ABSTRACT
The dynamic behaviour of atomic-size disarrangements of atoms-point defects (self-interstitial atoms (SIAs) and vacancies)-often governs the macroscopic properties of crystalline materials. However, the dynamics of SIAs have not been fully uncovered because of their rapid migration. Using a combination of high-voltage transmission electron microscopy and exhaustive kinetic Monte Carlo simulations, we determine the dynamics of the rapidly migrating SIAs from the formation process of the nanoscale SIA clusters in tungsten as a typical body-centred cubic (BCC) structure metal under the constant-rate production of both types of point defects with high-energy electron irradiation, which must reflect the dynamics of individual SIAs. We reveal that the migration dimension of SIAs is not three-dimensional (3D) but one-dimensional (1D). This result overturns the long-standing and well-accepted view of SIAs in BCC metals and supports recent results obtained by ab-initio simulations. The SIA dynamics clarified here will be one of the key factors to accurately predict the lifetimes of nuclear fission and fusion materials.
ABSTRACT
The autosomal dominant cerebellar ataxias (ADCAs) comprise a genetically and clinically heterogenous group of neurodegenerative disorders. Very recently, a C-to-T single nucleotide substitution in the puratrophin-1 gene was found to be strongly associated with a form of ADCA linked to chromosome 16q22.1 (16q-linked ADCA; OMIM 600223). We found the C-to-T substitution in the puratrophin-1 gene in 20 patients with ataxia (16 heterozygotes and four homozygotes) and four asymptomatic carriers in 9 of 24 families with an unknown type of ADCA. We also found two cases with 16q-linked ADCA among 43 sporadic patients with late-onset cortical cerebellar atrophy (LCCA). The mean age at onset in the 22 patients was 61.8 years, and that of homozygous patients was lower than that of heterozygous ones in one family. Neurological examination revealed that the majority of our patients showed exaggerated deep tendon reflexes in addition to the cardinal symptom of cerebellar ataxia (100%), and 37.5% of them had sensorineural hearing impairment, whereas sensory axonal neuropathy was absent. The frequency of 16q-linked ADCA was about 1/10 of our series of 110 ADCA families, making it the third most frequent ADCA in Japan.
Subject(s)
Cerebellar Ataxia/genetics , Chromosomes, Human, Pair 16 , Genes, Dominant , Guanine Nucleotide Exchange Factors/genetics , Spectrin/genetics , Age of Onset , Aged , Aged, 80 and over , Cerebellar Ataxia/pathology , DNA Mutational Analysis/methods , Family Health , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction/methodsSubject(s)
Brain Ischemia/complications , Functional Laterality/physiology , Parkinson Disease, Secondary/etiology , Substantia Nigra/pathology , Aged , Female , Humans , Magnetic Resonance Imaging/methods , Substantia Nigra/diagnostic imaging , Tomography, Emission-Computed , Tomography, X-Ray Computed/methodsABSTRACT
A novel series of pivaloyloxy benzene derivatives has been identified as potent and selective human neutrophil elastase (HNE) inhibitors. Convergent syntheses were developed in order to identify the inhibitors which are intravenously effective in an animal model. A compound of particular interest is the sulfonanilide-containing analogues. Structure-activity relationships are discussed. Structural requirements for metabolic stabilization are also discussed.
