953 research outputs found

    Measurement of the temperature of an ultracold ion source using time-dependent electric fields

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    We report on a measurement of the characteristic temperature of an ultracold rubidium ion source, in which a cloud of laser-cooled atoms is converted to ions by photo-ionization. Extracted ion pulses are focused on a detector with a pulsed-field technique. The resulting experimental spot sizes are compared to particle-tracking simulations, from which a source temperature T=(1±2)T = (1 \pm 2) mK and the corresponding transversal reduced emittance ϵr=7.9X109\epsilon_r = 7.9 X 10^{-9} m rad eV\sqrt{\rm{eV}} are determined. We find that this result is likely limited by space charge forces even though the average number of ions per bunch is 0.022.Comment: 8 pages, 11 figure

    Gab2 deficiency prevents Flt3-ITD driven acute myeloid leukemia in vivo

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    Internal tandem duplications (ITD) of the FMS-like tyrosine kinase 3 (FLT3) predict poor prognosis in acute myeloid leukemia (AML) and often co-exist with inactivating DNMT3A mutations. In vitro studies implicated Grb2-associated binder 2 (GAB2) as FLT3-ITD effector. Utilizing a Flt3-ITD knock-in, Dnmt3a haploinsufficient mouse model, we demonstrate that Gab2 is essential for the development of Flt3-ITD driven AML in vivo, as Gab2 deficient mice displayed prolonged survival, presented with attenuated liver and spleen pathology and reduced blast counts. Furthermore, leukemic bone marrow from Gab2 deficient mice exhibited reduced colony-forming unit capacity and increased FLT3 inhibitor sensitivity. Using transcriptomics, we identify the genes encoding for Axl and the Ret co-receptor Gfra2 as targets of the Flt3-ITD/Gab2/Stat5 axis. We propose a pathomechanism in which Gab2 increases signaling of these receptors by inducing their expression and by serving as downstream effector. Thereby, Gab2 promotes AML aggressiveness and drug resistance as it incorporates these receptor tyrosine kinases into the Flt3-ITD signaling network. Consequently, our data identify GAB2 as a promising biomarker and therapeutic target in human AML
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