| 1. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 2. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Tim Brix Nerenst, Tim Brix, et al.
(författare)
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Sequential Design Process for Screening and Optimization of Robust and Reliability Based on Finite Element Analysis and Meta-Modelling
- 2022
-
Ingår i: Journal of Computing and Information Science in Engineering. - : ASME International. - 1530-9827 .- 1944-7078. ; 22:4
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Tidskriftsartikel (refereegranskat)abstract
- A new medical device can take years to develop from early concept to product launch. Three approaches are often combined to mitigate risks: Failure Modes and Effects Analysis (FMEA), simulation and modeling, and physical test programs. Although widely used, all three approaches are generally time-consuming and have their shortcomings: The risk probabilities in FMEA's are often based on educated guesses, even in later development stages as data on the distribution of performance is not available. Thus, the traditional use of safety factors in structural analysis versus the probabilistic approach to risk management presents an obvious misfit. Therefore, the above three approaches are not ideal for addressing the design engineer's key question; how should the design be changed to improve robustness and failure rates. The present work builds upon the existing Robust and Reliability-Based Design Optimization (R2BDO) and adjusts it to address the key questions above using Finite Element Analysis (FEA). The two main features of the presented framework are screening feasible design concepts early in the embodiment phase and subsequently optimizing the design's probabilistic performance (i.e., reduce failure rates) while using minimal computational resources. A case study in collaboration with a medical design and manufacturing company demonstrates the new framework. The optimization minimizes the failure rate (and improves design robustness) concerning three constraint functions (torque, strain, and contact pressure). Furthermore, the study finds that the new framework significantly improves the design's performance function (failure rate) with limited computational resources.
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| 4. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 5. |
- Neasham, David, et al.
(författare)
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Occupation and risk of lymphoma : a multicentre prospective cohort study (EPIC)
- 2011
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 68:1, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.
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| 6. |
- Nerenst, Tim Brix, et al.
(författare)
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Probabilistic Performance Evaluation and Optimization of Medical Plastic Moulded Components Subject to Large Scale Production
- 2021
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Ingår i: ASME International Mechanical Engineering Congress and Exposition, Proceedings (IMECE). - 9780791885567
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Konferensbidrag (refereegranskat)abstract
- A new medical device can take years to develop from early concept to product launch. The long development process can be attributed to the severe consequences for the patient if the device malfunctions. Three approaches are often combined to mitigate risks: rigorous simulation and modeling, physical test programs, and Failure Mode Effect Analysis (FMEA) - all of which are time-consuming. Physical test programs are often carried out on prototype components from the same batch and, therefore, limited in revealing the actual distribution of performance. The risk probabilities are subsequently based on educated guesses. Furthermore, simulation and modeling are usually performed on nominal geometry - not accounting for variation - and only provide a safety factor against failure. The traditional use of safety factors in structural analysis versus the probabilistic approach to risk management presents an obvious misfit. Therefore, these three approaches are not ideal for addressing the two key questions that the design engineer has: 1) How often will the design fail, and 2) How should the design be changed to improve robustness and failure rates. The present work builds upon the existing Robust and Reliability-Based Design Optimization (R2BDO) and adjusts it to address the key questions above using finite element analysis. The key feature of the new framework is the focus on minimal use of computational resources while being able to screen feasible design concepts early in the embodiment phase and subsequently optimize their probabilistic performance. A case study in collaboration with a medical design and manufacturing company demonstrates the new framework. The case study includes FEA contact modeling between two plastic molded components with twelve geometrical variables. The optimization focuses on minimizing the failure rate (and improving design robustness) concerning three constraint functions (contact pressure, strain, torque). The study finds that the new framework achieves significant improvements to the component’s performance function (failure rate) with minimal computational resources.
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| 7. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 8. |
- Ali, Liaqat, et al.
(författare)
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Effects of nutrition strategy on the levels of nutrients and bioactive compounds in blackberries
- 2012
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Ingår i: European Food Research and Technology. - : Springer Science and Business Media LLC. - 1438-2377 .- 1438-2385. ; 234:1, s. 33-44
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Tidskriftsartikel (refereegranskat)abstract
- The effects of nutrition strategy on levels of nutrients and bioactive compounds in fruit and leaves of blackberries were studied in greenhouse-grown blackberry plants fertilised with combinations of two levels (low, high) of nitrogen (60 and 100 kg ha -1, respectively) and potassium (66.4 and 104 kg ha -1, respectively). Plant concentrations of organic phytochemicals were quantitatively analysed by high-performance liquid chromatography. High amounts of both fertilisers produced high amounts of all nutrients and bioactive compounds analysed in fruit except total acidity and ellagic acid. There were major differences in compounds affecting taste in fruit, e. g., sugars (fructose and glucose), total soluble solids and pH, and also in anthocyanin content. The concentrations of secondary metabolites, vitamin C and ellagic acid in fruit also varied significantly between treatments, although the differences were smaller. Storage of blackberries showed variable effects in the different levels of compounds, and the changes found were small. Nutrient regime did not affect blackberry leaves to the same extent, and only minor changes were found. The findings show that by optimising plant nutrition, phytonutrient levels can be maximised and maintained in fresh and stored berry crops, especially those grown in greenhouses, where conditions can easily be regulated.
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| 9. |
- Andersson, Mats, et al.
(författare)
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Toward an enzyme-based oxygen scavenging laminate. Influence of industrial lamination conditions on the performance of glucose oxidase
- 2002
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 1097-0290 .- 0006-3592. ; 79:1, s. 37-42
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Tidskriftsartikel (refereegranskat)abstract
- The laminate consisted of several polymer layers, aluminium, and one cellulose-based layer containing the active enzymatic system (e.g., glucose oxidase, catalase, glucose, and CaCO3). During the industrial lamination process, the enzyme layer was exposed to three temperature spikes up to 325degreesC without significant enzyme inactivation. Ninety-seven percent of the glucose oxidase activity still remained after the lamination process. The best laminate had an oxygen absorbing capacity of 7.6 +/- 1.0 L/m(2). A reference that was not laminated expressed a corresponding oxygen absorbing capacity of 7.1 +/- 0.8 L/m(2).
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| 10. |
- Andersson, Thorbjörn, et al.
(författare)
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Degradation of low density polyethylene during extrusion. : IV. Off-flavor compounds in extruded films of stabilized LDPE
- 2005
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Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 95:3, s. 583-595
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Tidskriftsartikel (refereegranskat)abstract
- This study was aimed at finding a correlation between the experienced off-flavor in packed foods and the presence of specific degradation products in LDPE pack-aging films. The possibility to trap degradation products by chemical reactions with scavengers, i.e., a zeolite additive or antioxidants, was investigated This would prevent degradation products from migrating to the polymer film surface and further into food in contact with the film. It was found that off-flavor noted in water packed in LDPE films depended on extrusion temperature and exposure time for the melt to oxygen, that is, the parameters that influence the contents of oxidation products that are able to migrate from the polymer film. It was also found that adsorption of oxidative degradation products in a zeolite additive or protection of LDPE by using antioxidants could prevent off-flavor in the packed product (water). However, the antioxidant should be selected with regard to extrusion temperature because thermal instability in the additive might jeopardize the intended effect. Multifunctional antioxidants seem to provide improved protection, the most effective one evaluated in this work being Irganox E201, i.e., vitamin E. Concentrations of oxidized degradation products are well correlated to the perceived off-flavor in the packed water. The highest correlation between off-flavor and oxidized components was found for ketones in the range of C 7 to C9 and aldehydes in the range of C6 to C9.
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| 11. |
- Andersson, Thorbjörn, et al.
(författare)
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Degradation of low density polyethylene during extrusion : III. Volatile compounds in extruded films creating off-flavor
- 2005
-
Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 95:4, s. 847-858
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Tidskriftsartikel (refereegranskat)abstract
- This study was aimed at finding a correlation between the experienced off-flavor in packaged foods and the presence of specific degradation products in PE packaging films. The possibility to trap degradation products by chemical reactions with scavengers, that is, zeolites and maleic anhydride grafted LLDPE, were investigated. This trapping would prevent the degradation products from migrating to the polymer film surface and further into food in contact with the film. This work concludes that off-flavor in water packed in LDPE-films depends on extrusion temperature and the content of oxidation products in the polymer film. At lower extrusion temperatures, reactive additives to the LDPE material could control the release of off-flavor giving compo nents. Adsorbents, such as zeolites, which are able to adsorb degradation products, are effective also at higher extrusion temperatures. The amount of oxidized degradation products in the films correlated well to the perceived off-flavor in the packed water. The presence of aldehydes and ketones have a clear impact on the off-flavor. The best correlation between off-flavor and oxidized components were found for C7-C9 ketones, and aldehydes in the range of C5 to C8.
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| 12. |
- Andersson, Thorbjörn, et al.
(författare)
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The effects of selected aldehydes, ketones and carboxylic acids on off-flavours in water
- 2005
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Ingår i: International journal of food science & technology. - : Wiley InterScience. - 0950-5423 .- 1365-2621. ; 40:9, s. 993-1004
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Tidskriftsartikel (refereegranskat)abstract
- The effects of selected aldehydes, ketones and carboxylic acids on the development of off-flavours in water were studied. Combinations of hexanal, octanal, 2-octanone, 5-nonanone, hexanoic acid and nonanoic acid were rated by the off-flavour intensities they created in water at concentrations just at or below the threshold value of each analyte. Two different sensory panels evaluated the off-flavours induced by different combinations of the analytes. The observations of the two panels agreed well. From these studies, it could be concluded that aldehydes play an important role in the development of off-flavours intensities in water. There were synergistic effects between aldehydes and ketones, as well as between aldehydes and carboxylic acids. Small amounts of aldehydes and carboxylic acids – well below their respective threshold values – caused an increase in the off-flavour intensity. No synergism between ketones and carboxylic acids could be observed
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| 13. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 14. |
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| 15. |
- Biasin, Elisa, et al.
