Study of the 27 Al(d, α) 25 Mg and 27 Al(d, p) 28 al nuclear reactions at 2 MeV deuteron energy

Differential excitation functions and angular distributions from 30° to 150° have been measured for the27Al(d, α)26Mg and27Al(d, p)28Al reactions leading to the ground state and to the first excited states of the residual nuclei25Mg and28Al, in the deuteron energy range (1.4≪2.3) MeV. The overall energy resolution was 10 keV for the differential excitation functions and 2 0 keV for the angular distributions. Fluctuations occurring in the differential excitation functions as well as in the integrated cross-sections have been analysed on the basis of the statistical theory. In particular, with the use of correlation functions, values of Γ=(40±10)keV and θ0≃30° have been deduced for the « coherence » energy and the « coherence » angle, respectively. The theoretical values of Γ and the average values of the integrated cross-sections have been evaluated using a consistent set of parameters. The analysis showed that the predictions of the statistical model agree with the experimental results for the27Al(d, α)25Mg reactions. Both statistical and nonstatistioal effects have been found to contribute to the27Al(d, p)28Al reaction for the proton transitions leading to the low-lying levels of the residual nucleus

The Impact of T Cell Intrinsic Antigen Adaptation on Peripheral Immune Tolerance

Overlapping roles have been ascribed for T cell anergy, clonal deletion, and regulation in the maintenance of peripheral immunological tolerance. A measurement of the individual and additive impacts of each of these processes on systemic tolerance is often lacking. In this report we have used adoptive transfer strategies to tease out the unique contribution of T cell intrinsic receptor calibration (adaptation) in the maintenance of tolerance to a systemic self-antigen. Adoptively transferred naïve T cells stably calibrated their responsiveness to a persistent self-antigen in both lymphopenic and T cell–replete hosts. In the former, this state was not accompanied by deletion or suppression, allowing us to examine the unique contribution of adaptation to systemic tolerance. Surprisingly, adapting T cells could chronically help antigen-expressing B cells, leading to polyclonal hypergammaglobulinemia and pathology, in the form of mild arthritis. The helper activity mediated by CD40L and cytokines was evident even if the B cells were introduced after extended adaptation of the T cells. In contrast, in the T cell–replete host, neither arthritis nor autoantibodies were induced. The containment of systemic pathology required host T cell–mediated extrinsic regulatory mechanisms to synergize with the cell intrinsic adaptation process. These extrinsic mechanisms prevented the effector differentiation of the autoreactive T cells and reduced their precursor frequency, in vivo

MOESM3 of Efficacy and safety of setipiprant in seasonal allergic rhinitis: results from Phase 2 and Phase 3 randomized, double-blind, placebo- and active-referenced studies

Additional file 3: Table S1. Setipiprant trough plasma concentrations across dose groups at the end* of weeks 1 and 2 during Phase 2 and Phase 3 trials

Longitudinal assessment of synovial, lymph node, and bone volumes in inflammatory arthritis in mice by in vivo magnetic resonance imaging and microfocal computed tomography

OBJECTIVE: Development of longitudinal 3D outcomes of inflammation and bone erosion in murine arthritis using contrast enhanced (CE) MRI and in vivo micro-CT; and in a pilot study, to determine the value of entrance criteria by age versus synovial volume in therapeutic intervention studies. METHODS: CE-MRI and in vivo micro-CT was performed on TNF-Tg and WT littermates to quantify the synovial and popliteal lymph node (LN) volumes and patella and talus bone volumes, respectively, which were validated with histology. These longitudinal outcome measures were used to assess the natural history of inflammatory-erosive arthritis. We also performed anti-TNF versus placebo efficacy studies in TNF-Tg mice in which treatment was initiated either by age (4–5 months) or synovial volume (3mm(3) as detected by CE-MRI). Linear regression was performed to analyze the correlation between synovitis and focal erosion. RESULTS: CE-MRI demonstrated the highly variable nature of TNF-induced joint inflammation. Initiation of treatment by synovial volume produced significantly larger treatment effects on synovial volume (p=0.04) and lymph node volume (p<0.01) than initiation by age. By correlating the MRI and microCT data we were able to demonstrate a significant relationship between changes in synovial and patellar volumes (R(2) =0.75; p<0.01). CONCLUSION: In vivo CE-MRI and micro-CT 3D outcome measures are powerful tools that accurately demonstrate the progression of inflammatory-erosive arthritis in mice. These methods can be used to identify mice with arthritis of similar severity before intervention studies are initiated and thus minimize heterogeneity in outcome studies of chronic arthritis seen between genetically identical littermates