Observation of metastable Aβ amyloid protofibrils by atomic force microscopy

AbstractBackground: Brain amyloid plaque, a diagnostic feature of Alzheimer's disease (AD), contains an insoluble fibrillar core that is composed primarily of variants of the β-amyloid protein (Aβ). As Aβ amyloid fibrils may initiate neurodegeneration, the inhibition of fibril formation is a possible therapeutic strategy. Very little is known about the early steps of the process, however.Results: Atomic force microscopy was used to follow amyloid fibril formation in vitro by the Aβ variants Aβ1-40 and Aβ1-42. Both variants first form small ordered aggregates that grow slowly and then rapidly disappear, while prototypical amyloid fibrils of two discrete morphologies appear. Aβ1-42 aggregates much more rapidly than Aβ1-40, which is consistent with its connection to early-onset AD. We propose that the metastable intermediate species be called Aβ amyloid protofibrils.Conclusions: Aβ protofibrils are likely to be intermediates in the in vitro assembly of Aβ amyloid fibrils, but their in vivo role has yet to be determined. Numerous reports of a nonfibrillar form of Aβ aggregate in the brains of individuals who are predisposed to AD suggest the existence of a precursor form, possibly the protofibril. Thus, stabilization of Aβ protofibrils may be a useful therapeutic strategy

Role of heavy-meson exchange in pion production near threshold

Recent calculations of $s$-wave pion production have severely underestimated the accurately known $pp\rightarrow pp\pi^0$\ total cross section near threshold. In these calculations, only the single-nucleon axial-charge operator is considered. We have calculated, in addition to the one-body term, the two-body contributions to this reaction that arise from the exchange of mesons. We find that the inclusion of the scalar $\sigma$-meson exchange current (and lesser contributions from other mesons) increases the cross section by about a factor of five, and leads to excellent agreement with the data. The results are neither very sensitive to changes in the distorting potential that generates the $NN$ wave function, nor to different choices for the meson-nucleon form factors. We argue that $pp\rightarrow pp\pi^0$\ data provide direct experimental evidence for meson-exchange contributions to the axial current.Comment: 28 Pages, IU-NTC #93-0

Dependence of pp->pp pi0 near Threshold on the Spin of the Colliding Nucleons

A polarized internal atomic hydrogen target and a stored, polarized beam are used to measure the spin-dependent total cross section Delta_sigma_T/sigma_tot, as well as the polar integrals of the spin correlation coefficient combination A_xx-A_yy, and the analyzing power A_y for pp-> pp pi0 at four bombarding energies between 325 and 400 MeV. This experiment is made possible by the use of a cooled beam in a storage ring. The polarization observables are used to study the contribution from individual partial waves.Comment: 6 pages, 1 table, 4 figures, corrected equations 2 and

Cross section and analyzing power of pol{p}p -> pn pi+ near threshold

The cross section and analyzing power of the pol{p}p -> pn pi+ reaction near threshold are estimated in terms of data obtained from the pol{p}p -> d pi+ and pp -> pp pi0 reactions. A simple final state interaction theory is developed which depends weakly upon the form of the pion-production operator and includes some Coulomb corrections. Within the uncertainties of the model and the input data, the approach reproduces well the measured energy dependence of the total cross section and the proton analyzing power at a fixed pion c.m. angle of 90deg, from threshold to T_p = 330 MeV. The variation of the differential cross section with pion angle is also very encouraging.Comment: 20 pages, Latex including 4 eps figure

Measurement of Inverse Pion Photoproduction at Energies Spanning the N(1440) Resonance

Differential cross sections for the process pi^- p -> gamma n have been measured at Brookhaven National Laboratory's Alternating Gradient Synchrotron with the Crystal Ball multiphoton spectrometer. Measurements were made at 18 pion momenta from 238 to 748 MeV/c, corresponding to E_gamma for the inverse reaction from 285 to 769 MeV. The data have been used to evaluate the gamma n multipoles in the vicinity of the N(1440) resonance. We compare our data and multipoles to previous determinations. A new three-parameter SAID fit yields 36 +/- 7 (GeV)^-1/2 X 10^-3 for the A^n_1/2 amplitude of the P_11.Comment: 14 pages, 8 figures, submitted to PR

A search for two body muon decay signals

Lepton family number violation is tested by searching for $\mu^+\to e^+X^0$ decays among the 5.8$\times 10^8$ positive muon decay events analyzed by the TWIST collaboration. Limits are set on the production of both massless and massive $X^0$ bosons. The large angular acceptance of this experiment allows limits to be placed on anisotropic $\mu^+\to e^+X^0$ decays, which can arise from interactions violating both lepton flavor and parity conservation. Branching ratio limits of order $10^{-5}$ are obtained for bosons with masses of 13 - 80 MeV/c$^2$ and with different decay asymmetries. For bosons with masses less than 13 MeV/c$^{2}$ the asymmetry dependence is much stronger and the 90% limit on the branching ratio varies up to $5.8 \times 10^{-5}$. This is the first study that explicitly evaluates the limits for anisotropic two body muon decays.Comment: 7 pages, 5 figures, 2 tables, accepted by PR

Measurement of the Muon Decay Parameter delta

The muon decay parameter delta has been measured by the TWIST collaboration. We find delta = 0.74964 +- 0.00066(stat.) +- 0.00112(syst.), consistent with the Standard Model value of 3/4. This result implies that the product Pmuxi of the muon polarization in pion decay, Pmu, and the muon decay parameter xi falls within the 90% confidence interval 0.9960 < Pmuxi < xi < 1.0040. It also has implications for left-right-symmetric and other extensions of the Standard Model.Comment: Extended to 5 pages. Referee's comments answere

Bose-Einstein Correlations of Three Charged Pions in Hadronic Z^0 Decays

Bose-Einstein Correlations (BEC) of three identical charged pions were studied in 4 x 10^6 hadronic Z^0 decays recorded with the OPAL detector at LEP. The genuine three-pion correlations, corrected for the Coulomb effect, were separated from the known two-pion correlations by a new subtraction procedure. A significant genuine three-pion BEC enhancement near threshold was observed having an emitter source radius of r_3 = 0.580 +/- 0.004 (stat.) +/- 0.029 (syst.) fm and a strength of \lambda_3 = 0.504 +/- 0.010 (stat.) +/- 0.041 (syst.). The Coulomb correction was found to increase the \lambda_3 value by \~9% and to reduce r_3 by ~6%. The measured \lambda_3 corresponds to a value of 0.707 +/- 0.014 (stat.) +/- 0.078 (syst.) when one takes into account the three-pion sample purity. A relation between the two-pion and the three-pion source parameters is discussed.Comment: 19 pages, LaTeX, 5 eps figures included, accepted by Eur. Phys. J.