(författare)
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Anisotropy enhanced X-ray scattering from solvated transition metal complexes
- 2018
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 25:2, s. 306-315
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Tidskriftsartikel (refereegranskat)abstract
- Time-resolved X-ray scattering patterns from photoexcited molecules in solution are in many cases anisotropic at the ultrafast time scales accessible at X-ray free-electron lasers (XFELs). This anisotropy arises from the interaction of a linearly polarized UV-Vis pump laser pulse with the sample, which induces anisotropic structural changes that can be captured by femtosecond X-ray pulses. In this work, a method for quantitative analysis of the anisotropic scattering signal arising from an ensemble of molecules is described, and it is demonstrated how its use can enhance the structural sensitivity of the time-resolved X-ray scattering experiment. This method is applied on time-resolved X-ray scattering patterns measured upon photoexcitation of a solvated di-platinum complex at an XFEL, and the key parameters involved are explored. It is shown that a combined analysis of the anisotropic and isotropic difference scattering signals in this experiment allows a more precise determination of the main photoinduced structural change in the solute, i.e. the change in Pt - Pt bond length, and yields more information on the excitation channels than the analysis of the isotropic scattering only. Finally, it is discussed how the anisotropic transient response of the solvent can enable the determination of key experimental parameters such as the instrument response function.The analysis of time-resolved X-ray scattering patterns collected at an XFEL upon photoexcitation of a di-platinum complex in solution is described. The analysis quantitatively considers the anisotropy of the signal.
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| 16. |
- Biasin, Elisa, et al.
(författare)
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Femtosecond X-Ray Scattering Study of Ultrafast Photoinduced Structural Dynamics in Solvated[Co(terpy)2]2$
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 1079-7114 .- 0031-9007. ; 117:1
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Tidskriftsartikel (refereegranskat)abstract
- We study the structural dynamics of photoexcited [Co(terpy)2]2+ in an aqueous solution with ultrafast x-ray diffuse scattering experiments conducted at the Linac Coherent Light Source. Through direct comparisons with density functional theory calculations, our analysis shows that the photoexcitation event leads to elongation of the Co-N bonds, followed by coherent Co-N bond length oscillations arising from the impulsive excitation of a vibrational mode dominated by the symmetrical stretch of all six Co-N bonds. This mode has a period of 0.33 ps and decays on a subpicosecond time scale. We find that the equilibrium bond-elongated structure of the high spin state is established on a single-picosecond time scale and that this state has a lifetime of ∼7 ps.
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| 17. |
- Biskaborn, Boris K., et al.
(författare)
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Permafrost is warming at a global scale
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Permafrost warming has the potential to amplify global climate change, because when frozen sediments thaw it unlocks soil organic carbon. Yet to date, no globally consistent assessment of permafrost temperature change has been compiled. Here we use a global data set of permafrost temperature time series from the Global Terrestrial Network for Permafrost to evaluate temperature change across permafrost regions for the period since the International Polar Year (2007–2009). During the reference decade between 2007 and 2016, ground temperature near the depth of zero annual amplitude in the continuous permafrost zone increased by 0.39 ± 0.15 °C. Over the same period, discontinuous permafrost warmed by 0.20 ± 0.10 °C. Permafrost in mountains warmed by 0.19 ± 0.05 °C and in Antarctica by 0.37 ± 0.10 °C. Globally, permafrost temperature increased by 0.29 ± 0.12 °C. The observed trend follows the Arctic amplification of air temperature increase in the Northern Hemisphere. In the discontinuous zone, however, ground warming occurred due to increased snow thickness while air temperature remained statistically unchanged.
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| 18. |
- Boffetta, Paolo, et al.
(författare)
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Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).
- 2010
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102:8, s. 529-537
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is widely believed that cancer can be prevented by high intake of fruits and vegetables. However, inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk. METHODS: We conducted a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess relationships between intake of total fruits, total vegetables, and total fruits and vegetables combined and cancer risk during 1992-2000. Detailed information on the dietary habit and lifestyle variables of the cohort was obtained. Cancer incidence and mortality data were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models. Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking. RESULTS: Of the initial 142 605 men and 335 873 women included in the study, 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar (200 g/d increased intake of fruits and vegetables combined, HR = 0.97, 95% CI = 0.96 to 0.99; 100 g/d increased intake of total vegetables, HR = 0.98, 95% CI = 0.97 to 0.99); intake of fruits showed a weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99, 95% CI = 0.98 to 1.00). The reduced risk of cancer associated with high vegetable intake was restricted to women (HR = 0.98, 95% CI = 0.97 to 0.99). Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol. CONCLUSIONS: A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study. Given the small magnitude of the observed associations, caution should be applied in their interpretation.
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| 19. |
- Busse Nielsen, Anders, et al.
(författare)
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Review of urban tree inventory methods used to collect data at single-tree level
- 2014
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Ingår i: Arboriculture & urban forestry. - 1935-5297 .- 2155-0778. ; 40, s. 96-111
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Tidskriftsartikel (refereegranskat)abstract
- With a growing number of urban tree inventory methods and diversifying use of tree inventory data by city authorities and researchers, there is a need to evaluate, review, and critically assess the inventory methods available. This study reviewed studies using urban tree inventories at single-tree level as their data source. Based on this, a bibliographic overview was established and a typology of contemporary urban tree inventory methods was created and used as a framework for evaluation and discussion of the measurement type and accuracy achievable with different methods. The authors found that data from urban tree inventories are currently being employed in research with an increasing number of focuses across a geographical scope that spans all continents except Africa. Four main types of urban tree inventories were distinguished: satellite-supported methods, airplane-supported methods, on-the-ground scanning or digital photography, and field surveys. Compiling results across studies and evaluating the parameters collected by these inventory methods and their accuracy of measurement revealed that the technology itself and current data processing methods limit the reliability of the data obtained from all methods except field surveys. The study authors recommend further technological development and scientific testing before these methods can replace field surveys.
