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

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 (R₀) 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 R₀= 1.2, 1.6, and 2.0 epidemics, closing schools for 8 weeks would have resulted in median net costs of $21.0 billion (95$8.0 - $45.3 billion). The median cost per influenza case averted would have been$14,185 ($5,423 -$30,565) for R₀= 1.2, $25,253 ($9,501 - $53,461) for R₀= 1.6, and$23,483 ($8,870 -$50,926) for R₀= 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

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