1. |
- Nordanstig, Annika, 1974, et al.
(författare)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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2. |
- Eriksson, Mats, 1966-, et al.
(författare)
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Discovery of an algal mitochondrial carbonic anhydrase : molecular cloning and characterization of a low-CO2-induced polypeptide in Chlamydomonas reinhardtii
- 1996
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 93:21, s. 12031-12034
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Tidskriftsartikel (refereegranskat)abstract
- In green unicellular algae, several polypeptides are induced upon exposure to limiting CO2. We report here on the localization and characterization of one of these, a 22-kDa polypeptide in Chlamydomonas reinhardtii. This nuclear-encoded polypeptide is induced in the mitochondria by a lowering of the partial pressure of CO2 in the growth medium from 5% to air CO2 levels. Sequencing of two different cDNA clones coding for the polypeptide identified it as a 20.7-kDa beta-type carbonic anhydrase (CA; carbonate dehydratase, carbonate hydro-lyase, EC 4.2.1.1). The two clones differ in their nucleotide sequences but code for identical proteins, showing that this CA is encoded by at least two genes. Northern blot hybridization reveals that mRNA transcripts are only present in cells transferred to air CO2 levels. A comparison of the deduced amino acid sequence with those of other beta-CAs shows the largest degree of similarity with CA from the cyanobacterium Synechocystis (50% identity and 66% similarity). To our knowledge, this is the first identification and characterization of a mitochondrial CA from a photosynthetic organism.
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3. |
- Flowers, Sarah A., et al.
(författare)
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Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking
- 2020
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:47, s. 16023-16036
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Tidskriftsartikel (refereegranskat)abstract
- The synovial fluid glycoprotein lubricin (also known as proteoglycan 4) is a mucin-type O-linked glycosylated biological lubricant implicated to be involved in osteoarthritis (OA) development. Lubricin's ability to reduce friction is related to its glycosylation consisting of sialylated and unsialylated Tn-antigens and core 1 and core 2 structures. The glycans on lubricin have also been suggested to be involved in crosslinking and stabilization of the lubricating superficial layer of cartilage by mediating interaction between lubricin and galectin-3. However, with the spectrum of glycans being found on lubricin, the glycan candidates involved in this interaction were unknown. Here, we confirm that the core 2 O-linked glycans mediate this lubricin-galectin-3 interaction, shown by surface plasmon resonance data indicating that recombinant lubricin (rhPRG4) devoid of core 2 structures did not bind to recombinant galectin-3. Conversely, transfection of Chinese hamster ovary cells with the core 2 GlcNAc transferase acting on a mucin-type O-glycoprotein displayed increased galectin-3 binding. Both the level of galectin-3 and the galectin-3 interactions with synovial lubricin were found to be decreased in late-stage OA patients, coinciding with an increase in unsialylated core 1 O-glycans (T-antigens) and Tn-antigens. These data suggest a defect in crosslinking of surface-active molecules in OA and provide novel insights into OA molecular pathology.
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4. |
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5. |
- Larsson, Alice, et al.
(författare)
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Do patients with large vessel occlusion ischemic stroke harboring prestroke disability benefit from thrombectomy?
- 2020
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 267, s. 2667-2674
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Evidence of endovascular treatment (EVT) for acute large vessel occlusion (LVO) ischemic stroke in patients harboring substantial prestroke disability is lacking due to their exclusion from randomized trials. Here, we used routine care observational data to compare outcomes in patients with and without prestroke disability receiving EVT for LVO ischemic stroke. Methods: Consecutive patients undergoing EVT for acute LVO ischemic stroke at the Sahlgrenska University Hospital from January 1st, 2015 to March 31st, 2018 were registered in the Sahlgrenska Stroke Recanalization Registry. Pre- and poststroke functional levels were assessed by the modified Rankin Scale (mRS). Outcomes were recanalization rate (mTICI = 2b/3), symptomatic intracranial hemorrhage [sICH], complications during hospital stay, and return to prestroke functional level and mortality at 3 months. Results: Among 591 patients, 90 had prestroke disability (mRS ≥ 3). The latter group were older, more often female, had more comorbidities and higher NIHSS scores before intervention compared to patients without prestroke disability. Recanalization rates (80.0% vs 85.0%, p = 0.211), sICH (2.2% vs 6.3% p = 0.086) and the proportion of patients returning to prestroke functional level (22.7% vs 14.8% p = 0.062) did not significantly differ between those with and without prestroke disability. Patients with prestroke disability had higher complication rates during hospital stay (55.2% vs 40.1% p < 0.01) and mortality at 3 months (48.9% vs 24.3% p < 0.001). Conclusion: One of five with prestroke disability treated with thrombectomy for a LVO ischemic stroke returned to their prestroke functional level. However, compared to patients without prestroke disability, mortality at 3 months was higher. © 2020, The Author(s).
