| 1. |
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| 2. |
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| 3. |
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| 4. |
- Müller, T D, et al.
(författare)
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Ghrelin.
- 2015
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Ingår i: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 437-60
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Tidskriftsartikel (refereegranskat)abstract
- The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.
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| 5. |
- Nelson, G., et al.
(författare)
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QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy
- 2021
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 284:1, s. 56-73
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Tidskriftsartikel (refereegranskat)abstract
- A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
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| 6. |
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| 7. |
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| 8. |
- Harpold, A. A., et al.
(författare)
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Laser vision : lidar as a transformative tool to advance critical zone science
- 2015
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Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 19:6, s. 2881-2897
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Tidskriftsartikel (refereegranskat)abstract
- Observation and quantification of the Earth's surface is undergoing a revolutionary change due to the increased spatial resolution and extent afforded by light detection and ranging (lidar) technology. As a consequence, lidar-derived information has led to fundamental discoveries within the individual disciplines of geomorphology, hydrology, and ecology. These disciplines form the cornerstones of critical zone (CZ) science, where researchers study how interactions among the geosphere, hydrosphere, and biosphere shape and maintain the 'zone of life', which extends from the top of unweathered bedrock to the top of the vegetation canopy. Fundamental to CZ science is the development of transdisciplinary theories and tools that transcend disciplines and inform other's work, capture new levels of complexity, and create new intellectual outcomes and spaces. Researchers are just beginning to use lidar data sets to answer synergistic, transdisciplinary questions in CZ science, such as how CZ processes co-evolve over long timescales and interact over shorter timescales to create thresholds, shifts in states and fluxes of water, energy, and carbon. The objective of this review is to elucidate the transformative potential of lidar for CZ science to simultaneously allow for quantification of topographic, vegetative, and hydrological processes. A review of 147 peer-reviewed lidar studies highlights a lack of lidar applications for CZ studies as 38 % of the studies were focused in geomorphology, 18 % in hydrology, 32 % in ecology, and the remaining 12 % had an interdisciplinary focus. A handful of exemplar transdisciplinary studies demonstrate lidar data sets that are well-integrated with other observations can lead to fundamental advances in CZ science, such as identification of feedbacks between hydrological and ecological processes over hillslope scales and the synergistic co-evolution of landscape-scale CZ structure due to interactions amongst carbon, energy, and water cycles. We propose that using lidar to its full potential will require numerous advances, including new and more powerful open-source processing tools, exploiting new lidar acquisition technologies, and improved integration with physically based models and complementary in situ and remote-sensing observations. We provide a 5-year vision that advocates for the expanded use of lidar data sets and highlights subsequent potential to advance the state of CZ science.
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| 9. |
- Valassi, E., et al.
(författare)
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High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry
- 2019
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 181:5, s. 461-472
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases the commonest cause of death soon after diagnosis, emphasizing the need for careful vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.
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| 10. |
- Weismuller, T. J., et al.
(författare)
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Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis
- 2017
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 152:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR, 0.90; P =.03, respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). CONCLUSIONS: In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.
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| 11. |
- Blideanu, V., et al.
(författare)
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Nucleon-induced reactions at intermediate energies : New data at 96 MeV and theoretical status
- 2004
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 70:1, s. 014607-
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Tidskriftsartikel (refereegranskat)abstract
- Double-differential cross sections for light charged particle production (up to A=4) were measured in 96 MeV neutron-induced reactions, at the TSL Laboratory Cyclotron in Uppsala (Sweden). Measurements for three targets, Fe, Pb, and U, were performed using two independent devices, SCANDAL and MEDLEY. The data were recorded with low-energy thresholds and for a wide angular range (20°–160°). The normalization procedure used to extract the cross sections is based on the np elastic scattering reaction that we measured and for which we present experimental results. A good control of the systematic uncertainties affecting the results is achieved. Calculations using the exciton model are reported. Two different theoretical approaches proposed to improve its predictive power regarding the complex particle emission are tested. The capabilities of each approach is illustrated by comparison with the 96 MeV data that we measured, and with other experimental results available in the literature.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Zanini, Luca, et al.
