| 1. |
- Franz, D, et al.
(författare)
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Towards long-term standardised carbon and greenhouse gas observations for monitoring Europe´s terrestrial ecosystems: a review
- 2018
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Ingår i: International Agrophysics. - : Walter de Gruyter GmbH. - 0236-8722 .- 2300-8725. ; 32, s. 439-455
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Tidskriftsartikel (refereegranskat)abstract
- Research infrastructures play a key role in launching a new generation of integrated long-term, geographically distributed observation programmes designed to monitor climate change, better understand its impacts on global ecosystems, and evaluate possible mitigation and adaptation strategies. The pan-European Integrated Carbon Observation System combines carbon and greenhouse gas (GHG; CO2, CH4, N2O, H2O) observations within the atmosphere, terrestrial ecosystems and oceans. High-precision measurements are obtained using standardised methodologies, are centrally processed and openly available in a traceable and verifiable fashion in combination with detailed metadata. The Integrated Carbon Observation System ecosystem station network aims to sample climate and land-cover variability across Europe. In addition to GHG flux measurements, a large set of complementary data (including management practices, vegetation and soil characteristics) is collected to support the interpretation, spatial upscaling and modelling of observed ecosystem carbon and GHG dynamics. The applied sampling design was developed and formulated in protocols by the scientific community, representing a trade-off between an ideal dataset and practical feasibility. The use of open-access, high-quality and multi-level data products by different user communities is crucial for the Integrated Carbon Observation System in order to achieve its scientific potential and societal value.
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| 2. |
- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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| 3. |
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| 4. |
- Meisgen, S, et al.
(författare)
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Auxilin is a novel susceptibility gene for congenital heart block which directly impacts fetal heart function
- 2022
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:8, s. 1151-1161
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal lupus erythematosus (NLE) may develop after transplacental transfer of maternal autoantibodies with cardiac manifestations (congenital heart block, CHB) including atrioventricular block, atrial and ventricular arrhythmias, and cardiomyopathies. The association with anti-Ro/SSA antibodies is well established, but a recurrence rate of only 12%–16% despite persisting maternal autoantibodies suggests that additional factors are required for CHB development. Here, we identify fetal genetic variants conferring risk of CHB and elucidate their effects on cardiac function.MethodsA genome-wide association study was performed in families with at least one case of CHB. Gene expression was analysed by microarrays, RNA sequencing and PCR and protein expression by western blot, immunohistochemistry, immunofluorescence and flow cytometry. Calcium regulation and connectivity were analysed in primary cardiomyocytes and cells induced from pleuripotent stem cells. Fetal heart performance was analysed by Doppler/echocardiography.ResultsWe identified DNAJC6 as a novel fetal susceptibility gene, with decreased cardiac expression of DNAJC6 associated with the disease risk genotype. We further demonstrate that fetal cardiomyocytes deficient in auxilin, the protein encoded by DNAJC6, have abnormal connectivity and Ca2+ homoeostasis in culture, as well as decreased cell surface expression of the Cav1.3 calcium channel. Doppler echocardiography of auxilin-deficient fetal mice revealed cardiac NLE abnormalities in utero, including abnormal heart rhythm with atrial and ventricular ectopias, as well as a prolonged atrioventricular time intervals.ConclusionsOur study identifies auxilin as the first genetic susceptibility factor in NLE modulating cardiac function, opening new avenues for the development of screening and therapeutic strategies in CHB.
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| 5. |
- Ramonet, M., et al.
(författare)
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The fingerprint of the summer 2018 drought in Europe on ground-based atmospheric CO 2 measurements : Atmospheric CO 2 anomaly
- 2020
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Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
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Tidskriftsartikel (refereegranskat)abstract
- During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO 2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO 2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO 2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO 2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO 2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO 2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO 2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO 2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO 2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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| 6. |
- Fagerberg, Linn, et al.
(författare)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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| 7. |
- Hoxha, A., et al.