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6. |
- Raoof, Mustafa, 1966-, et al.
(författare)
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Health-Related Quality-of-Life (HRQoL) on an Average of 12 Years After Gastric Bypass Surgery
- 2015
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 25:7, s. 1119-1127
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Tidskriftsartikel (refereegranskat)abstract
- It is evident that morbidly obese patients have a low health-related quality-of-life (HRQoL), and this low HRQoL has become a common reason for them to seek bariatric surgery. Several HRQoL studies demonstrate a dramatic postoperative improvement, but most of these have had a short follow-up period.An observational, cross-sectional study for HRQoL was conducted to study 486 patients (average age of 50.7 +/- 10.0 years, with 84 % of them being female) operated with gastric bypass (GBP) in the period 1993 to 2003 at the University Hospitals of A-rebro and Uppsala. Mean follow-up after gastric bypass was 11.5 +/- 2.7 years (range 7-17). Two HRQoL instruments were used, SF-36 and the Obesity-related Problems scale (OP). The study group was compared with two control groups, both matched for age and gender, one from the general population and one containing morbidly obese patients evaluated and awaiting bariatric surgery.The study group scored better in the SF-36 domains (all four physical domains and the vitality subscore) and OP scale compared to obese controls, but their HRQoL scores were lower than those of the general population. HRQoL was better among younger patients and in the following subgroups: men, patients with satisfactory weight loss, satisfied with the procedure, free from co-morbidities and gastrointestinal symptoms, employment, good oral status and those not hospitalised or regularly followed up for non-bariatric reasons.Long-term follow-up after GBP for morbid obesity showed better scores in most aspects of HRQoL compared to obese controls but did not achieve the levels of the general population. Patients with better medical outcome after gastric bypass operation had better HRQoL.
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7. |
- Shuoker, Bashar, et al.
(författare)
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Sialidases and fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The mucolytic human gut microbiota specialist Akkermansia muciniphila is proposed to boost mucin-secretion by the host, thereby being a key player in mucus turnover. Mucin glycan utilization requires the removal of protective caps, notably fucose and sialic acid, but the enzymatic details of this process remain largely unknown. Here, we describe the specificities of ten A. muciniphila glycoside hydrolases, which collectively remove all known sialyl and fucosyl mucin caps including those on double-sulfated epitopes. Structural analyses revealed an unprecedented fucosidase modular arrangement and explained the sialyl T-antigen specificity of a sialidase of a previously unknown family. Cell-attached sialidases and fucosidases displayed mucin-binding and their inhibition abolished growth of A. muciniphila on mucin. Remarkably, neither the sialic acid nor fucose contributed to A. muciniphila growth, but instead promoted butyrate production by co-cultured Clostridia. This study brings unprecedented mechanistic insight into the initiation of mucin O-glycan degradation by A. muciniphila and nutrient sharing between mucus-associated bacteria.
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8. |
- Åberg, Jan, 1977-, et al.
(författare)
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Pelagic and benthic net production of dissolved inorganic carbon in an unproductive subarctic lake
- 2007
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 52:3, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- 1. Both the pelagic and benthic net dissolved inorganic carbon (DIC) productions were measured in situ on four occasions from June to September 2004, in the unproductive Lake Diktar-Erik in subarctic Sweden. The stable isotopic signal (δ13C) of respired organic material was estimated from hypolimnion water data and data from a laboratory incubation using epilimnion water. 2. Both pelagic and benthic habitats were net heterotrophic during the study period, with a total net DIC production of 416 mg C m-2 day-1, of which the pelagic habitat contributed approximately 85%. The net DIC production decreased with depth both in the pelagic water and in the sediments, and most of the net DIC production occurred in the upper water column. 3. Temporal variations in both pelagic and benthic DIC production were small, although we observed a significant decrease in pelagic net DIC production after the autumn turnover. Water temperature was the single most important factor explaining temporal and vertical variations in pelagic DIC production. No single factor explained more than 10% of the benthic net DIC production, which probably was regulated by several interacting factors. 4. Pelagic DIC production, and thus most of the whole-lake net production of DIC, was mainly due to the respiration of allochthonous organic carbon. Stable isotope data inferred that nearly 100% of accumulated DIC in the hypolimnion water had an allochthonous carbon source. Similarly, in the laboratory incubation using epilimnion water, c. 85% of accumulated DIC was indicated to have an allochthonous organic carbon source.
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9. |
- Abraham-Nordling, Mirna, et al.
(författare)
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Incidence of hyperthyroidism in Sweden
- 2011
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:6, s. 899-905
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100000 inhabitants per year. This extended study has evaluated the incidence for similar to 40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. Methods:All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows:clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. Results:A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100 000 inhabitants per year. The incidence of GD was 21.0/100 000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100 000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. Conclusion:The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.
