The effect of overloads, underloads and stress ratio on plasticity‐induced crack opening level is examined for different ‘model’ materials. This study is focused on the consequences of the Bauschinger effect on the crack opening level. Various finite element analyses were conducted using ABAQUS to test these effects, involving the Chaboche constitutive equations that take into account both the Bauschinger effect of the material and its cyclic hardening or softening. The cyclic plastic behaviour of the material is found to strongly affect the crack behaviour after an overload or an underload. The experimental data obtained on a 0.4% carbon mild steel confirm the numerical results.

TOP1MT encodes a mitochondrial topoisomerase that is important for mtDNA regulation, and is involved in mitochondrial replication, transcription and translation. Two variants predicted to affect TOP1MT function (R199C and V338L) were identified by exome sequencing of a newborn with hypertrophic cardiomyopathy. As no pathogenic TOP1MT variants have been confirmed previously, we characterized these variants for their ability to rescue several TOP1MT functions in knockout cells. Consistent with a role for these TOP1MT variants contributing to the patient phenotype, comprehensive characterization suggests that both variants had impaired topoisomerase activity and demonstrates that neither variant was able to restore steady state levels of mitochondrial encoded proteins, nor reduced oxidative phosphorylation. However, the two variants behaved differently in some respects. While the R199C variant was better at restoring transcript levels, the V338L variant was able to restore mtDNA copy number and replication. These findings suggest that the different TOP1MT variants affect distinct TOP1MT functions. Altogether, these findings begin to provide insight into the many roles that TOP1MT plays in the maintenance and expression of the mitochondrial genome, and how impairments in this important protein may lead to human pathology.

Planteamos el problema del aparecer de la hylè husserliana, lo que nos conduce al problema de la auto-donación de la vida como condición de una fenomenología de la percepción. Para solucionar este problema, establecemos las condiciones de un diálogo entre Michel Henry, que pone énfasis sobre la auto-afección de la vida inmanente, y Merleau-Ponty, que privilegia una concepción intencional del cuerpo mundano. Tal diálogo nos permite identificar un prejuicio común, cuya superación podría ofrecer la posibilidad de una solución al problema del aparecer sensible desde la vida.

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