(författare)
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Identification of discrete epitopes of Ro52p200 and association with fetal cardiac conduction system manifestations in a rodent model
- 2016
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Ingår i: Clinical and Experimental Immunology. - : Wiley-Blackwell. - 0009-9104 .- 1365-2249. ; 186:3, s. 284-291
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Tidskriftsartikel (refereegranskat)abstract
- Congenital heart block (CHB) is a potentially lethal condition characterized by a third-degree atrioventricular block (AVB). Despite anti-Ro52 antibodies being detected in nearly 90% of mothers of affected children, CHB occurs in only 1-2% of anti-Ro/Sjogrens-syndrome-related antigen A (SSA) autoantibody-positive pregnancies. Maternal antibodies have been suggested to bind molecules crucial to fetal cardiac function; however, it remains unknown whether a single antibody profile associates with CHB or whether several specificities and cross-reactive targets exist. Here, we aimed to define further the reactivity profile of CHB-associated antibodies towards Ro52p200 (amino acid 200-239). We first analysed reactivity of a monoclonal anti-Ro52 antibody shown to induce AVB in rats (7.8C7) and of sera from anti-Ro52p200 antibody-positive mothers of children with CHB towards a panel of modified Ro52p200 peptides, and subsequently evaluated their potential to induce AVB in rats upon transfer during gestation. We observed that CHB maternal sera displayed a homogeneous reactivity profile targeting preferentially the C-terminal part of Ro52p200, in contrast to 7.8C7 that specifically bound the p200 N-terminal end. In particular, amino acid D233 appeared crucial to maternal antibody reactivity towards p200. Despite low to absent reactivity towards rat p200 and different binding profiles towards mutated rat peptides indicating recognition of different epitopes within Ro52p200, immunoglobulin (Ig)G purified from two mothers of children with CHB could induce AVB in rats. Our findings support the hypothesis that several fine antibody specificities and cross-targets may exist and contribute to CHB development in anti-Ro52 antibody-positive pregnancies.
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| 8. |
- Mphahlele M.J, Fernandes M.A, El-Nahas A.M, Ottosson H, Ndlovu S.M, Sithole H.M, Dladla B.S, De Waal D.
(författare)
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Solution Phase, Solid State and Computational Structural Studies of 2-Aryl-3-bromoquinolin-4(1H)-one Derivatives
- 2002
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Ingår i: J. Chem. Soc., Perkins Trans. 2. ; , s. 2159-2164
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
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| 10. |
- Ottosson, L., et al.
(författare)
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Structurally derived mutations define congenital heart block-related epitopes within the 200-239 amino acid stretch of the Ro52 protein
- 2005
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:2, s. 109-118
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Tidskriftsartikel (refereegranskat)abstract
- Congenital heart block is a passively transferred autoimmune condition, which affects the children of mothers with Ro/SSA autoantibodies. During pregnancy, the antibodies are transported across the placenta and affect the fetus. We have previously demonstrated that antibodies directed to the 200-239 amino acid (aa) stretch of the Ro52 component of the Ro/SSA antigen correlate with the development of congenital heart block. In this report, we investigated the antibody-antigen interaction of this target epitope in detail at a molecular and structural level. Peptides representing aa 200-239 (p200) with structurally derived mutations were synthesized to define the epitopes recognized by two Ro52 human monoclonal antibodies, S3A8 and M4H1, isolated from patient-derived phage display libraries. Analyses by ELISA, circular dichroism and MALDI-TOF-MS demonstrate that the antibody recognition is dependent on a partly a-helical fold within the putative leucine zipper of the 200-239 aa stretch and that the two human anti-p200 monoclonal antibodies, M4H1 and S3A8, recognize different epitopic structures within the p200 peptide. In addition, we investigated the representation of each fine specificity within the sera of mothers with children born with congenital heart block, and in such sera, antibodies of the S3A8 idiotype were more commonly detected and at higher levels than M4H1-like antibodies.
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| 11. |
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| 12. |
- Abalaka, Jacinta, et al.
(författare)
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Genetic diversity and population structure of the range restricted rock firefinch Lagonosticta sanguinodorsalis
- 2015
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Ingår i: Conservation Genetics. - : Springer Science and Business Media LLC. - 1566-0621 .- 1572-9737. ; 16:2, s. 411-418
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the degree of genetic population differentiation is important in conservation genetics for inferring gene flow between populations and for identifying small and isolated threatened populations. We evaluated the genetic variation within and between three populations of the rock firefinch (Lagonosticta sanguinodorsalis), a range restricted firefinch endemic to Nigeria and Cameroon. The populations were closely located (c. 100 km apart) within the species' core distribution in Central Nigeria. We found that the populations had similar levels of gene diversities (H (E) ) and low but significant inbreeding coefficients (F (IS) ). Despite the short distance between populations there was a weak but significant population structure, which indicates that the populations are somewhat isolated and affected by drift within the species' core distribution in Nigeria. The knowledge of the genetic status of the rock firefinch will serve as a foundation to future studies to help understand population demography and for managing and maintaining viable populations.
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| 13. |
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| 15. |
- Aucott, H, et al.