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10. |
- Albrectsen, Benedicte R., 1960-, et al.
(författare)
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Endophytic fungi in European aspen (Populus tremula) leaves - diversity, detection, and a suggested correlation with herbivory resistance
- 2010
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Ingår i: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 41:1, s. 17-28
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Tidskriftsartikel (refereegranskat)abstract
- According to the geographic mosaic theory of coevolution (GMTC), clines of traits reflecting local co-adaptation (including resistance genes) should be common between a host and its parasite and should persist across time. To test the GMTC-assumption of persistent clinal patterns we compared the natural prevalence of two parasites on aspen Populus tremula trees: mining moths of the genus Phyllocnistis and leaf rust Melampsora spp. Damage data were collated from the Swedish National Forest Damage Inventory (2004–2006). In addition, occurrence of the parasites was scored in field conditions in two common gardens in the north and south of Sweden over five growing seasons (2004–2008), then related to biomass (stem height and diameter) and to concentrations of eleven leaf phenolics. Phyllocnistis mainly occurred in the northern garden, a distribution range which was confirmed by the countrywide inventory, although Phyllocnistis was more abundant on southern clones, providing evidence for possible local maladaptation. Melampsora occurred all over the country and in both gardens, but built up more quickly on northern clones, which suggests a centre of local clone maladaptation in the north. Stem growth also followed a clinal pattern as did the concentration of three phenolic compounds: benzoic acid, catechin and cinnamic acid. However, only benzoic acid was related to parasite presence: negatively to Phyllocnistis and positively to Melampsora and it could thus be a potential trait under selection. In conclusion, clines of Phyllocnistis were stronger and more persistent compared to Melampsora, which showed contrasting clines of varying strength. Our data thus support the assumption of the GMTC model that clines exist in the border between hot and cold spots and that they may be less persistent for parasites with an elevated gene flow, and/or for parasites which cover relatively larger hot spots surrounded by fewer cold spots.
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11. |
- An, Junxue, et al.
(författare)
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Influence of Glycosylation on Interfacial Properties of Recombinant Mucins : Adsorption, Surface Forces, and Friction
- 2017
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Ingår i: Langmuir. - : American Chemical Society. - 0743-7463 .- 1520-5827. ; 33:18, s. 4386-4395
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Tidskriftsartikel (refereegranskat)abstract
- Interfacial properties of two brush-with-anchor mucins, C-P55 and C-PSLex, have been investigated at the aqueous solution/poly(methyl methacrylate) (PMMA) interface. Both are recombinant mucin-type fusion proteins, produced by fusing the glycosylated mucin part of P-selectin glycoprotein ligand-1 (PSLG-1) to the Fc part of a mouse immunoglobulin in two different cells. They are mainly expressed as dimers upon production. Analysis of the O-glycans shows that the C-PSLex mucin has the longer and more branched side chains, but C-P55 has slightly higher sialic acid content. The adsorption of the mucins to PMMA surfaces was studied by quartz crystal microbalance with dissipation. The sensed mass, including the adsorbed mucin and water trapped in the layer, was found to be similar for these two mucin layers. Atomic force microscopy with colloidal probe was employed to study surface and friction forces between mucin-coated PMMA surfaces. Purely repulsive forces of steric origin were observed between mucin layers on compression, whereas a small adhesion was detected between both mucin layers on decompression. This was attributed to chain entanglement. The friction force between C-PSLex-coated PMMA is lower than that between C-P55-coated PMMA at low loads, but vice versa at high loads. We discuss our results in terms of the differences in the glycosylation composition of these two mucins.
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12. |
- Andersson, Anders, et al.
(författare)
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A transcriptional timetable of autumn senescence
- 2004
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 5:4, s. R24-
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Tidskriftsartikel (refereegranskat)abstract
- Background We have developed genomic tools to allow the genus Populus (aspens and cottonwoods) to be exploited as a full-featured model for investigating fundamental aspects of tree biology. We have undertaken large-scale expressed sequence tag (EST) sequencing programs and created Populus microarrays with significant gene coverage. One of the important aspects of plant biology that cannot be studied in annual plants is the gene activity involved in the induction of autumn leaf senescence. Results On the basis of 36,354 Populus ESTs, obtained from seven cDNA libraries, we have created a DNA microarray consisting of 13,490 clones, spotted in duplicate. Of these clones, 12,376 (92%) were confirmed by resequencing and all sequences were annotated and functionally classified. Here we have used the microarray to study transcript abundance in leaves of a free-growing aspen tree (Populus tremula) in northern Sweden during natural autumn senescence. Of the 13,490 spotted clones, 3,792 represented genes with significant expression in all leaf samples from the seven studied dates. Conclusions We observed a major shift in gene expression, coinciding with massive chlorophyll degradation, that reflected a shift from photosynthetic competence to energy generation by mitochondrial respiration, oxidation of fatty acids and nutrient mobilization. Autumn senescence had much in common with senescence in annual plants; for example many proteases were induced. We also found evidence for increased transcriptional activity before the appearance of visible signs of senescence, presumably preparing the leaf for degradation of its components.
