45 research outputs found

    HTS Cable International Round Robin: 4.4 kA Critical Current Measurements

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    Loss of Wnt5a disrupts second heart field cell deployment and may contribute to OFT malformations in DiGeorge syndrome

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    International audienceOutflow tract (OFT) malformation accounts for ∼30% of human congenital heart defects and manifests frequently in TBX1 haplo-insufficiency associated DiGeorge (22q11.2 deletion) syndrome. OFT myocardium originates from second heart field (SHF) progenitors in the pharyngeal and splanchnic mesoderm (SpM), but how these progenitors are deployed to the OFT is unclear. We find that SHF progenitors in the SpM gradually gain epithelial character and are deployed to the OFT as a cohesive sheet. Wnt5a, a non-canonical Wnt, is expressed specifically in the caudal SpM and may regulate oriented cell intercalation to incorporate SHF progenitors into an epithelial-like sheet, thereby generating the pushing force to deploy SHF cells rostrally into the OFT. Using enhancer trap and Cre transgenes, our lineage tracing experiments show that in Wnt5a null mice, SHF progenitors are trapped in the SpM and fail to be deployed to the OFT efficiently, resulting in a reduction in the inferior OFT myocardial wall and its derivative, subpulmonary myocardium. Concomitantly, the superior OFT and subaortic myocardium are expanded. Finally, in chick embryos, blocking the Wnt5a function in the caudal SpM perturbs polarized elongation of SHF progenitors, and compromises their deployment to the OFT. Collectively, our results highlight a critical role for Wnt5a in deploying SHF progenitors from the SpM to the OFT. Given that Wnt5a is a putative transcriptional target of Tbx1, and the similar reduction of subpulmonary myocardium in Tbx1 mutant mice, our results suggest that perturbing Wnt5a-mediated SHF deployment may be an important pathogenic mechanism contributing to OFT malformations in DiGeorge syndrome

    A numerical and experimental investigation of planar asymmetric SQUID gradiometer characteristics

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    A low-cost, high-performance magnetic field sensor for applications such as biomagnetism and nondestructive evaluation can be fabricated by integrating a superconducting quantum interference device (SQUID) and a gradiometer on a single chip. Conventionally, the gradiometric pick-up loop would have a rectangular outline divided symmetrically about the midpoint of its length so that its spatial response was also symmetrical. However, it is also possible to divide the same outline asymmetrically, maintaining the field rejection order of the gradiometer by adding an extra crossover. The spatial response of this arrangement will also be asymmetric, which may be exploited to reduce the effects of the nearby SQUID as a magnetic anomaly or to enhance the sensitivity of the device to magnetic sources at a particular distance. The techniques to calculate the crossover positions are well established. Here we outline how different designs may be evaluated theoretically and report on first experimental results for three simple designs. Several devices have been fabricated using a well established Nb/Al–Al2O3/Nb trilayer process with high yields. The measurement of the spatial response of an asymmetric first-order gradiometer shows the expected magnetometer characteristics for a magnetic dipole source in the near field and first-order gradiometric characteristics for a far-field source. The balance of the integrated gradiometer appears to be better than one part in 104, and the magnetic field gradient sensitivity has been measured to be 100 fT cm−1 Hz−1/2
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