(författare)
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Neuroinflammation in Response to Intracerebral Injections of Different HMGB1 Redox Isoforms
- 2018
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Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 10:3, s. 215-227
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Neuroinflammation triggered by infection or trauma is the cause of central nervous system dysfunction. High-mobility group box 1 protein (HMGB1), released from stressed and dying brain cells, is a potent neuroinflammatory mediator. The proinflammatory functions of HMGB1 are tightly regulated by post-translational redox modifications, and we here investigated detailed neuroinflammatory responses induced by the individual redox isoforms. <b><i>Methods:</i></b> Male Dark Agouti rats received a stereotactic injection of saline, lipopolysaccharide, disulfide HMGB1, or fully reduced HMGB1, and were accessed for blood-brain barrier modifications using magnetic resonance imaging (MRI) and inflammatory responses by immunohistochemistry. <b><i>Results and Conclusions:</i></b> Significant blood-brain barrier disruption appeared 24 h after injection of lipopolysaccharide, disulfide HMGB1, or fully reduced HMGB1 compared to controls, as assessed in post-gadolinium T1-weighted MRI images and confirmed by increased uptake of FITC-conjugated dextran. Immunohistochemistry revealed that both HMGB1 isoforms also induced a local production of IL-1β. Additionally, disulfide HMGB1 increased major histocompatibility complex class II expression and apoptosis. Together, the results demonstrate that extracellular, cerebral HMGB1 causes significant blood-brain barrier disruption in a redox-independent manner and activates several components of neuroinflammation. Blocking HMGB1 might potentially improve clinical outcome in conditions such as stroke and traumatic brain injury.
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| 16. |
- Bennet, Hedvig, et al.
(författare)
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Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes.
- 2015
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Ingår i: Peptides. - : Elsevier BV. - 1873-5169 .- 0196-9781. ; 71, s. 113-120
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Tidskriftsartikel (refereegranskat)abstract
- Islet produced 5-hydroxy tryptamine (5-HT) is suggested to regulate islet hormone secretion in a paracrine and autocrine manner in rodents. Hitherto, no studies demonstrate a role for this amine in human islet function, nor is it known if 5-HT signaling is involved in the development of beta cell dysfunction in type 2 diabetes (T2D). To clarify this, we performed a complete transcriptional mapping of 5-HT receptors and processing enzymes in human islets and investigated differential expression of these genes in non-diabetic and T2D human islet donors. We show the expression of fourteen 5-HT receptors as well as processing enzymes involved in the biosynthesis of 5-HT at the mRNA level in human islets. Two 5-HT receptors (HTR1D and HTR2A) were over-expressed in T2D islet donors. Both receptors (5-HT1d and 5-HT2a) were localized to human alpha, beta and delta cells. 5-HT inhibited both insulin and glucagon secretion in non-diabetic islet donors. In islets isolated from T2D donors the amine significantly increased release of insulin in response to glucose. Our results suggest that 5-HT signaling participates in regulation of overall islet hormone secretion in non- diabetic individuals and over-expression of HTR1D and HTR2A may either contribute to islet dysfunction in T2D or arise as a consequence of an already dysfunctional islet.
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| 17. |
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| 26. |
- Bruze, Gustaf, et al.
