| 1. |
- Adiels, Martin, 1976, et al.
(författare)
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Role of apolipoprotein C-III overproduction in diabetic dyslipidaemia
- 2019
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Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 21:8, s. 1861-1870
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Tidskriftsartikel (refereegranskat)abstract
- - Aims: To investigate how apolipoprotein C-III (apoC-III) metabolism is altered in subjects with type 2 diabetes, whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of apoC-III, and whether improvement of glycaemic control using the glucagon-like peptide-1 analogue liraglutide for 16 weeks modifies apoC-III dynamics. Materials and Methods: Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5- 2 H 3 ]leucine using ultrasensitive mass spectrometry techniques. We compared apoC-III kinetics in two situations: in subjects with type 2 diabetes before and after liraglutide therapy, and in type 2 diabetic subjects with matched body mass index (BMI) non-diabetic subjects. Liver fat content, subcutaneous abdominal and intra-abdominal fat were determined using proton magnetic resonance spectroscopy. Results: Improved glycaemic control by liraglutide therapy for 16 weeks significantly reduced apoC-III secretion rate (561 ± 198 vs. 652 ± 196 mg/d, P = 0.03) and apoC-III levels (10.0 ± 3.8 vs. 11.7 ± 4.3 mg/dL, P = 0.035) in subjects with type 2 diabetes. Change in apoC-III secretion rate was significantly associated with the improvement in indices of glucose control (r = 0.67; P = 0.009) and change in triglyceride area under the curve (r = 0.59; P = 0.025). In line with this, the apoC-III secretion rate was higher in subjects with type 2 diabetes compared with BMI-matched non-diabetic subjects (676 ± 208 vs. 505 ± 174 mg/d, P = 0.042). Conclusions: The results reveal that the secretion rate of apoC-III is associated with elevation of triglyceride-rich lipoproteins in subjects with type 2 diabetes, potentially through the influence of glucose homeostasis on the production of apoC-III. © 2019 John Wiley & Sons Ltd
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| 2. |
- Björnson, Elias, 1988, et al.
(författare)
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Apolipoprotein B48 metabolism in chylomicrons and very low-density lipoproteins and its role in triglyceride transport in normo- and hypertriglyceridemic human subjects
- 2020
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 288:4, s. 422-438
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Tidskriftsartikel (refereegranskat)abstract
- Background Renewed interest in triglyceride-rich lipoproteins as causative agents in cardiovascular disease mandates further exploration of the integrated metabolism of chylomicrons and very low-density lipoproteins (VLDL). Methods Novel tracer techniques and an integrated multi-compartmental model were used to determine the kinetics of apoB48- and apoB100-containing particles in the chylomicron and VLDL density intervals in 15 subjects with a wide range of plasma triglyceride levels. Results Following a fat-rich meal, apoB48 appeared in the chylomicron, VLDL1 and VLDL2 fractions in all subjects. Chylomicrons cleared rapidly from the circulation but apoB48-containing VLDL accumulated, and over the day were 3-fold higher in those with high versus low plasma triglyceride. ApoB48-containing particles were secreted directly into both the chylomicron and VLDL fractions at rates that were similar across the plasma triglyceride range studied. During fat absorption, whilst most triglyceride entered the circulation in chylomicrons, the majority of apoB48 particles were secreted into the VLDL density range. Conclusion The intestine secretes apoB48-containing particles not only as chylomicrons but also directly into the VLDL1 and VLDL2 density ranges both in the basal state and during dietary lipid absorption. Over the day, apoB48-containing particles appear to comprise about 20-25% of circulating VLDL and, especially in those with elevated triglycerides, form part of a slowly cleared 'remnant' particle population, thereby potentially increasing CHD risk. These findings provide a metabolic understanding of the potential consequences for increased CHD risk when slowed lipolysis leads to the accumulation of remnants, especially in individuals with hypertriglyceridemia.
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| 3. |
- Björnson, Elias, 1988, et al.
(författare)
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Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics
- 2019
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:5, s. 562-577
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTriglyceride-rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low-density lipoproteins (VLDL). MethodsMass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL1 and VLDL2 density intervals. An integrated non-steady-state multicompartmental model was constructed to describe the metabolism of apoB48- and apoB100-containing lipoproteins following a fat-rich meal, as well as during prolonged fasting. ResultsThe kinetic model described the metabolism of apoB48 in CM, VLDL1 and VLDL2. It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL1 and VLDL2. ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50mgday(-1), and the increment during absorption was about 230mgday(-1). The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM. DiscussionThis novel non-steady-state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.
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| 4. |
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| 5. |
- Haglund, Jesper, 1973-, et al.
(författare)
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Practical exercises in university mechanics
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In the present study, four practical exercises were introduced in a university-level mechanics course, in order to provide students with shared, personal, embodied experiences of physical phenomena in relation to the taught content. The practical exercises were performed during 10-15 minutes with subsequent discussion in random groups of 3-4 students during recitation sessions. Two of the exercises involved physically experiencing the reduced force of raising a 5 kg weight with a rope and a system of pulleys compared to with a rope alone, and finding the centre of mass of an object by holding under the object with ones hands and moving the hands toward one another. Video analysis of selected episodes of students’ interaction with the exercises reveals how they coordinated gestures and spoken language in expressing their conceptual understanding of the phenomena. In a subsequent group interview, participant physics teacher students expressed that the exercises were useful for feeling physically what they had previously only calculated. Apart from grounding conceptual understanding in physical experiences, the course evaluation shows that participation in random small groups led to increased communication among students that did not know each other before, thereby contributing to the development of a learning community.
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| 6. |
- Taskinen, Marja-Riitta, et al.
(författare)
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Contribution of intestinal triglyceride-rich lipoproteins to residual atherosclerotic cardiovascular disease risk in individuals with type 2 diabetes on statin therapy
- 2023
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Ingår i: DIABETOLOGIA. - 0012-186X .- 1432-0428. ; 66:12, s. 2307-2319
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: This study explored the hypothesis that significant abnormalities in the metabolism of intestinally derived lipoproteins are present in individuals with type 2 diabetes on statin therapy. These abnormalities may contribute to residual CVD risk.Methods: To investigate the kinetics of ApoB-48- and ApoB-100-containing lipoproteins, we performed a secondary analysis of 11 overweight/obese individuals with type 2 diabetes who were treated with lifestyle counselling and on a stable dose of metformin who were from an earlier clinical study, and compared these with 11 control participants frequency-matched for age, BMI and sex. Participants in both groups were on a similar statin regimen during the study. Stable isotope tracers were used to determine the kinetics of the following in response to a standard fat-rich meal: (1) apolipoprotein (Apo)B-48 in chylomicrons and VLDL; (2) ApoB-100 in VLDL, intermediate-density lipoprotein (IDL) and LDL; and (3) triglyceride (TG) in VLDL.Results: The fasting lipid profile did not differ significantly between the two groups. Compared with control participants, in individuals with type 2 diabetes, chylomicron TG and ApoB-48 levels exhibited an approximately twofold higher response to the fat-rich meal, and a twofold higher increment was observed in ApoB-48 particles in the VLDL1 and VLDL2 density ranges (all p < 0.05). Again comparing control participants with individuals with type 2 diabetes, in the latter, total ApoB-48 production was 25% higher (556 +/- 57 vs 446 +/- 57 mg/day; p < 0.001), conversion (fractional transfer rate) of chylomicrons to VLDL was around 40% lower (35 +/- 25 vs 82 +/- 58 pools/day; p=0.034) and direct clearance of chylomicrons was 5.6-fold higher (5.6 +/- 2.2 vs 1.0 +/- 1.8 pools/day; p < 0.001). During the postprandial period, ApoB-48 particles accounted for a higher proportion of total VLDL in individuals with type 2 diabetes (44%) compared with control participants (25%), and these ApoB-48 VLDL particles exhibited a fivefold longer residence time in the circulation (p < 0.01). No between-group differences were seen in the kinetics of ApoB-100 and TG in VLDL, or in LDL ApoB-100 production, pool size and clearance rate. As compared with control participants, the IDL ApoB-100 pool in individuals with type 2 diabetes was higher due to increased conversion from VLDL2.Conclusions/interpretation: Abnormalities in the metabolism of intestinally derived ApoB-48-containing lipoproteins in individuals with type 2 diabetes on statins may help to explain the residual risk of CVD and may be suitable targets for interventions.
