The novel selective BCR-ABL Breakpoint cluster region – Abelson murine leukemia viral oncogene homolog 1 (BCR-AML) inhibitor nilotinib (AMN107) is a tyrosine kinase inhibitor that is more potent against leukaemia cells in vitro than imatinib. As nilotinib might be used in the context of allogeneic stem cell transplantation where CD8+ T lymphocytes play a pivotal role in the graft-versus-leukaemia (GVL) effect, we investigated effects of nilotinib on this lymphocyte subpopulation. Nilotinib inhibits phytohemagglutinin (PHA)-induced proliferation of CD8+T lymphocytes in vitro at therapeutically relevant concentrations (0.5–4 μM). The inhibition of CD8+ T lymphocytes specific for leukaemia or viral antigens through nilotinib was associated with a reduced expansion of antigen peptide specific CD8+ T lymphocytes and with a decreased release of interferon—γ and granzyme B by these cells as analysed by flow cytometry and enzyme-linked immunospot (ELISPOT) assays. The inhibitory effect caused by nilotinib was two times stronger than by imatinib. These effects were mediated through the inhibition of the phosphorylation of ZAP-70, Lck and ERK 1/2 and the NF-κβ signalling transduction pathway. Taken together, we observed a strong suppressive impact of nilotinib on the CD8+ T lymphocyte function which should be considered carefully in the framework of allogeneic stem cell transplantation or other T cell based immunotherapies.

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In order to quantitatively evaluate the damage level in high-performance concrete (HPC) with pozzolanic minerals under constant amplitude cyclic loads, three methods for real-time damage detection are employed in the present work, i.e., dynamic modulus instrument, realtime strain collector, and digital speckle correlative method (DSCM). Six mechanical parameters at different numbers of loading cycles are real-time captured by these three methods. For a maximum applied fatigue stress equal to 70% of the static flexural strength, a cohesive crack is detected on the specimen surface by the DSCM system from 10% of concrete fatigue life. The nucleation and propagation of the cohesive crack is reflected by the change of the strain concentration zone in 2-dimensional strain fields. The experimental results show that the admixtures of Class F Fly Ash (FA) and S95 Ground Granulated Blast-furnace Slag (GGBS) in high proportions increase the strain and cohesivecrack opening displacement as well as remarkably improve the fatigue performance of HPC.