(författare)
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Measurement of Volatile Radionuclides Production and Release Yields followed by a Post-Irradiation Analysis of a Pb/Bi Filled Ta Target at ISOLDE
- 2014
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Ingår i: Nuclear Data Sheets. - : Elsevier BV. - 0090-3752. ; 119, s. 292-295
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Tidskriftsartikel (refereegranskat)abstract
- A crucial requirement in the development of liquid-metal spallation neutron target is knowledge of the composition and amount of volatile radionuclides that are released from the target during operation. It is also important to know the total amount produced, which could be released if there was an accident. One type is the lead-bismuth eutectic (LBE) target where different radionuclides can be produced following interaction with a high-energy proton beam, notably noble gases (Ar, Kr, Xe isotopes) and other relative volatile isotopes such as Hg and At. The results of an irradiation experiment performed at ISOLDE on a LBE target are compared with predictions from the MCNPX code using the latest developments on the Liege Intranuclear Cascade model (INCL4.6) and the CEM03 model. The calculations are able to reproduce the mass distribution of the radioisotopes produced, including the At production, where there is a significant contribution from secondary reactions. Subsequently, a post-irradiation examination of the irradiated target was performed. Investigations of both the tantalum target structure, in particular the beam window, and the lead-bismuth eutectic were performed using several experimental techniques. No sign of severe irradiation damage, previously observed in other ISOLDE targets, was found.
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| 19. |
- Aumayr, Friedrich, et al.
(författare)
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Roadmap on photonic, electronic and atomic collision physics : III. Heavy particles
- 2019
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Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 52:17
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Tidskriftsartikel (refereegranskat)abstract
- We publish three Roadmaps on photonic, electronic and atomic collision physics in order to celebrate the 60th anniversary of the ICPEAC conference. Roadmap III focusses on heavy particles: with zero to relativistic speeds. Modern theoretical and experimental approaches provide detailed insight into the wide range of many-body interactions involving projectiles and targets of varying complexity ranging from simple atoms, through molecules and clusters, complex biomolecules and nanoparticles to surfaces and crystals. These developments have been driven by technological progress and future developments will expand the horizon of the systems that can be studied. This Roadmap aims at looking back along the road, explaining the evolution of the field, and looking forward, collecting nineteen contributions from leading scientists in the field.
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| 20. |
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| 21. |
- Blösch, Günter, et al.
(författare)
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Twenty-three unsolved problems in hydrology (UPH) - a community perspective
- 2019
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Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
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Tidskriftsartikel (refereegranskat)abstract
- This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Ciappina, M. F., et al.
(författare)
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Double ionization of helium by ion impact analyzed using four-body Dalitz plots
- 2008
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 77:6, s. 62706-
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Tidskriftsartikel (refereegranskat)abstract
- We have performed experimental and theoretical studies of double ionization of helium by 6 MeV proton impact using a recently developed tool, four-particle Dalitz plots [Schulz , J. Phys. B 22, 3091 (2007)] which enable the representation of multiple differential cross sections as a function of all four fragments in a single spectrum without loss of any part of the total cross section. As a result, the relative importance of the various interactions between the fragments can be studied in great detail. Comparisons of experimental data with theoretical first-order calculations and simulations for the higher-order (TS-2) process show that elastic scattering between the heavy particles is surprisingly strong. For a large fraction of collision events, the final-state electron momenta are small compared to the momenta of the heavy particles. Our results suggest that an uncorrelated double ionization mechanism, involving two independent interactions of the projectile with both electrons, is significantly more important than previously expected for such fast collisions.
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| 26. |
- Dangtip, S, et al.
(författare)
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A facility for measurements of nuclear cross sections for fast neutron cancer therapy
- 2000
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Ingår i: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. - 0168-9002. ; 452:3, s. 484-504
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Tidskriftsartikel (refereegranskat)abstract
- A facility for measurements of neutron-induced double-differential light-ion production cross-sections, for application within. e.g.. fast neutron cancer therapy, is described. The central detection elements are three-detector telescopes consisting of two
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| 27. |
- Duda, LC, et al.
(författare)
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Polarized resonant inelastic X-ray scattering from single-crystal transition metal oxides
- 2000
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Ingår i: JOURNAL OF ELECTRON SPECTROSCOPY AND RELATED PHENOMENA. - : ELSEVIER SCIENCE BV. - 0368-2048. ; 110:1-3, s. 275-285
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Tidskriftsartikel (refereegranskat)abstract
- Inelastic X-ray scattering of synchrotron radiation at core resonances has turned soft X-ray emission spectroscopy into a new tool for probing the electronic structure of transition metal (TM) oxides at high resolution. In contrast to ordinary fluorescenc
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| 28. |
- Finan, B, et al.