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| 7. |
- Taskinen, M. R., et al.
(författare)
-
Role of endogenous incretins in the regulation of postprandial lipoprotein metabolism
- 2022
-
Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 187:1, s. 75-84
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Incretins are known to influence lipid metabolism in the intestine when administered as pharmacologic agents. The aggregate influence of endogenous incretins on chylomicron production and clearance is less clear, particularly in light of opposing effects of co-secreted hormones. Here, we tested the hypothesis that physiological levels of incretins may impact on production or clearances rates of chylomicrons and VLDL. Design and methods: A group of 22 overweight/obese men was studied to determine associations between plasma levels of glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) after a fat-rich meal and the production and clearance rates of apoB48- and apoB100-containing triglyceride-rich lipoproteins. Subjects were stratified by above- and below-median incretin response (area under the curve). Results: Stratification yielded subgroups that differed about two-fold in incretin response. There were neither differences in apoB48 production rates in chylomicrons or VLDL fractions nor in apoB100 or triglyceride kinetics in VLDL between men with above- vs below-median incretin responses. The men with above-median GLP-1 and GLP-2 responses exhibited higher postprandial plasma and chylomicron triglyceride levels, but this could not be related to altered kinetic parameters. No differences were found between incretin response subgroups and particle clearance rates. Conclusion: We found no evidence for a regulatory effect of endogenous incretins on contemporaneous chylomicron or VLDL metabolism following a standardised fat-rich meal. The actions of incretins at pharmacological doses may not be reflected at physiological levels of these hormones.
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| 8. |
- Andersson, Jan, et al.
(författare)
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Kartläggning av ägarskiften i företag : Utveckling och dokumentation av dataunderlag
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Myndigheten för tillväxtpolitiska utvärderingar och analyser, Tillväxtanalys, har haft i uppdrag av regeringen att genomföra kartläggning och analys av ägarskiften i företag. Uppdraget omfattade även att göra jämförelser mellan generationsskiften och andra typer av ägarskiften som inte är åldersbaserade samt belysa möjligheten att följa upp företagens skifte och dynamik över tid. Tillväxtanalys lämnade i oktober 2013 en delrapportering av uppdraget som avser dels en kartläggning av åldersstrukturen i företagsstocken, dels en fördjupad analys av ägarskiften. Denna rapport är en redovisning av uppdragets sista del som innebär utveckling och dokumentation av dataunderlag för identifiering av ägarförändringar.SCB har på uppdrag av Tillväxtanalys undersökt möjligheten att bättre identifiera ägarskiften genom att integrera och göra en matchningskontroll av kompletterande uppgifter gällande delägare i fåmansaktiebolag som kan hämtas från Skatteverket, SKV, med redan befintlig information om företagsdynamik, vilken finns i Företagens och arbetsställenas dynamik, FAD, och den registerbaserade arbetsmarknadsstatisken, RAMS, på SCB. För att göra detta studeras företagens ägarskiften mellan åren 2010 och 2011. Uppdraget omfattar även att beskriva FAD gällande syfte, metodik och innehåll.Cirka 80 procent av samtliga företag oberoende av bolagsform överlevde mellan åren 2010 och 2011. Resterande företag har på något sätt förändrats. Företag läggs ned och andra startar som en del i strukturomvandlingen. Dessutom ser vi att många företag och arbetsställen byter ägare. Näringslivet visar på en stor dynamik och dynamiken omfattar många olika typer av förändringar.Bearbetningarna visar att det med hjälp av RAMS och SKV:s register går att följa och framställa uppgifter om ägarförändringar på ett bra sätt. Detta gäller både för fåmansaktiebolag, där det går att följa individuellt ägande, och för övriga juridiska former där förändringar i organisationsnummer kan spåras, vilket indikerar ändrade ägarförhållanden. Analysen visar att SKV:s register är ett bra komplement till RAMS och FAD och tillför ytterligare information. Samkörningen av dessa registerdata ger mer information än vad som kan fås ut av respektive registerkällor separat. Det går dessutom att koppla på annan information om anställda, omsättning och olika mått på lönsamhet från andra register.Tillväxtanalys rekommenderar därför att SCB får tillgång till register gällande ägarandelar från Skatteverket under en längre tidsperiod än enbart de undersökta åren. Detta för att kunna sammanställa en databas som möjliggör bättre och mer precisa analyser av olika dimensioner av näringslivsdynamik och ägarförändringar. Det vore dessutom önskvärt att denna databas görs tillgänglig för forskning och studier som ökar kunskapen om olika dimensioner av näringslivets strukturomvandling.
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| 9. |
- Andersson, Jan, 1973-, et al.
(författare)
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Lärarstudenter konkretiserar energi genom energiteater
- 2019
-
Ingår i: Forum för forskningsbaserad NT-undervisning: Bidrag från konferensen FobasNT18 13 – 14 mars 2018 i Norrköping. - Linköping : Linköping University Electronic Press. - 9789176850442 ; , s. 23-38
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Vid Karlstads universitet har vi sedan hösten 2017 infört energiteater som en aktivitet i fysikkurser på samtliga grund- och ämneslärarutbildningar. Energiteater kan betraktas som en kompletterande undervisnings- och inlärningsform, där studenter förväntas att i mindre grupper tillsammans diskutera och sedan gestalta förekommande energiformer och energiomvandlingar i olika vardagsscenarier. I den här studien har videoinspelningar av en grupps gestaltningar kring två skilda scenarier analyserats i syfte att klargöra på vilket sätt energiteater stimulerar studenternas kommunikation och interaktion. Scenarierna involverarde energiomvandlingar som sker då en studsboll studsar mot marken, respektive de energiomvandlingar som sker i ett snurrande änglaspel. Resultatet visar att energiteater i stor utsträckning stimulerar utforskande samtal mellan studenterna, vilket kan betraktas somen meningsskapande dialog. Aktivitetens karaktär bidrar till att alla deltagare blir aktiva och förtrogna med förekommande energiformer och energiomvandlingar. Planerandet och genomförandet av gestaltningen skapar spontana kvalitativa diskussioner kring flödet av energi mellan olika system, som på ett naturligt sätt motiverar studenterna att vidareutveckla själva gestaltningen. Vi menar att energiteater kan stärka lärarstudenternas egen förståelse av energi, men att den även kan erbjuda en möjlig alternativ undervisningsansats för lärarstudenterna i sin blivande roll som lärare i skolan.
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| 10. |
- Andersson, Linda, 1973, et al.
(författare)
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Deficiency in perilipin 5 reduces mitochondrial function and membrane depolarization in mouse hearts.
- 2017
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Ingår i: The international journal of biochemistry & cell biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 91:Pt A, s. 9-13
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial triglycerides stored in lipid droplets are important in regulating the intracellular delivery of fatty acids for energy generation in mitochondria, for membrane biosynthesis, and as agonists for intracellular signaling. Previously, we showed that deficiency in the lipid droplet protein perilipin 5 (Plin5) markedly reduces triglyceride storage in cardiomyocytes and increases the flux of fatty acids into phospholipids. Here, we investigated whether Plin5 deficiency in cardiomyocytes alters mitochondrial function. We found that Plin5 deficiency reduced mitochondrial oxidative capacity. Furthermore, in mitochondria from Plin5((-/)(-)) hearts, the fatty acyl composition of phospholipids in mitochondrial membranes was altered and mitochondrial membrane depolarization was markedly compromised. These findings suggest that mitochondria isolated from hearts deficient in Plin5, have specific functional defects.
