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1.
  • Munn-Chernoff, M. A., et al. (författare)
  • Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
  • 2021
  • Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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  • Czamara, D, et al. (författare)
  • Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
  • Tidskriftsartikel (refereegranskat)abstract
    • Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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  • Berthomier, M., et al. (författare)
  • Alfven : magnetosphere-ionosphere connection explorers
  • 2012
  • Ingår i: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
  • Tidskriftsartikel (refereegranskat)abstract
    • The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
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  • Middeldorp, Christel M., et al. (författare)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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  • Neumann, A, et al. (författare)
  • A genome-wide association study of total child psychiatric problems scores
  • 2022
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8, s. e0273116-
  • Tidskriftsartikel (refereegranskat)abstract
    • Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.
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  • Bartels, M., et al. (författare)
  • Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3-16years from multiple raters in six cohorts in the EU-ACTION project
  • 2018
  • Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 27:9, s. 1105-1121
  • Tidskriftsartikel (refereegranskat)abstract
    • Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.
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  • Lockwood, M, et al. (författare)
  • Coordinated Cluster and ground-based instrument observations of transient changes in the magnetopause boundary layer during an interval of predominantly northward IMF : relation to reconnection pulses and FTE signatures
  • 2001
  • Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 19:10-12, s. 1613-1640
  • Forskningsöversikt (refereegranskat)abstract
    • We study a series of transient entries into the low-latitude boundary layer (LLBL) of all four Cluster spacecraft during an outbound pass through the mid-afternoon magnetopause ([X(GSM), Y(GSM), Z(GSM)] approximate to [2, 7, 9] R(E)). The events take place during an interval of northward IMF, as seen in the data from the ACE satellite and lagged by a propagation delay of 75 min that is well-defined by two separate studies: (1) the magnetospheric variations prior to the northward turning (Lockwood et al., 2001, this issue) and (2) the field clock angle seen by Cluster after it had emerged into the magnetosheath (Opgenoorth et al., 2001, this issue). With an additional lag of 16.5 min, the transient LLBL events cor-relate well with swings of the IMF clock angle (in GSM) to near 90degrees. Most of this additional lag is explained by ground-based observations, which reveal signatures of transient reconnection in the pre-noon sector that then take 10-15 min to propagate eastward to 15 MLT, where they are observed by Cluster. The eastward phase speed of these signatures agrees very well with the motion deduced by the cross-correlation of the signatures seen on the four Cluster spacecraft. The evidence that these events are reconnection pulses includes: transient erosion of the noon 630 nm (cusp/cleft) aurora to lower latitudes; transient and travelling enhancements of the flow into the polar cap, imaged by the AMIE technique; and poleward-moving events moving into the polar cap, seen by the EISCAT Svalbard Radar (ESR). A pass of the DMSP-F15 satellite reveals that the open field lines near noon have been opened for some time: the more recently opened field lines were found closer to dusk where the flow transient and the poleward-moving event intersected the satellite pass. The events at Cluster have ion and electron characteristics predicted and observed by Lockwood and Hapgood (1998) for a Flux Transfer Event (FTE), with allowance for magnetospheric ion reflection at Alfvenic disturbances in the magnetopause reconnection layer. Like FTEs, the events are about 1 R(E) in their direction of motion and show a rise in the magnetic field strength, but unlike FTEs, in general, they show no pressure excess in their core and hence, no characteristic bipolar signature in the boundary-normal component. However, most of the events were observed when the magnetic field was southward, i.e. on the edge of the interior magnetic cusp, or when the field was parallel to the magnetic equatorial plane. Only when the satellite begins to emerge from the exterior boundary (when the field was northward), do the events start to show a pressure excess in their core and the consequent bipolar signature. We identify the events as the first observations of FTEs at middle altitudes.
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  • Laitinen, T, et al. (författare)
  • Characterization of a common susceptibility locus for asthma-related traits
  • 2004
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 304:5668, s. 300-304
  • Tidskriftsartikel (refereegranskat)abstract
    • Susceptibility to asthma depends on variation at an unknown number of genetic loci. To identify susceptibility genes on chromosome 7p, we adopted a hierarchical genotyping design, leading to the identification of a 133-kilobase risk-conferring segment containing two genes. One of these coded for an orphan G protein–coupled receptor named GPRA (G protein–coupled receptor for asthma susceptibility), which showed distinct distribution of protein isoforms between bronchial biopsies from healthy and asthmatic individuals. In three cohorts from Finland and Canada, single nucleotide polymorphism–tagged haplotypes associated with high serum immunoglobulin E or asthma. The murine ortholog of GPRA was up-regulated in a mouse model of ovalbumin-induced inflammation. Together, these data implicate GPRA in the pathogenesis of atopy and asthma.