(författare)
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Associations of Bariatric Surgery With Changes in Interpersonal Relationship Status Results From 2 Swedish Cohort Studies
- 2018
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Ingår i: JAMA Surgery. - : American Medical Association. - 2168-6254 .- 2168-6262. ; 153:7, s. 654-661
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Bariatric surgery is a life-changing treatment for patients with severe obesity, but little is known about its association with interpersonal relationships.OBJECTIVES: To investigate if relationship status is altered after bariatric surgery.DESIGN, SETTING, AND PARTICIPANTS: Changes in relationship status after bariatric surgery were examined in 2 cohorts: (1) the prospective Swedish Obese Subjects (SOS) study, which recruited patients undergoing bariatric surgery from September 1, 1987, to January 31, 2001, and compared their care with usual nonsurgical care in matched obese control participants; and (2) participants from the Scandinavian Obesity Surgery Registry (SOReg), a prospective, electronically captured register that recruited patients from January 2007 through December 2012 and selected comparator participants from the general population matched on age, sex, and place of residence. Data was collected in surgical departments and primary health care centers in Sweden. The current analysis includes data collected up until July 2015 (SOS) and December 2012 (SOReg). Data analysis was completed from June 2016 to December 2017.MAIN OUTCOMES AND MEASURES: In the SOS study, information on relationship status was obtained from questionnaires. In the SOReg and general population cohort, information on marriage and divorce was obtained from the Swedish Total Population Registry.RESULTS: The SOS study included 1958 patients who had bariatric surgery (of whom 1389 [70.9%] were female) and 1912 matched obese controls (of whom 1354 [70.8%] were female) and had a median (range) follow-up of 10 (0.5-20) years. The SOReg cohort included 29 234 patients who had gastric bypass surgery (of whom 22 131 [75.6%] were female) and 283 748 comparators from the general population (of whom 214 342 [75.5%] were female), and had a median (range) follow-up of 2.9 (0.003-7.0) years. In the SOS study, the surgical patients received gastric banding (n = 368; 18.8%), vertical banded gastroplasty (n = 1331; 68.0%), or gastric bypass (n = 259; 13.2%); controls received usual obesity care. In SOReg, all 29 234 surgical participants received gastric bypass surgery. In the SOS study, bariatric surgery was associated with increased incidence of divorce/separation compared with controls for those in a relationship (adjusted hazard ratio [aHR] = 1.28; 95% CI, 1.03-1.60; P =.03) and increased incidence of marriage or new relationship (aHR = 2.03; 95% CI, 1.52-2.71; P <.001) in those who were unmarried or single at baseline. In the SOReg and general population cohort, gastric bypass was associated with increased incidence of divorce compared with married control participants (aHR = 1.41; 95% CI, 1.33-1.49; P <.001) and increased incidence of marriage in those who were unmarried at baseline (aHR = 1.35; 95% CI, 1.28-1.42; P <.001). Within the surgery groups, changes in relationship status were more common in those with larger weight loss.CONCLUSIONS AND RELEVANCE: In addition to its association with obesity comorbidities, bariatric surgery-induced weight loss is also associated with changes in relationship status.
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| 27. |
- Chi, Jinshu, et al.
(författare)
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The Net Landscape Carbon Balance—Integrating terrestrial and aquatic carbon fluxes in a managed boreal forest landscape in Sweden
- 2020
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:4, s. 2353-2367
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Tidskriftsartikel (refereegranskat)abstract
- The boreal biome exchanges large amounts of carbon (C) and greenhouse gases (GHGs) with the atmosphere and thus significantly affects the global climate. A managed boreal landscape consists of various sinks and sources of carbon dioxide (CO2), methane (CH4), and dissolved organic and inorganic carbon (DOC and DIC) across forests, mires, lakes, and streams. Due to the spatial heterogeneity, large uncertainties exist regarding the net landscape carbon balance (NLCB). In this study, we compiled terrestrial and aquatic fluxes of CO2, CH4, DOC, DIC, and harvested C obtained from tall-tower eddy covariance measurements, stream monitoring, and remote sensing of biomass stocks for an entire boreal catchment (~68 km2) in Sweden to estimate the NLCB across the land–water–atmosphere continuum. Our results showed that this managed boreal forest landscape was a net C sink (NLCB = 39 g C m−2 year−1) with the landscape–atmosphere CO2 exchange being the dominant component, followed by the C export via harvest and streams. Accounting for the global warming potential of CH4, the landscape was a GHG sink of 237 g CO2-eq m−2 year−1, thus providing a climate-cooling effect. The CH4 flux contribution to the annual GHG budget increased from 0.6% during spring to 3.2% during winter. The aquatic C loss was most significant during spring contributing 8% to the annual NLCB. We further found that abiotic controls (e.g., air temperature and incoming radiation) regulated the temporal variability of the NLCB whereas land cover types (e.g., mire vs. forest) and management practices (e.g., clear-cutting) determined their spatial variability. Our study advocates the need for integrating terrestrial and aquatic fluxes at the landscape scale based on tall-tower eddy covariance measurements combined with biomass stock and stream monitoring to develop a holistic understanding of the NLCB of managed boreal forest landscapes and to better evaluate their potential for mitigating climate change.
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| 28. |
- Chriett, S., et al.
(författare)
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SCRT1 is a novel beta cell transcription factor with insulin regulatory properties
- 2021
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 521
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.
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| 29. |
- de Vries, Claire E. E., et al.
