764 research outputs found

    Sharp large time behaviour in n-dimensional Fisher-KPP equations

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    We study the large time behaviour of the Fisher-KPP equation ∂tu = ∆u+u−u2 in spatial dimension N, when the initial datum is compactly supported. We prove the existence of a Lipschitz function s∞ of the unit sphere, such that u(t, x) approaches, as t goes to infinity, the function Uc∗ ( |x| − c∗t + Nc+∗2 lnt + s∞(|xx| )) , where Uc∗ is the 1D travelling front with minimal speed c∗ = 2. This extends an earlier result of Gärtner

    Intraneuronal Aβ detection in 5xFAD mice by a new Aβ-specific antibody

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    <p>Abstract</p> <p>Background</p> <p>The form(s) of amyloid-β peptide (Aβ) associated with the pathology characteristic of Alzheimer's disease (AD) remains unclear. In particular, the neurotoxicity of intraneuronal Aβ accumulation is an issue of considerable controversy; even the existence of Aβ deposits within neurons has recently been challenged by Winton and co-workers. These authors purport that it is actually intraneuronal APP that is being detected by antibodies thought to be specific for Aβ. To further address this issue, an anti-Aβ antibody was developed (MOAB-2) that specifically detects Aβ, but not APP. This antibody allows for the further evaluation of the early accumulation of intraneuronal Aβ in transgenic mice with increased levels of human Aβ in 5xFAD and 3xTg mice.</p> <p>Results</p> <p>MOAB-2 (mouse IgG<sub>2b</sub>) is a pan-specific, high-titer antibody to Aβ residues 1-4 as demonstrated by biochemical and immunohistochemical analyses (IHC), particularly compared to 6E10 (a commonly used commercial antibody to Aβ residues 3-8). MOAB-2 did not detect APP or APP-CTFs in cell culture media/lysates (HEK-APP<sub>Swe </sub>or HEK-APP<sub>Swe</sub>/BACE1) or in brain homogenates from transgenic mice expressing 5 familial AD (FAD) mutation (5xFAD mice). Using IHC on 5xFAD brain tissue, MOAB-2 immunoreactivity co-localized with C-terminal antibodies specific for Aβ40 and Aβ42. MOAB-2 did not co-localize with either N- or C-terminal antibodies to APP. In addition, no MOAB-2-immunreactivity was observed in the brains of 5xFAD/BACE<sup>-/- </sup>mice, although significant amounts of APP were detected by N- and C-terminal antibodies to APP, as well as by 6E10. In both 5xFAD and 3xTg mouse brain tissue, MOAB-2 co-localized with cathepsin-D, a marker for acidic organelles, further evidence for intraneuronal Aβ, distinct from Aβ associated with the cell membrane. MOAB-2 demonstrated strong intraneuronal and extra-cellular immunoreactivity in 5xFAD and 3xTg mouse brain tissues.</p> <p>Conclusions</p> <p>Both intraneuronal Aβ accumulation and extracellular Aβ deposition was demonstrated in 5xFAD mice and 3xTg mice with MOAB-2, an antibody that will help differentiate intracellular Aβ from APP. However, further investigation is required to determine whether a molecular mechanism links the presence of intraneuronal Aβ with neurotoxicity. As well, understanding the relevance of these observations to human AD patients is critical.</p

    Unusual interplay between superconductivity and field-induced charge order in YBa2Cu3Oy

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    We present a detailed study of the temperature (T) and magnetic field (H) dependence of the electronic density of states (DOS) at the Fermi level, as deduced from specific heat and Knight shift measurements in underdoped YBa2Cu3Oy. We find that the DOS becomes field-independent above a characteristic field H_{DOS} and that the H_{DOS}(T) line displays an unusual inflection near the onset of the long range 3D charge-density wave order. The unusual S-shape of H_{DOS}(T) is suggestive of two mutually-exclusive orders that eventually establish a form of cooperation in order to coexist at low T. On theoretical grounds, such a collaboration could result from the stabilisation of a pair-density wave state, which calls for further investigations in this region of the phase diagramComment: 6 pages, 4 figure

    Dissipation of vibration in rough contact

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    The relationship which links the normal vibration occurring during the sliding of rough surfaces and the nominal contact area is investigated. Two regimes are found. In the first one, the vibrational level does not depend on the contact area, while in the second one, it is propor- tional to the contact area. A theoretical model is proposed. It is based on the assumption that the vibrational level results from a competition between two processes of vibration damping, the internal damping of the material and the contact damping occurring at the interface

    How can humans understand their automated cars? HMI principles, problems and solutions

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    As long as vehicles do not provide full automation, the design and function of the Human Machine Interface (HMI) is crucial for ensuring that the human “driver” and the vehicle-based automated systems collaborate in a safe manner. When the driver is decoupled from active control, the design of the HMI becomes even more critical. Without mutual understanding, the two agents (human and vehicle) will fail to accurately comprehend each other’s intentions and actions. This paper proposes a set of design principles for in-vehicle HMI and reviews some current HMI designs in the light of those principles. We argue that in many respects, the current designs fall short of best practice and have the potential to confuse the driver. This can lead to a mismatch between the operation of the automation in the light of the current external situation and the driver’s awareness of how well the automation is currently handling that situation. A model to illustrate how the various principles are interrelated is proposed. Finally, recommendations are made on how, building on each principle, HMI design solutions can be adopted to address these challenges
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