48 research outputs found
Silver Matrix Composite Reinforced by Aluminium-Silver Intermetallic Phases
Silver and aluminum powders (82 mass % Ag and 18 mass % Al) were mixed and hot extruded at 673 K with extrusion ratio λ = 25. Performed X-ray diffraction analysis of as extruded rod revealed the development of Ag3Al and Ag2Al-type intermetallic phases. Structural observations and both chemical and diffraction analysis of structural components confirmed the growth of mentioned phases in the vicinity of elementary Al and Ag granules. No pores or voids were observed in the material. Mechanical properties of the composite, UTS = 490MPa, YS = 440 MPa, HV2 = 136, were relatively high if compared to commercial Ag and Cu products. Hot compression tests pointed to the good hot workability of the composite at deformation temperature range 473 K - 773 K.
The differential scanning calorimetry tests were performed in order to estimate structural processes during heating of Ag/Al composite that lead to thermodynamically stable liquid state. It was found that characteristic temperature of three endothermic peaks correspond to (1) peritectoid transformation μ-Ag3Al → ζ-Ag2Al + (Ag), (2) the eutectic melting ζ-Ag2Al + (Al) → L, (3) melting of the ζ-Ag2Al phase.
The Vickers hardness of the samples annealed at 673 K, for the time range up to 6900 minutes, was also determined. It was concluded that mutual diffusion of elements between Ag and Al granules and the growth of μ-Ag3Al and ζ-Ag2Al grains during annealing at 673 K result in a slight hardening of the composite
Silver Matrix Composite Reinforced by Aluminium-Silver Intermetallic Phases
Silver and aluminum powders (82 mass % Ag and 18 mass % Al) were mixed and hot extruded at 673 K with extrusion ratio λ = 25. Performed X-ray diffraction analysis of as extruded rod revealed the development of Ag3Al and Ag2Al-type intermetallic phases. Structural observations and both chemical and diffraction analysis of structural components confirmed the growth of mentioned phases in the vicinity of elementary Al and Ag granules. No pores or voids were observed in the material. Mechanical properties of the composite, UTS = 490MPa, YS = 440 MPa, HV2 = 136, were relatively high if compared to commercial Ag and Cu products. Hot compression tests pointed to the good hot workability of the composite at deformation temperature range 473 K - 773 K
Bifidobacterium breve Exopolysaccharide Blocks Dendritic Cell Maturation and Activation of CD4+ T Cells
Exopolysaccharide (EPS) is a bacterial extracellular carbohydrate moiety which has been associated with immunomodulatory activity and host protective effects of several gut commensal bacteria. Bifidobacterium breve are early colonizers of the human gastrointestinal tract (GIT) but the role of EPS in mediating their effects on the host has not been investigated for many strains. Here, we characterized EPS production by a panel of human B. breve isolates and investigated the effect of EPS status on host immune responses using human and murine cell culture-based assay systems. We report that B. breve EPS production is heterogenous across strains and that immune responses in human THP-1 monocytes are strain-specific, but not EPS status-specific. Using wild type and isogenic EPS deficient mutants of B. breve strains UCC2003 and JCM7017 we show that EPS had strain-specific divergent effects on cytokine responses from murine bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs). The B. breve UCC2003 EPS negative (EPS–) strain increased expression of cytokine genes (Tnfa, Il6, Il12a, and Il23a) relative to untreated BMDCs and BMDCs treated with wild type strain. B. breve UCC2003 and JCM7017 EPS– strains increased expression of dendritic cell (DC) activation and maturation marker genes (Cd80, Cd83, and Cd86) relative to untreated BMDCs. Consistent with this, BMDCs co-cultured with B. breve UCC2003 and JCM7017 EPS– strains engineered to express OVA antigen activated OVA-specific OT-II CD4+ T-cells in a co-culture antigen-presentation assay while EPS proficient strains did not. Collectively, these data indicate that B. breve EPS proficient strains use EPS to prevent maturation of DCs and activation of antigen specific CD4+ T cells responses to B. breve. This study identifies a new immunomodulatory role for B. breve EPS and suggests it may be important for immune evasion of adaptive immunity by B. breve and contribute to host-microbe mutualism
Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial
Background: Sjögren's syndrome is an autoimmune disease characterised by dry eyes and mouth, systemic features, and reduced quality of life. There are no disease-modifying treatments. A new biologic, ianalumab (VAY736), with two modes of suppressing B cells, has previously shown preliminary efficacy. This dose-finding trial aimed to assess the safety and efficacy of different subcutaneous doses of ianalumab in patients with moderate to severe primary Sjögren's syndrome. Methods: VAY736A2201 was a randomised, parallel, double-blind, placebo-controlled, phase 2b dose-finding study done in 56 centres in 19 countries. Patients aged 18–75 years with primary Sjögren's syndrome with moderate to severe disease activity (European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI] score ≥6) and symptom severity (EULAR Sjögren's Syndrome Patient Reported Index score ≥5) were eligible. Participants were randomly assigned (1:1:1:1) to receive subcutaneous placebo or ianalumab (5 mg, 50 mg, or 300 mg) every 4 weeks for 24 weeks using a secure, online randomisation system. Randomisation was stratified by the ESSDAI score at baseline (≥10 or <10). Study personnel and patients were masked to treatment assignment. The primary outcome was the change in ESSDAI score from baseline to 24 weeks in all randomly assigned patients. Dose-related change in disease activity (ESSDAI) from baseline at week 24 was assessed by multiple comparison procedure with modelling analysis. Safety was measured in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02962895. Findings: Between June 27, 2017, and Dec 06, 2018, 293 patients were screened, 190 of whom were randomly assigned (placebo n=49, ianalumab 5 mg n=47, ianalumab 50 mg n=47, ianalumab 300 mg n=47). Statistically significant dose-responses were seen for overall disease activity (ESSDAI score) in four of the five dose-response models tested (p<0·025 in four models, p=0·060 in one model). The ESSDAI score decreased from baseline in all ianalumab groups, with the maximal ESSDAI score change from baseline observed in the ianalumab 300 mg group: placebo-adjusted least-squares mean change from baseline −1·92 points (95% CI −4·15 to 0·32; p=0·092). There were four serious adverse events in three patients considered treatment-related (pneumonia [n=1] and gastroenteritis [n=1] in the placebo group; appendicitis plus tubo-ovarian abscess in the same patient in the ianalumab 50 mg group). Interpretation: The study met its primary objective, showing a dose-related decrease in disease activity as measured by ESSDAI at week 24. Overall, ianalumab was well tolerated and safe, with no increase in infections. To our knowledge, this is the first large, randomised, controlled trial in primary Sjögren's syndrome that met its primary endpoint, and its results mean there is potential for more studies of this mechanism in the future. Funding: Novartis