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| 20. |
- Bussy, Aurélie, et al.
(författare)
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Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
- 2023
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 44:7, s. 2684-2700
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
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| 21. |
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| 22. |
- Canton, Sophie, et al.
(författare)
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Toward Highlighting the Ultrafast Electron Transfer Dynamics at the Optically Dark Sites of Photocatalysts
- 2013
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Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 4:11, s. 1972-1976
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Tidskriftsartikel (refereegranskat)abstract
- Building a detailed understanding of the structure function relationship is a crucial step in the optimization of molecular photocatalysts employed in water splitting schemes. The optically dark nature of their active sites usually prevents a complete mapping of the photoinduced dynamics. In this work, transient X-ray absorption spectroscopy highlights the electronic and geometric changes that affect such a center in a bimetallic model complex. Upon selective excitation of the ruthenium chromophore, the cobalt moiety is reduced through intramolecular electron transfer and undergoes a spin flip accompanied by an average bond elongation of 0.20 +/- 0.03 angstrom. The analysis is supported by simulations based on density functional theory structures (B3LYP*/TZVP) and FEFF 9.0 multiple scattering calculations. More generally, these results exemplify the large potential of the technique for tracking elusive intermediates that impart unique functionalities in photochemical devices.
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| 23. |
- Canton, Sophie, et al.
(författare)
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Visualizing the non-equilibrium dynamics of photoinduced intramolecular electron transfer with femtosecond X-ray pulses.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Ultrafast photoinduced electron transfer preceding energy equilibration still poses many experimental and conceptual challenges to the optimization of photoconversion since an atomic-scale description has so far been beyond reach. Here we combine femtosecond transient optical absorption spectroscopy with ultrafast X-ray emission spectroscopy and diffuse X-ray scattering at the SACLA facility to track the non-equilibrated electronic and structural dynamics within a bimetallic donor-acceptor complex that contains an optically dark centre. Exploiting the 100-fold increase in temporal resolution as compared with storage ring facilities, these measurements constitute the first X-ray-based visualization of a non-equilibrated intramolecular electron transfer process over large interatomic distances. Experimental and theoretical results establish that mediation through electronically excited molecular states is a key mechanistic feature. The present study demonstrates the extensive potential of femtosecond X-ray techniques as diagnostics of non-adiabatic electron transfer processes in synthetic and biological systems, and some directions for future studies, are outlined.
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| 24. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 25. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
-
Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
-
Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 26. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 27. |
- Gasull, Magda, et al.
(författare)
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Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort
- 2019
-
Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 169, s. 417-433
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.
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| 28. |
- Gaudet, Mia M., et al.
(författare)
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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
-
Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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| 29. |
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| 30. |
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| 31. |
- Haldrup, Kristoffer, et al.
(författare)
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Ultrafast X-Ray Scattering Measurements of Coherent Structural Dynamics on the Ground-State Potential Energy Surface of a Diplatinum Molecule
- 2019
-
Ingår i: Physical Review Letters. - 0031-9007. ; 122:6
-
Tidskriftsartikel (refereegranskat)abstract
- We report x-ray free electron laser experiments addressing ground-state structural dynamics of the diplatinum anion Pt2POP4 following photoexcitation. The structural dynamics are tracked with <100 fs time resolution by x-ray scattering, utilizing the anisotropic component to suppress contributions from the bulk solvent. The x-ray data exhibit a strong oscillatory component with period 0.28 ps and decay time 2.2 ps, and structural analysis of the difference signal directly shows this as arising from ground-state dynamics along the PtPt coordinate. These results are compared with multiscale Born-Oppenheimer molecular dynamics simulations and demonstrate how off-resonance excitation can be used to prepare a vibrationally cold excited-state population complemented by a structure-dependent depletion of the ground-state population which subsequently evolves in time, allowing direct tracking of ground-state structural dynamics.
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| 32. |
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| 33. |
- Hmelo, Laura R., et al.
(författare)
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Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange
- 2015
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Ingår i: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 10:11, s. 1820-1841
-
Tidskriftsartikel (refereegranskat)abstract
- Allelic exchange is an efficient method of bacterial genome engineering. This protocol describes the use of this technique to make gene knockouts and knock-ins, as well as single-nucleotide insertions, deletions and substitutions, in Pseudomonas aeruginosa. Unlike other approaches to allelic exchange, this protocol does not require heterologous recombinases to insert or excise selective markers from the target chromosome. Rather, positive and negative selections are enabled solely by suicide vector-encoded functions and host cell proteins. Here, mutant alleles, which are flanked by regions of homology to the recipient chromosome, are synthesized in vitro and then cloned into allelic exchange vectors using standard procedures. These suicide vectors are then introduced into recipient cells by conjugation. Homologous recombination then results in antibiotic-resistant single-crossover mutants in which the plasmid has integrated site-specifically into the chromosome. Subsequently, unmarked double-crossover mutants are isolated directly using sucrose-mediated counter-selection. This two-step process yields seamless mutations that are precise to a single base pair of DNANA. The entire procedure requires similar to 2 weeks.