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13. |
- Bandaru, Sashidar, et al.
(författare)
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Targeting filamin A reduces macrophage activity and atherosclerosis. : Filamin A in atherogenesis
- 2019
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Ingår i: Circulation. - 1524-4539. ; 140:1, s. 67-79
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Tidskriftsartikel (refereegranskat)abstract
- The actin-binding protein FLNA (filamin A) regulates signal transduction important for cell locomotion, but the role of macrophage-specific FLNA during atherogenesis has not been explored.We analyzed FLNA expression in human carotid atherosclerotic plaques by immunofluorescence. We also produced mice with Flna-deficient macrophages by breeding conditional Flna-knockout mice ( Flna o/fl) with mice expressing Cre from the macrophage-specific lysosome M promoter ( LC). Atherosclerosis in vivo was studied by transplanting bone marrow from male Flna o/fl/ LC mice to atherogenic low-density lipoprotein receptor-deficient ( Ldlr-/-) mice; and by infecting Flna o/fl and Flna o/fl/ LC mice with AdPCSK9 (adenoviral vector overexpressing proprotein convertase subtilisin/kexin type 9). Furthermore, C57BL/6 mice were infected with AdPCSK9 and then treated with the calpain inhibitor calpeptin to inhibit FLNA cleavage.We found that macrophage FLNA expression was higher in advanced than in intermediate human atherosclerotic plaques. Flna o/fl/ LC macrophages proliferated and migrated less than controls; expressed lower levels of phosphorylated AKT and ERK1/2; exhibited reduced foam cell formation and lipid uptake; and excreted more lipids. The deficiency of Flna in macrophages markedly reduced the size of aortic atherosclerotic plaques in both Ldlr-/-BMT: Flnao/fl/LC and AdPCSK9-infected Flna o/fl/ LC mice. Intima/media ratios and numbers of CD68-positive macrophages in atherosclerotic plaques were lower in Flna-deficient mice than in control mice. Moreover, we found that STAT3 interacts with a calpain-cleaved carboxyl-terminal fragment of FLNA. Inhibiting calpain-mediated FLNA cleavage with calpeptin in macrophages reduced nuclear levels of phosphorylated STAT3, interleukin 6 secretion, foam cell formation, and lipid uptake. Finally, calpeptin treatment reduced the size of atherosclerotic plaques in C57BL/6 mice infected with AdPCSK9.Genetic inactivation of Flna and chemical inhibition of calpain-dependent cleavage of FLNA impaired macrophage signaling and function, and reduced atherosclerosis in mice, suggesting that drugs targeting FLNA may be useful in the treatment of atherosclerosis.
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14. |
- Barmano, Neshro, 1980-, et al.
(författare)
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The association between alcohol consumption, cardiac biomarkers, left atrial size and re-ablation in patients with atrial fibrillation referred for catheter ablation
- 2019
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Ingår i: PLOS ONE. - San Francisco, CA, United States : Public Library of Science. - 1932-6203. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundInformation on alcohol consumption in patients undergoing radiofrequency ablation (RFA) of atrial fibrillation (AF) is often limited by the reliance on self-reports. The aim of this study was to describe the long-term alcohol consumption, measured as ethyl glucuronide in hair (hEtG), in patients undergoing RFA due to AF, and to examine potential associations with cardiac biomarkers, left atrial size and re-ablation within one year after the initial RFA.MethodsThe amount of hEtG was measured in patients referred for RFA, and a cut-off of 7 pg/mg was used. N-terminal pro B-type natriuretic peptide (NT-proBNP) and the mid-regional fragment of pro atrial natriuretic peptide (MR-proANP) were examined and maximum left atrium volume index (LAVI) was measured. The number of re-ablations was examined up to one year after the initial RFA. Analyses were stratified by gender, and adjusted for age, systolic blood pressure, body mass index, presence of heart failure and heart rhythm for analyses regarding NT-proBNP, MR-proANP and LAVI and heart rhythm being replaced by type of AF for analyses regarding re-ablation.ResultsIn total, 192 patients were included in the study. Median (25th– 75th percentile) NT-proBNP in men with hEtG ≥ 7 vs. < 7 pg/mg was 250 (96–695) vs. 130 (49–346) pg/ml (p = 0.010), and in women it was 230 (125–480) vs. 230 (125–910) pg/ml (p = 0.810). Median MR-proANP in men with hEtG ≥ 7 vs. < 7 pg/mg was 142 (100–224) vs. 117 (83–179) pmol/l (p = 0.120) and in women it was 139 (112–206) vs. 153 (93–249) pmol/l (p = 0.965). The median of