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Proneurogenic compounds have recently shown promise in some mouse models of Alzheimer's pathology. Antagonists at Group II metabotropic glutamate receptors (Group II mGluR: mGlu2, mGlu3) are reported to stimulate neurogenesis. Agonists at those receptors trigger γ-secretase-inhibitor-sensitive biogenesis of Aβ42 peptides from isolated synaptic terminals, which is selectively suppressed by antagonist pretreatment. We have assessed the therapeutic potential of chronic pharmacological inhibition of Group II mGluR in Dutch APP (Alzheimer's amyloid precursor protein E693Q) transgenic mice that accumulate Dutch amyloid-β (Aβ) oligomers but never develop Aβ plaques. BCI-838 is a clinically well-tolerated, orally bioavailable, investigational prodrug that delivers to the brain BCI-632, the active Group II mGluR antagonist metabolite. Dutch Aβ-oligomer-forming APP transgenic mice (APP E693Q) were dosed with BCI-838 for 3 months. Chronic treatment with BCI-838 was associated with reversal of transgene-related amnestic behavior, reduction in anxiety, reduction in levels of brain Aβ monomers and oligomers, and stimulation of hippocampal neurogenesis. Group II mGluR inhibition may offer a unique package of relevant properties as an Alzheimer's disease therapeutic or prophylactic by providing both attenuation of neuropathology and stimulation of repair.

The transport of thermal plasma and fast ions in electrostatic microturbulence is studied. Strong density and potential fluctuations (δn/n ∼ δ/kTe ∼ 0.5, f ∼ 5-50 kHz) are observed in the large plasma device (LAPD) [W. Gekelman, H. Pfister, Z. Lucky, Rev. Sci. Instrum. 62, 2875 (1991)] in density gradient regions produced by obstacles with slab or cylindrical geometry. Wave characteristics and the associated plasma transport are modified by driving sheared E × B drift through biasing the obstacle and by modification of the axial magnetic fields (Bz) and the plasma species. Cross-field plasma transport is suppressed with small bias and large Bz and is enhanced with large bias and small Bz. The transition in thermal plasma confinement is well explained by the cross-phase between density and potential fluctuations. Large gyroradius lithium fast ion beam (ρfast/ρs ∼ 10) orbits through the turbulent region. Scans with a collimated analyzer give detailed profiles of the fast ion spatial-temporal distribution. Fast-ion transport decreases rapidly with increasing fast-ion energy and gyroradius. Background waves with different scale lengths also alter the fast ion transport. Experimental results agree well with gyro-averaging theory. When the fast ion interacts with the wave for most of a wave period, a transition from super-diffusive to sub-diffusive transport is observed, as predicted by diffusion theory. Besides turbulent-wave-induced fast-ion transport, the static radial electric field (Er) from biasing the obstacle leads to drift of the fast-ion beam centroid. The drift and broadening of the beam due to static Er are evaluated both analytically and numerically. Simulation results indicate that the Er induced transport is predominately convective. © 2012 American Institute of Physics.

The transport of thermal plasma and fast ions in electrostatic microturbulence is studied. Strong density and potential fluctuations (δn/n ∼ δ/kTe ∼ 0.5, f ∼ 5-50 kHz) are observed in the large plasma device (LAPD) [W. Gekelman, H. Pfister, Z. Lucky, Rev. Sci. Instrum. 62, 2875 (1991)] in density gradient regions produced by obstacles with slab or cylindrical geometry. Wave characteristics and the associated plasma transport are modified by driving sheared E × B drift through biasing the obstacle and by modification of the axial magnetic fields (Bz) and the plasma species. Cross-field plasma transport is suppressed with small bias and large Bz and is enhanced with large bias and small Bz. The transition in thermal plasma confinement is well explained by the cross-phase between density and potential fluctuations. Large gyroradius lithium fast ion beam (ρfast/ρs ∼ 10) orbits through the turbulent region. Scans with a collimated analyzer give detailed profiles of the fast ion spatial-temporal distribution. Fast-ion transport decreases rapidly with increasing fast-ion energy and gyroradius. Background waves with different scale lengths also alter the fast ion transport. Experimental results agree well with gyro-averaging theory. When the fast ion interacts with the wave for most of a wave period, a transition from super-diffusive to sub-diffusive transport is observed, as predicted by diffusion theory. Besides turbulent-wave-induced fast-ion transport, the static radial electric field (Er) from biasing the obstacle leads to drift of the fast-ion beam centroid. The drift and broadening of the beam due to static Er are evaluated both analytically and numerically. Simulation results indicate that the Er induced transport is predominately convective. © 2012 American Institute of Physics.