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| 34. |
- Jacobsson, Annelie, et al.
(författare)
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Effects of type of packaging material on shelf-life of fresh broccoli by means of changes in weight, colour and texture
- 2004
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Ingår i: European Food Research and Technology. - : Springer Science and Business Media LLC. - 1438-2377 .- 1438-2385. ; 218:2, s. 157-163
-
Tidskriftsartikel (refereegranskat)abstract
- Five polymeric films were studied to determine their ability to retain the colour, weight and texture of broccoli (Brassica oleracea L. var. Italica "Monterey"). The materials were oriented polypropylene (OPP), polyvinyl chloride (PVC) and two different low-density polyethylenes (LDPE), one of which contained a sachet reported to absorb ethylene. The broccoli was packaged and stored at 4 and 10 °C for 4 weeks. The weight, colour, chlorophyll content and texture were monitored during storage as well as O 2 and CO2 concentrations inside the packages. Packaging prolonged the broccoli shelf-life by up to 14 days. The shelf-life varied depending on the packaging material and quality parameter considered. The atmosphere was modified inside the packages; however, no package provided the recommended atmosphere (O2 1-2% and CO2 5-10%) for broccoli. Packaging in OPP resulted in the highest CO2 concentration, 6%, while the lowest O2 concentration, 9%, was created in the LDPE package without a sachet for ethylene absorption. Storage in LDPE without ethylene absorber resulted in the overall longest shelf-life. Broccoli stored in PVC deteriorated faster than broccoli packaged in the other materials. The influence of packaging material was greater at the higher temperature.
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| 35. |
- Jacobsson, A, et al.
(författare)
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Influence of packaging material and storage condition on the sensory quality of broccoli
- 2004
-
Ingår i: Food Quality and Preference. - 0950-3293 .- 1873-6343. ; 15:4, s. 301-310
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Tidskriftsartikel (refereegranskat)abstract
- The sensory quality of broccoli stored in modified atmosphere packages was studied. Oriented polypropylene (OPP), polyvinyl chloride (PVC) and low-density polyethylene (LDPE) were used as packaging materials. The LDPE contained an ethylene-absorbing sachet. The samples were stored for I week, either at a constant temperature of 10 degreesC or for 3 days at 4 degreesC, followed by 4 days at 10 degreesC. The atmospheres that were developed inside the different packaging materials during storage differed significantly. After storage, the broccoli was evaluated both raw and cooked using a triangle test and a quantitative descriptive analysis. The triangle test showed significant differences in the smell of broccoli stored in different packaging materials after cooking. No differences were detected in the raw broccoli. The quantitative descriptive analysis showed significant differences in the fresh smell and flavour, the chewing resistance, and the crispness, between samples after cooking. Overall, including all the sensory properties studied, broccoli packaged in LDPE (5% O-2 7% CO2) that contained an ethylene absorber was perceived to be the sample most similar to fresh broccoli. There were no differences in weight loss between broccoli stored in the different packaging materials. (C) 2003 Elsevier Ltd. All rights reserved.
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| 36. |
- Jacobsson, A., et al.
(författare)
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Influence of packaging material and storage temperature on texture, colour, and weight of broccoli.
- 2003
-
Ingår i: ISHS Acta Horticulturae. - 0567-7572. ; 600, s. 323-323
-
Konferensbidrag (refereegranskat)abstract
- Sophisticated packaging solutions can be used in order to preserve vegetables during storage and transport. Polymeric films with selective barriers matching the respiration of the produce, thereby creating an ideal atmosphere inside the package, are available on the market. Fresh broccoli (Brassica oleracea L. var. italica ‘Monterey’) heads were packed in 4 different commercially available polymeric films, and stored at 4 and 10°C respectively. During storage the weight, colour, chlorophyll content and texture were monitored. The investigated polymer materials were oriented polypropylene (OPP), polyvinyl chloride (PVC) and two types of polyethylene (PE) packagings. The choice of packaging material had an impact on the measured quality parameters of broccoli. Storage in OPP resulted in the longest storage life. Broccoli stored in PVC film deteriorated faster than broccoli packaged in the other materials. It was also observed that the influence of the type of packaging material was more important at the higher temperature. The implications of this work for the packaging and storage of fresh broccoli will be discussed.
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| 37. |
- Jacobsson, A, et al.
