Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer's disease-related pathologies in male triple-transgenic mice

<p>Abstract</p> <p>Background</p> <p>Several transgenic animal models genetically predisposed to develop Alzheimer's disease (AD)-like pathology have been engineered to facilitate the study of disease pathophysiology and the vetting of potential disease-modifying therapeutics. The triple transgenic mouse model of AD (3xTg-AD) harbors three AD-related genetic loci: human PS1^M146V, human APP^swe, and human tau^P301L. These mice develop both amyloid plaques and neurofibrillary tangle-like pathology in a progressive and age-dependent manner, while these pathological hallmarks are predominantly restricted to the hippocampus, amygdala, and the cerebral cortex the main foci of AD neuropathology in humans. This model represents, at present, one of the most advanced preclinical tools available and is being employed ever increasingly in the study of mechanisms underlying AD, yet a detailed regional and temporal assessment of the subtleties of disease-related pathologies has not been reported.</p> <p>Methods and results</p> <p>In this study, we immunohistochemically documented the evolution of AD-related transgene expression, amyloid deposition, tau phosphorylation, astrogliosis, and microglial activation throughout the hippocampus, entorhinal cortex, primary motor cortex, and amygdala over a 26-month period in male 3xTg-AD mice. Intracellular amyloid-beta accumulation is detectable the earliest of AD-related pathologies, followed temporally by phospho-tau, extracellular amyloid-beta, and finally paired helical filament pathology. Pathology appears to be most severe in medial and caudal hippocampus. While astrocytic staining remains relatively constant at all ages and regions assessed, microglial activation appears to progressively increase temporally, especially within the hippocampal formation.</p> <p>Conclusion</p> <p>These data fulfill an unmet need in the ever-widening community of investigators studying 3xTg-AD mice and provide a foundation upon which to design future experiments that seek to examine stage-specific disease mechanisms and/or novel therapeutic interventions for AD.</p

Efficient multiple time scale molecular dynamics: using colored noise thermostats to stabilize resonances

Multiple time scale molecular dynamics enhances computational efficiency by updating slow motions less frequently than fast motions. However, in practice the largest outer time step possible is limited not by the physical forces but by resonances between the fast and slow modes. In this paper we show that this problem can be alleviated by using a simple colored noise thermostatting scheme which selectively targets the high frequency modes in the system. For two sample problems, flexible water and solvated alanine dipeptide, we demonstrate that this allows the use of large outer time steps while still obtaining accurate sampling and minimizing the perturbation of the dynamics. Furthermore, this approach is shown to be comparable to constraining fast motions, thus providing an alternative to molecular dynamics with constraints.Comment: accepted for publication by the Journal of Chemical Physic

Single color and single flavor color superconductivity

We survey the non-locked color-flavor-spin channels for quark-quark (color superconducting) condensates in QCD, using an NJL model. We also study isotropic quark-antiquark (mesonic) condensates. We make mean-field estimates of the strength and sign of the self-interaction of each condensate, using four-fermion interaction vertices based on known QCD interactions. For the attractive quark pairing channels, we solve the mean-field gap equations to obtain the size of the gap as a function of quark density. We also calculate the dispersion relations for the quasiquarks, in order to see how fully gapped the spectrum of fermionic excitations will be. We use our results to specify the likely pairing patterns in neutral quark matter, and comment on possible phenomenological consequences

Micro-resonator soliton generated directly with a diode laser

An external-cavity diode laser is reported with ultralow noise, high power coupled to a fiber, and fast tunability. These characteristics enable the generation of an optical frequency comb in a silica micro-resonator with a single-soliton state. Neither an optical modulator nor an amplifier was used in the experiment. This demonstration greatly simplifies the soliton generation setup and represents a significant step forward to a fully integrated soliton comb system.Comment: 7 pages, 5 figure

Ariel - Volume 10 Number 6

Executive Editors Madalyn Schaefgen David Reich Business Manager David Reich News Editors Medical College Edward Zurad CAHS John Guardiani World Mark Zwanger Features Editors Meg Trexler Jim O\u27Brien Editorials Editor Jeffrey Banyas Photography and Sports Editor Stuart Singer Commons Editor Brenda Peterso

Extended polarized semiclassical model for quantum-dot cavity QED and its application to single-photon sources

We present a simple extension of the semi-classical model for a two-level system in a cavity, in order to incorporate multiple polarized transitions, such as those appearing in neutral and charged quantum dots (QDs), and two nondegenerate linearly polarized cavity modes. We verify the model by exact quantum master equation calculations, and experimentally using a neutral QD in a polarization non-degenerate micro-cavity, in both cases we observe excellent agreement. Finally, the usefulness of this approach is demonstrated by optimizing a single-photon source based on polarization postselection, where we find an increase in the brightness for optimal polarization conditions as predicted by the model.Comment: 8 pages, for simple code see https://doi.org/10.5281/zenodo.347666