| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
- Jiang, Xiao, et al.
(författare)
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Highly Efficient Solid-State Dye-Sensitized Solar Cells Based on Triphenylamine Dyes
- 2011
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Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 21:15, s. 2944-2952
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Tidskriftsartikel (refereegranskat)abstract
- Two triphenylamine-based metal-free organic sensitizers, D35 with a single anchor group and M14 with two anchor groups, have been applied in dye-sensitized solar cells (DSCs) with a solid hole transporting material or liquid iodide/triiodide based electrolyte. Using the molecular hole conductor 2,2',7,7'-tetrakis-(N,N-di-p-methoxyphenyl-amine)9,9'-spirobifluorene (spiro-OMeTAD), good overall conversion efficiencies of 4.5% for D35 and 4.4% for M14 were obtained under standard AM 1.5G illumination (100 mW cm(-2)). Although M14 has a higher molar extinction coefficient (by similar to 60%) and a slightly broader absorption spectrum compared to D35, the latter performs slightly better due to longer lifetime of electrons in the TiO(2), which can be attributed to differences in the molecular structure. In iodide/triiodide electrolyte-based DSCs, D35 outperforms M14 to a much greater extent, due to a very large increase in electron lifetime. This can be explained by both the greater blocking capability of the D35 monolayer and the smaller degree of interaction of triiodide (iodine) with D35 compared to M14. The present work gives some insight into how the molecular structure of sensitizer affects the performance in solid-state and iodide/triiodide-based DSCs.
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| 3. |
- Karlsson, Martin, et al.
(författare)
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Compaction of agglomerates of aerosol nanoparticles: A compilation of experimental data
- 2005
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Ingår i: Journal of Nanoparticle Research. - : Springer Science and Business Media LLC. - 1572-896X .- 1388-0764. ; 7:1, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- The compacting behavior of agglomerated aerosol nanoparticles in the size range between 7 and 150 nm was investigated using available literature data. We observed a characteristic behavior, which can be described by three separate steps. When comparing the first step, the compaction from agglomerates into spherules, differences could be observed for nanoparticles of different materials. It is seen from the available data that smaller particles compact at lower temperatures. For most materials where data available (Ag, Au, Fe, W, PbS and SnO2), the compaction temperatures were found to lie in a temperature interval, between 1/3 and 1/2 of the bulk melting temperature. For the data available on TiO2, on the other hand, the compaction temperature corresponds to about 2/3 of the bulk melting temperature. Thus, a fundamental difference might exist in the sintering behavior of titania as compared with other materials. This difference may be attributed to a lower degree of cleanliness of the titania particles.
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| 4. |
- Karlsson, Martin, et al.
(författare)
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Size- and compostition-controlled Au-Ga aerosol nanoparticles
- 2004
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 1521-7388 .- 0278-6826. ; 38:9, s. 948-954
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Tidskriftsartikel (refereegranskat)abstract
- A simple gas-phase method has been developed for producing size- and composition-controlled nanoparticles of binary alloys. The process includes the formation and classification of aerosol nanoparticles of one material and the subsequent condensation of a controlled shell of another. The shell thickness is controlled by the evaporation temperature of the second material. Here we study the Au-Ga system with particle compositions ranging from pure Au to 50 atomic percent Ga. Transmission electron microscopy was used to study the morphology, composition, and structure of the generated particles.
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| 5. |
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| 6. |
- Pousette, Anders, 1959, et al.
(författare)
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Informationssäkerhetskultur i praktiken: Populärvetenskaplig sammanfattning
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Projektet Informationssäkerhetskultur i praktiken har finansierats av MSB under åren 2019–2024 med syftet att förklara och belysa hur informationssäkerhetskulturen i organisationer kan förändras till det bättre. Fokus har varit på olika sätt att mäta och förändra kulturen. Projektet har genomförts av forskare i tre organisationer. Upplägget är tvärvetenskapligt med forskare specialiserade inom ämnen såsom fredsstudier, statsvetenskap, informatik, psykologi och cyberförsvar. Det tvärvetenskapliga angreppssättet har, förutom de resultat som presenteras i denna rapport, inneburit stort kunskapsutbyte mellan forskare i projektet och förbättrat deras förståelse för de problem och dilemman som kopplas till hantering av informationssäkerhetskulturer. Projektets forskningsplan inkluderade flera datainsamlingsinsatser och interventioner i samhällsviktiga organisationer. Eftersom kunskap om en organisations informationssäkerhet kan missbrukas av illasinnade aktörer förutsatte projektet stort förtroende och engagemang från dessa organisationer. Det krävde också förtroende och engagemang från enskilda individer inom dessa organisationer som förväntades delta i studierna. Den pandemi som drabbade världen i början av projektet innebar att många av de planer som gjorts behövde justeras och förändras. Organisationer och personer som trots detta valt att stödja studien förtjänar därför ett tack utöver det vanliga. Stort tack!
