3,736 research outputs found

    Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau.

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    While a number of genome-wide association studies have identified microtubule-associated protein tau as a strong risk factor for Parkinson's disease (PD), little is known about the mechanism through which human tau can predispose an individual to this disease. Here, we demonstrate that expression of human wild-type tau is sufficient to disrupt the survival of dopaminergic neurons in a Drosophila model. Tau triggers a synaptic pathology visualized by vesicular monoamine transporter-pHGFP that precedes both the age-dependent formation of tau-containing neurofibrillary tangle-like pathology and the progressive loss of DA neurons, thereby recapitulating the pathological hallmarks of PD. Flies overexpressing tau also exhibit progressive impairments of both motor and learning behaviors. Surprisingly, contrary to common belief that hyperphosphorylated tau could aggravate toxicity, DA neuron degeneration is alleviated by expressing the modified, hyperphosphorylated tau(E14). Together, these results show that impairment of VMAT-containing synaptic vesicle, released to synapses before overt tauopathy may be the underlying mechanism of tau-associated PD and suggest that correction or prevention of this deficit may be appropriate targets for early therapeutic intervention

    Analytical behaviour of concrete-encased CFST box stub columns under axial compression

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    [EN] Concrete-encased CFST (concrete-filled steel tube) members have been widely used in high-rise buildings and bridge structures. In this paper, the axial performance of a typical concrete-encased CFST box member with inner CFST and outer reinforced concrete (RC) is investigated. A finite element analysis (FEA) model is established to analyze the compressive behavior of the composite member. The material nonlinearity and the interaction between concrete and steel tube are considered. A good agreement is achieved between the measured and predicted results in terms of the failure mode and the load-deformation relation. The verified FEA model is then used to conduct the full range analysis on the load versus deformation relations. The loading distributions of different components inclouding concrete, steel tube and longitudinal bar during four stages are discussed. Typical failure modes, internal force distribution, stress development and the contact stress between concrete and steel tube are also presented. The parametric study on the compressive behavior is conducted to investigate the effects of various parameters, e.g. the strength of concrete and steel, longitudinal bar ratio and stirrup space on the sectional capacity and the ductility of the concrete-encased CSFT box member.Chen, J.; Han, L.; Wang, F.; Mu, T. (2018). Analytical behaviour of concrete-encased CFST box stub columns under axial compression. En Proceedings of the 12th International Conference on Advances in Steel-Concrete Composite Structures. ASCCS 2018. Editorial Universitat Politècnica de València. 401-408. https://doi.org/10.4995/ASCCS2018.2018.6966OCS40140

    On the Impossibility of General Parallel Fast-Forwarding of Hamiltonian Simulation

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    Hamiltonian simulation is one of the most important problems in the field of quantum computing. There have been extended efforts on designing algorithms for faster simulation, and the evolution time T for the simulation greatly affect algorithm runtime as expected. While there are some specific types of Hamiltonians that can be fast-forwarded, i.e., simulated within time o(T), for some large classes of Hamiltonians (e.g., all local/sparse Hamiltonians), existing simulation algorithms require running time at least linear in the evolution time T. On the other hand, while there exist lower bounds of ?(T) circuit size for some large classes of Hamiltonian, these lower bounds do not rule out the possibilities of Hamiltonian simulation with large but "low-depth" circuits by running things in parallel. As a result, physical systems with system size scaling with T can potentially do a fast-forwarding simulation. Therefore, it is intriguing whether we can achieve fast Hamiltonian simulation with the power of parallelism. In this work, we give a negative result for the above open problem in various settings. In the oracle model, we prove that there are time-independent sparse Hamiltonians that cannot be simulated via an oracle circuit of depth o(T). In the plain model, relying on the random oracle heuristic, we show that there exist time-independent local Hamiltonians and time-dependent geometrically local Hamiltonians on n qubits that cannot be simulated via an oracle circuit of depth o(T/n^c), where the Hamiltonians act on n qubits, and c is a constant. Lastly, we generalize the above results and show that any simulators that are geometrically local Hamiltonians cannot do the simulation much faster than parallel quantum algorithms

    Tailoring excitonic states of van der Waals bilayers through stacking configuration, band alignment and valley-spin

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    Excitons in monolayer semiconductors have large optical transition dipole for strong coupling with light field. Interlayer excitons in heterobilayers, with layer separation of electron and hole components, feature large electric dipole that enables strong coupling with electric field and exciton-exciton interaction, at the cost that the optical dipole is substantially quenched (by several orders of magnitude). In this letter, we demonstrate the ability to create a new class of excitons in transition metal dichalcogenide (TMD) hetero- and homo-bilayers that combines the advantages of monolayer- and interlayer-excitons, i.e. featuring both large optical dipole and large electric dipole. These excitons consist of an electron that is well confined in an individual layer, and a hole that is well extended in both layers, realized here through the carrier-species specific layer-hybridization controlled through the interplay of rotational, translational, band offset, and valley-spin degrees of freedom. We observe different species of such layer-hybridized valley excitons in different heterobilayer and homobilayer systems, which can be utilized for realizing strongly interacting excitonic/polaritonic gases, as well as optical quantum coherent controls of bidirectional interlayer carrier transfer either with upper conversion or down conversion in energy
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