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Sökning: WFRF:(Andersson Helena) > (2020-2024)

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  • Ghosheh, Nidal, 1975-, et al. (författare)
  • Human Pluripotent Stem Cell-Derived Hepatocytes Show Higher Transcriptional Correlation with Adult Liver Tissue than with Fetal Liver Tissue
  • 2020
  • Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:10, s. 4816-4827
  • Tidskriftsartikel (refereegranskat)abstract
    • Human pluripotent stem cell-derived hepatocytes (hPSC-HEP) display many properties of mature hepatocytes, including expression of important genes of the drug metabolizing machinery, glycogen storage, and production of multiple serum proteins. To this date, hPSC-HEP do not, however, fully recapitulate the complete functionality of in vivo mature hepatocytes. In this study, we applied versatile bioinformatic algorithms, including functional annotation and pathway enrichment analyses, transcription factor binding-site enrichment, and similarity and correlation analyses, to datasets collected from different stages during hPSC-HEP differentiation and compared these to developmental stages and tissues from fetal and adult human liver. Our results demonstrate a high level of similarity between the in vitro differentiation of hPSC-HEP and in vivo hepatogenesis. Importantly, the transcriptional correlation of hPSC-HEP with adult liver (AL) tissues was higher than with fetal liver (FL) tissues (0.83 and 0.70, respectively). Functional data revealed mature features of hPSC-HEP including cytochrome P450 enzymes activities and albumin secretion. Moreover, hPSC-HEP showed expression of many genes involved in drug absorption, distribution, metabolism, and excretion. Despite the high similarities observed, we identified differences of specific pathways and regulatory players by analyzing the gene expression between hPSC-HEP and AL. These findings will aid future intervention and improvement of in vitro hepatocyte differentiation protocol in order to generate hepatocytes displaying the complete functionality of mature hepatocytes. Finally, on the transcriptional level, our results show stronger correlation and higher similarity of hPSC-HEP to AL than to FL. In addition, potential targets for further functional improvement of hPSC-HEP were also identified. 
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  • Klemetz, Viktor, et al. (författare)
  • Nationell luftövervakning : Sakrapport med data från övervakning inom Programområde Luft t. o. m. 2021
  • 2023
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Naturvårdsverket ansvarar för den nationella luftövervakningen i bakgrundsmiljö. I rapporten redovisas resultat från verksamheten inom Programområde Luft avseende mätningar (genomförda av IVL Svenska Miljöinstitutet (IVL),Institutionen för Miljövetenskap vid Stockholms universitet (SU), Institutionen för Mark och Miljö vid Sveriges lantbruksuniversitet (SLU), Chalmers tekniska högskola och Sveriges meteorologiska och hydrologiska institut (SMHI) till och med 2021 samt regionala modellberäkningar (utförda av SMHI) till och med 2020. För flertalet av de luftföroreningskomponenter som övervakas inom den nationella miljöövervakningen har det, sedan mätningarna startade för mellan 20 och 45 år sedan, generellt skett en avsevärd förbättring avseende såväl halter i luft som deposition i bakgrundsmiljö.Utvecklingen har dock varierat i något olika utsträckning beroende på komponenter och lokalisering i landet. Föroreningsbelastningen är oftast lägre ju längre norrut i landet man kommer.För de flesta ämnen som det finns miljökvalitetsnormer (MKN) respektive miljömål för ligger halterna avsevärt lägre än angivna gräns- och målvärden. Halterna av marknära ozon överskrider i dagsläget MKN för hälsa vid ett flertal mätstationer i södra Sverige.För såväl partiklar (i form av PM2,5) och bensen (i urban bakgrund) är risken låg att haltnivåer överstiger miljömålens preciseringar. 
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  • Lundtoft, Christian, et al. (författare)
  • Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases
  • 2022
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 74:8, s. 1440-1450
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjogrens syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2-33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7-5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account.
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  • Napoleone, Antonino, et al. (författare)
  • Fed-batch production assessment of a tetravalent bispecific antibody : A case study on piggyBac stably transfected HEK293 cells
  • 2021
  • Ingår i: New Biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 65, s. 9-19
  • Tidskriftsartikel (refereegranskat)abstract
    • The transition from preclinical biological drug development into clinical trials requires an efficient upscaling process. In this context, bispecific antibody drugs are particularly challenging due to their propensity to form aggregates and generally produce low titers. Here, the upscaling process for a tetravalent bispecific antibody expressed by a piggyBac transposon-mediated stable HEK293 cell pool has been evaluated. The project was performed as a case study at Testa Center, a non-GMP facility for scale-up testing of biologics in Sweden, and encompassed media adaptation strategies, fed-batch optimization and a novel antibody purification technology. The cell pool was adapted to different culture media for evaluation in terms of cell viability and titers compared to its original Expi293 Expression Medium. These parameters were assessed in both sequential stepwise adaption and direct media exchanges. By this, a more affordable medium was identified that did not require stepwise adaptation and with similar titers and viability as in the Expi293 Expression Medium. Fed-batch optimizations resulted in culture densities reaching up to 20 x 106 viable cells/mL with over 90 % viability 12 days postinoculum, and antibody titers three times higher than corresponding batch cultures. By implementing a novel high-speed protein A fiber technology (Fibro PrismA) with a capture residence time of only 7.5 s, 8 L of supernatant could be purified in 4.5 h without compromising the purity, structural integrity and function of the bispecific antibody. Results from this study related to medium adaptation and design of fed-batch protocols will be highly beneficial during the forthcoming scale-up of this therapeutic antibody.
