1. |
- Fernandez, J. L. Abelleira, et al.
(författare)
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A Large Hadron Electron Collider at CERN
- 2012
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 39:7
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Tidskriftsartikel (refereegranskat)
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2. |
- Swat, M. J., et al.
(författare)
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Pharmacometrics Markup Language (PharmML) : Opening New Perspectives for Model Exchange in Drug Development
- 2015
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Ingår i: CPT. - : American Society for Clinical Pharmacology & Therapeutics. - 2163-8306. ; 4:6, s. 316-319
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Tidskriftsartikel (refereegranskat)abstract
- The lack of a common exchange format for mathematical models in pharmacometrics has been a long-standing problem. Such a format has the potential to increase productivity and analysis quality, simplify the handling of complex workflows, ensure reproducibility of research, and facilitate the reuse of existing model resources. Pharmacometrics Markup Language (PharmML), currently under development by the Drug Disease Model Resources (DDMoRe) consortium, is intended to become an exchange standard in pharmacometrics by providing means to encode models, trial designs, and modeling steps.
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3. |
- Imai, Y., et al.
(författare)
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Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury
- 2008
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 133:2, s. 235-249
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Tidskriftsartikel (refereegranskat)abstract
- Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.
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4. |
- Zamora-Ros, R., et al.
(författare)
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Impact of thearubigins on the estimation of total dietary flavonoids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2013
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 67:7, s. 779-782
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Tidskriftsartikel (refereegranskat)abstract
- Thearubigins (TR) are polymeric flavanol-derived compounds formed during the fermentation of tea leaves. Comprising similar to 70% of total polyphenols in black tea, TR may contribute majorly to its beneficial effects on health. To date, there is no appropriate food composition data on TR, although several studies have used data from the US Department of Agriculture (USDA) database to estimate TR intakes. We aimed to estimate dietary TR in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and assess the impact of including TR or not in the calculation of the total dietary flavonoid intake. Dietary data were collected using a single standardized 24-h dietary recall interviewer-administered to 36 037 subjects aged 35-74 years. TR intakes were calculated using the USDA database. TR intakes ranged from 0.9 mg/day in men from Navarra and San Sebastian in Spain to 532.5 mg/day in men from UK general population. TR contributed <5% to the total flavonoid intake in Greece, Spain and Italy, whereas in the UK general population, TR comprised 48% of the total flavonoids. High heterogeneity in TR intake across the EPIC countries was observed. This study shows that total flavonoid intake may be greatly influenced by TR, particularly in high black tea-consuming countries. Further research on identification and quantification of TR is needed to get more accurate dietary TR estimations.
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5. |
- Malbrunot, C., et al.
(författare)
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Spectroscopy apparatus for the measurement of the hyperfine structure of antihydrogen
- 2014
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Ingår i: Hyperfine Interactions. - : Springer Science and Business Media LLC. - 0304-3843 .- 1572-9540. ; 228:1-3, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- The ASACUSA CUSP collaboration at the Antiproton Decelerator (AD) of CERN is planning to measure the ground-state hyperfine splitting of antihydrogen (H̄) using an atomic spectroscopy beamline. We describe here the latest developments on the spectroscopy apparatus developed to be coupled to the H̄ production setup (CUSP).
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6. |
- Brouwer-Brolsma, Elske M., et al.
(författare)
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Combining traditional dietary assessment methods with novel metabolomics techniques: Present efforts by the Food Biomarker Alliance
- 2017
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Ingår i: Proceedings of the Nutrition Society. - 0029-6651 .- 1475-2719. ; 76:4, s. 619-627
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Tidskriftsartikel (refereegranskat)abstract
- FFQ, food diaries and 24 h recall methods represent the most commonly used dietary assessment tools in human studies on nutrition and health, but food intake biomarkers are assumed to provide a more objective reflection of intake. Unfortunately, very few of these biomarkers are sufficiently validated. This review provides an overview of food intake biomarker research and highlights present research efforts of the Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI-HDHL) Food Biomarkers Alliance (FoodBAll). In order to identify novel food intake biomarkers, the focus is on new food metabolomics techniques that allow the quantification of up to thousands of metabolites simultaneously, which may be applied in intervention and observational studies. As biomarkers are often influenced by various other factors than the food under investigation, FoodBAll developed a food intake biomarker quality and validity score aiming to assist the systematic evaluation of novel biomarkers. Moreover, to evaluate the applicability of nutritional biomarkers, studies are presently also focusing on associations between food intake biomarkers and diet-related disease risk. In order to be successful in these metabolomics studies, knowledge about available electronic metabolomics resources is necessary and further developments of these resources are essential. Ultimately, present efforts in this research area aim to advance quality control of traditional dietary assessment methods, advance compliance evaluation in nutritional intervention studies, and increase the significance of observational studies by investigating associations between nutrition and health.
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7. |
- Crombie, D. E., et al.