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| 7. |
- Seblova, Dominika, et al.
(författare)
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Does Prolonged Education Causally Affect Dementia Risk When Adult Socioeconomic Status Is Not Altered? A Swedish Natural Experiment in 1.3 Million Individuals
- 2021
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 190:5, s. 817-826
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Tidskriftsartikel (refereegranskat)abstract
- Intervening on modifiable risk factors to prevent dementia is of key importance, since progress-modifying treatments are not currently available. Education is inversely associated with dementia risk, but causality and mechanistic pathways remain unclear. We aimed to examine the causality of this relationship in Sweden using, as a natural experiment, data on a compulsory schooling reform that extended primary education by 1 year for 70% of the population between 1936 and 1949. The reform introduced substantial exogenous variation in education that was unrelated to pupils' characteristics. We followed 18 birth cohorts (n = 1,341,842) from 1985 to 2016 (up to ages 79-96 years) for a dementia diagnosis in the National Inpatient and Cause of Death registers and fitted Cox survival models with stratified baseline hazards at the school-district level, chronological age as the time scale, and cohort indicators. Analyses indicated very small or negligible causal effects of education on dementia risk (main hazard ratio = 1.01, 95% confidence interval: 0.98, 1.04). Multiple sensitivity checks considering only compliers, the pre-/post- design, differences in health-care-seeking behavior, and the impact of exposure misclassification left the results essentially unaltered. The reform had limited effects on further adult socioeconomic outcomes, such as income. Our findings suggest that without mediation through adult socioeconomic position, education cannot be uncritically considered a modifiable risk factor for dementia.
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| 8. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 9. |
- Yang, Lei, et al.
(författare)
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Comparing spiro-OMeTAD and P3HT hole conductors in efficient solid state dye-sensitized solar cells
- 2012
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 14:2, s. 779-789
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Tidskriftsartikel (refereegranskat)abstract
- Two hole conductor materials, spiro-OMeTAD and P3HT, were compared in solid-state dye-sensitized solar cells. Two organic dyes containing one anchor unit (D35) or two anchor units (M3) were used in the comparison. Absorbed photon to current conversion efficiency close to unity was obtained for the devices with spiro-OMeTAD. Energy conversion efficiencies of 4.7% and 4.9% were measured for the devices with spiro-OMeTAD and the dyes D35 and M3, respectively. For the devices using the P3HT hole conductor the results were rather different comparing the two dye molecules, with energy conversion efficiencies of 3.2% and 0.5% for D35 and M3, respectively. Photo-induced absorption measurements suggest that the regeneration of the dyes, and the polymer infiltration, is not complete using P3HT, while spiro-OMeTAD regenerates the dyes efficiently. However, the TiO(2)/D35/P3HT system shows rather high energy conversion efficiency and electrochemical oxidation of the dyes on TiO(2) indicates that D35 have a more efficient dye to dye hole conduction than M3, which thereby might explain the higher performance. The dye hole conduction may therefore be of significant importance for optimizing the energy conversion in such hybrid TiO(2)/dye/polymer systems.
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| 10. |
- Öhlén, Mats, 1977-, et al.
