| 1. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 2. |
- 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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| 3. |
- Jansson, John-Olov, 1954, et al.
(författare)
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Body weight homeostat that regulates fat mass independently of leptin in rats and mice.
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:2, s. 427-432
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Tidskriftsartikel (refereegranskat)abstract
- Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.
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| 4. |
- Johansson, Linda C, 1983, et al.
(författare)
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Lipidic phase membrane protein serial femtosecond crystallography.
- 2012
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Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 9:3, s. 263-265
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Tidskriftsartikel (refereegranskat)abstract
- X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology. Here we recorded interpretable diffraction data from micrometer-sized lipidic sponge phase crystals of the Blastochloris viridis photosynthetic reaction center delivered into an X-FEL beam using a sponge phase micro-jet.
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| 5. |
- Kool, Erik C., et al.
(författare)
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A radio-detected type Ia supernova with helium-rich circumstellar material
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 617:7961, s. 477-482
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Tidskriftsartikel (refereegranskat)abstract
- Type Ia supernovae (SNe Ia) are thermonuclear explosions of degenerate white dwarf stars destabilized by mass accretion from a companion star1, but the nature of their progenitors remains poorly understood. A way to discriminate between progenitor systems is through radio observations; a non-degenerate companion star is expected to lose material through winds2 or binary interaction3 before explosion, and the supernova ejecta crashing into this nearby circumstellar material should result in radio synchrotron emission. However, despite extensive efforts, no type Ia supernova (SN Ia) has ever been detected at radio wavelengths, which suggests a clean environment and a companion star that is itself a degenerate white dwarf star4,5. Here we report on the study of SN 2020eyj, a SN Ia showing helium-rich circumstellar material, as demonstrated by its spectral features, infrared emission and, for the first time in a SN Ia to our knowledge, a radio counterpart. On the basis of our modelling, we conclude that the circumstellar material probably originates from a single-degenerate binary system in which a white dwarf accretes material from a helium donor star, an often proposed formation channel for SNe Ia (refs. 6,7). We describe how comprehensive radio follow-up of SN 2020eyj-like SNe Ia can improve the constraints on their progenitor systems.
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| 6. |
- Alvarez Vadillo, Ines, et al.
(författare)
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Centralised Architecture for the Automatic Self-Configuration of Industrial Networks
- 2023
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Ingår i: IEEE Int. Conf. Emerging Technol. Factory Autom., ETFA. - : Institute of Electrical and Electronics Engineers Inc.. - 9798350339918
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Konferensbidrag (refereegranskat)abstract
- Novel production paradigms aim at increasing the efficiency and flexibility of production systems. Nonetheless, traditional industrial infrastructures lack the mechanisms needed to support these new paradigms. One of the main limiting factors is the architecture, which follows the automation pyramid in which subsystems are divided in layers depending on their functionalities. This allowed to meet the timing and dependability requirements of the production subsystems, however at the cost of limiting the exchange of information required to provide increased flexibility to the system. For this reason, in this paper we propose a new industrial architecture with a single network infrastructure to connect all the devices that conform to the industrial systems. On top of that, we design an Automatic Network Configurator to support the automatic configuration of the system. To assess the feasibility of our design and evaluate its performance, we implement the first instance of the architecture capable of supporting changes in the traffic requirements during run-time, i.e., without stopping or disrupting the system's operation. Furthermore, we use the implemented instance to measure the time required for reconfigurations.
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| 7. |
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| 8. |
- Basu, K., et al.
(författare)
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Non-parametric modeling of the intra-cluster gas using APEX-SZ bolometer imaging data
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 519:Article Number: A29
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We aim to demonstrate the usability of mm-wavelength imaging data obtained from the APEX-SZ bolometer array to derive the radial temperature profile of the hot intra-cluster gas out to radius r(500) and beyond. The goal is to study the physical properties of the intra-cluster gas by using a non-parametric de-projection method that is, aside from the assumption of spherical symmetry, free from modeling bias. Methods. We use publicly available X-ray spectroscopic-imaging data in the 0.7-2 keV energy band from the XMM-Newton observatory and our Sunyaev-Zel'dovich Effect (SZE) imaging data from the APEX-SZ experiment at 150 GHz to de-project the density and temperature profiles for a well-studied relaxed cluster, Abell 2204. We derive the gas density, temperature and entropy profiles assuming spherical symmetry, and obtain the total mass profile under the assumption of hydrostatic equilibrium. For comparison with X-ray spectroscopic temperature models, a re-analysis of recent Chandra observation is done with the latest calibration updates. We compare the results with that from an unrelaxed cluster, Abell 2163, to illustrate some differences between relaxed and merging systems. Results. Using the non-parametric modeling, we demonstrate a decrease of gas temperature in the cluster outskirts, and also measure gas entropy profiles, both of which are done for the first time independently of X-ray spectroscopy using the SZE and X-ray imaging data. The gas entropy measurement in the central 100 kpc shows the usability of APEX-SZ data for inferring cluster dynamical states with this method. The contribution of the SZE systematic uncertainties in measuring T-e at large radii is shown to be small compared to XMM-Newton and Chandra systematic spectroscopic errors. The total mass profile obtained using the hydrostatic equilibrium assumption is in agreement with the published X-ray and weak lensing results; the upper limit on M-200 derived from the non-parametric method is consistent with the NFW model prediction from weak lensing analysis.
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| 9. |
- Bergsjö, Dag Henrik, 1980, et al.
(författare)
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Assessing product development efficiency at Volvo Powertrain Focus on systems engineering and lean principles at two global sites
- 2013
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Ingår i: 23rd Annual International Symposium of the International Council on Systems Engineering, INCOSE 2013. ; 2, s. Pages 1481-1492
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Konferensbidrag (refereegranskat)abstract
- Measuring the performance of a development process is highly difficult, especially before it has led to an outcome such as a product. Furthermore, even with a diagnosis at hand showing the strengths and weaknesses of the development process, the information can seldom be used to answer the paramount question: How should the organization allocate its process improvement resources to best support its objectives?This paper presents a survey-based method for identifying which areas for process improvement are likely to have the strongest impact on company objectives, called outcomes. The survey has been completed by respondents within the organization and uses the data to present three different analyses. The first analysis shows the perceived current fulfillment within the organization of a number of principles identified as important for successful development. The second analysis is a regression analysis commonly used in marketing research to measure the impact of each principle on five outcomes: Efficiency/Effectiveness, Lead-Time, Innovation, Satisfaction and Product Quality. The two first analyses are then combined to a third analysis that provides a pie chart for each outcome with the principles possessing the highest potential for further improving that particular outcome.A case study at the automotive company, Volvo Powertrain, shows how the method was used to assess and compare process improvement potential at two development sites. The results clearly show that the analyses provide different views of what principles deserve attention for process improvement activities at the case company. The two principles deemed to be most attractive, based on their impact on outcomes, were currently neither among the highest nor the lowest performing principles. As a result of the study, Volvo Powertrain chose to start several improvement activities to work with the high-potential principles. The improvement can then be measured using annual surveys to track improvements and manage deviations from the plan.
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