25 research outputs found

    Demonstration of Universal Parametric Entangling Gates on a Multi-Qubit Lattice

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    We show that parametric coupling techniques can be used to generate selective entangling interactions for multi-qubit processors. By inducing coherent population exchange between adjacent qubits under frequency modulation, we implement a universal gateset for a linear array of four superconducting qubits. An average process fidelity of F=93%\mathcal{F}=93\% is estimated for three two-qubit gates via quantum process tomography. We establish the suitability of these techniques for computation by preparing a four-qubit maximally entangled state and comparing the estimated state fidelity against the expected performance of the individual entangling gates. In addition, we prepare an eight-qubit register in all possible bitstring permutations and monitor the fidelity of a two-qubit gate across one pair of these qubits. Across all such permutations, an average fidelity of F=91.6Β±2.6%\mathcal{F}=91.6\pm2.6\% is observed. These results thus offer a path to a scalable architecture with high selectivity and low crosstalk

    Modulation of the Ξ²-Catenin Signaling Pathway by the Dishevelled-Associated Protein Hipk1

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    BACKGROUND:Wnts are evolutionarily conserved ligands that signal through beta-catenin-dependent and beta-catenin-independent pathways to regulate cell fate, proliferation, polarity, and movements during vertebrate development. Dishevelled (Dsh/Dvl) is a multi-domain scaffold protein required for virtually all known Wnt signaling activities, raising interest in the identification and functions of Dsh-associated proteins. METHODOLOGY:We conducted a yeast-2-hybrid screen using an N-terminal fragment of Dsh, resulting in isolation of the Xenopus laevis ortholog of Hipk1. Interaction between the Dsh and Hipk1 proteins was confirmed by co-immunoprecipitation assays and mass spectrometry, and further experiments suggest that Hipk1 also complexes with the transcription factor Tcf3. Supporting a nuclear function during X. laevis development, Myc-tagged Hipk1 localizes primarily to the nucleus in animal cap explants, and the endogenous transcript is strongly expressed during gastrula and neurula stages. Experimental manipulations of Hipk1 levels indicate that Hipk1 can repress Wnt/beta-catenin target gene activation, as demonstrated by beta-catenin reporter assays in human embryonic kidney cells and by indicators of dorsal specification in X. laevis embryos at the late blastula stage. In addition, a subset of Wnt-responsive genes subsequently requires Hipk1 for activation in the involuting mesoderm during gastrulation. Moreover, either over-expression or knock-down of Hipk1 leads to perturbed convergent extension cell movements involved in both gastrulation and neural tube closure. CONCLUSIONS:These results suggest that Hipk1 contributes in a complex fashion to Dsh-dependent signaling activities during early vertebrate development. This includes regulating the transcription of Wnt/beta-catenin target genes in the nucleus, possibly in both repressive and activating ways under changing developmental contexts. This regulation is required to modulate gene expression and cell movements that are essential for gastrulation

    Mechanism of activation of the Formin protein Daam1

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    The Formin proteins are central players in mediating cytoskeletal reorganization and are epistatically positioned in a pathway downstream of Rho activation. These proteins exist in the cytoplasm in an autoinhibited state, which is mediated by intramolecular interactions between the amino-terminal GTPase binding domain (GBD) that encompasses the diaphanous inhibitory domain (DID) and the carboxyl-terminal diaphanous autoregulatory domain (DAD). It has been proposed that the binding of Rho within the GBD releases this molecule from autoinhibition by disrupting the DID/DAD interactions. Here we report that Daam1 is not significantly activated by Rho binding but rather by its interaction with Dishevelled (Dvl). Removal of the DAD domain disrupts interactions between Dvl and Daam1, and the binding of Dvl to Daam1 disrupts the interaction between the GBD and DAD that mediates Daam1 autoinhibition. Mutations within or removal of the DAD converts Daam1 into an active protein that can induce Rho activation. We further demonstrate that Dvl synergizes with Daam1 to regulate gastrulation during Xenopus embryogenesis and that expression of activated Daam1 can rescue impaired convergent extension movements resulting from deregulated noncanonical Wnt signaling. Our studies together define the importance of a carboxyl-terminal binding partner, Dvl, that leads to the activation of Daam1
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