(författare)
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Outcomes of the first global multidisciplinary consensus meeting including persons living with obesity to standardize patient-reported outcome measurement in obesity treatment research
- 2022
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Ingår i: Obesity Reviews. - : John Wiley & Sons. - 1467-7881 .- 1467-789X. ; 23:8
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Tidskriftsartikel (refereegranskat)abstract
- Quality of life is a key outcome that is not rigorously measured in obesity treatment research due to the lack of standardization of patient-reported outcomes (PROs) and PRO measures (PROMs). The S.Q.O.T. initiative was founded to Standardize Quality of life measurement in Obesity Treatment. A first face-to-face, international, multidisciplinary consensus meeting was conducted to identify the key PROs and preferred PROMs for obesity treatment research. It comprised of 35 people living with obesity (PLWO) and healthcare providers (HCPs). Formal presentations, nominal group techniques, and modified Delphi exercises were used to develop consensus-based recommendations. The following eight PROs were considered important: self-esteem, physical health/functioning, mental/psychological health, social health, eating, stigma, body image, and excess skin. Self-esteem was considered the most important PRO, particularly for PLWO, while physical health was perceived to be the most important among HCPs. For each PRO, one or more PROMs were selected, except for stigma. This consensus meeting was a first step toward standardizing PROs (what to measure) and PROMs (how to measure) in obesity treatment research. It provides an overview of the key PROs and a first selection of the PROMs that can be used to evaluate these PROs.
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| 30. |
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| 31. |
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| 33. |
- Eliasson, Björn, 1959, et al.
(författare)
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Cardiovascular disease and mortality in patients with type 2 diabetes after bariatric surgery in Sweden: A nationwide, matched, observational cohort study
- 2015
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Ingår i: Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 3:11, s. 847-854
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Tidskriftsartikel (refereegranskat)abstract
- Background: In patients with diabetes and obesity specifically, no studies have examined mortality after bariatric surgery. We did a nationwide study in Sweden to examine risks of cardiovascular disease and mortality in patients with obesity and diabetes who had undergone bariatric surgery (Roux-en-Y gastric bypass [RYGB]). Methods: In this nationwide, matched, observational cohort study, we merged data for patients who had undergone RYGB registered in the Scandinavian Obesity Surgery Registry with other national databases, and identified matched controls (on the basis of sex, age, BMI, and calendar time [year]) who had not undergone bariatric surgery from the National Diabetes Registry. We assessed risks of cardiovascular disease and death using a Cox proportional-hazards regression model and other methods to examine the treatment effect while accounting for residual confounding. Primary outcomes were total mortality, cardiovascular death, and fatal or non-fatal myocardial infarction. Findings: Between Jan 1, 2007, and Dec 31, 2014, we obtained data for 6132 patients who had undergone RYGB and 6132 control patients who had not. Median follow-up was 3·5 years (IQR 2·1-4·7). We noted a 58% relative risk reduction (hazard ratio [HR] 0·42, 95% CI 0·30-0·57; p<0·0001) in overall mortality in the RYGB group compared with the controls. The risk of fatal or non-fatal myocardial infarction was 49% lower (HR 0·51, 0·29-0·91; p=0·021) and that of cardiovascular death was 59% lower (0·41, 0·19-0·90; p=0·026) in the RYGB group than in the control group. 5 year absolute risks of death were 1·8% (95% CI 1·5-2·2) in the RYGB group and 5·8% (5·0-6·8) in the control group. Interpretation: Our findings provide support for the benefits of RYGB surgery for patients with obesity and type 2 diabetes. The causes of these beneficial effects may be the weight reduction per se, changes in physiology and metabolism, improved care and treatment, improvements in lifestyle and risk factors, or combinations of these factors. Funding: Swedish Association of Local Authorities and Regions and Region Västra Götaland. © 2015 Elsevier Ltd.
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| 37. |
- Fagerberg, Linn, et al.
(författare)
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Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:6, s. 2439-2448
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Tidskriftsartikel (refereegranskat)abstract
- A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas (www.proteinatlas.org).
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| 38. |
- Fallqvist, Mikael, et al.
(författare)
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Nucleation And Growth Of Cvd α-Al2O3 On TiXOY Template
- 2012
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Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 207, s. 254-261
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Tidskriftsartikel (refereegranskat)abstract
- The microstructure, phase and chemical composition of TixOy templates used to nucleate α-Al2O3 on Ti(C,N) coated cemented carbide have been elucidated using scanning electron microscopy, X-ray diffraction, Auger electron spectroscopy and Time-of-Flight Secondary Ion Mass Spectrometry. Further, the adhesive strength of the α-Al2O3–TixOy–Ti(C,N) interfaces was investigated using scratch adhesion testing.The present study confirmed that the as-deposited template consisted of a Ti4O7 phase which during subsequent deposition of the Al2O3 layer transformed to a Ti3O5 phase and that the grown Al2O3 layer consisted of 100% α-Al2O3. Furthermore, the results showed that the lowest interfacial strength within the multilayer structure was exhibited by the Ti(C,N)–TixOy interface and that the transformation of Ti4O7 to Ti3O5 in the template resulted in formation of pores in the Ti(C,N)-template interface lowering the interfacial strength even more. The use of surface analysis techniques such as Auger electron spectroscopy and especially Time-of-Flight Secondary Ion Mass Spectrometry enabled trace element analyses using depth profiling to characterise the thin interfacial layers in detail.
