| 1. |
- 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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| 2. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- Berger, Christian, 1980, et al.
(författare)
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Simulations on consumer tests: A systematic evaluation approach in an industrial case study
- 2014
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Ingår i: 2014 17th IEEE International Conference on Intelligent Transportation Systems, ITSC 2014. - : IEEE. - 9781479960781
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Konferensbidrag (refereegranskat)abstract
- Context: Consumer tests for vehicles have long a tradition of almost two decades in Europe to assess vehicular safety abilities. For active safety systems like an emergency braking guard, different consumer-test-organizations (CTOs) around the world intensify now the challenges for automotive Original Equipment Manufacturer (OEM) in terms of specific test protocols.
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| 6. |
- 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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