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7.
  • Olofsdotter Stensöta, Helena, 1965, et al. (författare)
  • Fördomar eller okunskap - könsasymmetrier i handläggning?
  • 2020
  • Ingår i: Arbetsmarknad & Arbetsliv. - Karlstad : Karlstads universitet. - 1400-9692 .- 2002-343X. ; 26:2, s. 91-110
  • Tidskriftsartikel (refereegranskat)abstract
    • Kvinnor har något svårare att få ersättning än män från arbetsskadeförsäkringen. Tidigare studier fokuserar främst på egenskaper hos de försäkrade, vi undersöker istället om bedömningar i handläggningen kan bidra till skillnaderna genom omedvetna bias och/eller kunskapsluckor. Vi använder ett datamaterial bestående dels av en enkät med ett vinjettexperiment som riktats till samtliga handläggare och dels reellaarbetsskadeakter. Undersökningen ger inte stöd för att handläggarna diskriminerar utifrån kön, men att den medicinska bedömningen ofta är undermålig. Vi rekommenderar utökad utbildning av handläggare för att undvika rättsosäkra bedömningar och risk för ojämlikhet i utfall av arbetsskadeärenden med avseende på kön.
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8.
  • Alexanderson, Helena, et al. (författare)
  • Buried by sand – the abandoned medieval town at Falsterbo, S Sweden
  • 2024
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Archaeological investigations have revealed cultural layers with remnants of houses and streets below up to four metres of sand at the southern end of the Falsterbo peninsula in southernmost Sweden. The cultural layers have been dated to the 15th – 16th centuries, based on finds of, for example, coins and ceramics, and interpreted to represent the medieval town Falsterbo. It has been assumed that the houses in this once central part of town, close to the church, were abandoned due to strong sand drift that eventually buried most of the structures. Here we will present results of luminescence dating, portable luminescence analysis and other geological analyses of the sand below, between and above the cultural layers. The lowermost sand is interpreted as beach sand, while all other sand beds – separating and covering the different phases of houses – are interpreted as aeolian sand. Preliminary results suggest a hiatus between the deposition of the beach sand and the first aeolian sand, followed by relatively rapid sand accumulation after final abandonment.
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  • Almqvist, Linnea, 1987- (författare)
  • Asthma epidemiology : prognosis of asthma with onset in childhood and in adulthood
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Aim: to update the knowledge on the epidemiology of asthma with onset in childhood and adulthood as well as examine the importance of risk factors in early childhood and clinical characteristics on the incidence and prognosis of asthma.Methods: The thesis is based on the epidemiological research program Obstructive Lung Disease in Northern Sweden (OLIN) studies. Pediatric cohort: recruited in 1996 (age 8y, n=3430, 97% of invited) and followed annually by questionnaire about asthma, allergy and risk factors until 19y and a postal questionnaire at 28y. Clinical examinations included skin prick tests (SPT at 8, 12 and 19y) and spirometry (19y). Adult cohort: 309 adults (age 20–60y) with asthma onset in the last 12 months were recruited 1995-99 and re-examined in 2012-14 (n=205). Structured interviews, spirometry and SPT were performed at recruitment and follow-up and bronchial hyperreactivity (BHR) at recruitment.Results: The asthma incidence rate was 10-13/1000/year in childhood and adolescence and 6/1000/year in young adulthood. Several risk factors in early life were associated with asthma onset in childhood, adolescence and young adulthood, e.g. family history of asthma, <3 months breastfeeding, rhinoconjunctivitis and positive SPT at 8y, while low birthweight, maternal smoking during pregnancy, severe respiratory infections and eczema were associated with onset in childhood and adolescence. Among those with asthma at 8y, 62% still had asthma at 28y and this was associated with positive SPT, rhinoconjunctivitis, severe respiratory infection in childhood, and bronchial hyperreactivity (BHR) in adolescence. Coexistence of asthma, rhinitis and eczema increased by age, especially among those with a positive SPT. However, having all three conditions was uncommon. In the 15y follow-up adult onset asthma, 89% had persistent asthma. Better lung function at recruitment and less severe BHR was associated with remission. Remission rate of adult onset asthma was <1% per year.Conclusion: The incidence of asthma was high during childhood and adolescence and then decreased in young adulthood. Factors in early life that were associated with incident asthma during childhood were still associated with the incidence in adult age. Among those with asthma onset by 8 years, 62%, still had asthma as young adults. The coexistence of asthma, rhinitis and eczema varied from 8 to 28y without following a specific pattern, only a small proportion reported having all three conditions. Remission of adult onset asthma was rare. 
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