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| 39. |
- Hakamies-Blomqvist, Liisa, et al.
(författare)
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Quality of life in patients with metastatic breast cancer receiving either docetaxel or sequential methotrexate and 5-fluorouracil : A multicentre randomised phase III trial by the Scandinavian breast group
- 2000
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 36:11, s. 1411-7
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the effects of two alternative chemotherapy regimes on the quality of life (QoL) of patients with advanced breast cancer. In a multicentre trial, 283 patients were randomised to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Initial compliance in the QoL study was 96% and the overall compliance 82%. QoL data were available for 245 patients (T 130 and 115 MF). Both treatment groups showed some improvement in emotional functioning during treatment, with a significant difference favouring the MF group at treatment cycles 5 and 6. In the T group, the scores on the other functional scales remained stable throughout the first six cycles. There were significant differences favouring the MF group on the social functioning scale at treatment cycle 6 and on the Global QoL scale at treatment cycles 5 and 6. On most symptom and single-item scales there were no statistically significant differences between the groups. However, at baseline, the T patients reported more appetite loss, at treatment cycles 2-4, the MF patients reported more nausea/vomiting, and at treatment cycle 6, the T patients reported more symptoms of fatigue, dyspnoea and insomnia. There were no statistically significant differences between the groups in the mean change scores of the functional and symptom scales. Interindividual variance was, however, larger in the T group. Differences in QoL between the two treatment groups were minor. Hence, given the expectancy of comparable QoL outcomes, the choice of treatment should be made on the basis of the expected clinical effect.
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| 40. |
- Hakamies-Blomqvist, Liisa, et al.
(författare)
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Timing of quality of life (QoL) assessments as a source of error in oncological trials
- 2001
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Ingår i: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 35:5, s. 709-16
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Tidskriftsartikel (refereegranskat)abstract
- AIM OF THE STUDY: To produce an empirical estimate of the nature and magnitude of the error produced by incorrect timing quality of life (QoL) measurements in patients receiving chemotherapy. DESIGN: In a multicentre trial, 283 patients were randomized to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). The QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The study design was retrospective. Data were analysed using t-tests. RESULTS: Erroneous timing affected the QoL findings in both treatment arms. At baseline, there were statistically significant differences in the MF group on the nausea/vomiting scale, with ill-timed assessment showing more symptoms, and in the T group on the physical functioning scale with ill-timed assessments indicating better QoL. The mean scores of correct vs. incorrect timings over the first 14 cycles showed statistically significant differences on several scales. In the MF group, ill-timed assessments indicated significantly worse physical functioning and global QoL, and significantly more of the following symptoms: fatigue, nausea/vomiting, insomnia, appetite loss, and constipation. In the T group, ill-timed assessment showed better physical functioning, less dyspnoea and more insomnia than correctly timed assessments. The reasons for erroneous timing were not always detectable retrospectively. However, in some cases the MF group, being in standard treatment, seemed to have followed a clinical routine not involving the active participation of the study nurse responsible, whereas patients in the experimental T group were more consistently taken care of by the study nurses. CONCLUSIONS: Incorrect timing of QoL assessments in oncological trials jeopardises both the reliability of the QoL findings within treatment and the validity of QoL outcome comparisons between treatments. This issue should be emphasized in the planning of both the study design and clinical routines.
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| 41. |
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| 42. |
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| 45. |
- Högberg, Peter, et al.
(författare)
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Large-scale forest girdling shows that current photosynthesis drives soil respiration
- 2001
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 411:6839, s. 789-792
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Tidskriftsartikel (refereegranskat)abstract
- The respiratory activities of plant roots, of their mycorrhizal fungi and of the free-living microbial heterotrophs (decomposers) in soils are significant components of the global carbon balance, but their relative contributions remain uncertain. To separate mycorrhizal root respiration from heterotrophic respiration in a boreal pine forest, we conducted a large-scale tree-girdling experiment, comprising 9 plots each containing about 120 trees. Tree-girdling involves stripping the stem bark to the depth of the current xylem at breast height terminating the supply of current photosynthates to roots and their mycorrhizal fungi without physically disturbing the delicate root-microbe-soil system. Here we report that girdling reduced soil respiration within 1-2 months by about 54% relative to respiration on ungirdled control plots, and that decreases of up to 37% were detected within 5 days. These values clearly show that the flux of current assimilates to roots is a key driver of soil respiration; they are conservative estimates of root respiration, however, because girdling increased the use of starch reserves in the roots. Our results indicate that models of soil respiration should incorporate measures of photosynthesis and of seasonal patterns of photosynthate allocation to roots.
