Development and design of a narrow-gauge hydrogen-hybrid locomotive

Hydrogen used as an energy carrier is a promising alternative to diesel for autonomous railway motive power, but, globally, few prototypes exist. In 2012, the Institution of Mechanical Engineers held the inaugural Railway Challenge, in which the participating teams had to develop, design and construct a locomotive to run on 10.25 inch (260.35 mm) gauge track while meeting certain set design criteria as well as competing in operational challenges. The University of Birmingham Railway Challenge Team’s locomotive design is described in this paper. The vehicle is the UK’s first hydrogen-powered locomotive and is called Hydrogen Pioneer. The drive-system consists of a hydrogen tank, a 1.1 kW proton-exchange-membrane fuel cell stack, a 4.3 kWh battery pack and two 2.2 kW permanent-magnet traction motors. The development of the locomotive, from the original concept to the final design, and the design validation are all presented in this paper. The locomotive completed successfully all challenges through which the proof of the concept of a hydrogen-hybrid locomotive was established

The Arabidopsis Nα^\alpha -acetyltransferase NAA60 locates to the plasma membrane and is vital for the high salt stress response

International audienceIn humans and plants, N-terminal acetylation plays a central role in protein homeostasis, affects 80 % of proteins in the cytoplasm and is catalyzed by five ribosome-associated N-acetyltransferases (NatA-E). Humans also possess a Golgi-associated NatF (HsNAA60) that is essential for Golgi integrity. Remarkably, NAA60 is absent in fungi and was not identified in plants. Here we identify and characterize the first plasma membrane-anchored post-translationally acting N-acetyltransferase AtNAA60 in the reference plant Arabidopsis thaliana by the combined application of reverse genetics, global proteomics, live-cell imaging, microscale thermophoresis, CD-spectroscopy, nano differential scanning fluorometry, intrinsic tryptophan fluorescence and X-ray crystallography. We demonstrate that AtNAA60 like HsNAA60 is membrane-localized in vivo by an α-helical membrane anchor at its C-terminus, but in contrast to HsNAA60, AtNAA60 localizes to the plasma membrane. The AtNAA60 crystal structure provides insights into substrate-binding, the broad substrate specificity and the catalytic mechanism probed by structure-based mutagenesis. Characterization of the NAA60 loss-of-function mutants (naa60-1 and naa60-2) uncovers a plasma membrane-localized substrate of AtNAA60 and the importance of NAA60 during high salt stress. Our findings provide evidence for the plant-specific evolution of a plasma membrane-anchored N-acetyltransferase that is vital for adaptation to stress

Functional Dominance of CHIP-Mutated Hematopoietic Stem Cells in Patients Undergoing Autologous Transplantation

Clonal hematopoiesis of indeterminate potential (CHIP) is caused by recurrent somatic mutations leading to clonal blood cell expansion. However, direct evidence of the fitness of CHIP-mutated human hematopoietic stem cells (HSCs) in blood reconstitution is lacking. Because myeloablative treatment and transplantation enforce stress on HSCs, we followed 81 patients with solid tumors or lymphoid diseases undergoing autologous stem cell transplantation (ASCT) for the development of CHIP. We found a high incidence of CHIP (22%) after ASCT with a high mean variant allele frequency (VAF) of 10.7%. Most mutations were already present in the graft, albeit at lower VAFs, demonstrating a selective reconstitution advantage of mutated HSCs after ASCT. However, patients with CHIP mutations in DNA-damage response genes showed delayed neutrophil reconstitution. Thus, CHIP-mutated stem and progenitor cells largely gain on clone size upon ASCT-related blood reconstitution, leading to an increased future risk of CHIP-associated complications