| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
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| 5. |
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| 6. |
- Mikkelsen, T N, et al.
(författare)
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Experimental design of multifactor climate change experiments with elevated CO2, warming and drought: the CLIMAITE project
- 2008
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Ingår i: Functional Ecology. - : Wiley. - 1365-2435 .- 0269-8463. ; 22:1, s. 185-195
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings indicate that the interactions among CO2, temperature and water can be substantial, and that the combined effects on the biological systems of several factors may not be predicted from experiments with one or a few factors. Therefore realistic multifactorial experiments involving a larger set of main factors are needed. We describe a new Danish climate change-related field scale experiment, CLIMAITE, in a heath/grassland ecosystem. CLIMAITE is a full factorial combination of elevated CO2, elevated temperature and prolonged summer drought. The manipulations are intended to mimic anticipated major environmental changes at the site by year 2075 as closely as possible. The impacts on ecosystem processes and functioning (at ecophysiological levels, through responses by individuals and communities to ecosystem-level responses) are investigated simultaneously. The increase of [CO2] closely corresponds with the scenarios for year 2075, while the warming treatment is at the lower end of the predictions and seems to be the most difficult treatment to increase without unwanted side effects on the other variables. The drought treatment follows predictions of increased frequency of drought periods in summer. The combination of the treatments does not create new unwanted side effects on the treatments relative to the treatments alone.
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| 7. |
- Timotijevic, L., et al.
(författare)
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Designing a research infrastructure (RI) on food behaviour and health : Balancing user needs, business model, governance mechanisms and technology
- 2021
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Ingår i: Trends in Food Science & Technology. - : Elsevier Ltd. - 0924-2244 .- 1879-3053. ; 116, s. 405-414
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Tidskriftsartikel (refereegranskat)abstract
- Background: A better understanding of food-related behaviour and its determinants can be achieved through harmonisation and linking of the various data-sources and knowledge platforms. Scope: We describe the key decision-making in the development of a prototype of the Determinants and Intake Platform (DI Platform), a data platform that aims to harmonise and link data on consumer food behaviour. It will be part of the Food Nutrition Health Research Infrastructure (FNH-RI) that will facilitate health, social and food sciences. Approach: The decision-making was based on the evidence of user needs and data characteristics that guided the specification of the key building blocks of the DI Platform. Eight studies were carried out, including consumer online survey; interview studies of key DI Platform stakeholders; desk research and workshops. Key findings: Consumers were most willing to share data with universities, then industry and government. Trust, risk perception and altruism predicted willingness to share. For most other stakeholders non-proprietary data was most likely to be shared. Lack of data standards, and incentives for sharing were the main barriers for sharing data among the key stakeholders. The value of various data types would hugely increase if linked with other sources. Finding the right balance between optimizing data sharing and minimizing ethical and legal risks was considered a key challenge. Conclusions: The development of DI Platform is based on careful balancing of the user, technical, business, legal and ethical requirements, following the FAIR principles and the need for financial sustainability, technical flexibility, transparency and multi-layered organisational governance.
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| 8. |
- Fowler, D., et al.
(författare)
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Atmospheric composition change : Ecosystems-Atmosphere interactions
- 2009
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 43:33, s. 5193-5267
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Forskningsöversikt (refereegranskat)abstract
- Ecosystems and the atmosphere: This review describes the state of understanding the processes involved in the exchange of trace gases and aerosols between the earth's surface and the atmosphere. The gases covered include NO, NO2, HONO, HNO3, NH3, SO2, DMS, Biogenic VOC, O-3, CH4, N2O and particles in the size range 1 nm-10 mu m including organic and inorganic chemical species. The main focus of the review is on the exchange between terrestrial ecosystems, both managed and natural and the atmosphere, although some new developments in ocean-atmosphere exchange are included. The material presented is biased towards the last decade, but includes earlier work, where more recent developments are limited or absent. New methodologies and instrumentation have enabled, if not driven technical advances in measurement. These developments have advanced the process understanding and upscaling of fluxes, especially for particles, VOC and NH3. Examples of these applications include mass spectrometric methods, such as Aerosol Mass Spectrometry (AMS) adapted for field measurement of atmosphere-surface fluxes using micrometeorological methods for chemically resolved aerosols. Also briefly described are some advances in theory and techniques in micrometeorology. For some of the compounds there have been paradigm shifts in approach and application of both techniques and assessment. These include flux measurements over marine surfaces and urban areas using micrometeorological methods and the up-scaling of flux measurements using aircraft and satellite remote sensing. The application of a flux-based approach in assessment of O-3 effects on vegetation at regional scales is an important policy linked development secured through improved quantification of fluxes. The coupling of monitoring, modelling and intensive flux measurement at a continental scale within the NitroEurope network represents a quantum development in the application of research teams to address the underpinning science of reactive nitrogen in the cycling between ecosystems and the atmosphere in Europe. Some important developments of the science have been applied to assist in addressing policy questions, which have been the main driver of the research agenda, while other developments in understanding have not been applied to their wider field especially in chemistry-transport models through deficiencies in obtaining appropriate data to enable application or inertia within the modelling community. The paper identifies applications, gaps and research questions that have remained intractable at least since 2000 within the specialized sections of the paper, and where possible these have been focussed on research questions for the coming decade.
