Opposing synaptic regulation of amyloid-β metabolism by NMDA receptors in vivo

The concentration of amyloid-β (Aβ) within the brain extracellular space is one determinant of whether the peptide will aggregate into toxic species that are important in Alzheimer’s disease (AD) pathogenesis. Some types of synaptic activity can regulate Aβ levels. Here we demonstrate two distinct mechanisms that are simultaneously activated by NMDA receptors and regulate brain interstitial fluid (ISF) Aβ levels in opposite directions in the living mouse. Depending on the dose of NMDA administered locally to the brain, ISF Aβ levels either increase or decrease. Low doses of NMDA increase action potentials and synaptic transmission which leads to an elevation in synaptic Aβ generation. In contrast, high doses of NMDA activate signaling pathways that lead to ERK (extracellular-regulated kinase) activation, which reduces processing of APP into Aβ. This depression in Aβ via APP processing occurs despite dramatically elevated synaptic activity. Both of these synaptic mechanisms are simultaneously active, with the balance between them determining whether ISF Aβ levels will increase or decrease. NMDA receptor antagonists increase ISF Aβ levels, suggesting that basal activity at these receptors normally suppresses Aβ levels in vivo. This has implications for understanding normal Aβ metabolism as well as AD pathogenesis

Localization length in a random magnetic field

Kubo formula is used to get the d.c conductance of a statistical ensemble of two dimensional clusters of the square lattice in the presence of random magnetic fluxes. Fluxes traversing lattice plaquettes are distributed uniformly between minus one half and plus one half of the flux quantum. The localization length is obtained from the exponential decay of the averaged conductance as a function of the cluster side. Standard results are recovered when this numerical approach is applied to Anderson model of diagonal disorder. The localization length of the complex non-diagonal model of disorder remains well below 10 000 (in units of the lattice constant) in the main part of the band in spite of its exponential increase near the band edges.Comment: 12 two-column pages including 10 figures (epsfig), revtex, to appear in PR

Signatures of Stripe Phases in Hole Doped La2NiO4La_2NiO_4

We study nickelate-centered and oxygen-centered stripe phases in doped La$_{2}$NiO$_{4}$ materials. We use an inhomogeneous Hartree-Fock and random-phase approximation approach including both electron-electron and electron-lattice(e-l) coupling for a layer of La$_{2}$NiO$_{4}$. We find that whether the ground state after commensurate hole doping comprises Ni-centered or O-centered charge-localized stripes depends sensitively on the e-l interaction. With increasing e-l interaction strength, a continuous transition from an O-centered stripe phase to a Ni-centered one is found. Various low- and high-energy signatures of these two kinds of stripe phases are predicted, which can clearly distinguish them. These signatures reflect the strongly correlated spin-charge-lattice features in the vicinity of Ni-centered or O-centered stripe domains. The importance of e-l interaction for recent experiments on stripe phases is discussed.Comment: 11 pages, 12 figures, to appear in Phys.Rev.B(July 1,1998

Optimal trapping wavelengths of Cs2_2 molecules in an optical lattice

The present paper aims at finding optimal parameters for trapping of Cs$_2$ molecules in optical lattices, with the perspective of creating a quantum degenerate gas of ground-state molecules. We have calculated dynamic polarizabilities of Cs$_2$ molecules subject to an oscillating electric field, using accurate potential curves and electronic transition dipole moments. We show that for some particular wavelengths of the optical lattice, called "magic wavelengths", the polarizability of the ground-state molecules is equal to the one of a Feshbach molecule. As the creation of the sample of ground-state molecules relies on an adiabatic population transfer from weakly-bound molecules created on a Feshbach resonance, such a coincidence ensures that both the initial and final states are favorably trapped by the lattice light, allowing optimized transfer in agreement with the experimental observation

Formulae for zero-temperature conductance through a region with interaction

The zero-temperature linear response conductance through an interacting mesoscopic region attached to noninteracting leads is investigated. We present a set of formulae expressing the conductance in terms of the ground-state energy or persistent currents in an auxiliary system, namely a ring threaded by a magnetic flux and containing the correlated electron region. We first derive the conductance formulae for the noninteracting case and then give arguments why the formalism is also correct in the interacting case if the ground state of a system exhibits Fermi liquid properties. We prove that in such systems, the ground-state energy is a universal function of the magnetic flux, where the conductance is the only parameter. The method is tested by comparing its predictions with exact results and results of other methods for problems such as the transport through single and double quantum dots containing interacting electrons. The comparisons show an excellent quantitative agreement.Comment: 18 pages, 18 figures; to appear in Phys. Rev.