(författare)
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Ideologisk konvergens mellan öst och väst? : de europeiska partifamiljerna 1990-2013
- 2015
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Ingår i: Nordisk Østforum. - : Universitetsforlaget. - 0801-7220 .- 1891-1773. ; 29:2, s. 167-189
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we compare ideological positions of political parties in Eastern and Western Europe. As the Communist regimes collapsed and new democracies began to emerge in Eastern Europe, it became obvious that historical and cultural differences existed in relation to Western Europe. This was not least visible among the political parties. When the West European parties initiated contacts with potential sister parties in the East, noticeable differences were revealed in several issues. In general, the eastern parties appeared to be more nationalist, more populist and less tolerant towards minorities than their Western sister parties. The question raised in this paper is whether these differences, have faded or not during the 25-year period after 1989. In order to perform this analysis, the three largest and most influential party families are selected: the Christian Democratic EPP, the Social Democratic PES and the Liberal ALDE. Departing from election manifesto data compiled by the Comparative Manifesto Project, we have performed a time series analysis ranging from 1990 to 2013. Here, the Eastern parties are compared to their Western sister parties within each party family. Firstly, they are compared along the general left-right dimension, and secondly they are compared in specific issues, which have been conceived as delicate matter: the view on the EU, nationalism and view on multiculturalism.
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| 11. |
- Abbott, Benjamin W., et al.
(författare)
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Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
- 2016
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Almstedt, Karin, 1980-, et al.
(författare)
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Unfolding a folding disease: folding, misfolding and aggregation of the marble brain syndrome-associated mutant H107Y of human carbonic anhydrase II
- 2004
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Ingår i: Journal of Molecular Biology. - Oxford : Elsevier. - 0022-2836 .- 1089-8638. ; 342:2, s. 619-633
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Tidskriftsartikel (refereegranskat)abstract
- Most loss-of-function diseases are caused by aberrant folding of important proteins. These proteins often misfold due to mutations. The disease marble brain syndrome (MBS), known also as carbonic anhydrase II deficiency syndrome (CADS), can manifest in carriers of point mutations in the human carbonic anhydrase II (HCA II) gene. One mutation associated with MBS entails the His107Tyr substitution. Here, we demonstrate that this mutation is a remarkably destabilizing folding mutation. The loss-of-function is clearly a folding defect, since the mutant shows 64% of CO2 hydration activity compared to that of the wild-type at low temperature where the mutant is folded. On the contrary, its stability towards thermal and guanidine hydrochloride (GuHCl) denaturation is highly compromised. Using activity assays, CD, fluorescence, NMR, cross-linking, aggregation measurements and molecular modeling, we have mapped the properties of this remarkable mutant. Loss of enzymatic activity had a midpoint temperature of denaturation (Tm) of 16 °C for the mutant compared to 55 °C for the wild-type protein. GuHCl-denaturation (at 4 °C) showed that the native state of the mutant was destabilized by 9.2 kcal/mol. The mutant unfolds through at least two equilibrium intermediates; one novel intermediate that we have termed the molten globule light state and, after further denaturation, the classical molten globule state is populated. Under physiological conditions (neutral pH; 37 °C), the His107Tyr mutant will populate the molten globule light state, likely due to novel interactions between Tyr107 and the surroundings of the critical residue Ser29 that destabilize the native conformation. This intermediate binds the hydrophobic dye 8-anilino-1-naphthalene sulfonic acid (ANS) but not as strong as the molten globule state, and near-UV CD reveals the presence of significant tertiary structure. Notably, this intermediate is not as prone to aggregation as the classical molten globule. As a proof of concept for an intervention strategy with small molecules, we showed that binding of the CA inhibitor acetazolamide increases the stability of the native state of the mutant by 2.9 kcal/mol in accordance with its strong affinity. Acetazolamide shifts the Tm to 34 °C that protects from misfolding and will enable a substantial fraction of the enzyme pool to survive physiological conditions.
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| 16. |
- Alvez, Maria Bueno, et al.
(författare)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 17. |
- Ammenberg, Jonas, et al.