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| 9. |
- Hartoog, O. E., et al.
(författare)
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VLT/X-Shooter spectroscopy of the afterglow of the Swift GRB 130606A Chemical abundances and reionisation at z similar to 6
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
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Tidskriftsartikel (refereegranskat)abstract
- Context: The reionisation of the Universe is a process that is thought to have ended around z similar to 6, as inferred from spectroscopy of distant bright background sources, such as quasars (QSO) and gamma-ray burst (GRB) afterglows. Furthermore, spectroscopy of a GRB afterglow provides insight in its host galaxy, which is often too dim and distant to study otherwise.Aims: For the Swift GRB 130606A at z = 5.913 we have obtained a high S/N spectrum covering the full optical and near-IR wavelength region at intermediate spectral resolution with VLT/X-Shooter. We aim to measure the degree of ionisation of the intergalactic medium (IGM) between z = 5.02-5.84 and to study the chemical abundance pattern and dust content of its host galaxy.Methods: We estimated the UV continuum of the GRB afterglow using a power-law extrapolation, then measured the flux decrement due to absorption at Ly alpha,beta, and gamma wavelength regions. Furthermore, we fitted the shape of the red damping wing of Lya. The hydrogen and metal absorption lines formed in the host galaxy were fitted with Voigt profiles to obtain column densities. We investigated whether ionisation corrections needed to be applied.Results: Our measurements of the Ly alpha-forest optical depth are consistent with previous measurements of QSOs, but have a much smaller uncertainty. The analysis of the red damping wing yields a neutral fraction x(HI) < 0.05 (3 sigma). We obtain column density measurements of H, Al, Si, and Fe; for C, O, S and Ni we obtain limits. The ionisation due to the GRB is estimated to be negligible (corrections < 0.03 dex), but larger corrections may apply due to the pre-existing radiation field (up to 0.4 dex based on sub-DLA studies). Assuming that [Si/Fe] = +0.79 +/- 0.13 is due to dust depletion, the dust-to-metal ratio is similar to the Galactic value.Conclusions: Our measurements confirm that the Universe is already predominantly ionised over the redshift range probed in this work, but was slightly more neutral at z > 5.6. GRBs are useful probes of the ionisation state of the IGM in the early Universe, but because of internal scatter we need a larger statistical sample to draw robust conclusions. The high [Si/Fe] in the host can be due to dust depletion, a-element enhancement, or a combination of both. The very high value of [Al/Fe] = 2.40 +/- 0.78 might be due to a proton capture process and is probably connected to the stellar population history. We estimate the host metallicity to be -1.7 < [M/H] < -0.9 (2%-13% of solar).
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| 10. |
- Leiva, R. A., et al.
(författare)
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High real-world effectiveness of 12-week elbasvir/grazoprevir without resistance testing in the treatment of patients with HCV genotype 1a infection in Norway
- 2023
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:3, s. 264-268
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The recommended treatment duration of hepatitis C virus (HCV) genotype 1a (GT1a) infection with elbasvir/grazoprevir (EBR/GZR) in the presence of a high baseline viral load and resistance associated substitutions (RAS) is 16 weeks with ribavirin added. The objective of this study was to evaluate the real-world effectiveness of 12 weeks of EBR/GZR without ribavirin and regardless of baseline viral load and RAS testing. Method: This retrospective, observational cohort study was performed at five Norwegian hospitals that did not systematically utilize RAS testing. All adult patients with chronic HCV GT1a and compensated liver disease who had received 12 weeks of EBR/GZR without ribavirin and baseline RAS testing, were included. The primary endpoint was sustained virologic response at week 12 (SVR12), or if not available, at week 4 (SVR4). Results: We included 433 patients and attained SVR data on 388. The mean age was 45.7 years (22–73 years). 67.2% were male. HIV co-infection was present in 3.8% (16/424) and cirrhosis in 4% (17/424). The viral load was >800 000 IU/mL in 55.0% (235/427) of patients. Overall SVR was achieved in 97.2% (377/388). SVR was achieved in 98.3% (169/172) of those with viral load ≤800 000 IU/mL and in 96.2% (202/210) of those with viral load >800 000 IU/mL. Conclusion: We observed high SVR rates among patients with HCV GT1a infection treated with EBR/GZR for 12 weeks without ribavirin, with no regard to baseline viral load and no RAS testing. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 11. |
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| 12. |
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| 14. |
- Bronden, A., et al.