maximum LAVI was 30.1 (26.7–33.9) vs. 25.8 (21.4–32.0) ml/m2 (p = 0.017) in men, and 25.0 (18.9–29.6) vs. 25.7 (21.7–34.6) ml/m2 (p = 0.438) in women, with hEtG ≥ 7 vs. < 7 pg/ml, respectively. Adjusted analyses showed similar results, except for MR-proANP turning out significant in men with hEtG ≥ 7 vs. < 7 pg/mg (p = 0.047). The odds ratio of having a re-ablation was 3.5 (95% CI 1.3–9.6, p = 0.017) in men with hEtG ≥ 7 vs. < 7 pg/mg, while there was no significant difference in women.ConclusionsIn male patients with AF and hEtG ≥ 7 pg/mg, NT-proBNP and MR-proANP were higher, LA volumes larger, and there was a higher rate of re-ablations, as compared to men with hEtG < 7 pg/mg. This implies that men with an alcohol consumption corresponding to an hEtG-value ≥ 7, have a higher risk for LA remodelling that could potentially lead to a deterioration of the AF situation.
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15. |
- Bergström, Ann-Kristin, 1968-, et al.
(författare)
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Effects of nitrogen enrichment on zooplankton biomass and N:P recycling ratios across a DOC gradient in northern-latitude lakes
- 2021
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Ingår i: Hydrobiologia. - : Springer. - 0018-8158 .- 1573-5117. ; 848:21, s. 4991-5010
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Tidskriftsartikel (refereegranskat)abstract
- We used data from whole-lake studies to assess how changes in food quantity (phytoplankton biomass) and quality (phytoplankton community composition, seston C:P and N:P) with N fertilization affect zooplankton biomass, community composition and C:N:P stoichiometry, and their N:P recycling ratio along a gradient in lake DOC concentrations. We found that despite major differences in phytoplankton biomass with DOC (unimodal distributions, especially with N fertilization), no major differences in zooplankton biomass were detectable. Instead, phytoplankton to zooplankton biomass ratios were high, especially at intermediate DOC and after N fertilization, implying low trophic transfer efficiencies. An explanation for the observed low phytoplankton resource use, and biomass responses in zooplankton, was dominance of colony forming chlorophytes of reduced edibility at intermediate lake DOC, combined with reduced phytoplankton mineral quality (enhanced seston N:P) with N fertilization. N fertilization, however, increased zooplankton N:P recycling ratios, with largest impact at low DOC where phytoplankton benefitted from light sufficiently to cause enhanced seston N:P. Our results suggest that although N enrichment and increased phytoplankton biomass do not necessarily increase zooplankton biomass, bottom-up effects may still impact zooplankton and their N:P recycling ratio through promotion of phytoplankton species of low edibility and altered mineral quality.
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16. |
- Bhalerao, Rupali, et al.
(författare)
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Gene expression in autumn leaves
- 2003
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Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 131:2, s. 430-442
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Tidskriftsartikel (refereegranskat)abstract
- Two cDNA libraries were prepared, one from leaves of a field-grown aspen (Populus tremula) tree, harvested just before any visible sign of leaf senescence in the autumn, and one from young but fully expanded leaves of greenhouse-grown aspen (Populus tremula X tremuloides). Expressed sequence tags (ESTs; 5,128 and 4,841, respectively) were obtained from the two libraries. A semiautomatic method of annotation and functional classification of the ESTs, according to a modified Munich Institute of Protein Sequences classification scheme, was developed, utilizing information from three different databases. The patterns of gene expression in the two libraries were strikingly different. In the autumn leaf library, ESTs encoding metallothionein, early light-inducible proteins, and cysteine proteases were most abundant. Clones encoding other proteases and proteins involved in respiration and breakdown of lipids and pigments, as well as stress-related genes, were also well represented. We identified homologs to many known senescence-associated genes, as well as seven different genes encoding cysteine proteases, two encoding aspartic proteases, five encoding metallothioneins, and 35 additional genes that were up-regulated in autumn leaves. We also indirectly estimated the rate of plastid protein synthesis in the autumn leaves to be less that 10% of that in young leaves.
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17. |
- Bjersing, Jan, 1966, et al.
