95 research outputs found
Familial amyloid precursor protein mutants cause caspase-6-dependent but amyloid β-peptide-independent neuronal degeneration in primary human neuron cultures.
Although familial Alzheimer disease (AD)-associated autosomal dominant mutants have been extensively studied, little is known about the underlying molecular mechanisms of neurodegeneration induced by these mutants in AD. Wild-type, Swedish or London amyloid precursor protein (APP) transfection in primary human neurons induced neuritic beading, in which several co-expressed proteins, such as enhanced green fluorescent protein, red fluorescent protein (RFP)-tau and RFP-ubiquitin, accumulated. APP-induced neuritic beading was dependent on caspase-6 (Casp6), because it was inhibited with 5 μM z-VEID-fmk or with dominant-negative Casp6. Neuritic beading was independent from APP-mediated amyloid β-peptide (Aβ) production, because the APPM596V (APPMV) mutant, which cannot generate Aβ, still induced Casp6-dependent neuritic beading. However, the beaded neurons underwent Casp6- and Aβ-dependent cell death. These results indicate that overexpression of wild-type or mutant APP causes Casp6-dependent but Aβ-independent neuritic degeneration in human neurons. Because Casp6 is activated early in AD and is involved in axonal degeneration, these results suggest that the inhibition of Casp6 may represent an efficient early intervention against familial forms of AD. Furthermore, these results indicate that removing Aβ without inhibiting Casp6 may have little effect in preventing the progressive dementia associated with sporadic or familial AD
Solitary waves in the Nonlinear Dirac Equation
In the present work, we consider the existence, stability, and dynamics of
solitary waves in the nonlinear Dirac equation. We start by introducing the
Soler model of self-interacting spinors, and discuss its localized waveforms in
one, two, and three spatial dimensions and the equations they satisfy. We
present the associated explicit solutions in one dimension and numerically
obtain their analogues in higher dimensions. The stability is subsequently
discussed from a theoretical perspective and then complemented with numerical
computations. Finally, the dynamics of the solutions is explored and compared
to its non-relativistic analogue, which is the nonlinear Schr{\"o}dinger
equation. A few special topics are also explored, including the discrete
variant of the nonlinear Dirac equation and its solitary wave properties, as
well as the PT-symmetric variant of the model
Strain-induced pseudomagnetic field and Landau levels in photonic structures
Magnetic effects at optical frequencies are notoriously weak. This is
evidenced by the fact that the magnetic permeability of nearly all materials is
unity in the optical frequency range, and that magneto-optical devices (such as
Faraday isolators) must be large in order to allow for a sufficiently strong
effect. In graphene, however, it has been shown that inhomogeneous strains can
induce 'pseudomagnetic fields' that behave very similarly to real fields. Here,
we show experimentally and theoretically that, by properly structuring a
dielectric lattice, it is possible to induce a pseudomagnetic field at optical
frequencies in a photonic lattice, where the propagation dynamics is equivalent
to the evolution of an electronic wavepacket in graphene. To our knowledge,
this is the first realization of a pseudomagnetic field in optics. The induced
field gives rise to multiple photonic Landau levels (singularities in the
density of states) separated by band gaps. We show experimentally and
numerically that the gaps between these Landau levels give rise to transverse
confinement of the optical modes. The use of strain allows for the exploration
of magnetic effects in a non-resonant way that would be otherwise inaccessible
in optics. Employing inhomogeneous strain to induce pseudomagnetism suggests
the possibility that aperiodic photonic crystal structures can achieve greater
field-enhancement and slow-light effects than periodic structures via the high
density-of-states at Landau levels. Generalizing these concepts to other
systems beyond optics, for example with matter waves in optical potentials,
offers new intriguing physics that is fundamentally different from that in
purely periodic structures.Comment: 24 pages including supplementary information section, 4 figure
Caspase-mediated cleavage of actin and tubulin is a common feature and sensitive marker of axonal degeneration in neural development and injury
Would school closure for the 2009 H1N1 influenza epidemic have been worth the cost?: a computational simulation of Pennsylvania