(författare)
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Glucose-lowering effects and mechanisms of the bile acid-sequestering resin sevelamer
- 2018
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 20:7, s. 1623-1631
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Tidskriftsartikel (refereegranskat)abstract
- Aims Sevelamer, a non-absorbable amine-based resin used for treatment of hyperphosphataemia, has been demonstrated to have a marked bile acid-binding potential alongside beneficial effects on lipid and glucose metabolism. The aim of this study was to investigate the glucose-lowering effect and mechanism(s) of sevelamer in patients with type 2 diabetes. Materials and Methods In this double-blinded randomized controlled trial, we randomized 30 patients with type 2 diabetes to sevelamer (n = 20) or placebo (n = 10). Participants were subjected to standardized 4-hour liquid meal tests at baseline and after 7 days of treatment. The main outcome measure was plasma glucagon-like peptide-1 excursions as measured by area under the curve. In addition, blood was sampled for measurements of glucose, lipids, glucose-dependent insulinotropic polypeptide, C-peptide, glucagon, fibroblast growth factor-19, cholecystokinin and bile acids. Assessments of gastric emptying, resting energy expenditure and gut microbiota composition were performed. Results Sevelamer elicited a significant placebo-corrected reduction in plasma glucose with concomitant reduced fibroblast growth factor-19 concentrations, increased de novo synthesis of bile acids, a shift towards a more hydrophilic bile acid pool and increased lipogenesis. No glucagon-like peptide-1-mediated effects on insulin, glucagon or gastric emptying were evident, which points to a limited contribution of this incretin hormone to the glucose-lowering effect of sevelamer. Furthermore, no sevelamer-mediated effects on gut microbiota composition or resting energy expenditure were observed. Conclusions Sevelamer reduced plasma glucose concentrations in patients with type 2 diabetes by mechanisms that seemed to involve decreased intestinal and hepatic bile acid-mediated farnesoid X receptor activation.
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| 15. |
- Bruton, M, et al.
(författare)
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Expression of High Mobility Group Protein B1 in Cardiac Tissue of Elderly Patients with Coronary Artery Disease with or without Inflammatory Rheumatic Disease
- 2017
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Ingår i: Gerontology. - : S. Karger AG. - 1423-0003 .- 0304-324X. ; 63:4, s. 337-349
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> It is known from clinical practice and observational studies that elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a significantly increased risk for cardiovascular diseases such as coronary artery disease (CAD) and heart failure. The molecular mechanism, however, is still not known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly conserved single polypeptide expressed in all mammal eukaryotic cells, has been identified to mediate myocardial dysfunction in vitro once released from the nuclei of cardiomyocytes. <b><i>Objective:</i></b> To investigate whether HMGB1 and its receptors are expressed in cardiac muscles of elderly patients with CAD with or without IRD. <b><i>Methods:</i></b> HMGB1 and its 3 well-known receptors, receptor for advanced glycation end products, Toll-like receptor 2 (TLR2), and TLR4, were examined by immunohistochemistry on myocardial biopsy specimens from 18 elderly patients with CAD (10 with IRD, 8 without IRD). Furthermore, total HMGB1 protein levels were measured by Western blot from the cardiac biopsies in 5 patients with and 5 without IRD. <b><i>Results:</i></b> Pathologic cytosolic HMGB1 in cardiomyocytes was massively recorded in all patients with IRD, but only slightly expressed in 1 patient without IRD. Total HMGB1 levels were also consistently lower in myocardial muscle biopsies of patients with IRD compared to those without IRD. Furthermore, all 3 HMGB1 receptors were expressed in cardiomyocytes of all patients. <b><i>Conclusion:</i></b> The increased cytosolic expression of HMGB1 in cardiomyocytes and the lower total amount of HMGB1 in the cardiac specimens of IRD patients is consistent with a greater release of HMGB1 from the myocardial nuclei in IRD than non-IRD individuals. Thus, the HMGB1 signaling pathways may be more easily activated in elderly CAD patients with concomitant IRD and trigger a detrimental inflammatory process causing severe cardiovascular problems. Therefore, targeting HMGB1 in IRD patients might reduce the risk for cardiovascular events.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Jonsson, D., et al.