(författare)
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Impact of site-specific nucleobase deletions on the arthritogenicity of DNA
- 2004
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Ingår i: Inflammation. - 0360-3997. ; 28:3, s. 159-68
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Tidskriftsartikel (refereegranskat)abstract
- Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG ODN) potently stimulate the innate and acquired immune system. We have compared the in vivo and in vitro inflammatogenic properties of CpG ODNs containing a specific nucleobase deletion either 5'-upstream (ODN-2) or 3'-downstream (ODN-3) of the CpG motif, comparing with a prototype CpG ODN (ODN-1). The frequency of arthritis was similar after intra-articular (i.a.) injections of ODN-1 or ODN-3, but was significantly lower (p < 0.02) after i.a. injections of ODN-2. In vitro production of the pro-inflammatory cytokine TNF-alpha was higher in mouse spleen cell cultures exposed to ODN-2 in comparison to ODN-1. In addition, the level of IL-10 induced by ODN-2 was higher than that induced by ODN-1. On the other hand, TNF-alpha, IL-10, and MCP-1 levels, as well as splenocyte proliferative responses were all significantly lower for ODN-3 than for ODN-1. These results suggest that a 5'-upstream nucleobase deletion reduces arthritogenicity, while maintaining or increasing the production of pro- and anti-inflammatory factors. In contrast, a 3'-downstream nucleobase deletion has no effect on arthritogenicity, despite significantly lower levels of proliferation and pro- and anti-inflammatory cytokines, compared with ODN-1. This study indicates that specific structural elements within the ODN sequence but outside the CpG motif, modulate the immunostimulatory properties of CpG ODNs.
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18. |
- Bylesjö, Max, et al.
(författare)
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Integrated analysis of transcript, protein and metabolite data to study lignin biosynthesis in hybrid aspen
- 2009
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 8:1, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- Tree biotechnology will soon reach a mature state where it will influence the overall supply of fiber, energy and wood products. We are now ready to make the transition from identifying candidate genes, controlling important biological processes, to discovering the detailed molecular function of these genes on a broader, more holistic, systems biology level. In this paper, a strategy is outlined for informative data generation and integrated modeling of systematic changes in transcript, protein and metabolite profiles measured from hybrid aspen samples. The aim is to study characteristics of common changes in relation to genotype-specific perturbations affecting the lignin biosynthesis and growth. We show that a considerable part of the systematic effects in the system can be tracked across all platforms and that the approach has a high potential value in functional characterization of candidate genes.
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19. |
- Cherian, Reeja Maria, et al.
(författare)
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A Panel of Recombinant Mucins Carrying a Repertoire of Sialylated O-Glycans Based on Different Core Chains for Studies of Glycan Binding Proteins.
- 2015
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 5:3, s. 1810-31
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Tidskriftsartikel (refereegranskat)abstract
- Sialylated glycans serve as key elements of receptors for many viruses, bacteria, and bacterial toxins. The microbial recognition and their binding specificity can be affected by the linkage of the terminal sugar residue, types of underlying sugar chains, and the nature of the entire glycoconjugate. Owing to the pathobiological significance of sialylated glycans, we have engineered Chinese hamster ovary (CHO) cells to secrete mucin-type immunoglobulin-fused proteins carrying terminal α2,3- or α2,6-linked sialic acid on defined O-glycan core saccharide chains. Besides stably expressing P-selectin glycoprotein ligand-1/mouse immunoglobulin G2b cDNA (PSGL-1/mIgG2b), CHO cells were stably transfected with plasmids encoding glycosyltransferases to synthesize core 2 (GCNT1), core 3 (B3GNT6), core 4 (GCNT1 and B3GNT6), or extended core 1 (B3GNT3) chains with or without the type 1 chain-encoding enzyme B3GALT5 and ST6GAL1. Western blot and liquid chromatography-mass spectrometry analysis confirmed the presence of core 1, 2, 3, 4, and extended core 1 chains carrying either type 1 (Galb3GlcNAc) or type 2 (Galb4GlcNAc) outer chains with or without α2,6-linked sialic acids. This panel of recombinant mucins carrying a repertoire of sialylated O-glycans will be important tools in studies aiming at determining the fine O-glycan binding specificity of sialic acid-specific microbial adhesins and mammalian lectins.
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20. |
- Cherian, Reeja Maria, et al.