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| 11. |
- Andersson, Linda, 1973, et al.
(författare)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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| 12. |
- Andersson, Linda, 1973, et al.
(författare)
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Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischemia
- 2015
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 107:4, s. 478-486
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Tidskriftsartikel (refereegranskat)abstract
- In myocardial ischemia, vascular endothelial growth factor (VEGF) induces permeability by activating a signalling pathway that includes VEGF receptor 2 (VEGFR2), resulting in increased oedema and inflammation and thereby expanding the area of tissue damage. In this study, we investigated the role of receptor-interacting protein 2 (Rip2) in VEGF signalling and myocardial ischemia/reperfusion injury.
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| 13. |
- Andersson, Ulf, 1973-, et al.
(författare)
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Organic Acquisitions in the Internationalization Process of the Business Firm
- 1998
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Ingår i: Management International Review. ; 37:2, s. 67-84
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Tidskriftsartikel (refereegranskat)abstract
- This paper has two closely related purposes. A first purpose is to increase ouunderstanding of foreign acquisitions by considering them within the conteof the internationalization process of the firm. Second, by focusing on the rof acquisitions the paper is meant to contribute to a development of the moof the internationalization process of the firm. By focusing the embedded nture of the business firm it places attention on the role of organic acquisitias contrasted to the discontinuous changes associated with foreign acquisitions.A conceptual result is that the paper offers a framework for analyzing the rof foreign acquisitions in the internationalization process of the business firThis framework takes into consideration both antecedents to and consequencof acquisitions.An empirical result is the finding that there seems to be a strong tendency amonacquired firms to remain unaffected by the revised legal boundaries long afthe acquisition. Thus, the result of acquisitions seems primarily to be strengtening old rather than establishing new market network positions.
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| 14. |
- Brugés, Javier Mauricio
(författare)
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Surface characterization methods for quality assessment of polyethylene-coated paperboard
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In manufacturing processes, the quality of a product often depends on its surface, and careful control of surface properties is critical to meet customer requirements. A thin layer of polyethylene (PE) is applied to paperboard to increase barrier functionality and high optical quality of the product. For PE-coated paperboard, product quality inspection is performed at the end of the manufacturing process by taking a portion of the reel to the laboratory for quality inspection. These associated offline characterization methods are destructive and time consuming and are representative of only a small portion of the product.The overall goal of this thesis is to provide new methods to characterize the Surface properties of PE-coated paperboard. Specifically, to determine imaging techniques for measuring surface parameters that affect its barrier functionality and surface roughness.In this thesis, two methods for surface characterization of PE-coated paperboard are presented to quantify the two most important product-related quality parameters, i.e. barrier functionality and optical quality, which are affected by the presence of defects in the coating and by the surface roughness of the product, respectively. First, a full-Stokes imaging polarimeter (FSIP) is used to detect the presence of PE-coated material and to distinguish between coated and uncoated samples at the pixel level. Second, a three-dimensional scanning electron microscope (3D SEM) is employed to calculate the Surface roughness of PE-coated paperboard. These surface characterization techniques offer an advantage over the industry standard due to the high speed and non-contact nature of the measurement, while increasing the throughput of the sample surface parameters studied.A classification accuracy of 99, 74% is achieved using a FSIP to distinguish between PE- and non-PE-coated paperboard at pixel level. Using the 3D SEM technique to measure the topography of PE-coated samples results in a faster method that is comparable in accuracy to a chromatic confocal microscope (CCM). The surface roughness measured with the 3D SEM differs from the standard method by up to 6% and good agreement with statistical parameters is found.In general, surface analysis of PE-coated is often a complex and difficult task for imaging techniques and suitable methods need to be evaluated for their sensitivity to measure the desired surface parameters. The presented characterization techniques inspect larger areas of PE-coated paperboard compared to current industry standards. These methods provide a quantitative solution for surface characterization to inspect the surface parameters necessary to assure the product’s quality.
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| 15. |
- Brugés Martelo, Javier Mauricio, et al.
(författare)
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Surface topography characterization of high-quality PE coated paperboard using confocal chromatic microscope and 3D SEM stereo-photogrammetry technique
- 2017
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Konferensbidrag (refereegranskat)abstract
- Coating paperboard enhances printability and optical quality of the product as well as other important properties like packaging performance and shelf-life. To obtain high quality products a quality control of the manufacturing process requires identifying those manufacturing parameters that affect it. Roughness measurement and characterization of coating thickness are examples of these control parameters. Optical instruments measuring these quantities range from laboratory equipment to in-line and on-line sensors. However, the variety of instruments and sometimes misunderstanding of their limitations generate uncorrelated measurements, which are no longer valid to their comparison. The new ISO 25178 standard for surface texture provides guidelines to metrologists to address some this problem. Here, we report a case study for surface characterization of high quality printing polyethylene (PE) coated paperboard for high quality printing, where surface roughness is a key parameter. Two imaging methods to create topographic measurements will be compared, i.e. a confocal chromatic microscope and a scanning electron microscope (SEM). For the latter, stereo photogrammetry is used and 3D topographic profiles are obtained from Alicona MeX software. Leach and Haitjema [Leach, R., & Haitjema, H. (2010). Bandwidth characteristics and comparisons of surface texture measuring instruments. Measurement Science and Technology, 21(3), 032001] addressed the topic on how to design comparisons when using different instruments for areal texture measurement. We use their bandwidth matching concept, since it provides an extension to the ISO 25178 guidelines, ensuring that the instrumentation used to characterize the samples are within its measuring limits and further analysis of the results can be correlated. It is important to adopt a good metrology practice in order to translate these parameters into our future work. We expect to extend these findings into a real-time optical sensor, which later can be implemented in an industrial manufacturing environment for high optical quality paper and paperboard.
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| 16. |
- Chaudhari, Aditi, et al.
(författare)
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ARAP2 promotes GLUT1-mediated basal glucose uptake through regulation of sphingolipid metabolism
- 2016
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1861:11, s. 1643-1651
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Tidskriftsartikel (refereegranskat)abstract
- Lipid droplet formation, which is driven by triglyceride synthesis, requires several droplet-associated proteins. We identified ARAP2 (an ADP-ribosylation factor 6 GTPase-activating protein) in the lipid droplet proteome of NIH-3T3 cells and showed that knockdown of ARAP2 resulted in decreased lipid droplet formation and triglyceride synthesis. We also showed that ARAP2 knockdown did not affect fatty acid uptake but reduced basal glucose uptake, total levels of the glucose transporter GLUT1, and GLUT1 levels in the plasma membrane and the lipid micro-domain fraction (a specialized plasma membrane domain enriched in sphingolipids). Microarray analysis showed that ARAP2 knockdown altered expression of genes involved in sphingolipid metabolism. Because sphingolipids are known to play a key role in cell signaling, we performed lipidomics to further investigate the relationship between ARAP2 and sphingolipids and potentially identify a link with glucose uptake. We found that ARAP2 knockdown increased glucosylceramide and lactosylceramide levels without affecting ceramide levels, and thus speculated that the rate-limiting enzyme in glycosphingolipid synthesis, namely glucosylceramide synthase (GCS), could be modified by ARAP2. In agreement with our hypothesis, we showed that the activity of GCS was increased by ARAP2 knockdown and reduced by ARAP2 overexpression. Furthermore, pharmacological inhibition of GCS resulted in increases in basal glucose uptake, total GLUT1 levels, triglyceride biosynthesis from glucose, and lipid droplet formation, indicating that the effects of GCS inhibition are the opposite to those resulting from ARAP2 knockdown. Taken together, our data suggest that ARAP2 promotes lipid droplet formation by modifying sphingolipid metabolism through GCS.