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| 46. |
- Höskuldsdottir, G., et al.
(författare)
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Effects of bariatric surgery on the incidence of heart failure and atrial fibrillation in patients with type 2 diabetes and obesity
- 2020
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:Suppl. 1, s. S262-S262
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: To study the effects of obesity treatment with gastric bypass surgery on hospitalization for heart failure (HF) and atrial fibrillation (AF) in patients with type 2 diabetes (T2D) and obesity. We also studied the effects of gastric bypass surgery on mortality in a subgroup of individuals with preexisting heart failure.Materials and methods: In this register-based nationwide cohort study we compared individuals with T2D and obesity that underwent Roux-en-Y gastric bypass surgery (RYGB) with matched individuals with T2D and obesity that did not undergo surgery. Data was gathered by linking the Swedish National Diabetes Register and Scandinavian Obesity Surgery Registry. Matching of individuals for age, gender, BMI and calendar time was done using a time updated propensity score. The main outcome measures were hospitalization for HF and/or AF, and mortality in patients with preexisting HF. The risk for heart failure, AF and death were assessed using a Cox-proportional hazards regression model that addressed measured confounding.Results: We identified 5321 individuals with T2D and obesity that had undergone RYGB between January 2007 and December 2013 and 5321 matched controls. The individuals includedwere between 18 and 65 years old and had a BMI > 27.5 kg/m2. The follow-up time for hospitalization was until the end of 2015 (mean 4.5 years) and the end of 2016 for death. Our results show a 73% lower risk for HF (HR 0.27 (0.19, 0.38) p<0.001), 41% for AF (HF 0.59 (0.44, 0.78) p < 0.001), and 77% for concomitant AF and HF (HR0.23 (0.12, 0.46) p < 0.001) in the surgically treated group. In patients with preexisting HF we observed significantly lower mortality in the group that underwent surgery (HR0.23 (0.12, 0.43) p < 0.001).Conclusion: Bariatric surgery may reduce risk for HF and AF in patients with T2D and obesity, speculatively via positive cardiovascular and renal effects. Obesity treatment with surgery may also be a valuable alternative in selected patients with T2D and HF.
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| 47. |
- Intarasiri, Saweat, et al.
(författare)
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Effects of low-fluence swift iodine ion bombardment on the crystallization of ion-beam-synthesized silicon carbide
- 2007
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 101:8, s. 084311-
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Tidskriftsartikel (refereegranskat)abstract
- Ion beam synthesis using high-fluence carbon ion implantation in silicon in combination with subsequent or in situ thermal annealing has been shown to be able to form nanocrystalline cubic SiC (3C-SiC) layers in silicon. In this study, a silicon carbide layer was synthesized by 40-keV C 12 + implantation of a p -type (100) Si wafer at a fluence of 6.5× 1017 ions cm2 at an elevated temperature. The existence of the implanted carbon in Si substrate was investigated by time-of-flight energy elastic recoil detection analysis. The SiC layer was subsequently irradiated by 10-30 MeV I 127 ions to a very low fluence of 1012 ions cm2 at temperatures from 80 to 800 °C to study the effect on the crystallization of the SiC layer. Infrared spectroscopy and Raman scattering measurement were used to monitor the formation of SiC and detailed information about the SiC film properties was obtained by analyzing the peak shape of the Si-C stretching mode absorption. The change in crystallinity of the synthesized layer was probed by glancing incidence x-ray diffraction measurement and transmission electron microscopy was also used to confirm the results and to model the crystallization process. The results from all these measurements showed in a coherent way that the synthesized structure was a polycrystalline layer with nanometer sized SiC crystals buried in a-Si matrix. The crystallinity of the SiC layer was enhanced by the low-fluence swift heavy ion bombardment and also favored by higher energy, higher fluence, and higher substrate temperature. It is suggested that electronic stopping plays a dominant role in the enhancement.
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| 48. |
- Ivanchenko, M, et al.
