| 1. |
- Alijagic, Andi, 1992-, et al.
(författare)
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Particle Safety Assessment in Additive Manufacturing : From Exposure Risks to Advanced Toxicology Testing.
- 2022
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Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 4
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Forskningsöversikt (refereegranskat)abstract
- Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle-spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.
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| 2. |
- Boström, Lena, 1960-, et al.
(författare)
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Digital visualisering i skolan : Mittuniversitetets slutrapport från förstudien
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den här studiens syfte har varit tvåfaldigt, nämligen att testa alternativa lärmetoder via ett digitalt läromedel i matematik i en kvasiexperimentell studie samt att tillämpa metoder av användarupplevelser för interaktiva visualiseringar, och därigenom öka kunskapen kring hur upplevd kvalitet beror på använd teknik. Pilotstudien sätter också fokus på flera angelägna områden inom skolutveckling både regionalt och nationellt samt viktiga aspekter när det gäller kopplingen teknik, pedagogik och utvärderingsmetoder inom “den tekniska delen”. Det förra handlar om sjunkande matematikresultat i skolan, praktiknära skolforskning, stärkt digital kompetens, visualisering och lärande samt forskning om visualisering och utvärdering. Den senare svarar på frågor om vilka tekniska lösningar som tidigare använts och med vilket syfte har de skapats samt hur visualiseringar har utvärderats enligt läroböcker och i forskningslitteratur. När det gäller elevernas resultat, en av de stora forskningsfrågorna i studien, så fann vi inga signifikanta skillnader mellan traditionell undervisning och undervisning med visualiseringsläromedlet (3D). Beträffande elevers attityder till matematikmomentet kan konstateras att i kontrollgruppen för årskurs 6 förbättrades attityden signifikans, men inte i klass 8. Gällande flickors och pojkars resultat och attityder kan vi konstatera att flickorna i båda klasserna hade bättre förkunskaper än pojkarna samt att i årskurs 6 var flickorna mer positiva till matematikmomentet än pojkarna i kontrollgruppen. Därutöver kan vi inte skönja några signifikanta skillnader. Andra viktiga rön i studien var att provkonstruktionen inte var optimal samt att tiden för provgenomförande har stor betydelse när på dagen det genomfördes. Andra resultat resultaten i den kvalitativa analysen pekar på positiva attityder och beteenden från eleverna vid arbetet med det visuella läromedlet. Elevernas samarbete och kommunikation förbättrades under lektionerna. Vidare pekade lärarna på att med 3D-läromedlet gavs större möjligheter till att stimulera flera sinnen under lärprocessen. En tydlig slutsats är att 3D-läromedlet är ett viktigt komplement i undervisningen, men kan inte användas helt självt. Vi kan varken sälla oss till de forskare som anser att 3D-visualisering är överlägset som läromedel för elevers resultat eller till de forskare som varnar för dess effekter för elevers kognitiva överbelastning. Våra resultat ligger mer i linje med de slutsatser Skolforskningsinstitutet (2017) drar, nämligen att undervisning med digitala läromedel i matematik kan ha positiva effekter, men en lika effektiv undervisning kan möjligen designas på andra sätt. Däremot pekar resultaten i vår studie på ett flertal störningsmoment som kan ha påverkat möjliga resultat och behovet av god teknologin och välutvecklade programvaror. I studien har vi analyserat resultaten med hjälp av två övergripande ramverk för integrering av teknikstöd i lärande, SAMR och TPACK. Det förra ramverket bidrog med en taxonomi vid diskussionen av hur väl teknikens möjligheter tagits tillvara av läromedel och i läraktiviteter, det senare för en diskussion om de didaktiska frågeställningarna med fokus på teknikens roll. Båda aspekterna är högaktuella med tanke på den ökande digitaliseringen i skolan. Utifrån tidigare forskning och denna pilotstudie förstår vi att det är viktigt att designa forskningsmetoderna noggrant. En randomisering av grupper vore önskvärt. Prestandamått kan också vara svåra att välja. Tester där personer får utvärdera användbarhet (usability) och användarupplevelse (user experience, UX) baserade på både kvalitativa och kvantitativa metoder blir viktiga för själva användandet av tekniken, men det måste till ytterligare utvärderingar för att koppla tekniken och visualiseringen till kvaliteten i lärandet och undervisningen. Flera metoder behövs således och det blir viktigt med samarbete mellan olika ämnen och discipliner.
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| 3. |
- Flowers, Sarah A., et al.