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| 17. |
- Cinato, Mathieu, et al.
(författare)
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Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractility
- 2023
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- The adult heart develops hypertrophy to reduce ventricular wall stress and maintain cardiac function in response to an increased workload. Although pathological hypertrophy generally prog-resses to heart failure, physiological hypertrophy may be car-dioprotective. Cardiac-specific overexpression of the lipid-droplet protein perilipin 5 (Plin5) promotes cardiac hypertrophy, but it is unclear whether this response is beneficial. We analyzed RNA -sequencing data from human left ventricle and showed that car-diac PLIN5 expression correlates with up-regulation of cardiac contraction-related processes. To investigate how elevated cardiac Plin5 levels affect cardiac contractility, we generated mice with cardiac-specific overexpression of Plin5 (MHC-Plin5 mice). These mice displayed increased left ventricular mass and cardiomyocyte size but preserved heart function. Quantitative proteomics identified sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) as a Plin5-interacting protein. In situ proximity ligation assay further confirmed the Plin5/SERCA2 interaction. Live imaging showed in-creases in intracellular Ca2+ release during contraction, Ca2+ removal during relaxation, and SERCA2 function in MHC-Plin5 versus WT cardiomyocytes. These results identify a role of Plin5 in improving cardiac contractility through enhanced Ca2+ signaling.
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| 18. |
- Cinato, Mathieu, et al.
(författare)
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Role of Perilipins in Oxidative Stress-Implications for Cardiovascular Disease
- 2024
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Ingår i: ANTIOXIDANTS. - 2076-3921. ; 13:2
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Forskningsöversikt (refereegranskat)abstract
- Oxidative stress is the imbalance between the production of reactive oxygen species (ROS) and antioxidants in a cell. In the heart, oxidative stress may deteriorate calcium handling, cause arrhythmia, and enhance maladaptive cardiac remodeling by the induction of hypertrophic and apoptotic signaling pathways. Consequently, dysregulated ROS production and oxidative stress have been implicated in numerous cardiac diseases, including heart failure, cardiac ischemia-reperfusion injury, cardiac hypertrophy, and diabetic cardiomyopathy. Lipid droplets (LDs) are conserved intracellular organelles that enable the safe and stable storage of neutral lipids within the cytosol. LDs are coated with proteins, perilipins (Plins) being one of the most abundant. In this review, we will discuss the interplay between oxidative stress and Plins. Indeed, LDs and Plins are increasingly being recognized for playing a critical role beyond energy metabolism and lipid handling. Numerous reports suggest that an essential purpose of LD biogenesis is to alleviate cellular stress, such as oxidative stress. Given the yet unmet suitability of ROS as targets for the intervention of cardiovascular disease, the endogenous antioxidant capacity of Plins may be beneficial.
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| 19. |
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| 20. |
- Drevinge, Christina, 1983, et al.
(författare)
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Perilipin 5 is protective in the ischemic heart
- 2016
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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| 21. |
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| 22. |
- Klevstig, Martina, et al.
(författare)
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Cardiac expression of the microsomal triglyceride transport protein protects the heart function during ischemia
- 2019
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Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 0022-2828 .- 1095-8584. ; 137, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The microsomal triglyceride transport protein (MTTP) is critical for assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins and is most abundant in the liver and intestine. Surprisingly, MTTP is also expressed in the heart. Here we tested the functional relevance of cardiac MTTP expression. Materials and methods: We combined clinical studies, advanced expression analysis of human heart biopsies and analyses in genetically modified mice lacking cardiac expression of the MTTP-A isoform of MTTP. Results: Our results indicate that lower cardiac MTTP expression in humans is associated with structural and perfusion abnormalities in patients with ischemic heart disease. MTTP-A deficiency in mice heart does not affect total MTTP expression, activity or lipid concentration in the heart. Despite this, MTTP-A deficient mice displayed impaired cardiac function after a myocardial infarction. Expression analysis of MTTP indicates that MTTP expression is linked to cardiac function and responses in the heart. Conclusions: Our results indicate that MTTP may play an important role for the heart function in conjunction to ischemic events.
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| 23. |
- Klevstig, Martina, et al.
(författare)
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Targeting acid sphingomyelinase reduces cardiac ceramide accumulation in the post-ischemic heart
- 2016
-
Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 0022-2828 .- 1095-8584. ; 93, s. 69-72
-
Tidskriftsartikel (refereegranskat)abstract
- Ceramide accumulation is known to accompany acute myocardial ischemia, but its role in the pathogenesis of ischemic heart disease is unclear. In this study, we aimed to determine how ceramides accumulate in the ischemic heart and to determine if cardiac function following ischemia can be improved by reducing ceramide accumulation. To investigate the association between ceramide accumulation and heart function, we analyzed myocardial left ventricle biopsies from subjects with chronic ischemia and found that ceramide levels were higher in biopsies from subjects with reduced heart function. Ceramides are produced by either de novo synthesis or hydrolysis of sphingomyelin catalyzed by acid and/or neutral sphingomyelinase. We used cultured HL-1 cardiomyocytes to investigate these pathways and showed that acid sphingomyelinase activity rather than neutral sphingomyelinase activity or de novo sphingolipid synthesis was important for hypoxia-induced ceramide accumulation. We also used mice with a partial deficiency in acid sphingomyelinase (Smpd1(+/-) mice) to investigate if limiting ceramide accumulation under ischemic conditions would have a beneficial effect on heart function and survival. Although we showed that cardiac ceramide accumulation was reduced in Smpd1(+/-) mice 24 h after an induced myocardial infarction, this reduction was not accompanied by an improvement in heart function or survival. Our findings show that accumulation of cardiac ceramides in the post-ischemic heart is mediated by acid sphingomyelinase. However, targeting ceramide accumulation in the ischemic heart may not be a beneficial treatment strategy.
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| 24. |
- Laudette, Marion, et al.
(författare)
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Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function
- 2023
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:7, s. 1537-1552
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Tidskriftsartikel (refereegranskat)abstract
- Aims Pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CMPcsk9−/− mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells. Methods and results Mice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular dilatation at 28 weeks of age and died prematurely. Transcriptomic analyses revealed alterations of signalling pathways linked to cardiomyopathy and energy metabolism in hearts from CM-Pcsk9−/− mice vs. wild-type littermates. In agreement, levels of genes and proteins involved in mitochondrial metabolism were reduced in CM-Pcsk9−/− hearts. By using a Seahorse flux analyser, we showed that mitochondrial but not glycolytic function was impaired in cardiomyocytes from CM-Pcsk9−/− mice. We further showed that assembly and activity of electron transport chain (ETC) complexes were altered in isolated mitochondria from CM-Pcsk9−/− mice. Circulating lipid levels were unchanged in CM-Pcsk9−/− mice, but the lipid composition of mitochondrial membranes was altered. In addition, cardiomyocytes from CM-Pcsk9−/− mice had an increased number of mitochondria–endoplasmic reticulum contacts and alterations in the morphology of cristae, the physical location of the ETC complexes. We also showed that acute Pcsk9 silencing in adult cardiomyocyte-like cells reduced the activity of ETC complexes and impaired mitochondrial metabolism. Conclusion PCSK9, despite its low expression in cardiomyocytes, contributes to cardiac metabolic function, and PCSK9 deficiency in cardiomyocytes is linked to cardiomyopathy, impaired heart function, and compromised energy production.