(författare)
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Destructive effects of murine arthritogenic antibodies to type II collagen on cartilage explants in vitro
- 2005
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Certain monoclonal antibodies (mAbs) to type II collagen (CII) induce arthritis in vivo after passive transfer and have adverse effects on chondrocyte cultures and inhibit self assembly of collagen fibrils in vitro. We have examined whether such mAbs have detrimental effects on pre-existing cartilage. Bovine cartilage explants were cultured over 21 days in the presence of two arthritogenic mAbs to CII (CIIC1 or M2139), a non-arthritogenic mAb to CII (CIIF4) or a control mAb (GAD6). Penetration of cartilage by mAb was determined by immunofluorescence on frozen sections and correlated with changes to the extracellular matrix and chondrocytes by morphometric analysis of sections stained with toluidine blue. The effects of mAbs on matrix components were examined by Fourier transform infrared microspectroscopy (FTIRM). A possible role of Fc-binding was investigated using F(ab)2 from CIIC1. All three mAbs to CII penetrated the cartilage explants and CIIC1 and M2139, but not CIIF4, had adverse effects that included proteoglycan loss correlating with mAb penetration, the later development in cultures of an abnormal superficial cellular layer, and an increased proportion of empty chondrons. FTIRM showed depletion and denaturation of CII at the explant surface in the presence of CIIC1 or M2139, which paralleled proteoglycan loss. The effects of F(ab)2 were greater than those of intact CIIC1. Our results indicate that mAbs to CII can adversely affect preformed cartilage, and that the specific epitope on CII recognised by the mAb determines both arthritogenicity in vivo and adverse effects in vitro. We conclude that antibodies to CII can have pathogenic effects that are independent of inflammatory mediators or Fc-binding.
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8. |
- Daskova, Nikola, et al.
(författare)
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Multi-omics signatures in new-onset diabetes predict metabolic response to dietary inulin: findings from an observational study followed by an interventional trial
- 2023
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Ingår i: Nutrition and Diabetes. - 2044-4052. ; 13:1, s. 7-
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics. METHOD: Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention. RESULTS: MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds. CONCLUSION: We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.
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9. |
- El-Sayed, A M, et al.
(författare)
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Sex pheromone of a North American population of the spotted tentiform leafminer, Phyllonorycter blancardella
- 2005
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Ingår i: Entomologia Experimentalis et Applicata. - : Wiley. - 0013-8703 .- 1570-7458. ; 116:2, s. 143-148
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Tidskriftsartikel (refereegranskat)abstract
- The major sex pheromone compound of the spotted tentiform leafminer, Phyllonorycter blancardella (F.) (Lepidoptera: Gracillariidae), from Ontario, Canada, was identified as (10E)-dodecen-1-yl acetate (E10-12:Ac) using chemical analysis and field trapping experiments. The minor compounds (10E)-dodecen-1-ol (E10-12:OH) (4.6%), dodecan-1-ol (12:OH) (2.3%), and (10Z)-dodecen-1-yl acetate (Z10-12:Ac) 1.6% were also identified. The dienic acetate (4E,10E)-dodecadien-1-yl acetate (E4,E10-12:Ac), a compound reported to be attractive to P. blancardella, was not found in the glands of this population. A two-component blend of the major and one of each the three minor compounds, in ratios similar to those found in the sex pheromone gland, did not increase the attractiveness of traps baited with synthetic pheromone. The minor compounds E10-12:OH and 12:OH were not attractive to P. blancardella when tested individually. Z10-12:Ac was attractive to P. blancardella, although traps baited with this compound captured only 2% of the moths that were captured in traps baited with the main compound. A four-component blend of the major and each of the three minor compounds (100 : 1 : 1 : 1) was not more attractive than the major compound alone. The related species Phyllonorycter mespilella was captured in traps baited with E10-12:Ac.
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10. |
- Forster, M., et al.
(författare)
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Genetic control of antibody production during collagen-induced arthritis development in heterogeneous stock mice
- 2012
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify genetic factors driving pathogenic autoantibody formation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA), in order to better understand the etiology of RA and identify possible new avenues for therapeutic intervention. METHODS: We performed a genome-wide analysis of quantitative trait loci controlling autoantibody to type II collagen (anti-CII), anti-citrullinated protein antibody (ACPA), and rheumatoid factor (RF). To identify loci controlling autoantibody production, we induced CIA in a heterogeneous stock-derived mouse cohort, with contribution of 8 inbred mouse strains backcrossed to C57BL/10.Q. Serum samples were collected from 1,640 mice before arthritis onset and at the peak of the disease. Antibody concentrations were measured by standard enzyme-linked immunosorbent assay, and linkage analysis was performed using a linear regression-based method. RESULTS: We identified loci controlling formation of anti-CII of different IgG isotypes (IgG1, IgG3), antibodies to major CII epitopes (C1, J1, U1), antibodies to a citrullinated CII peptide (citC1), and RF. The anti-CII, ACPA, and RF responses were all found to be controlled by distinct genes, one of the most important loci being the immunoglobulin heavy chain locus. CONCLUSION: This comprehensive genetic analysis of autoantibody formation in CIA demonstrates an association not only of anti-CII, but interestingly also of ACPA and RF, with arthritis development in mice. These results underscore the importance of non-major histocompatibility complex genes in controlling the formation of clinically relevant autoantibodies.
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