The interplay between double exchange, super-exchange, and Lifshitz localization in doped manganites

Considering the disorder caused in manganites by the substitution of Mn by Fe or Ga, we accomplish a systematic study of doped manganites begun in previous papers. To this end, a disordered model is formulated and solved using the Variational Mean Field technique. The subtle interplay between double exchange, super-exchange, and disorder causes similar effects on the dependence of T_C on the percentage of Mn substitution in the cases considered. Yet, in La$_{2/3}$Ca$_{1/3}$Mn$_{1-y}$Ga$_y$O$_3$ our results suggest a quantum critical point (QCP) for $y\approx 0.1-0.2$, associated to the localization of the electronic states of the conduction band. In the case of La$_x$Ca$_x$Mn$_{1-y}$Fe$_y$O$_3$ (with $x=1/3,3/8$) no such QCP is expected.Comment: 6 pages + 3 postscript figures. Largely extended discussio

Constrained-path quantum Monte Carlo simulations of the zero-temperature disordered two-dimensional Hubbard model

We study the effects of disorder on long-range antiferromagnetic correlations in the half-filled, two dimensional, repulsive Hubbard model at T=0. A mean field approach is first employed to gain a qualitative picture of the physics and to guide our choice for a trial wave function in a constrained path quantum Monte Carlo (CPQMC) method that allows for a more accurate treatment of correlations. Within the mean field calculation, we observe both Anderson and Mott insulating antiferromagnetic phases. There are transitions to a paramagnet only for relatively weak coupling, U < 2t in the case of bond disorder, and U < 4t in the case of on-site disorder. Using ground-state CPQMC we demonstrate that this mean field approach significantly overestimates magnetic order. For U=4t, we find a critical bond disorder of Vc = (1.6 +- 0.4)t even though within mean field theory no paramagnetic phase is found for this value of the interaction. In the site disordered case, we find a critical disorder of Vc = (5.0 +- 0.5)t at U=4t.Comment: Revtex, 13 pages, 15 figures. Minor changes to title and abstract, discussion and references added, figures 5, 6, 8, 9 replaced with easier to read version

Pairing fluctuations and pseudogaps in the attractive Hubbard model

The two-dimensional attractive Hubbard model is studied in the weak to intermediate coupling regime by employing a non-perturbative approach. It is first shown that this approach is in quantitative agreement with Monte Carlo calculations for both single-particle and two-particle quantities. Both the density of states and the single-particle spectral weight show a pseudogap at the Fermi energy below some characteristic temperature T*, also in good agreement with quantum Monte Carlo calculations. The pseudogap is caused by critical pairing fluctuations in the low-temperature renormalized classical regime $\omega < T$ of the two-dimensional system. With increasing temperature the spectral weight fills in the pseudogap instead of closing it and the pseudogap appears earlier in the density of states than in the spectral function. Small temperature changes around T* can modify the spectral weight over frequency scales much larger than temperature. Several qualitative results for the s-wave case should remain true for d-wave superconductors.Comment: 20 pages, 12 figure

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

<p>Abstract</p> <p>Background</p> <p>Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.</p> <p>Methods</p> <p>Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂= 80%) and hyperoxic (FiO₂= 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.</p> <p>Results</p> <p>Hypoxia enhanced hyperpnoea-induced P_di,twand P_ga,twreductions both immediately after hyperpnoea (P_di,tw: normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw: normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all <it>P </it>< 0.05) and after 30 min of recovery (P_di,tw: normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw: normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all <it>P </it>< 0.05). No significant difference in P_di,twor P_ga,twreductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.</p> <p>Conclusions</p> <p>These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂transport as during exercise in altitude or in hypoxemic patients.</p

CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver

This work was funded by a Wellcome Trust Investigator Award to MKM funding KS and LP, MRC Career Development Award to CD, MRC Clinical Research Training Fellowship to DP, Wellcome Trust Henry Dale Fellowship to VM