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| 25. |
- Levin, Malin, 1973, et al.
(författare)
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Cardiomyocytes, sphingolipids and cardio myotoxicity
- 2023
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Ingår i: Current Opinion in Lipidology. - 0957-9672. ; 34:4, s. 180-188
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose of reviewSphingolipids are structurally diverse membrane lipids localized in lipid bilayers. Sphingolipids are not only important structural components of cellular membranes, but they are also important regulators of cellular trafficking and signal transduction and are implicated in several diseases. Here, we review the latest insights into sphingolipids and their role in cardiac function and cardiometabolic disease.Recent findingsThe underlying mechanisms linking sphingolipids to cardiac dysfunction are still not fully clarified. Sphingolipids, and in particular ceramides, have emerged as important players in lipotoxicity, mediating inflammation, impaired insulin signalling and apoptosis. In addition, recent findings highlight the importance of glycosphingolipid homeostasis in cardiomyocyte membranes, where they are required to maintain & beta;-adrenergic signalling and contractile capacity to preserve normal heart function. Thus, glycosphingolipid homeostasis in cardiac membranes characterizes a novel mechanism linking sphingolipids to cardiac disease.Modulation of cardiac sphingolipids may represent a promising therapeutic approach. Sustained investigation of the link between sphingolipids and cardiomyocyte function is therefore needed and we hope that this review may inspire researchers to further elucidate the action of these lipids.
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| 26. |
- Li, Lu, 1964, et al.
(författare)
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ARF6 Regulates Neuron Differentiation through Glucosylceramide Synthase
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3
-
Tidskriftsartikel (refereegranskat)abstract
- The small GTPase ADP ribosylation factor 6 (ARF6) mediates endocytosis and has in addition been shown to regulate neuron differentiation. Here we investigated whether ARF6 promotes differentiation of Neuro-2a neuronal cells by modifying the cellular lipid composition. We showed that knockdown of ARF6 by siRNA in Neuro-2a cells increased neuronal outgrowth as expected. ARF6 knockdown also resulted in increased glucosylceramide levels and decreased sphingomyelin levels, but did not affect the levels of ceramide or phospholipids. We speculated that the ARF6 knockdown-induced increase in glucosylceramide was caused by an effect on glucosylceramide synthase and, in agreement, showed that ARF6 knockdown increased the mRNA levels and activity of glucosylceramide synthase. Finally, we showed that incubation of Neuro-2a cells with the glucosylceramide synthase inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) normalized the increased neuronal outgrowth induced by ARF6 knockdown. Our results thus show that ARF6 regulates neuronal differentiation through an effect on glucosylceramide synthase and glucosylceramide levels.
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| 27. |
- Mardani, Ismena, et al.
(författare)
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Plin2-deficiency reduces lipophagy and results in increased lipid accumulation in the heart.
- 2019
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Myocardial dysfunction is commonly associated with accumulation of cardiac lipid droplets (LDs). Perilipin 2 (Plin2) is a LD protein that is involved in LD formation, stability and trafficking events within the cell. Even though Plin2 is highly expressed in the heart, little is known about its role in myocardial lipid storage. A recent report shows that cardiac overexpression of Plin2 result in massive myocardial steatosis suggesting that Plin2 stabilizes LDs. In this study, we hypothesized that deficiency in Plin2 would result in reduced myocardial lipid storage. In contrast to our hypothesis, we found increased accumulation of triglycerides in hearts, and specifically in cardiomyocytes, from Plin2-/- mice. Although Plin2-/- mice had markedly enhanced lipid levels in the heart, they had normal heart function under baseline conditions and under mild stress. However, after an induced myocardial infarction, stroke volume and cardiac output were reduced in Plin2-/- mice compared with Plin2+/+ mice. We further demonstrated that the increased triglyceride accumulation in Plin2-deficient hearts was caused by altered lipophagy. Together, our data show that Plin2 is important for proper hydrolysis of LDs.
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| 28. |
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| 29. |
- Olofsson, Sven-Olof, 1947, et al.
(författare)
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Triglyceride containing lipid droplets and lipid droplet-associated proteins.
- 2008
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Ingår i: Current opinion in lipidology. - 0957-9672. ; 19:5, s. 441-7
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Cytosolic lipid droplets are now recognized as dynamic organelles. This review summarizes our current understanding of the mechanisms involved in the formation of lipid droplets, the importance of lipid droplet-associated proteins and the link between lipid droplet accumulation and development of insulin resistance. RECENT FINDINGS: Lipid droplets are formed as primordial droplets and they increase in size by fusion. This fusion process requires the alpha-soluble N-ethylmaleimide-sensitive factor adaptor protein receptor SNAP23, which is also involved in the insulin-dependent translocation of a glucose transporter to the plasma membrane. Recent data suggest that SNAP23 is the link between increased lipid droplet accumulation and development of insulin resistance. Lipid droplets also form tight interactions with other organelles. Furthermore, additional lipid droplet-associated proteins have been identified and shown to play a role in droplet assembly and turnover, and in sorting and trafficking events. SUMMARY: Recent studies have identified a number of key proteins that are involved in the formation and turnover of lipid droplets, and SNAP23 has been identified as a link between accumulation of lipid droplets and development of insulin resistance. Further understanding of lipid droplet biology could indicate potential therapeutic targets to prevent accumulation of lipid droplets and associated complications.
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| 30. |
- Pirazzi, Carlo, et al.
(författare)
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Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro
- 2012
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 57:6, s. 1276-1282
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The robust association between non-alcoholic fatty liver disease (NAFLD) and the genetic variant I148M (rs738409) in PNPLA3 has been widely replicated. The aim of this study was to investigate the effect of the PNPLA3 I148M mutation on: (1) hepatic secretion of very low density lipoproteins (VLDL) in humans; and (2) secretion of apolipoprotein B (apoB) from McA-RH 7777 cells, which secrete VLDL-sized apoB-containing lipoproteins. Methods: VLDL kinetics was analyzed after a bolus infusion of stable isotopes in 55 overweight/obese men genotyped for the PNPLA3 I148M variant. Intracellular lipid content, apoB secretion and glycerolipid metabolism were studied in McA-RH 7777 cells overexpressing the human 1481 wild type or 148M mutant PNPLA3 protein. Results: In humans, carriers of the PNPLA3 148M allele had increased liver fat compared to 1481 homozygotes, and kinetic analysis showed a relatively lower secretion of the large, triglyceride-rich VLDL (VLDL1) in 148M carriers vs. 1481 homozygotes for the same amount of liver fat. McA-RH 7777 cells overexpressing the 148M mutant protein showed a higher intracellular triglyceride content with a lower apoB secretion and fatty acid efflux, compared to cells overexpressing the 1481 wild type protein. The responses with 148M matched those observed in cells expressing the empty vector, indicating that the mutation results in loss of function. Conclusions: We have shown that PNPLA3 affects the secretion of apoB-containing lipoproteins both in humans and in vitro and that the 148M protein is a loss-of-function mutation. We propose that PNPLA3 148M promotes intracellular lipid accumulation in the liver by reducing the lipidation of VLDL.
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| 31. |
- Pirazzi, Carlo, et al.
