Aharonov-Bohm oscillations in a mesoscopic ring with a quantum dot

We present an analysis of the Aharonov-Bohm oscillations for a mesoscopic ring with a quantum dot inserted in one of its arms. It is shown that microreversibility demands that the phase of the Aharonov-Bohm oscillations changes {\it abruptly} when a resonant level crosses the Fermi energy. We use the Friedel sum rule to discuss the conservation of the parity of the oscillations at different conductance peaks. Our predictions are illustrated with the help of a simple one channel model that permits the variation of the potential landscape along the ring.Comment: 11 pages, Revtex style, 3 figures under request. Submitted to Phys. Rev. B (rapid communications

Microscopic Theory of Josephson Mesoscopic Constrictions

We present a microscopic theory for the d.c. Josephson effect in model mesoscopic constrictions. Our method is based on a non-equilibrium Green function formalism which allows for a self-consistent determination of the order parameter profile along the constriction. The various regimes defined by the different length scales (Fermi wavelength $\lambda_F$, coherence length $\xi_0$ and constriction length $L_C$) can be analyzed, including the case where all these lengths are comparable. For the case $\lambda_F \tilde{<} (L_C,\xi_0)$ phase oscillations with spatial period $\lambda_F/2$ can be observed. In the case of $L_C>\xi_0$ solutions with a phase-slip center inside the constriction can be found, in agreement with previous phenomenological theories.Comment: 4 pages (RevTex 3.0), 3 postscript figures available upon request, 312456-C

Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice

Differential DNA methylation defects of H19/IGF2 are associated with congenital growth disorders characterized by opposite clinical pictures. Due to structural differences between human and mouse, the mechanisms by which mutations of the H19/IGF2 Imprinting Control region (IC1) result in these diseases are undefined. To address this issue, we previously generated a mouse line carrying a humanized IC1 (hIC1) and now replaced the wildtype with a mutant IC1 identified in the overgrowth-associated Beckwith-Wiedemann syndrome. The new humanized mouse line shows pre/post-natal overgrowth on maternal transmission and pre/post-natal undergrowth on paternal transmission of the mutation. The mutant hIC1 acquires abnormal methylation during development causing opposite H19/Igf2 imprinting defects on maternal and paternal chromosomes. Differential and possibly mosaic Igf2 expression and imprinting is associated with asymmetric growth of bilateral organs. Furthermore, tissue-specific imprinting defects result in deficient liver- and placenta-derived Igf2 on paternal transmission and excessive Igf2 in peripheral tissues on maternal transmission, providing a possible molecular explanation for imprinting-associated and phenotypically contrasting growth disorders.Differential DNA methylation defects of H19/IGF2 are associated with congenital growth disorders characterized by opposite clinical pictures. Due to structural differences between human and mouse, the mechanisms by which mutations of the H19/IGF2 Imprinting Control region (IC1) result in these diseases are undefined. To address this issue, we previously generated a mouse line carrying a humanized IC1 (hIC1) and now replaced the wildtype with a mutant IC1 identified in the overgrowth-associated Beckwith-Wiedemann syndrome. The new humanized mouse line shows pre/post-natal overgrowth on maternal transmission and pre/post-natal undergrowth on paternal transmission of the mutation. The mutant hIC1 acquires abnormal methylation during development causing opposite H19/Igf2 imprinting defects on maternal and paternal chromosomes. Differential and possibly mosaic Igf2 expression and imprinting is associated with asymmetric growth of bilateral organs. Furthermore, tissue-specific imprinting defects result in deficient liver- and placenta-derived Igf2 on paternal transmission and excessive Igf2 in peripheral tissues on maternal transmission, providing a possible molecular explanation for imprinting-associated and phenotypically contrasting growth disorders