(författare)
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Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans
- 2013
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Ingår i: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 5:209, s. 209ra151-
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Tidskriftsartikel (refereegranskat)abstract
- Compared to best-in-class GLP-1 mono-agonists, unimolecular co-agonists of GLP-1 and GIP with optimized pharmacokinetics enhance glycemic and metabolic benefits in mammals.
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| 29. |
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| 30. |
- Gottselig, N., et al.
(författare)
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Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers
- 2017
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:10, s. 1592-1607
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Tidskriftsartikel (refereegranskat)abstract
- Biogeochemical cycling of elements largely occurs in dissolved state, but many elements may also be bound to natural nanoparticles (NNP, 1-100 nm) and fine colloids (100-450 nm). We examined the hypothesis that the size and composition of stream water NNP and colloids vary systematically across Europe. To test this hypothesis, 96 stream water samples were simultaneously collected in 26 forested headwater catchments along two transects across Europe. Three size fractions (~1-20 nm, >20-60 nm, and >60 nm) of NNP and fine colloids were identified with Field Flow Fractionation coupled to inductively coupled plasma mass spectrometry and an organic carbon detector. The results showed that NNP and fine colloids constituted between 2 ± 5% (Si) and 53 ± 21% (Fe; mean ± SD) of total element concentrations, indicating a substantial contribution of particles to element transport in these European streams, especially for P and Fe. The particulate contents of Fe, Al, and organic C were correlated to their total element concentrations, but those of particulate Si, Mn, P, and Ca were not. The fine colloidal fractions >60 nm were dominated by clay minerals across all sites. The resulting element patterns of NNP <60 nm changed from North to South Europe from Fe- to Ca-dominated particles, along with associated changes in acidity, forest type, and dominant lithology.
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| 31. |
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| 32. |
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| 33. |
- Hartmann, Michael, et al.
(författare)
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Increasing robustness and sensitivity of protein microarrays through microagitation and automation
- 2006
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Ingår i: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670 .- 1873-4324. ; 564:1, s. 66-73
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Tidskriftsartikel (refereegranskat)abstract
- Assay systems that employ protein microarrays for the analysis of complex samples are powerful tools to generate a high amount of data from a limiting amount of sample. Due to miniaturization, these systems are susceptible to fluctuations during signal generation and the use of uniform conditions for sample incubation and during the assay procedure is required to get reproducible results. Diffusion limits may prevent constant conditions on all parts of the array and can lead to the decease of the sensitivity of the array. Therefore, we set-up an automated assay system integrating a novel microagitation device using surface acoustic wave (SAW) technology. Multiplexed assays for the detection of autoantibodies from human serum and sandwich immunoassay for the detection of matrix metalloproteases (MMPs) were used to evaluate the system. Diffusion-rate limited solid phase reactions were enhanced by microagitation using the SAW technology resulting in up to three-fold higher signals.
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| 34. |
- Holmes, Felicity Alice, 1995-
(författare)
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Glacier-Ocean Interactions in the Arctic : Contemporary calving and frontal melt from field observations, remote sensing, and numerical modelling
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Globally, glaciers are losing mass as a result of the changing climate, with this mass loss having a considerable societal impact through rising sea levels. Glaciers which terminate in the oceans are particularly vulnerable to changing external conditions as a result of high sensitivity at their marine margins. Both changing meteorological patterns as well as changing ocean heat content and transport have been previously identified as potential drivers for contemporary rapid glacier retreat and acceleration. However, uncertainties remain and provide motivation for studies which improve our process understanding. Here, we use a combination of field data, remotely sensed data, and targeted numerical modelling experiments to investigate marine terminating glacier response to external changes. This is done in order to address uncertainties around mass loss at the inaccessible glacier-ocean interface. In particular, focus is paid to the processes of submarine melt and calving, together referred to as frontal ablation. Submarine melt is the melting of glacier termini by warm ocean waters below the waterline, whilst calving is the breaking off of icebergs from glacier termini. The two processes are interlinked, with submarine melting undercutting the glacier terminus and contributing to calving, whilst calving events can expose larger areas of the glacier margin to submarine melt. To look for relationships between frontal ablation and external forcings, four glacier-fjord systems were studied to varying extents; two grounded glaciers in Svalbard (Kronebreen and Tunabreen) and two glaciers with floating ice tongues in Greenland (Ryder glacier and Petermann glacier). Both submarine melt and calving were examined at various different scales, both temporally and spatially. Specifically, analysis was carried out from the scale of individual calving events up to decadal long time series of glacier margin change. Much of the data used focused on specific glaciological variables such as satellite-derived velocities, margin positions, model simulations, and time-lapse photography of calving events. However, as glaciers and their adjacent fjord or ocean environments impact on each other, data such as water temperatures were also collected from glacier proximal fjord environments. The results from both the observational data and model experiments suggest that ocean temperatures are of great importance for the frontal ablation of glaciers in the Arctic, but that the relationship is complex. Heterogeneous glacier response to external forcings highlights how site specific factors such as bathymetry and fjord geometry can add an additional layer of complexity and make it challenging to scale up results from one glacier to an entire region. However, there are some strong indications that it is the presence of warm air temperatures in conjunction with warm ocean temperatures that is most important for driving frontal ablation - highlighting the need to situate glacier behaviour within a wider environmental context.