(författare)
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Excited state polarizabilities in solution obtained by cubic response theory : Calculations on para-, ortho-, and meta-nitroaniline
- 1998
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 109:15, s. 6351-6357
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Tidskriftsartikel (refereegranskat)abstract
- We show that response theory implemented with a self-consistent reaction field theory model is a viable approach to simulate excited state polarizabilities of molecules in solution. The excited state polarizabilities are in this approach given by the double residue of the ground state cubic response functions, accounting for both equilibrium and nonequilibrium contributions to the interaction with the outer medium. The effects of the inertial polarization of the solvent on the polarizabilities of the solutes are shown to strongly depend on the solvent configuration, whether the solvent is in equilibrium or in nonequilibrium with the charge distribution of the investigated compound. The inertial polarization vector in the nonequilibrium solvent configuration represents the equilibrated solvent configuration when solvating the ground state of the solute. This inertial polarization vector is not in equilibrium with any of the excited states and therefore one observes a rather different behavior between nonequilibrium and equilibrium solvent descriptions of the solute. Illustrative calculations are presented for para-, meta-, and ortho-nitroanilines in gas and solution phases. Results have been compared with experimental data where available. © 1998 American Institute of Physics.
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| 20. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 21. |
- Luo, Y., et al.
(författare)
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Dielectric and optical properties of pure liquids by means of ab initio reaction field theory
- 1998
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Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics. - : American Physical Society (APS). - 1063-651X .- 1095-3787. ; 57:4, s. 4778-4785
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Tidskriftsartikel (refereegranskat)abstract
- A general Onsager-type reaction field theory approach for simulating dielectric and optical properties is proposed, thereby giving a unified description for both macroscopic and microscopic properties of pure liquids. A demonstration is given for ab initio computations of the refractive index, the density fluctuation of the refractive index, and the local field factors of benzene and acetonitrile in the liquid phase, showing good agreement with available experimental data.
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| 22. |
- Luo, Y., et al.
(författare)
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Some recent developments of high-order response theory
- 1998
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Ingår i: International Journal of Quantum Chemistry. - 0020-7608 .- 1097-461X. ; 70:1, s. 219-239
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Tidskriftsartikel (refereegranskat)abstract
- We review some recent developments of high-order response theory and illustrate the utility of this theory for a selection of nonlinear properties. © 1998 John Willey & Sons, Inc.
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| 23. |
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| 24. |
- Norman, P., et al.
(författare)
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Hyperpolarizability depolarization ratios of nitroanilines
- 1997
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 107:21, s. 9063-9066
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Tidskriftsartikel (refereegranskat)abstract
- The depolarization ratios for the first hyperpolarizabilities of para-, meta-, and ortho-nitroanilines have been calculated in gas and solution phases. The results resolve ambiguities in the interpretation of experimental results for these quantities, and pinpoint the actual problems in previous simulations. It is argued that extraction of individual components of β of low symmetry molecules from experimental depolarization measurements alone is difficult, and that the support from simulations to extract the proper information is indispensable in most cases.
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| 25. |
- Sadlej, J., et al.
(författare)
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Properties and Spectroscopies
- 2007
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Ingår i: Continuum Solvation Models in Chemical Physics: From Theory to Applications. - Chichester, UK : John Wiley & Sons. - 9780470029381 ; , s. 125-312
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Bokkapitel (refereegranskat)
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| 26. |
- Stelzenmuller, V., et al.
(författare)
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Evaluation of marine spatial planning requires fit for purpose monitoring strategies
- 2021
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Ingår i: Journal of Environmental Management. - : Elsevier BV. - 0301-4797. ; 278
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Tidskriftsartikel (refereegranskat)abstract
- Marine spatial planning (MSP) has rapidly become the most widely used integrated, place-based management approach in the marine environment. Monitoring and evaluation of MSP is key to inform best practices, adaptive management and plan iteration. While standardised evaluation frameworks cannot be readily applied, accounting for evaluation essentials such as the definition of evaluation objectives, indicators and stakeholder engagement of stakeholders is a prerequisite for meaningful evaluation outcomes. By way of a literature review and eleven practical MSP case studies, we analysed present day trends in evaluation approaches and unravelled the adoption of evaluation essentials for three categories for monitoring and evaluation for plan making, plan outcomes, and policy implementation. We found that at a global scale the focus of MSP evaluation has shifted over the past decade from evaluating predominantly plan outcomes towards the evaluation of plan making. Independent of the scope of the evaluation, evaluation approaches varied greatly from formal and structured processes, building for instance on MSP goals and objectives, to informal processes based on stakeholder interviews. We noted a trend in the adoption of formalised approaches where MSP evaluations have increasingly become linked to MSP policy goals and objectives. However, the enhanced use of MSP objectives and indicators did not result in a more straightforward reporting of outcomes, e.g. such as the achievement of specific MSP objectives. Overall, we found weak linkages between defined MSP objectives, indicators and available monitoring data. While the apparent shift towards a focus on objectives is promising, we highlight the need of fit-for purpose monitoring data to enable effective evaluation of those objectives. Hence, effective MSP and adaptive management processes require customised and concurrent monitoring and evaluation strategies and procedures. We argue that evaluation processes would also benefit from a better understanding of the general environmental, socio-economic and socio-cultural effects of MSP. Therefore, to understand better environmental effects of MSP, we praise that forthcoming MSP processes need to deepen the understanding and considerations of cause-effect pathways between human activities and changes of ecosystem state through the adoption of targeted cumulative effects assessments.