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  • Sundén, Henrik, 1978, et al. (författare)
  • Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators
  • 2015
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 1520-4804 .- 0022-2623. ; 58:3, s. 1569-1574
  • Tidskriftsartikel (refereegranskat)abstract
    • To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.
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  • Horbury, T., et al. (författare)
  • Cross-scale : A multi-spacecraft mission to study cross-scale coupling in space plasmas
  • 2006
  • Ingår i: European Space Agency, (Special Publication) ESA SP. ; , s. 561-568
  • Konferensbidrag (refereegranskat)abstract
    • Collisionless astrophysical plasmas exhibit complexity on many scales: if we are to understand their properties and effects, we must measure this complexity. We can identify a small number of processes and phenomena, one of which is dominant in almost every space plasma region of interest: shocks, reconnection and turbulence. These processes act to transfer energy between locations, scales and modes. However, this transfer is characterised by variability and 3D structure on at least three scales: electron kinetic, ion kinetic and fluid. It is the nonlinear interaction between physical processes at these scales that is the key to understanding these phenomena and predicting their effects. However, current and planned multi-spacecraft missions such as Cluster and MMS only study variations on one scale in 3D at any given time - we must measure the three scales simultaneously fully to understand the energy transfer processes. We propose a mission, called Cross-Scale, to study these processes. Cross-Scale would comprise three nested groups, each consisting of up to four spacecraft. Each group would have a different spacecraft separation, at approximately the electron and ion gyroradii, and a larger MHD scale. We would therefore be able to measure variations on all three important physical scales, simultaneously, for the first time. The spacecraft would fly in formation through key regions of near-Earth space: The solar wind, bowshock, magnetosheath, magnetopause and magnetotail.
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  • Pulkkinen, T. I., et al. (författare)
  • Magnetospheric modes and solar wind energy coupling efficiency
  • 2010
  • Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115:3, s. A03207-
  • Tidskriftsartikel (refereegranskat)abstract
    • Using observations and two different global MHD simulations, we demonstrate that the solar wind speed controls the magnetospheric response such that the higher the speed, the more dynamic and irregular is the magnetospheric response. For similar level of driving solar wind electric field, the magnetospheric modes can be organized in terms of speed: Low speed produces steady convection events, intermediate speeds result in periodic sawtooth oscillations, and high speeds drive large geomagnetic storms. We show that the control parameter of energy transfer and coupling is the electric field along the large-scale X line. We demonstrate using global MHD simulations that for slowly varying interplanetary magnetic field (IMF), the reconnection line is tilted approximately by an angle theta/2, where theta is the IMF clock angle. Then, for clock angles away from northward, the magnetospheric energy entry and response scale with the electric field along the reconnection line (E-PAR), rather than the traditionally used E-Y. If we define the energy coupling efficiency as response/E-PAR, we can show it to be independent of the IMF clock angle and only weakly dependent on the solar wind dynamic pressure. These results demonstrate the ability of the localized reconnection line to control the energy input through the entire magnetopause.
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  • Vuoksimaa, E., et al. (författare)
  • Higher aggression is related to poorer academic performance in compulsory education
  • 2021
  • Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 62:3, s. 327-338
  • Tidskriftsartikel (refereegranskat)abstract
    • Background To conduct a comprehensive assessment of the association between aggression and academic performance in compulsory education. Method We studied aggression and academic performance in over 27,000 individuals from four European twin cohorts participating in the ACTION consortium (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies). Individual level data on aggression at ages 7-16 were assessed by three instruments (Achenbach System of Empirically Based Assessment, Multidimensional Peer Nomination Inventory, Strengths and Difficulties Questionnaire) including parental, teacher and self-reports. Academic performance was measured with teacher-rated grade point averages (ages 12-14) or standardized test scores (ages 12-16). Random effect meta-analytical correlations with academic performance were estimated for parental ratings (in all four cohorts) and self-ratings (in three cohorts). Results All between-family analyses indicated significant negative aggression-academic performance associations with correlations ranging from -.06 to -.33. Results were similar across different ages, instruments and raters and either with teacher-rated grade point averages or standardized test scores as measures of academic performance. Meta-analytical r's were -.20 and -.23 for parental and self-ratings, respectively. In within-family analyses of all twin pairs, the negative aggression-academic performance associations were statistically significant in 14 out of 17 analyses (r = -.17 for parental- and r = -.16 for self-ratings). Separate analyses in monozygotic (r = -.07 for parental and self-ratings), same-sex dizygotic (r's = -.16 and -.17 for parental and self-ratings) and opposite-sex dizygotic (r's = -.21 and -.19 for parental and self-ratings) twin pairs suggested partial confounding by genetic effects. Conclusions There is a robust negative association between aggression and academic performance in compulsory education. Part of these associations were explained by shared genetic effects, but some evidence of a negative association between aggression and academic performance remained even in within-family analyses of monozygotic twin pairs.