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| 35. |
- Jakobsson, Martin, et al.
(författare)
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Evidence for an ice shelf covering the central Arctic Ocean during the penultimate glaciation
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis of a km-thick ice shelf covering the entire Arctic Ocean during peak glacial conditions was proposed nearly half a century ago. Floating ice shelves preserve few direct traces after their disappearance, making reconstructions difficult. Seafloor imprints of ice shelves should, however, exist where ice grounded along their flow paths. Here we present new evidence of ice-shelf groundings on bathymetric highs in the central Arctic Ocean, resurrecting the concept of an ice shelf extending over the entire central Arctic Ocean during at least one previous ice age. New and previously mapped glacial landforms together reveal flow of a spatially coherent, in some regions41-km thick, central Arctic Ocean ice shelf dated to marine isotope stage 6 (similar to 140 ka). Bathymetric highs were likely critical in the ice-shelf development by acting as pinning points where stabilizing ice rises formed, thereby providing sufficient back stress to allow ice shelf thickening.
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| 36. |
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| 37. |
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| 38. |
- Kirchner, Nina, et al.
(författare)
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Shallow ice approximation, second order shallow ice approximation, and full Stokes models : A discussion of their roles in palaeo-ice sheet modelling and development
- 2016
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 147, s. 136-147
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Tidskriftsartikel (refereegranskat)abstract
- Full Stokes ice sheet models provide the most accurate description of ice sheet flow, and can therefore be used to reduce existing uncertainties in predicting the contribution of ice sheets to future sea level rise on centennial time-scales. The level of accuracy at which millennial time-scale palaeo-ice sheet simulations resolve ice sheet flow lags the standards set by Full Stokes models, especially, when Shallow Ice Approximation (SIA) models are used. Most models used in paleo-ice sheet modeling were developed at a time when computer power was very limited, and rely on several assumptions. At the time there was no means of verifying the assumptions by other than mathematical arguments. However, with the computer power and refined Full Stokes models available today, it is possible to test these assumptions numerically. In this paper, we review (Ahlkrona et al., 2013a) where such tests were performed and inaccuracies in commonly used arguments were found. We also summarize (Ahlkrona et al., 2013b) where the implications of the inaccurate assumptions are analyzed for two paleo-models - the SIA and the SOSIA. We review these works without resorting to mathematical detail, in order to make them accessible to a wider audience with a general interest in palaeo-ice sheet modelling. Specifically, we discuss two implications of relevance for palaeo-ice sheet modelling. First, classical SIA models are less accurate than assumed in their original derivation. Secondly, and contrary to previous recommendations, the SOSIA model is ruled out as a practicable tool for palaeo-ice sheet simulations. We conclude with an outlook concerning the new Ice Sheet Coupled Approximation Level (ISCAL) method presented in Ahlkrona et al. (2016), that has the potential to match the accuracy standards of full Stokes model on palaeo-timescales of tens of thousands of years, and to become an alternative to hybrid models currently used in palaeo-ice sheet modelling. The method is applied to an ice sheet covering Svalbard.
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| 39. |
- Kirchner, Nina, et al.
