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The fatigue crack growth (FCG) behavior of PWA1484 single crystals was characterized in air under mixed-mode loading at 593 degree Celsius as a function of crystallographic orientation using an asymmetric four-point bend test technique. Most mixed-mode fatigue cracks deflected from the symmetry plane and propagated as transprecipitate, noncrystallographic cracks.

Discusses the abstract of the study 'Genetic Counseling of Dilated Cardiomyopathy Due to Lamin A/C Gene Mutations,' presented at the 21st Annual Education Conference of the National Society of Genetic Counselors held in Phoenix, Arizona in November 2002.

Thymopoietin or TMPO (indicated by its alternative gene symbol, LAP2, in this work) has been proposed as a candidate disease gene for dilated cardiomyopathy (DCM), since a LAP2 product associates with nucleoplasmic lamins A/C, which are encoded by the DCM gene LMNA. We developed a study to screen for genetic mutations in LAP2 in a large collection of DCM patients and families. A total of 113 subjects from 88 families (56 with familial DCM (FDC) and 32 with sporadic DCM) were screened for LAP2 mutations using denaturing high-performance liquid chromatography and sequence analysis. We found a single putative mutation affecting the LAP2alpha isoform in one FDC pedigree. The mutation predicts an Arg690Cys substitution (c.2068C>T; p.R690C) located in the C-terminal domain of the LAP2alpha protein, a region that is known to interact with lamin A/C. RT-PCR, Western blot analyses, and immunolocalization revealed low-level LAP2alpha expression in adult cardiac muscle, and localization to a subset of nuclei. Mutated Arg690Cys LAP2alpha expressed in HeLa cells localized to the nucleoplasm like wild-type LAP2alpha, with no effect on peripheral and nucleoplasmic lamin A distribution. However, the in vitro interaction of mutated LAP2alpha with the pre-lamin A C-terminus was significantly compromised compared to the wild-type protein. LAP2 mutations may represent a rare cause of DCM. The Arg690Cys mutation altered the observed LAP2alpha interaction with A-type lamins. Our finding implicates a novel nuclear lamina-associated protein in the pathogenesis of genetic forms of dilated cardiomyopathy., (Copyright 2005 Wiley-Liss, Inc.)

Background: Frontotemporal dementia (FTD) is a clinically heterogeneous condition that can be associated with clinical manifestations of an extrapyramidal disorder or motor neuron disease. A range of histologic patterns has been described in patients with FTD. The most common familial form of this condition is caused by mutations in the microtubule-associated protein tau gene (MAP tau) and is associated with neuronal or glial tau inclusions., Objectives: To determine the clinical, anatomic, and pathological features of San Francisco family A and to map the mutation responsible for disease in this family., Design: A systematic clinical, neuropsychologic, neuroimaging, and chromosome segregation analysis of San Francisco family A was performed. A pathological and biochemical assessment of a family member was made., Setting: Family study., Patients: San Francisco family A, with FTD, variable extrapyramidal symptoms, and prominent motor neuron disease. Afflicted family members do not have a MAP tau coding or splice regulatory sequence mutation, and the MAP tau is genetically excluded., Main Outcome Measures: Comparison of clinical, neuropsychologic, neuroimaging, and linkage findings of San Francisco family A with other familial forms of FTD and amyotrophic lateral sclerosis (ALS)., Results: The most probable location for the mutation responsible for this condition is on chromosome arm 17q, distal to the MAP tau. All previously identified susceptibility loci for FTD and ALS are excluded. Autopsy findings from an afflicted family member show distinctive tau and alpha-synuclein inclusions. Another unique feature is that the insoluble tau protein consists predominantly of the 4R/0N isoform., Conclusion: The condition affecting members of San Francisco family A is clinically, pathologically, and genetically distinct from previous familial forms of FTD and ALS.