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  • Apatenkov, S. V., et al. (författare)
  • Multi-spacecraft observation of plasma dipolarization/injection in the inner magnetosphere
  • 2007
  • Ingår i: Annales Geophysicae. - 0992-7689 .- 1432-0576. ; 25:3, s. 801-814
  • Tidskriftsartikel (refereegranskat)abstract
    • Addressing the origin of the energetic particle injections into the inner magnetosphere, we investigate the 23 February 2004 substorm using a favorable constellation of four Cluster (near perigee), LANL and Geotail spacecraft. Both an energy-dispersed and a dispersionless injection were observed by Cluster crossing the plasma sheet horn, which mapped to 9-12 R-E in the equatorial plane close to the midnight meridian. Two associated narrow equatorward auroral tongues/streamers propagating from the oval poleward boundary could be discerned in the global images obtained by IMAGE/WIC. As compared to the energy-dispersed event, the dispersionless injection front has important distinctions consequently repeated at 4 spacecraft: a simultaneous increase in electron fluxes at energies similar to 1.300 keV, similar to 25 nT increase in B-Z and a local increase by a factor 1.5-1.7 in plasma pressure. The injected plasma was primarily of solar wind origin. We evaluated the change in the injected flux tube configuration during the dipolarization by fitting flux increases observed by the PEACE and RAPID instruments, assuming adiabatic heating and the Liouville theorem. Mapping the locations of the injection front detected by the four spacecraft to the equatorial plane, we estimated the injection front thickness to be similar to 1 R-E and the earthward propagation speed to be similar to 200-400km/s (at 9-12 RE). Based on observed injection properties, we suggest that it is the underpopulated flux tubes (bubbles with enhanced magnetic field and sharp inner front propagating earthward), which accelerate and transport particles into the strong-field dipolar region.
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  • Hietala, H., et al. (författare)
  • Supermagnetosonic Jets behind a Collisionless Quasiparallel Shock
  • 2009
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:24, s. 245001-
  • Tidskriftsartikel (refereegranskat)abstract
    • The downstream region of a collisionless quasiparallel shock is structured containing bulk flows with high kinetic energy density from a previously unidentified source. We present Cluster multispacecraft measurements of this type of supermagnetosonic jet as well as of a weak secondary shock front within the sheath, that allow us to propose the following generation mechanism for the jets: The local curvature variations inherent to quasiparallel shocks can create fast, deflected jets accompanied by density variations in the downstream region. If the speed of the jet is super(magneto)sonic in the reference frame of the obstacle, a second shock front forms in the sheath closer to the obstacle. Our results can be applied to collisionless quasiparallel shocks in many plasma environments.
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  • Kaurisitie, K., Syrjsuo, M., Amm, O., Viljanen, A., Pulkkinen, T.I. and Opgenoorth, H.J. (författare)
  • A statistical study of evening sectorarcs and electrojets.
  • 2001
  • Ingår i: Advances in Space Research. ; 28, s. 16045-1610
  • Tidskriftsartikel (refereegranskat)abstract
    • We present results of a statistical study of evening sector auroral arcs associated with electrojets. The study (including similar to 1000 all-sky camera (ASC) frames) is based on data of the MIRACLE instrument network. An automatic search engine is used
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  • Pulkkinen, Karoliina, et al. (författare)
  • The value of values in climate science
  • 2022
  • Ingår i: Nature Climate Change. - : Springer Nature. - 1758-678X .- 1758-6798. ; 12:1, s. 4-6
  • Tidskriftsartikel (refereegranskat)
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  • Syrjäsuo, M., Pulkkinen, T.I., Pellinen, R.P., Janhunen, P., Kauristie, K., Viljanen, A., Opgenoorth, H.J., Karllson, P., Wallman, S., Eglitis, P., Nielsen, E. and Thomas, C. (författare)
  • Observations of substorm electrodynamics using the miracle network.
  • 2001
  • Ingår i: The 4th International Conference on Substorms, ICS4. - : Terra Scient. Publ. Comp. Tokyo, Japan. Kaje Hamana, Japan.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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  • Vuoksimaa, E, et al. (författare)
  • Aggression and academic performance
  • 2017
  • Ingår i: BEHAVIOR GENETICS. - 0001-8244. ; 47:6, s. 656-656
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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