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| 27. |
- Sylvester-Hvid, K. O., et al.
(författare)
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Cubic optical response of molecules in a nonequilibrium and equilibrium solvation model
- 1999
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 103:42, s. 8375-8383
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Tidskriftsartikel (refereegranskat)abstract
- The cubic response equations governing nonequilibrium and equilibrium solvation in the continuum approach are derived and implemented. We consider solvent effects on the frequency dependent second hyperpolarizability. We illustrate the effects of optical and static dielectric constants through sample calculations on H2O and H2CO.
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| 28. |
- Sylvester-Hvid, K. O., et al.
(författare)
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Nonlinear optical response of molecules in a nonequilibrium solvation model
- 1998
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 109:13, s. 5576-5584
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Tidskriftsartikel (refereegranskat)abstract
- The response equations governing nonequilibrium solvation in the continuum approach are derived and implemented for second order in response theory. Applications to a simple benchmark system consisting of a solvated water molecule are presented. We consider the role of nonequilibrium solvent configurations on the first hyperpolarizability. Effects of solvation parameters, such as optical and static dielectric constants, and frequency dispersion are discussed.
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| 29. |
- Sylvester-Hvid, K. O., et al.
(författare)
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Sign change of hyperpolarizabilities of solvated water, revised : Effects of equilibrium and nonequilibrium solvation
- 2004
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 108:41, s. 8961-8965
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Tidskriftsartikel (refereegranskat)abstract
- The second harmonic and electro-optical responses for the water molecule in its liquid state are theoretically revised. The continuum, semicontinuum, and supermolecular solvation models are employed using quadratic response theory at the Hartree-Fock level, either in the equilibrium or nonequilibrium implementation. The experimentally observed sign change of the second harmonic response of water on liquefaction is reproduced using the supermolecular and semicontinuum model for both equilibrium and nonequilibrium solvation. The conclusions of a previous study, which rested upon linear response theory in an equilibrium implementation, are confirmed. Also, the assumption of Kleinman symmetry and dispersion is addressed.
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| 30. |
- Törner, Marianne, 1953, et al.
(författare)
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A Nordic questionnaire for assessing safety climate (NOSACQ)
- 2008
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Ingår i: Procedings of 4th International Conference Working on Safety, Crete, Sept 30-Oct 3.
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Konferensbidrag (refereegranskat)abstract
- There is increasing scientific support for the causal relation between safety climate and safety performance. Many safety climate questionnaires are available, but their theoretical basis is sometimes unclear, and different types of psychological constructs intermixed. A questionnaire with documented validity and reliability in different contexts would make for better co-ordination of research in comparative studies. Theoretical advances concerning safety climate are also a prerequisite for effective practical use in working life. The aim of the present work was to develop a Nordic questionnaire for measuring safety climate, based on theory and previous empirical research. The Nordic development team of the Nordic Safety Climate Questionnaire (NOSACQ) had participants from all five Nordic countries. The work commenced in 2000 and was based on consensus meetings. Based on literature, safety climate was defined as shared perceptions among the members of a social unit, of policies, procedures and practices at management and group level, influencing safety in the organization at a given time. Dimensions to be included were to be selected on the criterion of substantial theoretical or empirical support for their validity for safety motivation or safety outcome. Items were compiled from literature and additional items were construed, when needed. The prototype questionnaire was administered in the construction industry in all five Nordic countries, in three consecutive pilot tests. The questionnaire was subsequently also tested in a sample of workers in the Swedish food processing industry. Instrument reliability was tested using structural equation modeling and Rasch analysis. The results of the pilot tests confirmed reliability and validity of the questionnaire. This supports the generic value of NOSACQ and that it has a potential for use in different industrial contexts. The instrument was also found to be valid for predicting self rated safety behavior, a proximal criterion of safety performance.
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| 31. |
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| 32. |
- Wallenius, Marianne, et al.