(författare)
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Influence of temperature, modified atmosphere packaging, and heat treatment on aroma compounds in broccoli
- 2004
-
Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 52:6, s. 1607-1614
-
Tidskriftsartikel (refereegranskat)abstract
- The aroma compounds in broccoli stored in different modified atmospheres were studied. The packaging materials used were oriented polypropylene (OPP), poly(vinyl chloride) (PVC), and low-density polyethylene (LDPE) containing an ethylene-absorbing sachet. All samples were stored for either 1 week at a constant temperature of 10 degreesC or for 3 days at 4 degreesC, followed by 4 days at 10 degreesC. The atmospheres that developed inside the packaging materials differed significantly. The broccoli samples were analyzed raw and after cooking, with regard to volatile compounds, using gas-phase (headspace) extraction followed by gas chromatography-mass spectrometry (GC-MS) and GC-olfactometry. Dimethyl sulfide (DMS), dimethyl disulfide (DMDS), dimethyl trisulfide (DMTS), hexanal, 3-cis-hexen-1-ol, nonanal, ethanol, and a group of thiocyanates were selected for a detailed study because these compounds cause off-odor and can be used as indicators of stress. Significant differences were found in the aroma profiles of the broccoli samples relative to the packaging materials used for storage. Storage in OPP (14% O-2, 10.5% CO2) resulted in most of the off-odors, while storage in LDPE (6% O-2, 7% CO2) and PVC (17.9% O-2, 4% CO2) was found to maintain the concentration of DMS, DMDS, and DMTS during storage. Heat treatment of the broccoli increased the content of aroma compounds as well as the number of compounds containing sulfur.
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| 38. |
- Jacobsson, A., et al.
(författare)
-
The effect of packaging material on the sensory properties of broccoli.
- 2003
-
Ingår i: ISHS Acta Horticulturae. - 0567-7572. ; 599, s. 323-323
-
Konferensbidrag (refereegranskat)abstract
- Three different commercially available polymeric films were studied to determine their effect on the sensory properties of fresh broccoli (Brassica oleracea L. var. Italica cv. ‘Marathon’). The polymer materials investigated were oriented polypropylene (OPP), polyvinyl chloride (PVC) and one low density polyethylene (LDPE) which contained an ethylene absorber. The fresh broccoli was packaged and stored for one week at 10°C or 3 days at 4°C followed by 4 days at 10°C. The oxygen and carbon dioxide concentrations inside the packages were monitored during storage. After storage the broccoli was evaluated according to sensory analyses, i.e. triangle test and quantitative descriptive analysis, by an analytical panel. The panel judged the broccoli according to smell, taste, texture and appearance. The triangle test showed significant differences between the smell of the broccoli samples, stored in the different packaging materials, when cooked. However, no differences between the raw broccoli, stored in the different packaging materials could be detected. The quantitative descriptive analysis showed that the following attributes; fresh smell and taste, chewing resistance, and crispness, differed significantly between the packaged broccoli when cooked. The appearance was shown to be the sensory property of broccoli most affected by the storage conditions, i.e. packaging material used and storage temperature. The results indicated the importance of the packaging material for maintaining the broccoli quality. However, one packaging material that was able to maintain all the studied sensory properties could not be identified.
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| 39. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 40. |
- Kjær, Kasper S., et al.
(författare)
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Finding intersections between electronic excited state potential energy surfaces with simultaneous ultrafast X-ray scattering and spectroscopy
- 2019
-
Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 10:22, s. 5749-5760
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Tidskriftsartikel (refereegranskat)abstract
- Light-driven molecular reactions are dictated by the excited state potential energy landscape, depending critically on the location of conical intersections and intersystem crossing points between potential surfaces where non-adiabatic effects govern transition probabilities between distinct electronic states. While ultrafast studies have provided significant insight into electronic excited state reaction dynamics, experimental approaches for identifying and characterizing intersections and seams between electronic states remain highly system dependent. Here we show that for 3d transition metal systems simultaneously recorded X-ray diffuse scattering and X-ray emission spectroscopy at sub-70 femtosecond time-resolution provide a solid experimental foundation for determining the mechanistic details of excited state reactions. In modeling the mechanistic information retrieved from such experiments, it becomes possible to identify the dominant trajectory followed during the excited state cascade and to determine the relevant loci of intersections between states. We illustrate our approach by explicitly mapping parts of the potential energy landscape dictating the light driven low-to-high spin-state transition (spin crossover) of [Fe(2,2′-bipyridine)3]2+, where the strongly coupled nuclear and electronic dynamics have been a source of interest and controversy. We anticipate that simultaneous X-ray diffuse scattering and X-ray emission spectroscopy will provide a valuable approach for mapping the reactive trajectories of light-triggered molecular systems involving 3d transition metals.
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| 41. |
- Kjær, Kasper S., et al.
(författare)
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Ligand manipulation of charge transfer excited state relaxation and spin crossover in [Fe(2,2'-bipyridine)2(CN)2]
- 2017
-
Ingår i: Structural Dynamics. - : AIP Publishing. - 2329-7778. ; 4:4
-
Tidskriftsartikel (refereegranskat)abstract
- We have used femtosecond resolution UV-visible and Kβ x-ray emission spectroscopy to characterize the electronic excited state dynamics of [Fe(bpy)2(CN)2], where bpy=2,20-bipyridine, initiated by metal-to-ligand charge transfer (MLCT) excitation. The excited-state absorption in the transient UV-visible spectra, associated with the 2,20-bipyridine radical anion, provides a robust marker for the MLCT excited state, while the transient Kβ x-ray emission spectra provide a clear measure of intermediate and high spin metal-centered excited states. From these measurements, we conclude that the MLCT state of [Fe(bpy)2(CN)2] undergoes ultrafast spin crossover to a metalcentered quintet excited state through a short lived metal-centered triplet transient species. These measurements of [Fe(bpy)2(CN)2] complement prior measurement performed on [Fe(bpy)3]2+ and [Fe(bpy)(CN)4]2- in dimethylsulfoxide solution and help complete the chemical series [Fe(bpy)N(CN)6-2N]2N-4, whereN=1-3. The measurements confirm that simple ligand modifications can significantly change the relaxation pathways and excited state lifetimes and support the further investigation of light harvesting and photocatalytic applications of 3d transition metal complexes.