A magnetized plasma cylinder (12 cm in diameter) is induced by an annular shape obstacle at the Large Plasma Device [W. Gekelman, H. Pfister, Z. Lucky, J. Bamber, D. Leneman, and J. Maggs, Rev. Sci. Instrum. 62, 2875 (1991)]. Sheared azimuthal flow is driven at the edge of the plasma cylinder through edge biasing. Strong fluctuations of density and potential ( n / n ~ e / kT e ~ 0. 5) are observed at the plasma edge, accompanied by a large density gradient (L n = ∇ ln n - 1 ~ 2 cm) and shearing rate ( ~ 300 kHz). Edge turbulence and cross-field transport are modified by changing the bias voltage (V bias) on the obstacle and the axial magnetic field (B z) strength. In cases with low V bias and large B z, improved plasma confinement is observed, along with steeper edge density gradients. The radially sheared flow induced by E B drift dramatically changes the cross-phase between density and potential fluctuations, which causes the wave-induced particle flux to reverse its direction across the shear layer. In cases with higher bias voltage or smaller B z, large radial transport and rapid depletion of the central plasma density are observed. Two-dimensional cross-correlation measurement shows that a mode with azimuthal mode number m = 1 and large radial correlation length dominates the outward transport in these cases. Linear analysis based on a two-fluid Braginskii model suggests that the fluctuations are driven by both density gradient (drift wave like) and flow shear (Kelvin-Helmholtz like) at the plasma edge. © 2012 American Institute of Physics.

A magnetized plasma cylinder (12 cm in diameter) is induced by an annular shape obstacle at the Large Plasma Device [W. Gekelman, H. Pfister, Z. Lucky, J. Bamber, D. Leneman, and J. Maggs, Rev. Sci. Instrum. 62, 2875 (1991)]. Sheared azimuthal flow is driven at the edge of the plasma cylinder through edge biasing. Strong fluctuations of density and potential ( n / n ~ e / kT e ~ 0. 5) are observed at the plasma edge, accompanied by a large density gradient (L n = ∇ ln n - 1 ~ 2 cm) and shearing rate ( ~ 300 kHz). Edge turbulence and cross-field transport are modified by changing the bias voltage (V bias) on the obstacle and the axial magnetic field (B z) strength. In cases with low V bias and large B z, improved plasma confinement is observed, along with steeper edge density gradients. The radially sheared flow induced by E B drift dramatically changes the cross-phase between density and potential fluctuations, which causes the wave-induced particle flux to reverse its direction across the shear layer. In cases with higher bias voltage or smaller B z, large radial transport and rapid depletion of the central plasma density are observed. Two-dimensional cross-correlation measurement shows that a mode with azimuthal mode number m = 1 and large radial correlation length dominates the outward transport in these cases. Linear analysis based on a two-fluid Braginskii model suggests that the fluctuations are driven by both density gradient (drift wave like) and flow shear (Kelvin-Helmholtz like) at the plasma edge. © 2012 American Institute of Physics.

Strong turbulent waves (nn ∼0.5, f ∼5-40 kHz) are observed in the upgraded Large Plasma Device W. Gekelman, H. Pfister, Z. Lucky, J. Bamber, D. Leneman, and J. Maggs, Rev. Sci. Instrum. 62, 2875 (1991) on density gradients produced by an annular obstacle. Energetic lithium ions (E fast / T i 300, fast / s ∼ 10) orbit through the turbulent region. Scans with a collimated analyzer and with probes give detailed profiles of the fast ion spatial distribution and of the fluctuating wave fields. The characteristics of the fluctuations are modified by changing the plasma species from helium to neon and by modifying the bias on the obstacle. Different spatial structure sizes (L s) and correlation lengths (Lcorr) of the wave potential fields alter the fast ion transport. The effects of electrostatic fluctuations are reduced due to gyro-averaging, which explains the difference in the fast-ion transport. A transition from super-diffusive to sub-diffusive transport is observed when the fast ion interacts with the waves for most of a wave period, which agrees with theoretical predictions. © 2011 American Institute of Physics.

Strong turbulent waves (nn ∼0.5, f ∼5-40 kHz) are observed in the upgraded Large Plasma Device W. Gekelman, H. Pfister, Z. Lucky, J. Bamber, D. Leneman, and J. Maggs, Rev. Sci. Instrum. 62, 2875 (1991) on density gradients produced by an annular obstacle. Energetic lithium ions (E fast / T i 300, fast / s ∼ 10) orbit through the turbulent region. Scans with a collimated analyzer and with probes give detailed profiles of the fast ion spatial distribution and of the fluctuating wave fields. The characteristics of the fluctuations are modified by changing the plasma species from helium to neon and by modifying the bias on the obstacle. Different spatial structure sizes (L s) and correlation lengths (Lcorr) of the wave potential fields alter the fast ion transport. The effects of electrostatic fluctuations are reduced due to gyro-averaging, which explains the difference in the fast-ion transport. A transition from super-diffusive to sub-diffusive transport is observed when the fast ion interacts with the waves for most of a wave period, which agrees with theoretical predictions. © 2011 American Institute of Physics.

The Doppler-shifted cyclotron resonance between fast ions and shear Alfv́n waves (SAWs) has been experimentally investigated with a test-particle fast-ion (Li+) beam launched in the helium plasma of the Large Plasma Device [Gekelman, Rev. Sci. Instrum. 62, 2875 (1991)]. Left- or right-hand circularly polarized SAWs are launched by an antenna with four current channels. A collimated fast-ion energy analyzer characterizes the resonance by measuring the nonclassical spreading of the averaged beam signal. Left-hand circularly polarized SAWs resonate with the fast ions but right-hand circularly polarized SAWs do not. The measured fast-ion profiles are compared with simulations by a Monte Carlo Lorentz code that uses the measured wave field data. © 2009 American Institute of Physics.

The Doppler-shifted cyclotron resonance between fast ions and shear Alfv́n waves (SAWs) has been experimentally investigated with a test-particle fast-ion (Li+) beam launched in the helium plasma of the Large Plasma Device [Gekelman, Rev. Sci. Instrum. 62, 2875 (1991)]. Left- or right-hand circularly polarized SAWs are launched by an antenna with four current channels. A collimated fast-ion energy analyzer characterizes the resonance by measuring the nonclassical spreading of the averaged beam signal. Left-hand circularly polarized SAWs resonate with the fast ions but right-hand circularly polarized SAWs do not. The measured fast-ion profiles are compared with simulations by a Monte Carlo Lorentz code that uses the measured wave field data. © 2009 American Institute of Physics.

The Doppler-shifted cyclotron resonance (ω- kzvz = f) between fast ions and shear Alfv́n waves is experimentally investigated (ω, wave frequency; kz, axial wavenumber; vz, fast-ion axial speed; f, fast-ion cyclotron frequency). A test particle beam of fast ions is launched by a Li+ source in the helium plasma of the LArge Plasma Device (LAPD) [W. Gekelman, H. Pfister, Z. Lucky, J. Bamber, D. Leneman, and J. Maggs, Rev. Sci. Instrum. 62, 2875 (1991)], with shear Alfv́n waves (SAW) (amplitude δ B/B up to 1%) launched by a loop antenna. A collimated fast-ion energy analyzer measures the nonclassical spreading of the beam, which is proportional to the resonance with the wave. A resonance spectrum is observed by launching SAWs at 0.3-0.8 ωci. Both the magnitude and frequency dependence of the beam-spreading are in agreement with the theoretical prediction using a Monte Carlo Lorentz code that launches fast ions with an initial spread in real/velocity space and random phases relative to the wave. Measured wave magnetic field data are used in the simulation. © 2008 American Institute of Physics.

The Doppler-shifted cyclotron resonance (ω- kzvz = f) between fast ions and shear Alfv́n waves is experimentally investigated (ω, wave frequency; kz, axial wavenumber; vz, fast-ion axial speed; f, fast-ion cyclotron frequency). A test particle beam of fast ions is launched by a Li+ source in the helium plasma of the LArge Plasma Device (LAPD) [W. Gekelman, H. Pfister, Z. Lucky, J. Bamber, D. Leneman, and J. Maggs, Rev. Sci. Instrum. 62, 2875 (1991)], with shear Alfv́n waves (SAW) (amplitude δ B/B up to 1%) launched by a loop antenna. A collimated fast-ion energy analyzer measures the nonclassical spreading of the beam, which is proportional to the resonance with the wave. A resonance spectrum is observed by launching SAWs at 0.3-0.8 ωci. Both the magnitude and frequency dependence of the beam-spreading are in agreement with the theoretical prediction using a Monte Carlo Lorentz code that launches fast ions with an initial spread in real/velocity space and random phases relative to the wave. Measured wave magnetic field data are used in the simulation. © 2008 American Institute of Physics.