(författare)
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No Excess Risks in Offspring With Paternal Preconception Exposure to Disease-Modifying Antirheumatic Drugs
- 2015
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191. ; 67:1, s. 296-301
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To examine pregnancy outcomes in the partners of male patients with inflammatory joint disease who were or were not exposed to disease-modifying antirheumatic drugs (DMARDs) before conception compared with the outcomes in reference subjects from the general population. Methods. Linkage of data from a longitudinal observational study of patients with inflammatory joint disease (the Norwegian Disease-Modifying Antirheumatic Drug [NOR-DMARD] registry study) and the Medical Birth Registry of Norway (MBRN) enabled a comparison of pregnancy outcomes in the partners of men with inflammatory joint disease. Outcomes of pregnancies in which the father was exposed to DMARDs within 12 weeks of conception and those in which the father was never exposed to DMARDs were analyzed separately and compared with the outcomes in reference subjects. Potential associations between DMARD exposure and adverse pregnancy outcomes were assessed by logistic regression analysis. Results. A total of 1,796 men with inflammatory joint disease were associated with 2,777 births in the MBRN. In 110 of these births, the father had been exposed to DMARDs within 12 weeks before conception, and in 230 births the father had never been exposed to DMARDs before conception. The DMARDs (monotherapy or combination treatment) to which the fathers were exposed most frequently within 12 weeks of conception were methotrexate (n = 49), sulfasalazine (n = 17), and tumor necrosis factor inhibitors (n = 57). Neither adverse pregnancy outcomes nor occurrence of congenital malformations differed between patients and reference subjects in either group. Conclusion. Preconception paternal exposure to DMARDs was not associated with an increase in adverse pregnancy outcomes. Importantly, no increased risk of congenital malformations was observed.
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| 33. |
- Aidas, Kestutis, et al.
(författare)
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On the performance of quantum chemical methods to predict solvatochromic effects: The case of acrolein in aqueous solution.
- 2008
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 128:19, s. 1-194503
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Tidskriftsartikel (refereegranskat)abstract
- The performance of the Hartree-Fock method and the three density functionals B3LYP, PBE0, and CAM-B3LYP is compared to results based on the coupled cluster singles and doubles model in predictions of the solvatochromic effects on the vertical n-->pi(*) and pi-->pi(*) electronic excitation energies of acrolein. All electronic structure methods employed the same solvent model, which is based on the combined quantum mechanics/molecular mechanics approach together with a dynamical averaging scheme. In addition to the predicted solvatochromic effects, we have also performed spectroscopic UV measurements of acrolein in vapor phase and aqueous solution. The gas-to-aqueous solution shift of the n-->pi(*) excitation energy is well reproduced by using all density functional methods considered. However, the B3LYP and PBE0 functionals completely fail to describe the pi-->pi(*) electronic transition in solution, whereas the recent CAM-B3LYP functional performs well also in this case. The pi-->pi(*) excitation energy of acrolein in water solution is found to be very dependent on intermolecular induction and nonelectrostatic interactions. The computed excitation energies of acrolein in vacuum and solution compare well to experimental data.
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| 34. |
- Aidas, Kestutis, et al.
(författare)
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The Dalton quantum chemistry program system
- 2014
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Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 35. |
- Alexopoulou, E., et al.
(författare)
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Embryo Morphokinetics and Blastocyst Development After GnRH Agonist versus hCG Triggering in Normo-ovulatory Women: a Secondary Analysis of a Multicenter Randomized Controlled Trial
- 2021
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 28, s. 2972-2981
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Tidskriftsartikel (refereegranskat)abstract
- Gonadotropin-releasing hormone agonist (GnRHa) for final oocyte maturation, along with vitrification of all usable embryos followed by transfer in a subsequent frozen-thawed cycle, is the most effective strategy to avoid ovarian hyperstimulation syndrome (OHSS). However, less is known about the ovulation induction triggers effect on early embryo development and blastocyst formation. This study is a secondary analysis of a multicenter, randomized controlled trial, with the aim to compare embryo development in normo-ovulatory women, randomized to GnRHa or human chorionic gonadotropin (hCG) trigger. In all, 4056 retrieved oocytes were observed, 1998 from the GnRHa group (216 women) and 2058 from the hCG group (218 women). A number of retrieved oocytes, mature and fertilized oocytes, and high-quality embryos and blastocysts were similar between the groups. A sub-analysis in 250 women enrolled at the main trial site including 2073 oocytes was conducted to compare embryo morphokinetics and cleavage patterns with EmbryoScope time-lapse system. In total, 1013 oocytes were retrieved from the GnRHa group (124 women) and 1060 oocytes were retrieved from the hCG group (126 women). Morphokinetic parameters and cleavage patterns were comparable between the groups. However, embryos derived from the GnRHa group were less likely to perform rolling during their development than the embryos from the hCG trigger group (OR = 0.41 (95%CI 0.25; 0.67), p-value 0.0003). The comparable results on embryo development and utilization rates between the GnRHa and hCG triggers is of clinical relevance to professionals and infertile patients, when GnRHa trigger and freeze-all is performed to avoid OHSS development. ClinicalTrials.gov Identifier: NCT02746562
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| 36. |
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| 37. |
- Chen, H.Y., et al.
(författare)
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
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Tidskriftsartikel (refereegranskat)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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| 38. |
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| 39. |
- Curran, Samuel A, et al.