(författare)
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Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block
- 2021
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 80:2, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- Congenital heart block (CHB) with immune cell infiltration develops in the fetus after exposure to maternal Ro/La autoantibodies. CHB-related serology has been extensively studied, but reports on immune-cell profiles of anti-Ro/La-exposed neonates are lacking. In the current study, we characterised circulating immune-cell populations in anti-Ro/La+mothers and newborns, and explored potential downstream effects of skewed neonatal cell populations.MethodsIn total, blood from mothers (n=43) and neonates (n=66) was sampled at birth from anti-Ro/La+ (n=36) and control (n=30) pregnancies with or without rheumatic disease and CHB. Flow cytometry, microarrays and ELISA were used for characterising cells and plasma.ResultsSimilar to non-pregnant systemic lupus erythematosus and Sjögren-patients, anti-Ro/La+mothers had altered B-cell subset frequencies, relative T-cell lymphopenia and lower natural killer (NK)-cell frequencies. Surprisingly, their anti-Ro/La exposed neonates presented higher frequencies of CD56dimCD16hiNK cells (p<0.01), but no other cell frequency differences compared with controls. Type I and II interferon (IFN) gene-signatures were revealed in neonates of anti-Ro/La+ pregnancy, and exposure of fetal cardiomyocytes to type I IFN induced upregulation of several NK-cell chemoattractants and activating ligands. Intracellular flow cytometry revealed IFNγ production by NK cells, CD8+and CD4+T cells in anti-Ro/La exposed neonates. IFNγ was also detectable in their plasma.ConclusionOur study demonstrates an increased frequency of NK cells in anti-Ro/La exposed neonates, footprints of type I and II IFN and an upregulation of ligands activating NK cells in fetal cardiac cells after type I IFN exposure. These novel observations demonstrate innate immune activation in neonates of anti-Ro/La+pregnancy, which could contribute to the risk of CHB.
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| 49. |
- Jafri, S Hassan M, et al.
(författare)
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Control of junction resistances in molecular electronic devices fabricated by FIB
- 2011
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 88:8, s. 2629-2631
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Tidskriftsartikel (refereegranskat)abstract
- A major hurdle to realize molecular electronic devices (MEDs) is to make reliable electrical contacts to a single or a few molecules. Our nano-contact platform with a gap size of less than 25 nm with resistances above 1000 TΩ was built using combined techniques of photolithography, electron beam lithography and focused ion beam milling. In this study, we have used gold nanoparticles (AuNPs) to bridge the nanoelectrode gaps by dielectrophoretic trapping and thus obtain electrical contacts. The electrodes and/or the nanoparticles were functionalised with 1–2 nm long alkane-thiol molecules so that the electronic structure of these molecules determines the properties of the electrical junction. Molecules were introduced both by functionalising the nanogap and the nanoparticles and the results of both functionalisation protocols are compared. Here, we show the nanogap–nanoparticle bridge set-up containing metal–molecule junctions that can be used as a base for the development of molecular electronics containing only a few molecules under ambient conditions. Current–voltage (I–V) characterization of alkanethiol/gold junction showed non-linear response where mean geometric resistance of four different junctions could be tuned from 20 GΩ to 20 TΩ. The results from the measurements on 1-alkanethiol in such devices is a first step to demonstrate that this platform has the potential to obtain stable electronic devices having relatively small numbers of molecules with reliable metal molecule junction by combing top-down and bottom-up approaches.
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| 50. |
- Jafri, S. H. M., et al.
(författare)
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Identification of vibrational signatures from short chains of interlinked molecule-nanoparticle junctions obtained by inelastic electron tunnelling spectroscopy
- 2013
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 5:11, s. 4673-4677
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Tidskriftsartikel (refereegranskat)abstract
- Short chains containing a series of metal-molecule-nanoparticle nanojunctions are a nano-material system with the potential to give electrical signatures close to those from single molecule experiments while enabling us to build portable devices on a chip. Inelastic electron tunnelling spectroscopy (IETS) measurements provide one of the most characteristic electrical signals of single and few molecules. In interlinked molecule-nanoparticle (NP) chains containing typically 5-7 molecules in a chain, the spectrum is expected to be a superposition of the vibrational signatures of individual molecules. We have established a stable and reproducible molecule-AuNP multi-junction by placing a few 1,8-octanedithiol (ODT) molecules onto a versatile and portable nanoparticle-nanoelectrode platform and measured for the first time vibrational molecular signatures at complex and coupled few-molecule-NP junctions. From quantum transport calculations, we model the IETS spectra and identify vibrational modes as well as the number of molecules contributing to the electron transport in the measured spectra.
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