Inverse Hall Petch Like Mechanical Behaviour in Nanophase Al-Cu-Fe Quasicrystals: A New Phenomenon

The structural and mechanical stability of quasicrystals are important issues due to their potential for possible applications at high temperatures and stresses. The aim of the present work is, therefore, to review the earlier works on conventional crystalline and quasicrystalline materials and also to report the results and the analysis on the Hall Petch and inverse Hall Petch like behavior of nanoquasicrystalline Al62.5Cu25Fe12.5 alloys. It was observed that, at large grain sizes, the hardness increases with decreasing grain size, exhibiting the conventional Hall Petch relationship, whereas for smaller grains, inverse Hall Petch behavior was identified. The inverse Hall Fetch behavior in the nanoquasicrystalline phase could be attributed to thermally activated shearing of the grain boundaries, leading to grain boundary sliding in nanostructures of quasicrystalline grains. These results were analyzed based on the dislocation pile-up model as well as the grain boundary shearing models applicable to nanomaterials

Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy

Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown. Objective: To test the association between pathogenic somatic variants in the hippocampus and MTLE. Design, Setting, and Participants: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from 1988 through 2019, and clinical data were collected retrospectively. Whole-exome and gene-panel sequencing (each genomic region sequenced more than 500 times on average) were used to identify candidate pathogenic somatic variants. A subset of novel variants was functionally evaluated using cellular and molecular assays. Patients with nonlesional and lesional (mesial temporal sclerosis, focal cortical dysplasia, and low-grade epilepsy-associated tumors) drug-resistant MTLE who underwent anterior medial temporal lobectomy were eligible. All patients with available frozen tissue and appropriate consents were included. Control brain tissue was obtained from neurotypical donors at brain banks. Data were analyzed from June 2020 to August 2022. Exposures: Drug-resistant MTLE. Main Outcomes and Measures: Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex. Results: Of 105 included patients with MTLE, 53 (50.5%) were female, and the median (IQR) age was 32 (26-44) years; of 30 neurotypical controls, 11 (36.7%) were female, and the median (IQR) age was 37 (18-53) years. Eleven pathogenic somatic variants enriched in the hippocampus relative to the unaffected temporal neocortex (median [IQR] variant allele frequency, 1.92 [1.5-2.7] vs 0.3 [0-0.9]; P =.01) were detected in patients with MTLE but not in controls. Ten of these variants were in PTPN11, SOS1, KRAS, BRAF, and NF1, all predicted to constitutively activate Ras/Raf/mitogen-activated protein kinase (MAPK) signaling. Immunohistochemical studies of variant-positive hippocampal tissue demonstrated increased Erk1/2 phosphorylation, indicative of Ras/Raf/MAPK activation, predominantly in glial cells. Molecular assays showed abnormal liquid-liquid phase separation for the PTPN11 variants as a possible dominant gain-of-function mechanism. Conclusions and Relevance: Hippocampal somatic variants, particularly those activating Ras/Raf/MAPK signaling, may contribute to the pathogenesis of sporadic, drug-resistant MTLE. These findings may provide a novel genetic mechanism and highlight new therapeutic targets for this common indication for epilepsy surgery

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Grain size softening effect in Al62.5Cu25Fe12.5 nanoquasicrystals

Inverse Hall-Petch (IHP) behavior in nano-quasicrystalline Al 62.5 Cu 25 Fe 12.5 is reported. Powders with varying grain sizes were produced by mechanical milling of spray-formed quasicrystals. The hardness of the milled powders increased with decreasing grain size down to about 40 nm and decreased with further refinement, demonstrating the IHP behavior. This critical grain size was found to be larger compared to other metallic nanocrystalline alloys. This IHP behaviour has been attributed to the structural complexity in quasicrystals and to thermally activated shearing events of atoms at the grain boundaries

Grain size softening effect in Al62.5Cu25Fe12.5 nanoquasicrystals

Inverse Hall-Petch (IHP) behavior in nano-quasicrystalline Al62.5Cu25Fe12.5 is reported. Powders with varying grain sizes were produced by mechanical milling of spray-formed quasicrystals. The hardness of the milled powders increased with decreasing grain size down to about 40 nm and decreased with further refinement, demonstrating the IHP behavior. This critical grain size was found to be larger compared to other metallic nanocrystalline alloys. This IHP behaviour has been attributed to the structural complexity in quasicrystals and to thermally activated shearing events of atoms at the grain boundaries

Inverse Hall Petch Like Mechanical Behaviour in Nanophase Al-Cu-Fe Quasicrystals: A New Phenomenon

The structural and mechanical stability of quasicrystals are important issues due to their potential for possible applications at high temperatures and stresses. The aim of the present work is, therefore, to review the earlier works on conventional crystalline and quasicrystalline materials and also to report the results and the analysis on the Hall Petch and inverse Hall Petch like behavior of nanoquasicrystalline Al62.5Cu25Fe12.5 alloys. It was observed that, at large grain sizes, the hardness increases with decreasing grain size, exhibiting the conventional Hall Petch relationship, whereas for smaller grains, inverse Hall Petch behavior was identified. The inverse Hall Fetch behavior in the nanoquasicrystalline phase could be attributed to thermally activated shearing of the grain boundaries, leading to grain boundary sliding in nanostructures of quasicrystalline grains. These results were analyzed based on the dislocation pile-up model as well as the grain boundary shearing models applicable to nanomaterials

Modeling the strengthening effect of Al–Cu–Fe quasicrystalline particles in Al-based metal matrix composites

In this work, a model that simultaneously considers the combined strengthening contributions of load bearing, dislocation strengthening and matrix ligament size effects, which has been found to accurately describe the mechanical behavior of Al-based composites reinforced with complex intermetallic particles (Scudino et al. (2009) [8]), has been used to predict the mechanical properties of Al-based metal matrix composites containing different amounts of Al62.5Cu25Fe12.5 quasicrystalline reinforcing particles. The present results further demonstrate the validity of this model and confirm the importance of the characteristic matrix ligament size for explaining the strengthening effect of the composites containing large volume fractions of reinforcement