(författare)
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Shallow ice approximation, second order shallow ice approximation, and full Stokes models : A discussion of their roles in palaeo-ice sheet modelling and development
- 2016
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 135, s. 103-114
-
Forskningsöversikt (refereegranskat)abstract
- Full Stokes ice sheet models provide the most accurate description of ice sheet flow, and can therefore be used to reduce existing uncertainties in predicting the contribution of ice sheets to future sea level rise on centennial time-scales. The level of accuracy at which millennial time-scale palaeo-ice sheet simulations resolve ice sheet flow lags the standards set by Full Stokes models, especially, when Shallow Ice Approximation (SIA) models are used. Most models used in paleo-ice sheet modeling were developed at a time when computer power was very limited, and rely on several assumptions. At the time there was no means of verifying the assumptions by other than mathematical arguments. However, with the computer power and refined Full Stokes models available today, it is possible to test these assumptions numerically. In this paper, we review (Ahlkrona et al., 2013a) where such tests were performed and inaccuracies in commonly used arguments were found. We also summarize (Ahlkrona et al., 2013b) where the implications of the inaccurate assumptions are analyzed for two paleo-models - the SIA and the SOSIA. We review these works without resorting to mathematical detail, in order to make them accessible to a wider audience with a general interest in palaeo-ice sheet modelling. Specifically, we discuss two implications of relevance for palaeo-ice sheet modelling. First, classical SIA models are less accurate than assumed in their original derivation. Secondly, and contrary to previous recommendations, the SOSIA model is ruled out as a practicable tool for palaeo-ice sheet simulations. We conclude with an outlook concerning the new Ice Sheet Coupled Approximation Level (ISCAL) method presented in Ahlkrona et al. (2016), that has the potential to match the accuracy standards of full Stokes model on palaeo-timescales of tens of thousands of years, and to become an alternative to hybrid models currently used in palaeo-ice sheet modelling. The method is applied to an ice sheet covering Svalbard.
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| 41. |
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| 42. |
- McDonnell, J.J., et al.
(författare)
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How old is streamwater? : Open questions in catchment transit time conceptualization, modelling and analysis
- 2010
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Ingår i: Hydrological Processes. - : John Wiley & Sons. - 0885-6087 .- 1099-1085. ; 24:12, s. 1745-1754
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Tidskriftsartikel (refereegranskat)abstract
- The time water spends travelling subsurface through a catchment to the stream network (i.e. the catchment water transit time) fundamentally describes the storage, flow pathway heterogeneity and sources of water in a catchment. The distribution of transit times reflects how catchments retain and release water and solutes that in turn set biogeochemical conditions and affect contamination release or persistence. Thus, quan- tifying the transit time distribution provides an important constraint on biogeochemical processes and catchment sensitivity to anthropogenic inputs, contamination and land-use change. Although the assumptions and limitations of past and present transit time modelling approaches have been recently reviewed (McGuire and McDonnell, 2006), there remain many fundamental research challenges for understanding how transit time can be used to quantify catchment flow processes and aid in the development and testing of rainfall–runoff models. In this Commen- tary study, we summarize what we think are the open research questions in transit time research. These thoughts come from a 3-day workshop in January 2009 at the International Atomic Energy Agency in Vienna. We attempt to lay out a roadmap for this work for the hydrological commu- nity over the next 10 years. We do this by first defining what we mean (qualitatively and quantitatively) by transit time and then organize our vision around needs in transit time theory, needs in field studies of tran- sit time and needs in rainfall – runoff modelling. Our goal in presenting this material is to encourage widespread use of transit time information in process studies to provide new insights to catchment function and to inform the structural development and testing of hydrologic models.
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| 43. |
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| 44. |
- Nilsson, Johan, 1965-, et al.
