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- Backis, A., et al.
(författare)
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Time- and energy-resolved effects in the boron-10 based multi-grid and helium-3 based thermal neutron detectors
- 2021
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Ingår i: Measurement science and technology. - : IOP PUBLISHING LTD. - 0957-0233 .- 1361-6501. ; 32:3
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Tidskriftsartikel (refereegranskat)abstract
- The boron-10 based multi-grid detector is being developed as an alternative to helium-3 based neutron detectors. At the European Spallation Source, the detector will be used for time-of-flight neutron spectroscopy at cold to thermal neutron energies. The objective of this work is to investigate fine time- and energy-resolved effects of the Multi-Grid detector, down to a few mu eV, while comparing it to the performance of a typical helium-3 tube. Furthermore, it is to characterize differences between the detector technologies in terms of internal scattering, as well as the time reconstruction of similar to mu s short neutron pulses. The data were taken at the Helmholtz Zentrum Berlin, where the Multi-Grid detector and a helium-3 tube were installed at the ESS test beamline, V20. Using a Fermi-chopper, the neutron beam of the reactor was chopped into a few tens of mu s wide pulses before reaching the detector, located a few tens of cm downstream. The data of the measurements show an agreement between the derived and calculated neutron detection efficiency curve. The data also provide fine details on the effect of internal scattering, and how it can be reduced. For the first time, the chopper resolution was comparable to the timing resolution of the Multi-Grid detector. This allowed a detailed study of time- and energy resolved effects, as well as a comparison with a typical helium-3 tube.
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- Flesch, BK, et al.
(författare)
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Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms
- 2020
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Ingår i: Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. - : S. Karger AG. - 1660-3796. ; 47:5, s. 385-395
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> The human neutrophil antigen 2 (HNA-2), which is expressed on CD177, is undetectable in 3–5% of the normal population. Exposure of these HNA-2<sub>null</sub> individuals to HNA-2-positive cells can cause immunization and production of HNA-2 antibodies, which can induce immune neutropenia and transfusion-related acute lung injury. In HNA-2-positive individuals, neutrophils are divided into a CD177<sup>pos.</sup> and a CD177<sup>neg.</sup> subpopulation. The molecular background of HNA-2 deficiency and the bimodal expression pattern, however, are not completely decoded. <b><i>Study Design:</i></b> An international collaboration was conducted on the genetic analysis of HNA-2-phenotyped blood samples, including HNA-2-deficient individuals, mothers, and the respective children with neonatal immune neutropenia and regular blood donors. <b><i>Results:</i></b> From a total of 54 HNA-2<sub>null</sub> individuals, 43 were homozygous for the <i>CD177</i>*<i>787A>T</i> substitution. Six carried the <i>CD177</i>*<i>c.1291G>A</i> single nucleotide polymorphism. All HNA-2-positive samples with >40% CD177<sup>pos.</sup> neutrophils carried the *<i>787A</i> wild-type allele, whereas a lower rate of CD177<sup>pos.</sup> neutrophils was preferentially associated with *<i>c.787AT</i> heterozygosity. Interestingly, only the *<i>c.787A</i> allele sequence was detected in complementary DNA (cDNA) sequence analysis carried out on all *<i>c.787AT</i> heterozygous individuals. However, cDNA analysis after sorting of CD177<sup>pos.</sup> and CD177<sup>neg.</sup> neutrophil subsets from HNA-2-positive individuals showed identical sequences, which makes regulatory elements within the promoter unlikely to affect <i>CD177</i> gene transcription in different CD177 neutrophil subsets. <b><i>Conclusion:</i></b> This comprehensive study clearly demonstrates the impact of single nucleotide polymorphisms on the expression of HNA-2 on the neutrophil surface but challenges the hypothesis of regulatory epigenetic effects being implicated in the bimodal CD177 expression pattern.
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- Mustjoki, S., et al.
(författare)
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Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy
- 2009
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:8, s. 1398-1405
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Tidskriftsartikel (refereegranskat)abstract
- Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile. Leukemia (2009) 23, 1398-1405; doi:10.1038/leu.2009.46; published online 19 March 2009
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