(författare)
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PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:15, s. 4077-4085
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Tidskriftsartikel (refereegranskat)abstract
- Retinoids are micronutrients that are stored as retinyl esters in the retina and hepatic stellate cells (HSCs). HSCs are key players in fibrogenesis in chronic liver diseases. The enzyme responsible for hydrolysis and release of retinyl esters from HSCs is unknown and the relationship between retinoid metabolism and liver disease remains unclear. We hypothesize that the patatin-like phospholipase domain-containing 3 (PNPLA3) protein is involved in retinol metabolism in HSCs. We tested our hypothesis both in primary human HSCs and in a human cohort of subjects with non-alcoholic fatty liver disease (N = 146). Here we show that PNPLA3 is highly expressed in human HSCs. Its expression is regulated by retinol availability and insulin, and increased PNPLA3 expression results in reduced lipid droplet content. PNPLA3 promotes extracellular release of retinol from HSCs in response to insulin. We also show that purified wild-type PNPLA3 hydrolyzes retinyl palmitate into retinol and palmitic acid. Conversely, this enzymatic activity is markedly reduced with purified PNPLA3 148M, a common mutation robustly associated with liver fibrosis and hepatocellular carcinoma development. We also find the PNPLA3 I148M genotype to be an independent (P = 0.009 in a multivariate analysis) determinant of circulating retinol-binding protein 4, a reliable proxy for retinol levels in humans. This study identifies PNPLA3 as a lipase responsible for retinyl-palmitate hydrolysis in HSCs in humans. Importantly, this indicates a potential novel link between HSCs, retinoid metabolism and PNPLA3 in determining the susceptibility to chronic liver disease.
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| 32. |
- Taskinen, Marja-Riitta, et al.
(författare)
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Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes.
- 2021
-
Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636.
-
Tidskriftsartikel (refereegranskat)abstract
- Increased risk of atherosclerotic cardiovascular disease in subjects with type 2 diabetes is linked to elevated levels of triglyceride-rich lipoproteins and their remnants. The metabolic effects of PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors on this dyslipidemia were investigated using stable-isotope-labeled tracers. Approach and Results: Triglyceride transport and the metabolism of apos (apolipoproteins) B48, B100, C-III, and E after a fat-rich meal were investigated before and on evolocumab treatment in 13 subjects with type 2 diabetes. Kinetic parameters were determined for the following: apoB48 in chylomicrons; triglyceride in VLDL1 (very low-density lipoprotein) and VLDL2; and apoB100 in VLDL1, VLDL2, IDL (intermediate-density lipoprotein), and LDL (low-density lipoprotein). Evolocumab did not alter the kinetics of apoB48 in chylomicrons or apoB100 or triglyceride in VLDL1. In contrast, the fractional catabolic rates of VLDL2-apoB100 and VLDL2-triglyceride were both increased by about 45%, which led to a 28% fall in the VLDL2 plasma level. LDL-apoB100 was markedly reduced by evolocumab, which was linked to metabolic heterogeneity in this fraction. Evolocumab increased clearance of the more rapidly metabolized LDL by 61% and decreased production of the more slowly cleared LDL by 75%. ApoC-III kinetics were not altered by evolocumab, but the apoE fractional catabolic rates increased by 45% and the apoE plasma level fell by 33%. The apoE fractional catabolic rates was associated with the decrease in VLDL2- and IDL-apoB100 concentrations.Evolocumab had only minor effects on lipoproteins that are involved in triglyceride transport (chylomicrons and VLDL1) but, in contrast, had a profound impact on lipoproteins that carry cholesterol (VLDL2, IDL, LDL). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02948777.
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| 33. |
- Taskinen, M. R., et al.
(författare)
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Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes
- 2021
-
Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 23:5, s. 1191-1201
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To elucidate the impact of liraglutide on the kinetics of apolipoprotein (apo) B48- and apoB100-containing triglyceride-rich lipoproteins in subjects with type 2 diabetes (T2D) after a single fat-rich meal. Materials and Methods: Subjects with T2D were included in a study to investigate postprandial apoB48 and apoB100 metabolism before and after 16 weeks on 1.8 mg/day liraglutide (n = 14) or placebo (n = 4). Stable isotope tracer and compartmental modelling techniques were used to determine the impact of liraglutide on chylomicron and very low-density lipoprotein (VLDL) production and clearance after a single fat-rich meal. Results: Liraglutide reduced apoB48 synthesis in chylomicrons by 60% (p < .0001) and increased the triglyceride/apoB48 ratio (i.e. the size) of chylomicrons (p < .001). Direct clearance of chylomicrons, a quantitatively significant pathway pretreatment, decreased by 90% on liraglutide (p < .001). Liraglutide also reduced VLDL1-triglyceride secretion (p = .017) in parallel with reduced liver fat. Chylomicron-apoB48 production and particle size were related to insulin sensitivity (p = .015 and p < .001, respectively), but these associations were perturbed by liraglutide. Conclusions: In a physiologically relevant setting that mirrored regular feeding in subjects with T2D, liraglutide promoted potentially beneficial changes on postprandial apoB48 metabolism. Using our data in an integrated metabolic model, we describe how the action of liraglutide in T2D on chylomicron and VLDL kinetics could lead to decreased generation of remnant lipoproteins.
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| 34. |
- Wilk, Julie, 1962-, et al.
(författare)
-
Citizen Sensing Stakeholder Interaction Manual
- 2021
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Rapport (populärvet., debatt m.m.)abstract
- This stakeholder interaction manual was prepared in the ERA4CS project: Citizen Sensing - Urban climate resilience through a Participatory Risk Management System(PRMS). The Participatory Risk Management System includes an app by which end-users upload reports (weather observations, eventual impacts, level of personal comfort accompanied by comments and/or images) and a spatial-temporal visualization platform (the CitizenSensing web-portal) that allows users to view, explore and analyze the reports (see Navarra et al. 2020). The aim of the manual is to guide stakeholder interactions within the project to assess and gain deeper insight into the perceptions, priorities and reflections of stakeholders2 that were involved in the co-design process and organize the end-user3 campaigns.The “Getting Started” section contains general information about participants, workshops, aims, outcomes, preparations, equipment, opening and closing workshops and communication. The following sections contain participatory exercises that could be performed with stakeholders and/or end-users to inform and guide the co-design process of CitizenSensing researchers and municipal through the set-up, testing and assessment of the PRMS. The exercises are organized under a number of workshops4. These would be performed with several participants, but the same exercises could be performed at or smaller meetings with a few people or individuals.The workshop sections contain a number of interactive exercises that cover a number of themes: Climate-related issues and project pre-conditions (Workshop 1A)Risks, sensitive groups and locations and climate-related variables (Workshop 1B)Sensor networks, databases and municipal tasks (Workshop 2A)App requirements, critical levels and recommendations (Workshop 2B)Assessing possibilities for measurement/observation campaigns (Workshop 3)Designing the end-user campaigns (Workshop 4)Preparing the end-user campaigns (Workshop 5)Initiating the end-user campaigns (Workshop 6)Concluding the end-user campaigns (Workshop 7).Assessing stakeholder perspectives: Workshop (Workshop 8)Assessing stakeholder perspectives: InterviewsAppendices I and II contain pre-campaign and post-campaign surveys to be conducted at Workshops 4 and 5. Appendix III contains an interview guide that could be used in Workshops 8 or 9. Appendix IV contains a guide to exploring the web-portal that could be used in Workshops 8 or 9.
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| 35. |
- Andersson, Fredrik, 1973-
(författare)
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Mot framtiden på gamla spår? : Regionala intressegrupper och beslutsprocesser kring kustjärnvägarna i Norrland under 1900-talet
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this dissertation the construction of two coastal railways, the East Coast Line and the Bothnia Line, in the Norrland region of northern Sweden is used as a case study of how regionally based interest groups are formed, and how they gain access to decision-making processes on a national level. In periods when a number of preconditions were in place, a window of opportunity opened for the coastal railway that the regional elites could exploit. Among these was the ability to form a coherent regional interest group, through institutions that created platforms and power-bases that enable regional elites to co-operate and act on regional and national levels.The existence of an institutional framework that was adapitve towards regional railway promotion was also important. The study shows that the coastal railway had a very flexible role on the agenda, as it provided a fixed solution against which actors could pin a multitude of different problems. An important factor for explaining the development of the coastal railway question in Norrland was the ideological notion of the region itself. Being a vast, resource-rich and sparsely populated region, Norrland had almost always received special consideration in both public opinion and national policy making. It also created a remarkable stubbornness among the regional actors in working for the coastal railway. Regional interest groups had also learnt that linking their claims to Norrland's peripheral position had high legitimacy on the national arena, by claiming the need for regional fairness and/or the national importance of the regional export-intensive industries. This was instrumental in justifying the repeated exemptions from the national railway policy regimes that ultimately were decissive in making the regional elites successful.
