Gamma Prime Precipitate Evolution During Aging of a Model Nickel-Based Superalloy

The microstructural stability of nickel-based superalloys is critical for maintaining alloy performance during service in gas turbine engines. In this study, the precipitate evolution in a model polycrystalline Ni-based superalloy during aging to 1000 hours has been studied via transmission electron microscopy, atom probe tomography and neutron diffraction. Variations in phase composition and precipitate morphology, size and volume fraction were observed during aging, whilst the constrained lattice misfit remained constant at approximately zero. The experimental composition of the γ matrix phase was consistent with thermodynamic equilibrium predictions, whilst significant differences were identified between the experimental and predicted results from the γʹ phase. These results have implications for the evolution of mechanical properties in service and their prediction using modeling methods.The authors wish to acknowledge Mrs. S. Rhodes, Dr. H.T. Pang, Dr. D.M. Collins, and Dr. O.M.D.M. Messé for their assistance with the experiments performed. Funding was provided by the EPSRC/Rolls-Royce Strategic Partnership under EP/M005607/1 and EP/H022309/1. The Oxford Atom Probe facility was funded by the EPSRC under EP/M022803/1. Neutron diffraction beam time was supported through the Canadian Neutron Beam Centre under Experiment number 1258

A reverse genetics and genomics approach to gene paralog function and disease: Myokymia and the juxtaparanode.

The leucine-rich glioma-inactivated (LGI) family consists of four highly conserved paralogous genes, LGI1-4, that are highly expressed in mammalian central and/or peripheral nervous systems. LGI1 antibodies are detected in subjects with autoimmune limbic encephalitis and peripheral nerve hyperexcitability syndromes (PNHSs) such as Isaacs and Morvan syndromes. Pathogenic variations of LGI1 and LGI4 are associated with neurological disorders as disease traits including familial temporal lobe epilepsy and neurogenic arthrogryposis multiplex congenita 1 with myelin defects, respectively. No human disease has been reported associated with either LGI2 or LGI3. We implemented exome sequencing and family-based genomics to identify individuals with deleterious variants in LGI3 and utilized GeneMatcher to connect practitioners and researchers worldwide to investigate the clinical and electrophysiological phenotype in affected subjects. We also generated Lgi3-null mice and performed peripheral nerve dissection and immunohistochemistry to examine the juxtaparanode LGI3 microarchitecture. As a result, we identified 16 individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. Deep phenotypic characterization showed LGI3 LoF causes a potentially clinically recognizable PNHS trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons. Our data demonstrate bi-allelic LoF variants in LGI3 cause a clinically distinguishable disease trait of PNHS, most likely caused by disturbed Kv1 channel distribution in the absence of LGI3