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- Kringos, Nicole, et al.
(författare)
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Determination of Moisture Susceptibility of Mastic-Stone Bond Strength and Comparison to Thermodynamical Properties
- 2008
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Ingår i: 2008 Journal of the Association of Asphalt Paving Technologists. ; , s. 435-478
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Konferensbidrag (refereegranskat)abstract
- The fundamental characterization and quantification of the moisture susceptibility of asphaltic mixes is a very important and timely topic for the asphaltic pavements industry, and has thus far posed a serious challenge for asphalt mix designers. In this research a fundamental computational-experimental test procedure is demonstrated to measure the moisture susceptibility of the mastic-aggregate bond strength and bond energy. The methodology combines displacement controlled direct tension tests with numerical moisture diffusion analyses and is demonstrated for six different mastic-stone combinations which are frequently used in the Dutch open friction courses. From the results it can be seen that the computed adhesive moisture susceptibilities are consistent with the expected field performance. The measured bond moisture susceptibilities are furthermore compared with the thermodynamical work of adhesion. It is shown that, qualitatively, the moisture resistance performance ranking is similar, but that the actual bond energies show three to four orders of magnitude difference. From this it can be concluded that, even though the surface energy approach can be very useful in enhancing material selection procedures, it is still important to actually measure the mechanical strength of the selected aggregate-mastic bond with a mechanical test.
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- Turcinov, S, et al.
(författare)
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ULTRASOUND GUIDED BIOPSIES OF RA JOINTS AT TIME OF CLINICAL DIAGNOSIS CONTAIN PROFOUND T CELL CLONALITIES
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1321-1321
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a disease characterized by synovial joint inflammation, mainly affecting small joints. Histological findings in synovial biopsies ranges from inflammatory infiltration including ectopic lymphoid structures, to a cell sparse fibroid phenotype. T cells in affected joints are non-naïve and have by flow cytometry approaches been shown to have a wide TCR-beta chain gene usage. New technologies allow for analyses of paired TCR sequences and their antigen-specificities.Objectives:To study the alpha/beta-T cell receptor repertoire in single sorted T cells from synovial biopsies at time of RA-diagnosis.Meth ods:Synovial biopsies were taken, primarily using an ultrasound guided technique, from seventeen patients (12 ACPA+, 5 ACPA-) with rheumatoid arthritis. Fresh biopsies were enzymatically digested, followed by mild mechanical treatment, prior to flow cytometry cell sorting. Single cell index sorting of T cells was made into 384-well plates with PCR-buffer followed by a nested PCR and deep sequencing of the TCR amplicons. TCR-receptor sequences showing clonal expansion from four ACPA+ HLA-DRB1*0401 patients were further cloned into SKW3 cells for studies of their reactivity byin vitrostimulation with peptides of viral and citrullinated origin from the literature. A positive response, as measured by CD69-up regulation or IL-2 production, was used to define specificity.Results:Fourteen of the assessed joints were small (1 MTP, 4 MCP and 8 wrists), whereas the remaining three were large joints (2 knees and 1 ankle), table 1. Individual T cells could be isolated from all of these biopsies, with a variating CD4:CD8 ratio. Based on the flow cytometry phenotyping we could identify CD4 T cells of both Treg and T peripheral helper phenotype already at this early time point. Productive alpha/beta-TCR sequences could be retrieved from 16 out of 17 patients and clonal expansion (>1 copy/TCR) was seen in all but one of these patients, with clone sizes ranging between 2 – 34 copies of each TCR.Table 1.Patient characteristics.PatientsGender(F/M)HLA-SE allelesJointsJoint swelling prior to biopsy (months)Stiffness specific joint (median VAS)Pain specific joint (median VAS)ACPA+ (n = 12)9/3*0401, *0404, *0408, *01 and *101 MTP, 4 MCP, 6 wrists, 1 knee4 (1-12)a46 (0-84)45 (22-99)ACPA- (n = 5)3/2*04011 MCP, 2 wrists, 1 ankle, 1 knee5 (0.25-7)59 (15-73)47 (33-81)SKW3 cell lines(patients n = 4)4/0*0401/0404 n=2*0401 n=21 MTP, 3 wrists2 (1-6)50.5 (42-84)50 (40-99)aData not available for one patient. One patient with prior RA-diagnosis, but after 9 months of treatment remission lasting for 20 years.Artificial T cell lines were generated from the expanded clones of HLA-DRB1*04:01 RA subjects. Ourin vitrostimulation protocol identified virus specific CD4 T cells in all samples. So far, no citrulline reactivity has been found. HCMV, followed by HHV were the most commonly found viral reactivities, whereas others were found only in one donor (e.g. JCV, EBV). The majority of clones are thus “orphans”, to which we are still seeking the driving antigen.Conclusion:Clonally expanded T cells are found in the synovium of early RA patients and include virus-specific CD4+ T cells. Our data show that the local T cell repertoire is broad already at the time of RA diagnosisDisclosure of Interests:Sara Turcinov: None declared, Erik af Klint Paid instructor for: Abbvie (courses and lectures), An De Bondt Employee of: Janssen., Muhammad Sohel Mia: None declared, Anca Catrina: None declared, Frederik Stevenaert Employee of: Janssen, Vivianne Malmström Grant/research support from: VM has had research grants from Janssen Pharmaceutica
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- Engdahl, Cecilia, 1983, et al.
(författare)
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Estrogen induces St6gal1 expression and increases IgG sialylation in mice and patients with rheumatoid arthritis: A potential explanation for the increased risk of rheumatoid arthritis in postmenopausal women
- 2018
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rheumatoid arthritis (RA) preferentially affects women, with the peak incidence coinciding with estrogen decrease in menopause. Estrogen (E2) may therefore have intrinsic immune-regulatory properties that vanish with menopause. Fc sialylation is a crucial factor determining the inflammatory effector function of antibodies. We therefore analyzed whether E2 affects immunoglobulin G (IgG) sialylation. Methods: Postmenopausal (ovariectomized) mice were immunized with ovalbumin and treated with E2 or vehicle. Total and ovalbumin-specific IgG concentrations, sialylation, and Fcγ receptor expression were analyzed. Postmenopausal women with RA receiving hormone replacement therapy, including E2, or no treatment were analyzed for IgG sialylation. Furthermore, effects of E2 on the expression of the sialylation enzyme β-galactoside α2,6-sialyltransferase 1 (St6Gal1) were studied in mouse and human antibody-producing cells. Results: E2 treatment significantly increased Fc sialylation of total and ovalbumin-specific IgG in postmenopausal mice. Furthermore, E2 led to increased expression of inhibitory Fcγ receptor IIb on bone marrow leukocytes. Treatment with E2 also increased St6Gal1 expression in mouse and human antibody-producing cells, providing a mechanistic explanation for the increase in IgG-Fc sialylation. In postmenopausal women with RA, treatment with E2 significantly increased the Fc sialylation of IgG. Conclusions: E2 induces anti-inflammatory effector functions in IgG by inducing St6Gal1 expression in antibody-producing cells and by increasing Fc sialylation. These observations provide a mechanistic explanation for the increased risk of RA in conditions with low estrogen levels such as menopause. © 2018 The Author(s).
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