<p>Abstract</p> <p>Background</p> <p>During the 2009 H1N1 influenza epidemic, policy makers debated over whether, when, and how long to close schools. While closing schools could have reduced influenza transmission thereby preventing cases, deaths, and health care costs, it may also have incurred substantial costs from increased childcare needs and lost productivity by teachers and other school employees.</p> <p>Methods</p> <p>A combination of agent-based and Monte Carlo economic simulation modeling was used to determine the cost-benefit of closing schools (vs. not closing schools) for different durations (range: 1 to 8 weeks) and symptomatic case incidence triggers (range: 1 to 30) for the state of Pennsylvania during the 2009 H1N1 epidemic. Different scenarios varied the basic reproductive rate (R<sub>0</sub>) from 1.2, 1.6, to 2.0 and used case-hospitalization and case-fatality rates from the 2009 epidemic. Additional analyses determined the cost per influenza case averted of implementing school closure.</p> <p>Results</p> <p>For all scenarios explored, closing schools resulted in substantially higher net costs than not closing schools. For R<sub>0 </sub>= 1.2, 1.6, and 2.0 epidemics, closing schools for 8 weeks would have resulted in median net costs of 8.0 - 14,185 (30,565) for R<sub>0 </sub>= 1.2, 9,501 - 23,483 (50,926) for R<sub>0 </sub>= 2.0.</p> <p>Conclusions</p> <p>Our study suggests that closing schools during the 2009 H1N1 epidemic could have resulted in substantial costs to society as the potential costs of lost productivity and childcare could have far outweighed the cost savings in preventing influenza cases.</p
Public health management of antiviral drugs during the 2009 H1N1 influenza pandemic: a survey of local health departments in California
<p>Abstract</p> <p>Background</p> <p>The large-scale deployment of antiviral drugs from the Strategic National Stockpile during the 2009 H1N1 influenza response provides a unique opportunity to study local public health implementation of the medical countermeasure dispensing capability in a prolonged event of national significance. This study aims to describe the range of methods used by local health departments (LHDs) in California to manage antiviral activities and to gain a better understanding of the related challenges experienced by health departments and their community partners.</p> <p>Methods</p> <p>This research employed a mixed-methods approach. First, a multi-disciplinary focus group of pandemic influenza planners from key stakeholder groups in California was convened in order to generate ideas and identify critical themes related to the local implementation of antiviral activities during the H1N1 influenza response. These qualitative data informed the development of a web-based survey, which was distributed to all 61 LHDs in California for the purpose of assessing the experiences of a representative sample of local health agencies in a large region.</p> <p>Results</p> <p>Forty-four LHDs participated in this study, representing 72% of the local public health agencies in California. While most communities dispensed a modest number of publicly purchased antivirals, LHDs nevertheless drew on their previous work and engaged in a number of antiviral activities, including: acquiring, allocating, distributing, dispensing, tracking, developing guidance, and communicating to the public and clinical community. LHDs also identified specific antiviral challenges presented by the H1N1 pandemic, including: reconciling multiple sources and versions of antiviral guidance, determining appropriate uses and recipients of publicly purchased antivirals, and staffing shortages.</p> <p>Conclusions</p> <p>The 2009 H1N1 influenza pandemic presented an unusual opportunity to learn about the role of local public health in the management of antiviral response activities during a real public health emergency. Results of this study offer an important descriptive account of LHD management of publicly purchased antivirals, and provide practitioners, policy makers, and academics with a practice-based assessment of these events. The issues raised and the challenges faced by LHDs should be leveraged to inform public health planning for future pandemics and other emergency events that require medical countermeasure dispensing activities.</p
Increased Caspase-6 activity in the human anterior olfactory nuclei of the olfactory bulb is associated with cognitive impairment
Classical Simulation of Relativistic Quantum Mechanics in Periodic Optical Structures
Spatial and/or temporal propagation of light waves in periodic optical
structures offers a rather unique possibility to realize in a purely classical
setting the optical analogues of a wide variety of quantum phenomena rooted in
relativistic wave equations. In this work a brief overview of a few optical
analogues of relativistic quantum phenomena, based on either spatial light
transport in engineered photonic lattices or on temporal pulse propagation in
Bragg grating structures, is presented. Examples include spatial and temporal
photonic analogues of the Zitterbewegung of a relativistic electron, Klein
tunneling, vacuum decay and pair-production, the Dirac oscillator, the
relativistic Kronig-Penney model, and optical realizations of non-Hermitian
extensions of relativistic wave equations.Comment: review article (invited), 14 pages, 7 figures, 105 reference
Non-unitary Evolution of Quantum Logics
In this work we present a dynamical approach to quantum logics. By changing the standard formalism of quantum mechanics to allow non-Hermitian operators as generators of time evolution, we address the question of how can logics evolve in time. In this way, we describe formally how a non-Boolean algebra may become a Boolean one under certain conditions. We present some simple models which illustrate this transition and develop a new quantum logical formalism based in complex spectral resolutions, a notion that we introduce in order to cope with the temporal aspect of the logical structure of quantum theory
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