(författare)
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Ice-shelf damming in the glacial Arctic Ocean: dynamical regimes of a basin-covering kilometre-thick ice shelf
- 2017
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Ingår i: Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 11:4, s. 1745-1765
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Tidskriftsartikel (refereegranskat)abstract
- Recent geological and geophysical data suggest that a 1 km thick ice shelf extended over the glacial Arctic Ocean during Marine Isotope Stage 6, about 140 000 years ago. Here, we theoretically analyse the development and equilibrium features of such an ice shelf, using scaling analyses and a one-dimensional ice-sheet-ice-shelf model. We find that the dynamically most consistent scenario is an ice shelf with a nearly uniform thickness that covers the entire Arctic Ocean. Further, the ice shelf has two regions with distinctly different dynamics: a vast interior region covering the central Arctic Ocean and an exit region towards the Fram Strait. In the interior region, which is effectively dammed by the Fram Strait constriction, there are strong back stresses and the mean ice-shelf thickness is controlled primarily by the horizontally integrated mass balance. A narrow transition zone is found near the continental grounding line, in which the ice-shelf thickness decreases offshore and approaches the mean basin thickness. If the surface accumulation and mass flow from the continental ice masses are sufficiently large, the ice-shelf thickness grows to the point where the ice shelf grounds on the Lomonosov Ridge. As this occurs, the back stress increases in the Amerasian Basin and the ice-shelf thickness becomes larger there than in the Eurasian Basin towards the Fram Strait. Using a one-dimensional ice-dynamic model, the stability of equilibrium ice-shelf configurations without and with grounding on the Lomonosov Ridge are examined. We find that the grounded ice-shelf configuration should be stable if the two Lomonosov Ridge grounding lines are located on the opposites sides of the ridge crest, implying that the downstream grounding line is located on a downward sloping bed. This result shares similarities with the classical result on marine ice-sheet stability of Weertman, but due to interactions between the Amerasian and Eurasian ice-shelf segments the mass flux at the downstream grounding line decreases rather than increases with ice thickness.
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| 45. |
- Schmidt, Amand F., et al.
(författare)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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| 46. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 47. |
- Stokes, Chris R., et al.
(författare)
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On the reconstruction of palaeo-ice sheets : Recent advances and future challenges
- 2015
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 125, s. 15-49
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Forskningsöversikt (refereegranskat)abstract
- Reconstructing the growth and decay of palaeo-ice sheets is critical to understanding mechanisms of global climate change and associated sea-level fluctuations in the past, present and future. The significance of palaeo-ice sheets is further underlined by the broad range of disciplines concerned with reconstructing their behaviour, many of which have undergone a rapid expansion since the 1980s. In particular, there has been a major increase in the size and qualitative diversity of empirical data used to reconstruct and date ice sheets, and major improvements in our ability to simulate their dynamics in numerical ice sheet models. These developments have made it increasingly necessary to forge interdisciplinary links between sub-disciplines and to link numerical modelling with observations and dating of proxy records. The aim of this paper is to evaluate recent developments in the methods used to reconstruct ice sheets and outline some key challenges that remain, with an emphasis on how future work might integrate terrestrial and marine evidence together with numerical modelling. Our focus is on pan-ice sheet reconstructions of the last deglaciation, but regional case studies are used to illustrate methodological achievements, challenges and opportunities. Whilst various disciplines have made important progress in our understanding of ice-sheet dynamics, it is clear that data-model integration remains under-used, and that uncertainties remain poorly quantified in both empirically-based and numerical ice-Sheet reconstructions. The representation of past climate will continue to be the largest source of uncertainty for numerical modelling. As such, palaeo-observations are critical to constrain and validate modelling. State-of-the-art numerical models will continue to improve both in model resolution and in the breadth of inclusion of relevant processes, thereby enabling more accurate and more direct comparison with the increasing range of palaeo-observations. Thus, the capability is developing to use all relevant palaeo-records to more strongly constrain deglacial (and to a lesser extent pre-LGM) ice sheet evolution. In working towards that goal, the accurate representation of uncertainties is required for both constraint data and model outputs. Close cooperation between modelling and data-gathering communities is essential to ensure this capability is realised and continues to progress.
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| 48. |
- Toropov, AA, et al.
(författare)
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Temperature-dependent polarized luminescence of exciton polaritons in a ZnO film
- 2005
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Ingår i: Physica Status Solidi (a) applications and materials science. - : Wiley. - 1862-6300 .- 1862-6319. ; 202:3, s. 392-395
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Tidskriftsartikel (refereegranskat)abstract
- We report on the studies of linearly polarized photoluminescence (PL) in a (0001) oriented ZnO epitaxial film, grown by metal organic chemical vapor deposition on a GaN template. The emission of mixed longitudinal-transverse exciton polariton modes was observed up to 130 K that evidences polaritonic nature of the excitonic spectrum up to this elevated temperature.
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| 49. |
- Wain, Louise V, et al.
(författare)
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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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| 50. |
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