| 11. |
- 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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| 12. |
- Skulason, Skuli, et al.
(författare)
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A way forward with eco evo devo : an extended theory of resource polymorphism with postglacial fishes as model systems
- 2019
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Ingår i: Biological Reviews. - : John Wiley & Sons. - 1464-7931 .- 1469-185X. ; 94:5, s. 1786-1808
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Forskningsöversikt (refereegranskat)abstract
- A major goal of evolutionary science is to understand how biological diversity is generated and altered. Despite considerable advances, we still have limited insight into how phenotypic variation arises and is sorted by natural selection. Here we argue that an integrated view, which merges ecology, evolution and developmental biology (eco evo devo) on an equal footing, is needed to understand the multifaceted role of the environment in simultaneously determining the development of the phenotype and the nature of the selective environment, and how organisms in turn affect the environment through eco evo and eco devo feedbacks. To illustrate the usefulness of an integrated eco evo devo perspective, we connect it with the theory of resource polymorphism (i.e. the phenotypic and genetic diversification that occurs in response to variation in available resources). In so doing, we highlight fishes from recently glaciated freshwater systems as exceptionally well‐suited model systems for testing predictions of an eco evo devo framework in studies of diversification. Studies on these fishes show that intraspecific diversity can evolve rapidly, and that this process is jointly facilitated by (i) the availability of diverse environments promoting divergent natural selection; (ii) dynamic developmental processes sensitive to environmental and genetic signals; and (iii) eco evo and eco devo feedbacks influencing the selective and developmental environments of the phenotype. We highlight empirical examples and present a conceptual model for the generation of resource polymorphism – emphasizing eco evo devo, and identify current gaps in knowledge.
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| 13. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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| 14. |
- Bernal, Esteban, et al.
(författare)
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Prediction of rail surface damage in locomotive traction operations using laboratory-field measured and calibrated data
- 2022
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Ingår i: Engineering Failure Analysis. - : Elsevier BV. - 1350-6307 .- 1873-1961. ; 135
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Tidskriftsartikel (refereegranskat)abstract
- Rail damage prediction is a complex task because it depends on numerous tribological parameters and the dynamic conditions produced by the vehicles operating at different speeds and configurations. Shakedown maps and Whole-Life-Rail-Model/T-Gamma have been used to predict rail damage, but they involve assumptions that may reduce their accuracy. This paper proposes a simulation modelling method to predict rail surface damage based on a locomotive digital twin, calibrated shakedown maps and friction measurements. The method improves the accuracy of rail damage predictions by including slip-dependent friction characteristics, co-simulation of locomotive traction mechatronic system and the mechanical properties of the wheel and rail materials measured through tensile tests. A set of operating conditions are simulated on a high-performance computing cluster, with stress results being post processed into calibrated shakedown heatmaps. The method clearly indicated the influences of the different operating conditions on rail damage for specific combinations of wheel-rail materials and vehicle-track configurations.
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| 15. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 16. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 17. |
- Bombois, Xavier, et al.
(författare)
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On the informativity of direct identification experiments in dynamical networks
- 2023
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Ingår i: Automatica. - : Elsevier BV. - 0005-1098 .- 1873-2836. ; 148, s. 110742-
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Tidskriftsartikel (refereegranskat)abstract
- Data informativity is a crucial property to ensure the consistency of the prediction error estimate. This property has thus been extensively studied in the open-loop and in the closed-loop cases, but has only been briefly touched upon in the dynamic network case. In this paper, we consider the prediction error identification of the modules in a row of a dynamic network using the full input approach. Our main contribution is to propose a number of easily verifiable data informativity conditions for this identification problem. Among these conditions, we distinguish a sufficient data informativity condition that can be verified based on the topology of the network and a necessary and sufficient data informativity condition that can be verified via a rank condition on a matrix of coefficients that are related to a full-order model structure of the network. These data informativity conditions allow to determine different situations (i.e., different excitation patterns) leading to data informativity. In order to be able to distinguish between these different situations, we also propose an optimal experiment design problem that allows to determine the excitation pattern yielding a certain pre-specified accuracy with the least excitation power.
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| 18. |
- Bombois, Xavier, et al.
(författare)
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Robust optimal identification experiment design for multisine excitation
- 2021
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Ingår i: Automatica. - : Elsevier BV. - 0005-1098 .- 1873-2836. ; 125
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Tidskriftsartikel (refereegranskat)abstract
- In least costly experiment design, the optimal spectrum of an identification experiment is determined in such a way that the cost of the experiment is minimized under some accuracy constraint on the identified parameter vector. Like all optimal experiment design problems, this optimization problem depends on the unknown true system, which is generally replaced by an initial estimate. One important consequence of this is that we can underestimate the actual cost of the experiment and that the accuracy of the identified model can be lower than desired. Here, based on an a-priori uncertainty set for the true system, we propose a convex optimization approach that allows to prevent these issues from happening. We do this when the to-be-determined spectrum is the one of a multisine signal.
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| 19. |
- Chatterjee, Pratishtha, et al.
(författare)
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Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease.
- 2022
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:6, s. 1141-1154
-
Tidskriftsartikel (refereegranskat)abstract
- This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD).Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ-) or presence (Aβ+) of brain amyloidosis.Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ- CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ- CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ- CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume.These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.
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| 20. |
- Colin, Kevin, et al.
(författare)
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Data Informativity for the Closed-Loop Identification of MISO ARX Systems
- 2021
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Ingår i: IFAC PAPERSONLINE. - : Elsevier BV. - 2405-8963. ; , s. 779-784
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Konferensbidrag (refereegranskat)abstract
- In the Prediction Error identification framework, it is crucial that the collected data are informative with respect to the chosen model structure to get a consistent estimate. In this work, we focus on the data informativity property for the identification of multi-inputs single-output ARX systems in closed-loop and we derive a necessary and sufficient condition to verify if a given multisine external excitation combined with the feedback introduced by the controller yields informative data with respect to the chosen model structure.
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