Human Anti-Human MPL monoclonal Antibody, clone SFB360 [PE]

MPLW515K or W515L mutation plays an important role in the pathogenesis of myeloproliferative neoplasms (MPNs) through signaling molecules of the cytokine receptor axis. Besides MPLW515K or W515L, more than 30 atypical MPL mutations have been reported in patients who are negative for JAK2V617F, MPLW515K/L, and CALR mutations. Here, we aimed to identify the disease-causing mutations in the triple-negative case of ET. We described two MPL mutations in patients diagnosed with ET by target sequencing the hotspot mutation region of MPL gene. The MPLA497-L498ins4 is an insertion mutation detected recurrently in ET patients, and the MPLW515RQ516E is a novel double-point mutation found in an ET patient. Functional studies of MPLA497-L498ins4 and MPLW515RQ516E revealed that they are gain-of-function mutations. Mutants of MPLA497-L498ins4 and MPLW515RQ516E promoted autonomous proliferation on Ba/F3 cells in the absence of IL-3. Autonomous activation of TPO-R without ligand TPO was observed in MPLA497-L498ins4 and MPLW515RQ516E mutants. Lower percentage of cells in G1 phase and higher percentage of cells in S phase of two atypical MPL mutants were detected after culturing without any cytokines. These two atypical MPL mutations also presented increase in phosphorylation of signaling proteins including JAK2/STAT, PI3K/AKT, and MAPK/RAS. In summary, the MPLA497-L498ins4 and MPLW515RQ516E are gain-of-function mutations which may be novel driving factors participating in the pathogenesis of triple-negative MPN.

An accelerated supply and demand of energy has resulted in an increased need for efficient energy storage options, where storing energy in hydrogen gas emerges as one of the most attractive. In this study, a singular proton exchange membrane (PEM) electrolysis cell was designed using adequately low-cost materials, and tested using polarisation curves, cyclic voltammetry and AC impedance. A comparative study of various micro porous layer (MPL) materials was performed in an effort to find suitable options which are able to steadily operate under anodic conditions. The best performance was achieved using carbon cloth, however this material was unstable. Untreated porous titanium and nickel displayed increased stability, though these materials require further development to match the initial performance of carbon cloth as an MPL material. (C) 2019 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved.