Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer's disease.

Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD), increasing risk and decreasing age of disease onset. Many studies have demonstrated the detrimental effects of apoE4 in varying cellular contexts. However, the underlying mechanisms explaining how apoE4 leads to cognitive decline are not fully understood. Recently, the combination of human induced pluripotent stem cell (hiPSC) modeling of neurological diseases in vitro and electrophysiological studies in vivo have begun to unravel the intersection between apoE4, neuronal subtype dysfunction or loss, subsequent network deficits, and eventual cognitive decline. In this review, we provide an overview of the literature describing apoE4's detrimental effects in the central nervous system (CNS), specifically focusing on its contribution to neuronal subtype dysfunction or loss. We focus on γ-aminobutyric acid (GABA)-expressing interneurons in the hippocampus, which are selectively vulnerable to apoE4-mediated neurotoxicity. Additionally, we discuss the importance of the GABAergic inhibitory network to proper cognitive function and how dysfunction of this network manifests in AD. Finally, we examine how apoE4-mediated GABAergic interneuron loss can lead to inhibitory network deficits and how this deficit results in cognitive decline. We propose the following working model: Aging and/or stress induces neuronal expression of apoE. GABAergic interneurons are selectively vulnerable to intracellularly produced apoE4, through a tau dependent mechanism, which leads to their dysfunction and eventual death. In turn, GABAergic interneuron loss causes hyperexcitability and dysregulation of neural networks in the hippocampus and cortex. This dysfunction results in learning, memory, and other cognitive deficits that are the central features of AD

Parity-Violating Electron Scattering as a Probe of Supersymmetry

We compute the one-loop supersymmetric (SUSY) contributions to the weak charges of the electron ($Q_W^e$) and proton ($Q_W^p$) using the Minimal Supersymmetric Standard Model (MSSM). These $q^2=0$ vector couplings of the $Z^0$-boson to fermions will be determined in two fixed-target, parity-violating electron scattering experiments. The SUSY loop contributions to $Q_W^p$ and $Q_W^e$ can be substantial, leading to several percent corrections to the Standard Model values for these quantities. We show that the relative signs of the SUSY loop effects on $Q_W^e$ and $Q_W^p$ are correlated and positive over nearly all of the MSSM parameter space, whereas inclusion of R-parity nonconserving interactions can lead to opposite sign relative shifts in the weak charges. Thus, a comparison of $Q_W^p$ and $Q_W^e$ measurements could help distinguish between different SUSY scenarios.Comment: 4 pages, 2 figure

DISPATCH: A Numerical Simulation Framework for the Exa-scale Era. I. Fundamentals

We introduce a high-performance simulation framework that permits the semi-independent, task-based solution of sets of partial differential equations, typically manifesting as updates to a collection of `patches' in space-time. A hybrid MPI/OpenMP execution model is adopted, where work tasks are controlled by a rank-local `dispatcher' which selects, from a set of tasks generally much larger than the number of physical cores (or hardware threads), tasks that are ready for updating. The definition of a task can vary, for example, with some solving the equations of ideal magnetohydrodynamics (MHD), others non-ideal MHD, radiative transfer, or particle motion, and yet others applying particle-in-cell (PIC) methods. Tasks do not have to be grid-based, while tasks that are, may use either Cartesian or orthogonal curvilinear meshes. Patches may be stationary or moving. Mesh refinement can be static or dynamic. A feature of decisive importance for the overall performance of the framework is that time steps are determined and applied locally; this allows potentially large reductions in the total number of updates required in cases when the signal speed varies greatly across the computational domain, and therefore a corresponding reduction in computing time. Another feature is a load balancing algorithm that operates `locally' and aims to simultaneously minimise load and communication imbalance. The framework generally relies on already existing solvers, whose performance is augmented when run under the framework, due to more efficient cache usage, vectorisation, local time-stepping, plus near-linear and, in principle, unlimited OpenMP and MPI scaling.Comment: 17 pages, 8 figures. Accepted by MNRA

Supersymmetric Effects in Parity-Violating Deep Inelastic Electron-Nucleus Scattering

We compute the supersymmetric (SUSY) corrections to the parity-violating, deep inelastic electron-deuteron asymmetry. Working with the Minimal Supersymmetric Standard Model (MSSM) we consider two cases: R parity conserving and R parity-violating. Under these scenarios, we compare the SUSY effects with those entering other parity-violating observables. For both cases of the MSSM, we find that the magnitude of the SUSY corrections can be as large as about 1% and that they are strongly correlated with the effects on other parity-violating observables. A comparison of various low-energy parity-violating observables thus provides a potentially interesting probe of SUSY.Comment: 12 pages, 5 figure

Nonequilibrium inflaton dynamics and reheating: Back reaction of parametric particle creation and curved spacetime effects

We present a detailed and systematic analysis of the nonperturbative, nonequilibrium dynamics of a quantum field in the reheating phase of inflatonary cosmology, including full back reactions of the quantum field on the curved spacetime, as well as the fluctuations on the mean field. We use the O(N) field theory with unbroken symmetry in a spatially flat FRW universe to study the dynamics of the inflaton in the post-inflaton, preheating stage. Oscillations of the inflaton's zero mode induce parametric amplification of quantum fluctuations, resulting in a rapid transfer of energy to the inhomogeneous modes of the inflaton field. We adopt the coupled nonperturbative equations for the mean field and variance derived in a preceding paper [gr-qc/9706001] by means of a two-particle-irreducible (2PI), closed-time-path (CTP) effective action for curved spacetime while specialized to leading order in the 1/N expansion. Adiabatic regularization is employed. The renormalized dynamical equations are evolved numerically from initial data which are generic to the end state of slow roll in many inflatonary cosmological scenarios. The initial conditions consist of a large-amplitude, quasiclassical, oscillating mean field, and a variance given by the de Sitter-invariant vacuum. We find that for sufficiently large initial mean-field amplitudes in this model, the parametric resonance effect alone (in a collisionless approximation) is not an efficient means to "preheat" the quantum field. For small initial mean-field amplitude, damping of the mean field via parametric amplification of quantum fluctuations is seen to occur. Our results indicate that the self-consistent dynamics of spacetime plays an important role in determining the physics of the post-inflatonary Universe.Comment: 53 pages, 19 figures. The bound on the initial inflaton amplitude has been strengthened (the qualitative results of the paper are unchanged

MHD simulations of the formation and propagation of protostellar jets to observational length scales

We present 2.5-D global, ideal MHD simulations of magnetically and rotationally driven protostellar jets from Keplerian accretion discs, wherein only the initial magnetic field strength at the inner radius of the disc, $B_{\rm i}$, is varied. Using the AMR-MHD code AZEUS, we self-consistently follow the jet evolution into the observational regime ($>10^3\,\mathrm{AU}$) with a spatial dynamic range of $\sim6.5\times10^5$. The simulations reveal a three-component outflow: 1) A hot, dense, super-fast and highly magnetised 'jet core'; 2) a cold, rarefied, trans-fast and highly magnetised 'sheath' surrounding the jet core and extending to a tangential discontinuity; and 3) a warm, dense, trans-slow and weakly magnetised shocked ambient medium entrained by the advancing bow shock. The simulations reveal power-law relationships between $B_{\rm i}$ and the jet advance speed, $v_{\rm jet}$, the average jet rotation speed, $\langle v_\varphi\rangle$, as well as fluxes of mass, momentum, and kinetic energy. Quantities that do not depend on $B_{\rm i}$ include the plasma-$\beta$ of the transported material which, in all cases, seems to asymptote to order unity. Jets are launched by a combination of the 'magnetic tower' and 'bead-on-a-wire' mechanisms, with the former accounting for most of the jet acceleration---even for strong fields---and continuing well beyond the fast magnetosonic point. At no time does the leading bow shock leave the domain and, as such, these simulations generate large-scale jets that reproduce many of the observed properties of protostellar jets including their characteristic speeds and transported fluxes.Comment: 26 pages, 16 figures. Accepted for publication in MNRA

Rapid turnover of hyphae of mycorrhizal fungi determined by AMS microanalysis of C-14

Processes in the soil remain among the least well-characterized components of the carbon cycle. Arbuscular mycorrhizal (AM) fungi are ubiquitous root symbionts in many terrestrial ecosystems and account for a large fraction of photosynthate in a wide range of ecosystems; they therefore play a key role in the terrestrial carbon cycle. A large part of the fungal mycelium is outside the root ( the extraradical mycelium, ERM) and, because of the dispersed growth pattern and the small diameter of the hyphae (<5 micrometers), exceptionally difficult to study quantitatively. Critically, the longevity of these. ne hyphae has never been measured, although it is assumed to be short. To quantify carbon turnover in these hyphae, we exposed mycorrhizal plants to fossil ("carbon-14 - dead") carbon dioxide and collected samples of ERM hyphae ( up to 116 micrograms) over the following 29 days. Analyses of their carbon-14 content by accelerator mass spectrometry (AMS) showed that most ERM hyphae of AM fungi live, on average, 5 to 6 days. This high turnover rate reveals a large and rapid mycorrhizal pathway of carbon in the soil carbon cycle

Revivals of Coherence in Chaotic Atom-Optics Billiards

We investigate the coherence properties of thermal atoms confined in optical dipole traps where the underlying classical dynamics is chaotic. A perturbative expression derived for the coherence of the echo scheme of [Andersen et. al., Phys. Rev. Lett. 90, 023001 (2003)] shows it is a function of the survival probability or fidelity of eigenstates of the motion of the atoms in the trap. The echo coherence and the survival probability display "system specific" features, even when the underlying classical dynamics is chaotic. In particular, partial revivals in the echo signal and the survival probability are found for a small shift of the potential. Next, a "semi-classical" expression for the averaged echo signal is presented and used to calculate the echo signal for atoms in a light sheet wedge billiard. Revivals in the echo coherence are found in this system, indicating they may be a generic feature of dipole traps