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| 42. |
- Kjær, Kasper S., et al.
(författare)
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Solvent control of charge transfer excited state relaxation pathways in [Fe(2,2′-bipyridine)(CN)4]2-
- 2018
-
Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 20:6, s. 4238-4249
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Tidskriftsartikel (refereegranskat)abstract
- The excited state dynamics of solvated [Fe(bpy)(CN)4]2-, where bpy = 2,2′-bipyridine, show significant sensitivity to the solvent Lewis acidity. Using a combination of optical absorption and X-ray emission transient spectroscopies, we have previously shown that the metal to ligand charge transfer (MLCT) excited state of [Fe(bpy)(CN)4]2- has a 19 picosecond lifetime and no discernable contribution from metal centered (MC) states in weak Lewis acid solvents, such as dimethyl sulfoxide and acetonitrile.1,2 In the present work, we use the same combination of spectroscopic techniques to measure the MLCT excited state relaxation dynamics of [Fe(bpy)(CN)4]2- in water, a strong Lewis acid solvent. The charge-transfer excited state is now found to decay in less than 100 femtoseconds, forming a quasi-stable metal centered excited state with a 13 picosecond lifetime. We find that this MC excited state has triplet (3MC) character, unlike other reported six-coordinate Fe(ii)-centered coordination compounds, which form MC quintet (5MC) states. The solvent dependent changes in excited state non-radiative relaxation for [Fe(bpy)(CN)4]2- allows us to infer the influence of the solvent on the electronic structure of the complex. Furthermore, the robust characterization of the dynamics and optical spectral signatures of the isolated 3MC intermediate provides a strong foundation for identifying 3MC intermediates in the electronic excited state relaxation mechanisms of similar Fe-centered systems being developed for solar applications.
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| 43. |
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| 44. |
- Kunnus, Kristjan, et al.
(författare)
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Vibrational wavepacket dynamics in Fe carbene photosensitizer determined with femtosecond X-ray emission and scattering
- 2020
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- The non-equilibrium dynamics of electrons and nuclei govern the function of photoactive materials. Disentangling these dynamics remains a critical goal for understanding photoactive materials. Here we investigate the photoinduced dynamics of the [Fe(bmip)2]2+ photosensitizer, where bmip = 2,6-bis(3-methyl-imidazole-1-ylidine)-pyridine, with simultaneous femtosecond-resolution Fe Kα and Kβ X-ray emission spectroscopy (XES) and X-ray solution scattering (XSS). This measurement shows temporal oscillations in the XES and XSS difference signals with the same 278 fs period oscillation. These oscillations originate from an Fe-ligand stretching vibrational wavepacket on a triplet metal-centered (3MC) excited state surface. This 3MC state is populated with a 110 fs time constant by 40% of the excited molecules while the rest relax to a 3MLCT excited state. The sensitivity of the Kα XES to molecular structure results from a 0.7% average Fe-ligand bond length shift between the 1 s and 2p core-ionized states surfaces.
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| 45. |
- Lee, SangWook, et al.
(författare)
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Network analyses identify liver-specific targets for treating liver diseases
- 2017
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 13:8
-
Tidskriftsartikel (refereegranskat)abstract
- We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co-expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver-specific genes co-expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver-specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver-specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin-like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.
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| 46. |
- Lemke, Henrik T., et al.
(författare)
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Coherent structural trapping through wave packet dispersion during photoinduced spin state switching
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The description of ultrafast nonadiabatic chemical dynamics during molecular photo-transformations remains challenging because electronic and nuclear configurations impact each other and cannot be treated independently. Here we gain experimental insights, beyond the Born-Oppenheimer approximation, into the light-induced spin-state trapping dynamics of the prototypical [Fe(bpy) 3 ] 2+ compound by time-resolved X-ray absorption spectroscopy at sub-30-femtosecond resolution and high signal-to-noise ratio. The electronic decay from the initial optically excited electronic state towards the high spin state is distinguished from the structural trapping dynamics, which launches a coherent oscillating wave packet (265 fs period), clearly identified as molecular breathing. Throughout the structural trapping, the dispersion of the wave packet along the reaction coordinate reveals details of intramolecular vibronic coupling before a slower vibrational energy dissipation to the solution environment. These findings illustrate how modern time-resolved X-ray absorption spectroscopy can provide key information to unravel dynamic details of photo-functional molecules.
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| 47. |
- Loren, Niklas, et al.