(författare)
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Bacteria in the Adventitia of Cardiovascular Disease Patients with and without Rheumatoid Arthritis.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of atherosclerosis is significantly increased in rheumatoid arthritis (RA). Infection is one factor that may be involved in the pathogenesis of both diseases. The cause of RA and atherosclerosis is unknown, and infection is one of the factors that may be involved in the pathogenesis of both diseases. The aims of this study were to identify bacteria in the aortic adventitia of patients with cardiovascular disease (CVD) in the presence and absence of RA, and to determine the effect of identified candidate pathogens on Toll-like receptor (TLR)-dependent signalling and the proinflammatory response. The aortic adventitia of 11 CVD patients with RA (RA+CVD) and 11 CVD patients without RA (CVD) were collected during coronary artery bypass graft surgery. Bacteria were detected in four samples from CVD patients and three samples from RA+CVD patients and identified by 16S rRNA gene sequencing. Methylobacterium oryzae was identified in all three RA+CVD samples, representing 44.1% of the bacterial flora. The effect of M. oryzae on TLR-dependent signalling was determined by transfection of HEK-293 cells. Although mild TLR2 signalling was observed, TLR4 was insensitive to M. oryzae. Human primary macrophages were infected with M. oryzae, and a TLDA qPCR array targeting 90 genes involved in inflammation and immune regulation was used to profile the transcriptional response. A significant proinflammatory response was observed, with many of the up-regulated genes encoding proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α) and chemokines (CCR7, IL-8). The aortic adventitia of CVD patients contains a wide range of bacterial species, and the bacterial flora is significantly less diverse in RA+CVD than CVD patients. M. oryzae may stimulate an proinflammatory response that may aggravate and perpetuate the pathological processes underlying atherosclerosis in RA patients.
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| 40. |
- Das, Radhika, et al.
(författare)
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Convergent and divergent evolution of genomic imprinting in the marsupial Monodelphis domestica
- 2012
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 13, s. 394-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin specific monoallelic gene expression. It is postulated to have evolved in placental mammals to modulate intrauterine resource allocation to the offspring. In this study, we determined the imprint status of metatherian orthologues of eutherian imprinted genes. Results: L3MBTL and HTR2A were shown to be imprinted in Monodelphis domestica (the gray short-tailed opossum). MEST expressed a monoallelic and a biallelic transcript, as in eutherians. In contrast, IMPACT, COPG2, and PLAGL1 were not imprinted in the opossum. Differentially methylated regions (DMRs) involved in regulating imprinting in eutherians were not found at any of the new imprinted loci in the opossum. Interestingly, a novel DMR was identified in intron 11 of the imprinted IGF2R gene, but this was not conserved in eutherians. The promoter regions of the imprinted genes in the opossum were enriched for the activating histone modification H3 Lysine 4 dimethylation. Conclusions: The phenomenon of genomic imprinting is conserved in Therians, but the marked difference in the number and location of imprinted genes and DMRs between metatherians and eutherians indicates that imprinting is not fully conserved between the two Therian infra-classes. The identification of a novel DMR at a non-conserved location as well as the first demonstration of histone modifications at imprinted loci in the opossum suggest that genomic imprinting may have evolved in a common ancestor of these two Therian infra-classes with subsequent divergence of regulatory mechanisms in the two lineages.
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| 41. |
- Deyab, G, et al.
(författare)
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Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis
- 2021
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:7, s. e0253247-
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Tidskriftsartikel (refereegranskat)abstract
- The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.
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| 42. |
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| 43. |
- Elm, J., et al.
(författare)
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Rayleigh light scattering properties of atmospheric molecular clusters consisting of sulfuric acid and bases
- 2015
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 17:24, s. 15701-15709
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Tidskriftsartikel (refereegranskat)abstract
- The Rayleigh light scattering properties of (H2SO4)a(NH3)b and (H2SO4)a((CH3)2NH)b atmospheric molecular clusters have been investigated using a response theory approach. Using density functional theory the molecular structures and stepwise formation free energies of clusters with a and b up to 4 have been re-investigated. The Rayleigh scattering intensities are calculated from the dipole polarizability tensor α using the CAM-B3LYP functional by applying linear response methods. The intrinsic scattering properties of (H2SO4)a(NH3)b and (H2SO4)a((CH3)2NH)b indicate that amine containing clusters scatter light significantly more efficiently then their ammonia containing counterparts. Using the Atmospheric Cluster Dynamics Code (ACDC) the steady state cluster concentrations are estimated and the effective scattering is calculated. The effective scattering is shown to be highly dependent on the estimated concentrations and indicates that there exist competitive pathways, such as nucleation and coagulation, which influence the cluster distributions. The frequency dependence of the scattering is found to depend on the cluster composition and show increased responses when clusters contain more bases than acid molecules. Based on structures obtained using semi-empirical molecular dynamics simulations the Rayleigh scattering properties of clusters with up to 20 acid-base pairs are evaluated. This study represents the first step towards gaining a fundamental understanding of the scattering properties of small atmospheric clusters in the ambient atmosphere.