(författare)
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Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking
- 2020
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:47, s. 16023-16036
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Tidskriftsartikel (refereegranskat)abstract
- The synovial fluid glycoprotein lubricin (also known as proteoglycan 4) is a mucin-type O-linked glycosylated biological lubricant implicated to be involved in osteoarthritis (OA) development. Lubricin's ability to reduce friction is related to its glycosylation consisting of sialylated and unsialylated Tn-antigens and core 1 and core 2 structures. The glycans on lubricin have also been suggested to be involved in crosslinking and stabilization of the lubricating superficial layer of cartilage by mediating interaction between lubricin and galectin-3. However, with the spectrum of glycans being found on lubricin, the glycan candidates involved in this interaction were unknown. Here, we confirm that the core 2 O-linked glycans mediate this lubricin-galectin-3 interaction, shown by surface plasmon resonance data indicating that recombinant lubricin (rhPRG4) devoid of core 2 structures did not bind to recombinant galectin-3. Conversely, transfection of Chinese hamster ovary cells with the core 2 GlcNAc transferase acting on a mucin-type O-glycoprotein displayed increased galectin-3 binding. Both the level of galectin-3 and the galectin-3 interactions with synovial lubricin were found to be decreased in late-stage OA patients, coinciding with an increase in unsialylated core 1 O-glycans (T-antigens) and Tn-antigens. These data suggest a defect in crosslinking of surface-active molecules in OA and provide novel insights into OA molecular pathology.
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| 4. |
- Roos, Helena, 1974-, et al.
(författare)
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Promoting basic arithmetic competence in early school years - using a response to intervention model
- 2023
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Ingår i: Journal of Research in Special Educational Needs. - : John Wiley & Sons. - 1471-3802. ; 23:4, s. 263-388
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated whether mathematics education based on a multi-tiered response to intervention (RTI) model can support students' arithmetic competence in primary schools in Sweden. The intent was to identify and support students at risk of failure. In this study, 113 students participated in the intervention, and 30 students participated in the control group. Both groups were followed from Grade 1 to the end of Grade 2 and compared. During the first semester in Grade 1, all students were taught basic addition and subtraction with explicit instructions in Tier 1. Those who did not respond to Tier 1 after one semester were provided support within Tier 2 during the second semester. The same was repeated in grade 2 and the students that did not respond to Tier 2 were supported within Tier 3. At the end of Grade 2, students in the intervention group performed significantly higher on the basic arithmetic competence in the number range 1-9 than the control group. No significant difference was found in a test measuring basic arithmetic competence in the number range 10-19. This study shows that using multi-tiered RTI might be sufficient to identify and support students at risk in early arithmetic competence.
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| 5. |
- Alijagic, Andi, 1992-, et al.
(författare)
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A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
- 2023
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.
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| 6. |
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| 7. |
- Brogren, Helén, 1977, et al.
(författare)
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Heterogeneous glycosylation patterns of human PAI-1 may reveal its cellular origin.
- 2008
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Ingår i: Thrombosis research. - : Elsevier BV. - 0049-3848. ; 122:2, s. 271-81
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Tidskriftsartikel (refereegranskat)abstract
- The main inhibitor of intravascular fibrinolysis is plasminogen activator inhibitor 1 (PAI-1) which binds to and irreversibly inhibits tissue plasminogen activator (tPA). PAI-1 is present in blood, both in platelets and in plasma, and PAI-1 levels are associated with risk of atherothrombosis. Several tissues express PAI-1 but the source of plasma PAI-1 is not known. We recently found that platelets can de novo synthesize PAI-1 and the amount synthesized in vitro in 24 hours is 35-fold higher than required to maintain normal plasma levels. Recombinant human PAI-1 expressed in different cell types or secreted naturally by human cell lines, exhibit heterogeneous glycosylation patterns. The aim of this study was to investigate the hypothesis that platelets might be the source of plasma PAI-1 and that the cellular source of PAI-1 can be determined by its tissue-specific glycosylation pattern. PAI-1 was isolated from platelets, macrophages, endothelial cells, adipose tissue, as well as plasma from lean and obese subjects. The glycosylation was analyzed by nanoLC-MS/MS. PAI-1 isolated from cell lysates and conditioned media from macrophages, endothelial cells, and adipose tissue expressed heterogeneous glycosylation patterns. By contrast, no glycans were detected on PAI-1 isolated from plasma or platelets from healthy lean individuals. Hence, our data suggest that platelets may be the main source of plasma PAI-1 in lean individuals. Interestingly, plasma PAI-1 from obese subjects had a glycan composition similar to that of adipose tissue suggesting that obese subjects with elevated PAI-1 levels may have a major contribution from other tissues.
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| 8. |
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| 9. |
- 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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