(författare)
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Recombinant Mucin-Type Fusion Proteins with a Gal alpha 1,3Gal Substitution as Clostridium difficile Toxin A Inhibitors
- 2016
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Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 84:10, s. 2842-2852
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Tidskriftsartikel (refereegranskat)abstract
- The capability of a recombinant mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying Gal alpha 1,3Gal beta 1,4GlcNAc determinants to bind and inhibit Clostridium difficile toxin A (TcdA) was investigated. The fusion protein, produced by a glyco-engineered stable CHO-K1 cell line and designated C-PGC2, was purified by affinity and gel filtration chromatography from large-scale cultures. Liquid chromatography-mass spectrometry was used to characterize O-glycans released by reductive beta-elimination, and new diagnostic ions to distinguish Gal alpha 1,3Gal- from Gal alpha 1,4Gal-terminated O-glycans were identified. The C-PGC2 cell line, which was 20-fold more sensitive to TcdA than the wild-type CHO-K1, is proposed as a novel cell-based model for TcdA cytotoxicity and neutralization assays. The C-PGC2-produced fusion protein could competitively inhibit TcdA binding to rabbit erythrocytes, making it a high-efficiency inhibitor of the hemagglutination property of TcdA. The fusion protein also exhibited a moderate capability for neutralization of TcdA cytotoxicity in both C-PGC2 and CHO-K1 cells, the former with and the latter without cell surface Gal alpha 1,3Gal beta 1,4GlcNAc sequences. Future studies in animal models of C. difficile infection will reveal its TcdA-inhibitory effect and therapeutic potential in C. difficile-associated diseases.
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21. |
- Cherian, Reeja Maria, et al.
(författare)
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Recombinant Mucin-Type Fusion Proteins with a Galα1,3Gal Substitution as Clostridium difficile Toxin A Inhibitors.
- 2016
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Ingår i: Infection and immunity. - 1098-5522. ; 84:10, s. 2842-52
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Tidskriftsartikel (refereegranskat)abstract
- The capability of a recombinant mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying Galα1,3Galβ1,4GlcNAc determinants to bind and inhibit Clostridium difficile toxin A (TcdA) was investigated. The fusion protein, produced by a glyco-engineered stable CHO-K1 cell line and designated C-PGC2, was purified by affinity and gel filtration chromatography from large-scale cultures. Liquid chromatography-mass spectrometry was used to characterize O-glycans released by reductive β-elimination, and new diagnostic ions to distinguish Galα1,3Gal- from Galα1,4Gal-terminated O-glycans were identified. The C-PGC2 cell line, which was 20-fold more sensitive to TcdA than the wild-type CHO-K1, is proposed as a novel cell-based model for TcdA cytotoxicity and neutralization assays. The C-PGC2-produced fusion protein could competitively inhibit TcdA binding to rabbit erythrocytes, making it a high-efficiency inhibitor of the hemagglutination property of TcdA. The fusion protein also exhibited a moderate capability for neutralization of TcdA cytotoxicity in both C-PGC2 and CHO-K1 cells, the former with and the latter without cell surface Galα1,3Galβ1,4GlcNAc sequences. Future studies in animal models of C. difficile infection will reveal its TcdA-inhibitory effect and therapeutic potential in C. difficile-associated diseases.
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22. |
- Cherian, Reeja Maria, et al.
(författare)
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Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins
- 2014
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 24:1, s. 26-38
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Tidskriftsartikel (refereegranskat)abstract
- The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG(2b) (PSGL-1/mIgG(2b)), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG(2b) fusion protein, the pigeon alpha 1,4-galactosyltransferase (alpha 4Gal-T) and the core 2 beta 1,6-N-acetylglucosaminyltransferase (C2GnT-I). Western blot analyses of purified PSGL-1/mIgG(2b) and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. Western blot analysis indicated strong binding of Stx1, but not Stx2, to PSGL-1/mIgG(2b). In a Biacore assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of purified PSGL-1/mIgG(2b) and a P-k-albumin neoglycoprotein was analyzed. Stx1 and Stx2 bound with high avidity to both PSGL-1/mIgG(2b) and P-k-albumin, while the Stx1 binding was the strongest. In summary, we have shown that the pigeon alpha 4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. P1-decorated PSGL-1/mIgG(2b) bound with high avidity to both Stx1 and Stx2, and as such constitutes a potential therapeutic inhibitor of these toxins.
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23. |
- Derks, Jan, 1977, et al.