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| 44. |
- Eriksson, Ola, et al.
(författare)
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Analysis of long distance wakes of Horns Rev I using actuator disc approach
- 2014
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Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 555:1
-
Tidskriftsartikel (refereegranskat)abstract
- The wake recovery behind the Horns Rev wind farm is analysed to investigate the applicability of Large Eddy Simulations (LES) in combination with an actuator disc method (ACD) for farm to farm interaction studies. Periodic boundary conditions on the lateral boundaries are used to model the wind farm (as infinitely wide), using only two columns of turbines. The meteorological conditions of the site are taken into account by introducing wind shear and pre-generated synthetic turbulence to the simulation domain using body forces. Simulations are carried out to study the power production and the velocity deficit in the farm wake. The results are compared to the actual power production as well as to wind measurements at 2 km and 6 km behind the wind farm. The simulated power production inside the farm shows an overall good correlation with the real production, but is slightly overpredicted in the most downstream rows. The simulations overpredict the wake recovery, namely the wind velocity, at long distances behind the farm. Further studies are needed before the presented method can be applied for the simulation of long distance wakes. Suggested parameters to be studied are the development of the turbulence downstream in the domain and the impact of the grid resolution.
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| 45. |
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| 46. |
- Hait, A. S., et al.
(författare)
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Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans
- 2020
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Ingår i: Science Immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:54
-
Tidskriftsartikel (refereegranskat)abstract
- Recurrent herpesvirus infections can manifest in different forms of disease, including cold sores, genital herpes, and encephalitis. There is an incomplete understanding of the genetic and immunological factors conferring susceptibility to recurrent herpes simplex virus 2 (HSV2) infection in the central nervous system (CNS). Here, we describe two adult patients with recurrent HSV2 lymphocytic Mollaret's meningitis that each carry a rare monoallelic variant in the autophagy proteins ATG4A or LC3B2. HSV2-activated autophagy was abrogated in patient primary fibroblasts, which also exhibited significantly increased viral replication and enhanced cell death. HSV2 antigen was captured in autophagosomes of infected cells, and genetic inhibition of autophagy by disruption of autophagy genes, including ATG4A and LC3B2, led to enhanced viral replication and cell death in primary fibroblasts and a neuroblastoma cell line. Activation of autophagy by HSV2 was sensitive to ultraviolet (UV) irradiation of the virus and inhibited in the presence of acyclovir, but HSV2-induced autophagy was independent of the DNA-activated STING pathway. Reconstitution of wild-type ATG4A and LC3B2 expression using lentiviral gene delivery or electroporation of in vitro transcribed mRNA into patient cells restored virus-induced autophagy and the ability to control HSV2 replication. This study describes a previously unknown link between defective autophagy and an inborn error of immunity that can lead to increased susceptibility to HSV2 infection, suggesting an important role for autophagy in antiviral immunity in the CNS.
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| 47. |
- Harth, A., et al.
(författare)
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Few-cycle high-repetition rate OPCPA for multiphoton PEEM towards atto-PEEM
- 2016
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Ingår i: International Conference on Ultrafast Phenomena, UP 2016. - 9781943580187 ; Part F20-UP 2016
-
Konferensbidrag (refereegranskat)abstract
- We present a few-cycle high-repetition rate optical parametric amplifier for multiphoton PEEM experiments on semiconductor nanowires. This parametric amplifier is also used for the generation of high-order harmonics at 200kHz for future atto-PEEM experiments.
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| 48. |
- Hillers-Bendtsen, A. E., et al.
(författare)
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Modeling Absorption and Emission Spectroscopies of Symmetric and Asymmetric Azaoxahelicenes in Vacuum and Solution
- 2022
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 126:37, s. 6467-6472
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Tidskriftsartikel (refereegranskat)abstract
- Helicenes are of general interest due to the significant chiral signals in both absorption- and emission-based spectroscopy. Herein, the spectroscopic properties of four recently synthesized azaoxahelicenes are studied using density functional theory methods. The azaoxahelicenes have 7, 9, 10, and 13 units and one to two complete turns of the structure. UV-vis absorption and electronic circular dichroism spectra are determined both in vacuum and in solution using explicit solvation through a combined molecular dynamics/polarizable embedding framework. Additionally, emission and circularly polarized luminescence spectra are determined based on vibronic calculations. The resulting spectra are in good agreement with the experimentally available data, highlighting that both absorption- and emission-based spectra of the systems can be modeled computationally such that reliable predictions can be made for systems that are yet to be synthesized.
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| 49. |
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| 50. |
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