330 research outputs found

    Current-voltage characteristics of quasi-one-dimensional superconductors: An S-curve in the constant voltage regime

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    Applying a constant voltage to superconducting nanowires we find that its IV-characteristic exhibits an unusual S-behavior. This behavior is the direct consequence of the dynamics of the superconducting condensate and of the existence of two different critical currents: j_{c2} at which the pure superconducting state becomes unstable and j_{c1}<j_{c2} at which the phase slip state is realized in the system.Comment: 4 pages, 5 figures, replaced with minor change

    Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model.

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    Parkinson's disease (PD) is characterized by the presence of α-synuclein aggregates known as Lewy bodies and Lewy neurites, whose formation is linked to disease development. The causal relation between α-synuclein aggregates and PD is not well understood. We generated a new transgenic mouse line (MI2) expressing human, aggregation-prone truncated 1-120 α-synuclein under the control of the tyrosine hydroxylase promoter. MI2 mice exhibit progressive aggregation of α-synuclein in dopaminergic neurons of the substantia nigra pars compacta and their striatal terminals. This is associated with a progressive reduction of striatal dopamine release, reduced striatal innervation and significant nigral dopaminergic nerve cell death starting from 6 and 12 months of age, respectively. In the MI2 mice, alterations in gait impairment can be detected by the DigiGait test from 9 months of age, while gross motor deficit was detected by rotarod test at 20 months of age when 50% of dopaminergic neurons in the substantia nigra pars compacta are lost. These changes were associated with an increase in the number and density of 20-500 nm α-synuclein species as shown by dSTORM. Treatment with the oligomer modulator anle138b, from 9 to 12 months of age, restored striatal dopamine release, prevented dopaminergic cell death and gait impairment. These effects were associated with a reduction of the inner density of large α-synuclein aggregates and an increase in dispersed small α-synuclein species as revealed by dSTORM. The MI2 mouse model recapitulates the progressive dopaminergic deficit observed in PD, showing that early synaptic dysfunction is associated to fine behavioral motor alterations, precedes dopaminergic axonal loss and neuronal death that become associated with a more consistent motor deficit upon reaching a certain threshold. Our data also provide new mechanistic insight for the effect of anle138b's function in vivo supporting that targeting α-synuclein aggregation is a promising therapeutic approach for PD

    Proximity-driven source of highly spin-polarized ac current on the basis of superconductor/weak ferromagnet/superconductor voltage-biased Josephson junction

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    We theoretically investigate an opportunity to implement a source of highly spin-polarized ac current on the basis of superconductor/weak ferromagnet/superconductor (SFS) voltage-biased junction in the regime of essential proximity effect and calculate the current flowing through the probe electrode tunnel coupled to the ferromagnetic interlayer region. It is shown that while the polarization of the dc current component is generally small in case of weak exchange field of the ferromagnet, there is an ac component of the current in the system. This ac current is highly spin-polarized and entirely originated from the non-equilibrium proximity effect in the interlayer. The frequency of the current is controlled by the voltage applied to SFS junction. We discuss a possibility to obtain a source of coherent ac currents with a certain phase shift between them by tunnel coupling two probe electrodes at different locations of the interlayer region.Comment: 8 pages, 5 figure

    Motor coordination deficits in Alpk1 mutant mice with the inserted piggyBac transposon

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    <p>Abstract</p> <p>Background</p> <p>ALPK1 (α-kinase 1) is a member of an unconventional alpha-kinase family, and its biological function remains largely unknown. Here we report the phenotypic characterization of one mutant line, in which the <it>piggyBac </it>(<it>PB</it>) transposon is inserted into the <it>Alpk1 </it>gene.</p> <p>Results</p> <p>The <it>piggyBac</it>(<it>PB</it>) insertion site in mutants was mapped to the first intron of the <it>Alpk1 </it>gene, resulting in the effective disruption of the intact <it>Alpk1 </it>transcript expression. The transposon-inserted <it>Alpk1 </it>homozygous mutants (<it>Alpk1<sup>PB/PB</sup></it>) displayed severe defects in motor coordination in a series of behavioral analysis, including dowel test, hanging wire test, rotarod analysis and footprint analysis. However, the cerebellar architecture, Purkinje cell morphology and electrophysiology of the Purkinje cells appeared normal in mutants. The motor coordination deficits in the <it>Alpk1<sup>PB/PB </sup></it>mice were rescued by transgenic mice expressing the full-length <it>Alpk1</it>-coding sequence under the control of the ubiquitous expression promoter.</p> <p>Conclusions</p> <p>Our results indicate that ALPK1 plays an important role in the regulation of motor coordination. <it>Alpk1<sup>PB/PB </sup></it>mice would be a useful model to provide a clue to the better understanding of the cellular and molecular mechanisms of ALPK1 in the control of fine motor activities.</p

    Composite excitation of Josephson phase and spin waves in Josephson junctions with ferromagnetic insulator

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    Coupling of Josephson-phase and spin-waves is theoretically studied in a superconductor/ferromagnetic insulator/superconductor (S/FI/S) junction. Electromagnetic (EM) field inside the junction and the Josephson current coupled with spin-waves in FI are calculated by combining Maxwell and Landau-Lifshitz-Gilbert equations. In the S/FI/S junction, it is found that the current-voltage (I-V) characteristic shows two resonant peaks. Voltages at the resonant peaks are obtained as a function of the normal modes of EM field, which indicates a composite excitation of the EM field and spin-waves in the S/FI/S junction. We also examine another type of junction, in which a nonmagnetic insulator (I) is located at one of interfaces between S and FI. In such a S/I/FI/S junction, three resonant peaks appear in the I-V curve, since the Josephson-phase couples to the EM field in the I layer.Comment: 16 pages, 5 figure

    <sup>11</sup> C radiolabeling of anle253b: A putative PET tracer for Parkinson's disease that binds to α-synuclein fibrils in vitro and crosses the blood-brain barrier.

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    There is an urgent clinical need for imaging of α-synuclein (αSyn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of αSyn are rare. Diphenyl pyrazoles are known modulators of αSyn aggregation and thus bear potential for non-invasive detection of this biomarker in vivo. Here we demonstrate high-affinity binding of the family member anle253b to fibrillar αSyn and present a high-yielding site-selective radiosynthesis route for 11 C radiolabeling using in-situ generated [11 C]formaldehyde and reductive methylation. Radio-HPLC of the tracer after incubation with rat serum in vitro shows excellent stability of the molecule. Positron emission tomography in healthy animals is used to assess the pharmacokinetics and biodistribution of the tracer, showing good penetration of the blood-brain barrier and low background binding to the non-pathological brain

    General Relativistic Thermoelectric Effects in Superconductors

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    We discuss the general-relativistic contributions to occur in the electromagnetic properties of a superconductor with a heat flow. The appearance of general-relativistic contribution to the magnetic flux through a superconducting thermoelectric bimetallic circuit is shown. A response of the Josephson junctions to a heat flow is investigated in the general-relativistic framework. Some gravitothermoelectric effects which are observable in the superconducting state in the Earth's gravitational field are considered.Comment: 13 pages, 2 figure
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