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| 36. |
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| 37. |
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| 38. |
- Andersson, Jan Joel, et al.
(författare)
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The European Security Strategy : Reinvigorate, Revise or Reinvent?
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper argues that a strategic discussion on the EU’s external action is overdue, and that the future of the European Security Strategy (ESS) should be the centre of that discussion. The precise nature of an eventual new strategy, the process by which it is undertaken, and its intended effects are open questions, however. We offer background, analysis, and reform options as a contribution to a wider European debate on the future role of the EU as an actor on the global stage.
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| 39. |
- Andersson, Jan, 1973-
(författare)
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Laborativt arbete i fysikundervisningen : Något som behöver diskuteras!
- 2015
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BaksidestextI gymnasieskolans kursplaner för ämnet fysik framhålls det undersökande arbetssättet genom att betona att eleverna ska ges förutsättningar att utveckla förmågan att söka svar på frågor, planera, genomföra, tolka och redovisa experiment. Eleverna ska dessutom ges möjligheter att använda sina kunskaper i fysik för att kommunicera, argumentera och presentera slutsatser. Utgångspunkten i den här avhandlingen är att laborationsmomentet skapar en speciell diskurs där eleverna blir aktörer och läraren iträder rollen som observatör. I en sådan miljö skapas förutsättningar för att eleverna på ett naturligt sätt får möjlighet att prata och diskutera fysik, utifrån sina egna förutsättningar. Syftet med denna avhandling är att genom praktikbaserade studier tydliggöra hur fysiklaborationens utformning påverkar elevernas kommunikation och vidare hur eleverna använder språket vid laborationstillfället för att skapa förståelse. Detta bidrar till debatten om fysiklaborationens effektivitet, sett både ur ett undervisnings- och inlärningsperspektiv. Resultaten visar att olika laborationsformer är uppbyggda av liknande aktiviteter, men varierar i tid som ägnas åt de olika aktiviteterna. Aktiviteterna i sin tur skapar samtal av olika karaktär. Olika samtalsformer används för skilda syften. Ett analytiskt ramverk har skapats för att ingående kunna studera hur och vad eleverna talar om både på en lingvistisk och kognitiv nivå.
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| 40. |
- Andersson, Jan, 1973-
(författare)
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Learning Physics Through Communication During Laboratory Work : An empirical study at upper secondary school
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Laboratory work as a teaching and learning method is given prominence in the Swedish physics curriculum for upper secondary school. It is emphasised that students should be given opportunities to develop the ability to search for answers to questions, plan, conduct, interpret and present results. Moreover, students should also be encouraged to use their physics knowledge to communicate, argument and present conclusions. This thesis is based on the belief that physics laboratory work creates a special discourse, where the student becomes the actor and the teacher becomes the organiser and observer. Such an environment enables students to naturally engage in physics discussions using their own terms. The aim is to explore students’ laboratory work at upper secondary school in-depth, with respect to its design and influence on students’ communication. Through analysis of students’ communication, the purpose is to better understand the physics laboratory work’s possibilities as a teaching and learning method. This will contribute to ongoing debate about the effectiveness of laboratory work. The results show that laboratory work consists of similar activities but differs in amount of time allocated to the different activities. Different types of talk are used for different purposes. An analytical framework has been created to enable deeper investigations of how and what students are talking about at both a linguistic and cognitive level. Moreover, the analysis shows the importance of students acquiring knowledge about physics and understanding the value of using an investigative approach as well as acquiring core content physics knowledge.
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| 41. |
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| 42. |
- Andersson, Jan, 1973-, et al.
(författare)
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Primary teacher students' understanding of electromagnetic induction
- 2019
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Konferensbidrag (refereegranskat)abstract
- In the present study, a teaching sequence concerning electromagnetic induction was introduced to 24 primary teacher students divided into six groups, in order to provide the students with deeper knowledge about how kinetic energy can be transformed into electricity. The aim of this study was to investigate to what extent these teacher students, developed an understanding of electromagnetic induction, without using a mathematical language. The teaching sequence consisted of a group discussion, a practical exercise, computer simulations and a final didactical group reflection. We used a context rich problem, where students were asked to describe how a wind power plant works. During these discussions, the students realised that some kind of generator was needed, but they did not understand its function and concluded that they as teachers only needed to know that it gives rise to an energy transformation. The practical exercise contributed to a deeper understanding of the observed phenomenon, even though students’ ability to structure their inquiry varied a lot. The computer simulations turned out to be a valuable complement to the practical exercise. The practical experiment, together with the simulation, helped the students to understand how electrical current is produced. Based on our analysis, we can see how the different parts of the teaching activity, together but in different ways, help the students to develop their understanding and view of electromagnetic induction. The students’ final group reflections show how important it is to have good physics content knowledge to be able to value and take advantage of the children’s curiosity.
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| 43. |
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| 44. |
- Andersson, Jan, 1965-, et al.
(författare)
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The complexity of changes in modal choice : A quasi-experimental study
- 2023
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Ingår i: Transportation Research Part F. - : Elsevier. - 1369-8478 .- 1873-5517. ; 96:July, s. 36-47
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Tidskriftsartikel (refereegranskat)abstract
- Background: Changes in modal choice is argued to be one way to reduce the emission of greenhouse gases. Increasing modal choices in favour of more environmentally friendly travel modes requires a better understanding of how these choices are actually made. The first aim of this study is therefore to examine how modal choice is related to subjective experiences as perceived accessibility, perceived satisfaction , habit, both before , after an intervention promoting public transport. The second aim is to examine how modal choice is affected by the intervention. Finally, the third aim is to examine how subjective experiences as perceived accessibility, perceived satisfaction, and habit are affected by the intervention.Method: The design used is a before-and after-study with free public travel passes as the intervention (30-or 14-days free travel pass). Altogether, 52 travelers - distributed on two intervention groups and one control group - participated in the study. The 30-days free travel pass group constitutes 18 participants, the 14-days free travel pass group constitutes 19 participants while the control group constitutes 15 participants. During the before -period the participants were asked to register their modal choice using a digitalized application downloaded on their smart phones (the TravelVu app), to complete a short app-based questionnaire, and a web-based questionnaire. During the after-period, they were once again asked to register their modal choice and to complete a web-based questionnaire. All data collected were analyzed by variance or correlation analyses using the change between before-and after period as the dependent variable.Conclusion: The intervention did not affect the modal choice or the subjective experiences. Over time, the participants did however increase their use of public transport and their cognitive evaluation of their everyday travel overall, while they decreased their use of car and became less reflective and less interested in trying out new alternative travel modes. These changes might be attributed to their participation in the present study.
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| 45. |
- Andersson, Jan, 1973-, et al.
(författare)
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The Effectiveness of Laboratory Work in Physics : A Case Study at Upper Secondary School in Sweden
- 2012
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Ingår i: Proceedings of The World Conference on Physics Education 2012. - 9786053646587 ; , s. 729-740
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Konferensbidrag (refereegranskat)abstract
- The present paper reports on a case study that examined the effectiveness of a practical activity in physics, at a Swedish upper secondary school. A teacher and 19 students participated in the study. The students were observed while working with the topic motion, in a computer based laboratory environment (CBL). This case study is part of an ongoing longitudinal study, about the role of laboratory work with different degrees of freedom. The analysis of interviews, written reports and posttest, shows that the practical work was effective based on Millar’s model. Even so, the students had difficulties expressing what they learned from the activity. This study emphasizes the complexity of planning and conducting laboratory work that is effective, from several different aspects.