(författare)
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Reconstructive surgical therapy of peri-implantitis: A multicenter randomized controlled clinical trial
- 2022
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 33:9, s. 921-944
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the potential benefit of the use of a bone substitute material in the reconstructive surgical therapy of peri-implantitis. Methods In this multicenter randomized clinical trial, 138 patients (147 implants) with peri-implantitis were treated surgically, randomized by coin toss to either a control (access flap surgery) or a test group (reconstructive surgery using bone substitute material). Clinical assessments, including probing pocket depth (PPD), bleeding and suppuration on probing (BOP & SOP) as well as soft tissue recession (REC), were recorded at baseline, 6 and 12 months. Marginal bone levels (MBL), measured on intra-oral radiographs, and patient-reported outcomes (PROs) were recorded at baseline and 12 months. No blinding to group allocation was performed. The primary outcome at 12 months was a composite measure including (i) implant not lost, (ii) absence of BOP/SOP at all aspects, (iii) PPD <= 5 mm at all aspects and (iv) <= 1 mm recession of mucosal margin on the buccal aspect of the implant. Secondary outcomes included (i) changes of MBL, (ii) changes of PPD, BOP%, and buccal KM, (iii) buccal REC and (iv) patient-reported outcomes. Results During follow-up, four implants (one in the test group, three in the control group) in four patients were removed due to disease progression. At 12 months, a total of 69 implants in the test and 68 implants in the control group were examined. Thus, 16.4% and 13.5% of implants in the test and control group, respectively, met all predefined criteria of the composite outcome. PPD reduction and MBL gain were 3.7 mm and about 1.0 mm in both groups. Reduction in mean BOP% varied between 45% (test) and 50% (control), without significant differences between groups. Buccal REC was less pronounced in the test group (M = 0.7, SD = 0.9 mm) when compared to controls (M = 1.1, SD = 1.5 mm). PROs were favorable in both groups without significant differences. One case of allergic reaction to the antibiotic therapy was recorded. No other adverse events were noted. Conclusions Surgical therapy of peri-implantitis effectively improved the clinical and radiographic status at 12 months. While the use of a bone substitute material did not improve reductions of PPD and BOP, buccal REC was less pronounced in the test group. Patient satisfaction was high in both groups.
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24. |
- Eismark, Jan, 1962, et al.
(författare)
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Role of late soot oxidation for low emission combustion in a diffusion-controlled, High-EGR, heavy duty diesel engine
- 2009
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Ingår i: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191 .- 2688-3627.
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Tidskriftsartikel (refereegranskat)abstract
- Soot formation and oxidation are complex and competing processes during diesel combustion. The balance between the two processes and their history determines engine-out soot values. Besides the efforts to lower soot formation with measures to influence the flame lift-off distance for example or to use HCCI-combustion, enhancement of late soot oxidation is of equal importance for low-λ diffusion-controlled low emissions combustion with EGR. The purpose of this study is to investigate soot oxidation in a heavy duty diesel engine by statistical analysis of engine data and in-cylinder endoscopic high speed photography together with CFD simulations with a main focus on large scale in-cylinder gas motion. Results from CFD simulations using a detailed soot model were used to reveal details about the soot oxidation. A particular objective of the present study was to investigate the importance of enhancing soot oxidation after End of Injection (EOI) when temperature and NOx formation rapidly decreases. Geometrical measures to control flame propagation and different flame interactions were investigated. Such measures contribute to conserve available kinetic energy until late in the combustion period in an efficient way. Based on this combustion strategy it is possible to reach near zero engine-out soot emissions. Copyright © 2009 SAE International.
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25. |
- Gaunitz, Stefan, et al.
(författare)
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Avian influenza H5 hemagglutinin binds with high avidity to sialic acid on different O-linked core structures on mucin-type fusion proteins
- 2014
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Ingår i: Glycoconjugate Journal. - : Springer Science and Business Media LLC. - 0282-0080 .- 1573-4986. ; 31:2, s. 145-159
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between P-selectin glycoprotein ligand-1/mouse IgG(2b) (PSGL-1/mIgG(2b)) fusion protein carrying multiple copies of the influenza hemagglutinin receptor Sia alpha 2-3Gal on different O-glycan chains and recombinant human influenza H5N1 A/Vietnam/1203/04 hemagglutinin was investigated with a Biacore biosensor. The fusion protein was produced by stable cell lines in large scale cultures and purified with affinity- and gel filtration chromatography. The C-P55 and 293-P cell lines were established by transfecting the Chinese hamster ovary (CHO)-K1 and Human embryonic kidney (HEK)-293 cell lines with plasmids encoding the PSGL-1/mIgG(2b) fusion protein, while the C-PSLex cell line was engineered by transfecting CHO-K1 cells with the plasmids encoding the core 2 beta 1,6GnT-I and FUT-VII glycosyltransferases. Glycosylation was characterized by lectin Western blotting of the proteins and liquid chromatography - mass spectrometry of released non-derivatized O-glycans. Biacore experiments revealed that PSGL-1/mIgG(2b) is a good binding partner of H5. The binding curves displayed a slow dissociation indicating a multivalent binding. The H5 hemagglutinin binds with similar strength to PSGL-1/mIgG(2b) carrying mostly sialylated core 1 (clone C-P55), a mix of sialylated core 1 and sialylated lactosamine (clone 293-P) or mainly sialylated lactosamine (clone C-PSLex) O-glycans, indicating that this hemagglutinin is unable to discriminate between these structures. The potential use of the large, flexible PSGL-1/mIgG(2b) mucin-type fusion protein carrying Sia alpha 2-3Gal as a multivalent inhibitor of influenza virus is discussed.
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