(författare)
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Biogas Research Center, BRC : Slutrapport för etapp 1
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Biogas Research Center (BRC) är ett kompetenscentrum för biogasforskning som finansieras av Energimyndigheten, LiU och ett flertal externa organisationer med en tredjedel vardera. BRC har en mycket bred tvärvetenskaplig inriktning och sammanför biogasrelaterad kompetens från flera olika områden för att skapa interaktion på flera olika plan:mellan näringsliv, akademi och samhälle,mellan olika perspektiv, samtmellan olika discipliner och kompetensområden.BRC:s vision är:Resurseffektiva biogaslösningar finns genomförda i många nya tillämpningar och bidrar till en mer hållbar energiförsörjning, förbättrat miljötillstånd och goda affärer.BRC:s särskilda roll för att uppnå denna vision är att bidra med kunskapsförsörjning och process-/teknikutveckling för att facilitera utveckling, innovation och implementering av biogaslösningar. Resurseffektivitet är ett nyckelord, vilket handlar om att förbättra befintliga processer och system samt utveckla biogaslösningar i nya sektorer och möjliggöra användning av nya substrat.For BRC:s etapp 1, den första tvåårsperioden mellan 2012-2014, var forskningsprojekten organiserade enligt tabellen nedan. Den visar viktiga utmaningar för biogasproducenter och andra intressenter, samt hur dessa ”angreps” med åtta forskningsprojekt. Fem av projekten var av explorativ karaktär i bemärkelsen att de var bredare och mer framtidsorienterade - exempelvis utvärderade flera möjliga tekniska utvecklingsmöjligheter (EP1-5). Tre projekt hade ett tydligare fokus på teknik- och processutveckling (DP6-8).I den här slutrapporten ges en kortfattad bakgrundsbeskrivning och det finns en introduktion till vad den här typen av kompetenscentrum innebär generellt. Därefter finns mer detaljerad information om BRC, exempelvis gäller det centrumets etablering, relevans, vision, hörnstenar och utveckling. De deltagande organisationerna presenteras, både forskargrupperna vid Linköpings universitet och partners och medlemmar. Vidare finns en mer utförlig introduktion till och beskrivning av utmaningarna i tabellen och kortfattat information om forskningsprojekten, följt av ett kapitel som berör måluppfyllelse och den externa utvärdering som gjorts av BRC:s verksamhet. Detaljerad, listad information finns till stor del i bilagorna.Kortfattat kan det konstateras att måluppfyllelsen överlag är god. Det är speciellt positivt att så många vetenskapliga artiklar publicerats (eller är på gång att publiceras) kopplat till forskningsprojekten och även i det vidare centrumperspektivet. Helt klart förekommer en omfattande verksamhet inom och kopplat till BRC. I etapp 2 är det viktigt att öka andelen mycket nöjda partner och medlemmar, där nu hälften är nöjda och hälften mycket nöjda. Det handlar framför allt om stärkt kommunikation, interaktion och projektledning. Under 2015 förväntas åtminstone två doktorsexamina, där avhandlingarna har stor koppling till forskningen inom etapp 1.I början på år 2014 skedde en extern utvärdering av verksamheten vid BRC med huvudsyftet att bedöma hur väl centrumet lyckats med etableringen samt att granska om det fanns förutsättningar för framtida framgångsrik verksamhet. Generellt var utfallet mycket positivt och utvärderarna konstaterade att BRC på kort tid lyckats etablera en verksamhet som fungerar väl och engagerar det stora flertalet deltagande aktörer, inom relevanta områden och där de flesta involverade ser BRC som en befogad och väl fungerande satsning, som de har för avsikt att även fortsättningsvis stödja. Utvärderingen bidrog också med flera relevant tips och till att belysa utmaningar.Utöver denna slutrapport finns separata publikationer från forskningsprojekten.Arbetet som presenteras i rapporten har finansierats av Energimyndigheten och de medverkande organisationerna.
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| 18. |
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| 19. |
- Bernet, Néstor Vazquez, et al.
(författare)
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High-Quality Library Preparation for NGS-Based Immunoglobulin Germline Gene Inference and Repertoire Expression Analysis
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Next generation sequencing (NGS) of immunoglobulin (Ig) repertoires (Rep-seq) enables examination of the adaptive immune system at an unprecedented level. Applications include studies of expressed repertoires, gene usage, somatic hypermutation levels, Ig lineage tracing and identification of genetic variation within the Ig loci through inference methods. All these applications require starting libraries that allow the generation of sequence data with low error rate and optimal representation of the expressed repertoire. Here, we provide detailed protocols for the production of libraries suitable for human Ig germline gene inference and Ig repertoire studies. Various parameters used in the process were tested in order to demonstrate factors that are critical to obtain high quality libraries. We demonstrate an improved 5'RACE technique that reduces the length constraints of Illumina MiSeq based Rep-seq analysis but allows for the acquisition of sequences upstream of Ig V genes, useful for primer design. We then describe a 5' multiplex method for library preparation, which yields full length V(D)J sequences suitable for genotype identification and novel gene inference. We provide comprehensive sets of primers targeting IGHV, IGKV, and IGLV genes. Using the optimized protocol, we produced IgM, IgG, IgK, and IgL libraries and analyzed them using the germline inference tool IgDiscover to identify expressed germline V alleles. This process additionally uncovered three IGHV, one IGKV, and six IGLV novel alleles in a single individual, which are absent from the IMGT reference database, highlighting the need for further study of Ig genetic variation. The library generation protocols presented here enable a robust means of analyzing expressed Ig repertoires, identifying novel alleles and producing individualized germline gene databases from humans.
