted approach during vehicle development and internal assessments. As active safety systems are becoming an increasingly important element in a vehicle's safety concept and a differentiating feature, a systematic validation and assessment of such systems is necessary to successfully pass consumer tests and complimentarily identified, relevant traffic scenarios. Method: With this work, we extend our previous conference publication about EuroNCAP CCRs tests by additionally investigating US NCAP scenarios for an AEB system. Therefore, we systematically modeled the allowed variations with a graph where the paths represent concrete test scenarios. These paths are used in a virtual test environment to assess the AEB system. In our previous publication, we illustrated our method of test case generation and simulating consumer test scenarios by showing results of 27 specific test cases. In this work, we focused on integrating a test automatization routine as well as evaluating a set of test cases with a factor of 100 compared to our previous paper. Results: We demonstrate the approach for both EuroNCAP's and US NCAP's CCRs scenarios with a total quantity of more than 2,700 test cases including re-runs to systematically evaluate an AEB algorithm. Our results unveiled varying action points in time for the same initial values for a given consumer test scenario while applying different allowed variations. Conclusion: We foresee the importance of complementary virtual testing for real-world tests on proving grounds especially during the design phase. Our study shows that already small variations that yet accord with the test procedure specification influence the behavior of an active safety system and need to be investigated during development and vehicle testing.
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