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| 46. |
- Andersson, Jan, 1973-, et al.
(författare)
-
The laboratory work style's influence on students' communication
- 2017
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Ingår i: Journal of Baltic Science Education. - Siauliai, Lithuania : SMC “Scientia Educologica”. - 1648-3898 .- 2538-7138. ; 16:6, s. 958-979
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Tidskriftsartikel (refereegranskat)abstract
- More knowledge of how the actual design of the laboratory work influence students' communication, is needed to design and implement physics laboratory work lessons. The aim with this quantitative research, conducted at a Swedish upper secondary school, was to explore how the design of the laboratory work affects students' communication. Twenty students divided into five groups participated in this natural case study and were video recorded while performing four practical tasks with the theme uniformly accelerated motion, designed by their teacher. The four workstations were categorised based on three predefined descriptors: outcome, approach and procedure. Students' work at each workstation was coded according to five defined activities: planning, preparing equipment, collecting data, processing data and analysis of results. The activities were thereafter divided into shorter episodes that were coded for three different types of communication: disputational talk, cumulative talk and exploratory talk. The result shows that the amount of exploratory talk students engaged in are influenced by the style of the laboratory work and the character of the activity. Based on these research results, teachers can better accustom the laboratory work to facilitate fruitful physics discussions which endorse students' learning.
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| 47. |
- Andersson, Jan, 1973-, et al.
(författare)
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The relation between students' communicative moves during laboratory work in physics and outcomes of their actions
- 2017
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Ingår i: International Journal of Science Education. - : Informa UK Limited. - 0950-0693 .- 1464-5289. ; 39:2, s. 158-180
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Tidskriftsartikel (refereegranskat)abstract
- In this case study, we explore students' communication during practical work in physics at an upper secondary school in Sweden from a sociocultural perspective. We investigate the relation between the interaction and content of students' communication and outcomes of their actions, with the purpose of finding new knowledge for informing teachers in their choice of instruction. We make discourse analysis of how students interact but also of what students are discussing in terms of underlying content at a linguistic and cognitive level. Twenty students divided into five groups were video recorded while performing four practical tasks at different stations during laboratory work about motion. An analytical framework was developed and applied for one group to three parts of the transcripts in which three different talk-types occurred. Discursive, content, action and purposive moves in the process were identified for each talk-type at both linguistic and cognitive levels. These moves represent information concerning what the teacher actually assigns students to do, and how students make meaning of the activities. Through these different communicative moves, students experience how laboratory work can enhance their competence to collaborate in a scientific environment with complex practical and theoretical questions to solve quickly. Implications of the findings are discussed.
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| 48. |
- Andersson, Linda, 1973, et al.
(författare)
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PLD1 and ERK2 regulate cytosolic lipid droplet formation
- 2006
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Ingår i: J Cell Sci. ; 119:Pt 11, s. 2246-57
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Tidskriftsartikel (refereegranskat)abstract
- We have previously uncovered roles for phospholipase D (PLD) and an unknown cytosolic protein in the formation of cytosolic lipid droplets using a cell-free system. In this report, PLD1 has been identified as the relevant isoform, and extracellular signal-regulated kinase 2 (ERK2) as the cytosolic protein. Increased expression of PLD1 increased lipid droplet formation whereas knockdown of PLD1 using siRNA was inhibitory. A role for ERK2 in basal lipid droplet formation was revealed by overexpression or microinjection, and ablation by siRNA knockdown or pharmacological inhibition. Similar manipulations of other Map kinases such as ERK1, JNK1 or JNK2 and p38alpha or p38beta were without effect. Insulin stimulated the formation of lipid droplets and this stimulation was inhibited by knockdown of PLD1 (by siRNA) and by inhibition or knockdown (by siRNA) of ERK2. Inhibition of ERK2 eliminated the effect of PLD1 on lipid droplet formation without affecting PLD1 activity, suggesting that PLD1 functions upstream of ERK2. ERK2 increased the phosphorylation of dynein which increased the amount of the protein on ADRP-containing lipid droplets. Microinjection of antibodies to dynein strongly inhibited the formation of lipid droplets, demonstrating that dynein has a central role in this formation. Thus dynein is a possible target for ERK2.
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| 49. |
- Andersson, Per, et al.
(författare)
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Characteristics of patients with acute myocardial infarction contacting primary healthcare before hospitalisation: a cross-sectional study
- 2018
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Ingår i: BMC Family Practice. - : BMC. - 1471-2296. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: The characteristics of patients with on-going myocardial infarction (MI) contacting the primary healthcare (PHC) centre before hospitalisation are not well known. Prompt diagnosis is crucial in patients with MI, but many patients delay seeking medical care. The aims of this study was to 1) describe background characteristics, symptoms, actions and delay times in patients contacting the PHC before hospitalisation when falling ill with an acute MI, 2) compare those patients with acute MI patients not contacting the PHC, and 3) explore factors associated with a PHC contact in acute MI patients. Methods: This was a cross-sectional multicentre study, enrolling consecutive patients with MI within 24 hours of admission to hospital from Nov 2012 until Feb 2014. Results: A total of 688 patients with MI, 519 men and 169 women, were included; the mean age was 66 +/- 11 years. One in five people contacted PHC instead of the recommended emergency medical services (EMS), and 94% of these patients experienced cardinal symptoms of an acute MI; i.e., chest pain, and/or radiating pain in the arms, and/or cold sweat. Median delay time from symptom-onset-to-decision-to-seek-care was 2:15 hours in PHC patients and 0:40 hours in non-PHC patients (pamp;lt;0.01). The probability of utilising the PHC before hospitalisation was associated with fluctuating symptoms (OR 1.74), pain intensity (OR 0.90) symptoms during off-hours (OR 0.42), study hospital (OR 3.49 and 2.52, respectively, for two of the county hospitals) and a final STEMI diagnosis (OR 0.58). Conclusions: Ambulance services are still underutilized in acute MI patients. A substantial part of the patients contacts their primary healthcare centre before they are diagnosed with MI, although experiencing cardinal symptoms such as chest pain. There is need for better knowledge in the population about symptoms of MI and adequate pathways to qualified care. Knowledge and awareness amongst primary healthcare professionals on the occurrence of MI patients is imperative.
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| 50. |
- Andersson, Patrik U, 1970, et al.
(författare)
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Formation of Highly Rovibrationally Excited Ammonia from Dissociative Recombination of NH4
- 2010
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Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 1:17, s. 2519-2523
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Tidskriftsartikel (refereegranskat)abstract
- The internal energy distribution of ammonia formed in the dissociative recombination (DR) of NH4+ with electrons has been studied by an imaging technique at the ion storage ring CRYRING. The DR process resulted in the formation of NH3 + H (0.90 ± 0.01), with minor contributions from channels producing NH2 + H2 (0.05 ± 0.01) and NH2 + 2H (0.04 ± 0.02). The formed NH3 molecules were highly internally excited, with a mean rovibrational energy of 3.3 ± 0.4 eV, which corresponds to 70% of the energy released in the neutralization process. The internal energy distribution was semiquantitatively reproduced by ab initio direct dynamics simulations, and the calculations suggested that the NH3 molecules are highly vibrationally excited while rotational excitation is limited. The high internal excitation and the translational energy of NH3 and H will influence their subsequent reactivity, an aspect that should be taken into account when developing detailed models of the interstellar medium and ammonia-containing plasmas.
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