(författare)
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Sodium reduction in foods : Challenges and strategies for technical solutions
- 2023
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Ingår i: Journal of Food Science. - : John Wiley and Sons Inc. - 0022-1147 .- 1750-3841. ; 88:3, s. 885-
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Tidskriftsartikel (refereegranskat)abstract
- In many parts of the world, sodium consumption is higher than recommended levels, representing one of the most important food-related health challenges and leading to considerable economical costs for society. Therefore, there is a need to find technical solutions for sodium reduction that can be implemented by food producers and within food services. The aims of this review are to discuss the barriers related to sodium reduction and to highlight a variety of technical solutions. The barriers relate to consumer perception, microbiology, processing, and physicochemistry. Existing technical solutions include inhomogeneous salt distribution, coated salt particles, changing particle sizes and forms, surface coating, multisensory combinations, sodium replacements, double emulsions, adapted serum release by microstructure design, and adapted brittleness by microstructure design. These solutions, their implementation and the associated challenges, and applicable product categories are described. Some of these solutions are ready for use or are in their early development stages. Many solutions are promising, but in most cases, some form of adaptation or optimization is needed before application in specific products, and care must always be taken to ensure food safety. For instance, further research and innovation are required in the dynamic evolution of saltiness perception, consumer acceptance, the binding and migration of sodium, juiciness, microbiological safety, and the timing of salt addition during processing. Once implemented, these solutions will undoubtedly support food producers and food services in reducing sodium content and extend the application of the solutions to different foods. © 2022 Research Institutes of Sweden, Swedish Food Federation and Lyckeby Culinar AB.
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| 48. |
- Lützhøft, Ditte Olsen, et al.
(författare)
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Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model
- 2022
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Ingår i: BMC Microbiology. - : BioMed Central (BMC). - 1471-2180. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH.RESULTS: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.CONCLUSIONS: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.
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| 49. |
- Menvielle, Gwenn, et al.
(författare)
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The role of smoking and diet in explaining educational inequalities in lung cancer incidence.
- 2009
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101:5, s. 321-330
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies in many countries have reported higher lung cancer incidence and mortality in individuals with lower socioeconomic status. METHODS: To investigate the role of smoking in these inequalities, we used data from 391,251 participants in the European Prospective Investigation into Cancer and Nutrition study, a cohort of individuals in 10 European countries. We collected information on smoking (history and quantity), fruit and vegetable consumption, and education through questionnaires at study entry and gathered data on lung cancer incidence for a mean of 8.4 years. Socioeconomic status was defined as the highest attained level of education, and participants were grouped by sex and region of residence (Northern Europe, Germany, or Southern Europe). Relative indices of inequality (RIIs) of lung cancer risk unadjusted and adjusted for smoking were estimated using Cox regression models. Additional analyses were performed by histological type. RESULTS: During the study period, 939 men and 692 women developed lung cancer. Inequalities in lung cancer risk (RII(men) = 3.62, 95% confidence interval [CI] = 2.77 to 4.73, 117 vs 52 per 100,000 person-years for lowest vs highest education level; RII(women) = 2.39, 95% CI = 1.77 to 3.21, 46 vs 25 per 100,000 person-years) decreased after adjustment for smoking but remained statistically significant (RII(men) = 2.29, 95% CI = 1.75 to 3.01; RII(women) = 1.59, 95% CI = 1.18 to 2.13). Large RIIs were observed among men and women in Northern European countries and among men in Germany, but inequalities in lung cancer risk were reverse (RIIs < 1) among women in Southern European countries. Inequalities differed by histological type. Adjustment for smoking reduced inequalities similarly for all histological types and among men and women in all regions. In all analysis, further adjustment for fruit and vegetable consumption did not change the estimates. CONCLUSION: Self-reported smoking consistently explains approximately 50% of the inequalities in lung cancer risk due to differences in education.
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| 50. |
- Milne, Christopher J., et al.
(författare)
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Disentangling the evolution of electrons and holes in photoexcited ZnO nanoparticles
- 2023
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Ingår i: Structural Dynamics. - : American Institute of Physics (AIP). - 2329-7778. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of charge carriers in photoexcited room temperature ZnO nanoparticles in solution is investigated using ultrafast ultraviolet photoluminescence spectroscopy, ultrafast Zn K-edge absorption spectroscopy, and ab initio molecular dynamics (MD) simulations. The photoluminescence is excited at 4.66 eV, well above the band edge, and shows that electron cooling in the conduction band and exciton formation occur in <500 fs, in excellent agreement with theoretical predictions. The x-ray absorption measurements, obtained upon excitation close to the band edge at 3.49 eV, are sensitive to the migration and trapping of holes. They reveal that the 2 ps transient largely reproduces the previously reported transient obtained at 100 ps time delay in synchrotron studies. In addition, the x-ray absorption signal is found to rise in similar to 1.4 ps, which we attribute to the diffusion of holes through the lattice prior to their trapping at singly charged oxygen vacancies. Indeed, the MD simulations show that impulsive trapping of holes induces an ultrafast expansion of the cage of Zn atoms in <200 fs, followed by an oscillatory response at a frequency of similar to 100 cm-1, which corresponds to a phonon mode of the system involving the Zn sub-lattice.
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