| 1. |
- Kulmala, M., et al.
(författare)
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General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
- 2011
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.
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| 2. |
- Leonov, A. A., et al.
(författare)
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Separation of electrons and protons in the GAMMA-400 gamma-ray telescope
- 2015
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Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 56:7, s. 1538-1545
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Tidskriftsartikel (refereegranskat)abstract
- The GAMMA-400 telescope will measure the fluxes of gamma rays and cosmic-ray electrons and positrons in the energy range from 100 MeV to several TeV. These measurements will allow it to achieve the following scientific objectives: search for signatures of dark matter, investigation of gamma-ray point-like and extended sources, study of the energy spectrum of the Galactic and extragalactic diffuse emission, study of gamma-ray bursts and gamma-ray emission from the active Sun, together with high-precision measurements of the high-energy electrons and positrons spectra, protons and nuclei up to the knee. The bulk of cosmic rays are protons and helium nuclei, whereas the lepton component in the total flux is similar to 10(-3) at high energy. In the present paper, the simulated capability of the GAMMA-400 telescope to distinguish electrons and positrons from protons in cosmic rays is addressed. The individual contribution to the proton rejection from each detector system of GAMMA-400 is studied separately. The use of the combined information from all detectors allows us to reach a proton rejection of the order of similar to 4 x 10(5) for vertical incident particles and similar to 3 x 10(5) for particles with initial inclination of 30 degrees in the electron energy range from 50 GeV to 1 TeV. (C) 2015 COSPAR.
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| 3. |
- Lorenz, M. W., et al.
(författare)
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Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration
- 2018
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
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| 4. |
- Liao, X., et al.
(författare)
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Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?
- 2016
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:11, s. 1165-1173
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Tidskriftsartikel (refereegranskat)abstract
- Background The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Design Meta-analysis of individual participant data. Method From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Results Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. Conclusions The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions. © 2016 European Society of Cardiology.
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| 5. |
- Brugnara, Y., et al.
(författare)
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A collection of sub-daily pressure and temperature observations for the early instrumental period with a focus on the "year without a summer" 1816
- 2015
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 11:8, s. 1027-1047
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Tidskriftsartikel (refereegranskat)abstract
- The eruption of Mount Tambora (Indonesia) in April 1815 is the largest documented volcanic eruption in history. It is associated with a large global cooling during the following year, felt particularly in parts of Europe and North America, where the year 1816 became known as the "year without a summer". This paper describes an effort made to collect surface meteorological observations from the early instrumental period, with a focus on the years of and immediately following the eruption (1815–1817). Although the collection aimed in particular at pressure observations, correspondent temperature observations were also recovered. Some of the series had already been described in the literature, but a large part of the data, recently digitised from original weather diaries and contemporary magazines and newspapers, is presented here for the first time. The collection puts together more than 50 sub-daily series from land observatories in Europe and North America and from ships in the tropics. The pressure observations have been corrected for temperature and gravity and reduced to mean sea level. Moreover, an additional statistical correction was applied to take into account common error sources in mercury barometers. To assess the reliability of the corrected data set, the variance in the pressure observations is compared with modern climatologies, and single observations are used for synoptic analyses of three case studies in Europe. All raw observations will be made available to the scientific community in the International Surface Pressure Databank.
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| 6. |
- Udayappan, S. D., et al.
(författare)
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Intestinal Ralstonia pickettii augments glucose intolerance in obesity
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.
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| 7. |
- Bergström, I., et al.
(författare)
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Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone
- 2017
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 28:3, s. 1121-1131
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Loading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels. Introduction: Osteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone. Methods: Right tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with μCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure). Results: The cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (−14 and −3%, p < 0.01, respectively) and crystallinity (−1.4 and −0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites. Conclusion: Bone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.
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| 8. |
- Genberg, Johan, et al.
(författare)
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Light-absorbing carbon in Europe - measurement and modelling, with a focus on residential wood combustion emissions
- 2013
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 13:17, s. 8719-8738
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Tidskriftsartikel (refereegranskat)abstract
- The atmospheric concentration of elemental carbon (EC) in Europe during the six-year period 2005-2010 has been simulated with the EMEP MSC-W model. The model bias compared to EC measurements was less than 20% for most of the examined sites. The model results suggest that fossil fuel combustion is the dominant source of EC in most of Europe but that there are important contributions also from residential wood burning during the cold seasons and, during certain episodes, also from open biomass burning (wildfires and agricultural fires). The modelled contributions from open biomass fires to ground level concentrations of EC were small at the sites included in the present study, <3% of the long-term average of EC in PM10. The modelling of this EC source is subject to many uncertainties, and it was likely underestimated for some episodes. EC measurements and modelled EC were also compared to optical measurements of black carbon (BC). The relationships between EC and BC (as given by mass absorption cross section, MAC, values) differed widely between the sites, and the correlation between observed EC and BC is sometimes poor, making it difficult to compare results using the two techniques and limiting the comparability of BC measurements to model EC results. A new bottom-up emission inventory for carbonaceous aerosol from residential wood combustion has been applied. For some countries the new inventory has substantially different EC emissions compared to earlier estimates. For northern Europe the most significant changes are much lower emissions in Norway and higher emissions in neighbouring Sweden and Finland. For Norway and Sweden, comparisons to source-apportionment data from winter campaigns indicate that the new inventory may improve model-calculated EC from wood burning. Finally, three different model setups were tested with variable atmospheric lifetimes of EC in order to evaluate the model sensitivity to the assumptions regarding hygroscopicity and atmospheric ageing of EC. The standard ageing scheme leads to a rapid transformation of the emitted hydrophobic EC to hygroscopic particles, and generates similar results when assuming that all EC is aged at the point of emission. Assuming hydrophobic emissions and no ageing leads to higher EC concentrations. For the more remote sites, the observed EC concentration was in between the modelled EC using standard ageing and the scenario treating EC as hydrophobic. This could indicate too-rapid EC ageing in the model in relatively clean parts of the atmosphere.
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| 9. |
- Kulén, Martina, et al.
(författare)
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Methyl sulfonamide substituents improve the pharmacokinetic properties of bicyclic 2-pyridone based Chlamydia trachomatis inhibitors
- 2019
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Ingår i: MedChemComm. - : Royal Society of Chemistry. - 2040-2503 .- 2040-2511. ; 10:11, s. 1966-1987
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis infections are a global health problem and new approaches to treat C. trachomatis with drugs of high specificity would be valuable. A library of substituted ring fused 2-pyridones has been synthesized and evaluated for their ability to attenuate C. trachomatis infectivity. In vivo pharmacokinetic studies were performed, with the best candidates demonstrating that a C8-methylsulfonamide substituent improved pharmacokinetic properties important for oral administration. C8-Methyl sulfonamide analogue 30 inhibited C. trachomatis infectivity in low micromolar concentrations. Further pharmacokinetic evaluation at an oral dose of 10 mg kg(-1) showed an apparent bioavailability of 41%, compared to C8-cyclopropyl and -methoxy analogues which had negligible oral uptake. In vitro ADME (absorption, distribution, metabolism and excretion) testing of solubility and Caco-2 cell permeability revealed that both solubility and permeability is greatly improved with the C8-methyl sulfonamide 30, effectively moving it from BCS (Biopharmaceutical Classification System) class IV to II.
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| 10. |
- Lorenz, M. W., et al.
(författare)
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Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration
- 2015
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:10, s. 1921-1929
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVECarotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.RESEARCH DESIGN AND METHODSIn a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.RESULTSAverage mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).CONCLUSIONSDespite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.
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