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| 20. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 21. |
- Böttger, Michael, et al.
(författare)
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Electrospraying of colloidal nanoparticles for seeding of nanostructure growth
- 2007
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Ingår i: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 18:10
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Tidskriftsartikel (refereegranskat)abstract
- Nanometre-sized particles (1-100 nm) have unique properties receiving growing attention in wide areas of research. Here, a convenient method to deposit size-selected nanoparticles on surfaces by means of electrospraying colloidal suspensions in the aerosol phase is presented. We demonstrate the deposition of individual nanoparticles and the feasibility of this method in seeding gold particles for nanostructure growth. An advantage of the present method is the easy set-up and operation, using only commercially available machinery and substances. Problems regarding low deposition rates and colloidal remnants are approached, e. g. the aerosol flow is examined in a differential mobility analyser. This method is not material dependent and could be extended to deposit any colloidal particle.
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| 22. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 23. |
- Corcoran, Martin M., et al.
(författare)
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Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity
- 2016
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Ingår i: nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%. IgDiscover uses a cluster identification process to produce candidate sequences that, once filtered, results in individualized germline V gene databases. IgDiscover was tested in multiple species, validated by genomic cloning and cross library comparisons and produces comprehensive gene databases even where limited genomic sequence is available. IgDiscover analysis of the allelic content of the Indian and Chinese-origin rhesus macaques reveals high levels of immunoglobulin gene diversity in this species. Further, we describe a novel human IGHV3-21 allele and confirm significant gene differences between Balb/c and C57BL6 mouse strains, demonstrating the power of IgDiscover as a germline V gene discovery tool.
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| 24. |
- Coviello, Andrea D, et al.
(författare)
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p=1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4×10(-11)), GCKR (rs780093, 2p23.3, p=2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p=2.5×10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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| 25. |
- Dalin, Martin, 1982, et al.
(författare)
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Myocardial KRASG12D expression does not cause cardiomyopathy in mice
- 2014
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 101:2, s. 229-235
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Tidskriftsartikel (refereegranskat)abstract
- AimsGerm-line mutations in genes encoding components of the RAS/mitogen-activated protein kinase (MAPK) pathway cause developmental disorders called RASopathies. Hypertrophic cardiomyopathy (HCM) is the most common myocardial pathology and a leading cause of death in RASopathy patients. KRAS mutations are found in Noonan and cardio-facio-cutaneous syndromes. KRAS mutations, unlike mutations of RAF1 and HRAS, are rarely associated with HCM. This has been attributed to the fact that germ-line KRAS mutations cause only a moderate up-regulation of the MAPK pathway. Highly bioactive KRAS mutations have been hypothesized to cause severe cardiomyopathy incompatible with life. The aim of this study was to define the impact of KRASG12D expression in the heart.Methods and resultsTo generate mice with endogenous cardiomyocyte-specific KRASG12D expression (cKRASG12D mice), we bred mice with a Cre-inducible allele expressing KRASG12D from its endogenous promoter (Kras2LSL) to mice expressing Cre under control of the cardiomyocyte-specific α-myosin heavy chain promoter (αMHC-Cre). cKRASG12D mice showed high levels of myocardial ERK and AKT signalling. However, surprisingly, cKRASG12D mice were born in Mendelian ratios, appeared healthy, and had normal function, size, and histology of the heart.ConclusionMice with cardiomyocyte-specific KRAS G12D expression do not develop heart pathology. These results challenge the view that the level of MAPK activation correlates with the severity of HCM in RASopathies and suggests that MAPK-independent strategies may be of interest in the development of new treatments for these syndromes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.
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