Low dose pramipexole is neuroprotective in the MPTP mouse model of Parkinson's disease, and downregulates the dopamine transporter via the D(3 )receptor

BACKGROUND: Our aim was to determine if pramipexole, a D(3 )preferring agonist, effectively reduced dopamine neuron and fiber loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model when given at intraperitoneal doses corresponding to clinical doses. We also determined whether subchronic treatment with pramipexole regulates dopamine transporter function, thereby reducing intracellular transport of the active metabolite of MPTP, 1-methyl-4-phenylpyridinium (MPP+). METHODS: Ten 12-month old C57BL/6 mice were treated with MPTP (or saline) twice per day at 20 mg/kg s.c. (4 injections over 48 h). Mice were pretreated for 3 days and during the 2-day MPTP regimen with pramipexole (0.1 mg/kg/day) or saline. Stereological quantification of dopamine neuron number and optical density measurement of dopamine fiber loss were carried out at 1 week after treatment, using immunostaining for dopamine transporter (DAT) and tyrosine hydroxylase (TH). Additional wild-type (WT) and D(3 )receptor knockout (KO) mice were treated for 5 days with pramipexole (0.1 mg/kg/day) or vehicle. The kinetics of [(3)H]MPP+ and [(3)H]DA uptake (V(max )and K(m)) were determined 24 h later; and at 24 h and 14 days dopamine transporter density was measured by quantitative autoradiography. RESULTS: Pramipexole treatment completely antagonized the neurotoxic effects of MPTP, as measured by substantia nigra and ventral tegmental area TH-immunoreactive cell counts. MPTP- induced loss of striatal innervation, as measured by DAT-immunoreactivity, was partially prevented by pramipexole, but not with regard to TH-IR. Pramipexole also reduced DAT- immunoreactivity in non-MPTP treated mice. Subchronic treatment with pramipexole lowered the V(max )for [(3)H]DA and [(3)H]MPP(+ )uptake into striatal synaptosomes of WT mice. Pramipexole treatment lowered V(max )in WT but not D(3 )KO mice; however, D(3 )KO mice had lower V(max )for [(3)H]DA uptake. There was no change in DAT number in WT with pramipexole treatment or D(3 )KO mice at 24 h post-treatment, but there was a reduction in WT-pramipexole treated and not in D(3 )KO mice at 14 days post-treatment. CONCLUSION: These results suggest that protection occurs at clinically suitable doses of pramipexole. Protection could be due to a reduced amount of MPP(+ )taken up into DA terminals via DAT. D(3 )receptor plays an important role in this regulation of transporter uptake and availability

A scheme with two large extra dimensions confronted with neutrino physics

We investigate a particle physics model in a six-dimensional spacetime, where two extra dimensions form a torus. Particles with Standard Model charges are confined by interactions with a scalar field to four four-dimensional branes, two vortices accommodating ordinary type fermions and two antivortices accommodating mirror fermions. We investigate the phenomenological implications of this multibrane structure by confronting the model with neutrino physics data.Comment: LATEX, 24 pages, 9 figures, minor changes in the tex

The Drift Chambers Of The Nomad Experiment

We present a detailed description of the drift chambers used as an active target and a tracking device in the NOMAD experiment at CERN. The main characteristics of these chambers are a large area, a self supporting structure made of light composite materials and a low cost. A spatial resolution of 150 microns has been achieved with a single hit efficiency of 97%.Comment: 42 pages, 26 figure

Qweak: A Precision Measurement of the Proton's Weak Charge

The Qweak experiment at Jefferson Lab aims to make a 4% measurement of the parity-violating asymmetry in elastic scattering at very low $Q^2$ of a longitudinally polarized electron beam on a proton target. The experiment will measure the weak charge of the proton, and thus the weak mixing angle at low energy scale, providing a precision test of the Standard Model. Since the value of the weak mixing angle is approximately 1/4, the weak charge of the proton $Q_w^p = 1-4 \sin^2 \theta_w$ is suppressed in the Standard Model, making it especially sensitive to the value of the mixing angle and also to possible new physics. The experiment is approved to run at JLab, and the construction plan calls for the hardware to be ready to install in Hall C in 2007. The theoretical context of the experiment and the status of its design are discussed.Comment: 5 pages, 2 figures, LaTeX2e, to be published in CIPANP 2003 proceeding

Determination of the muon charge sign with the dipolar spectrometers of the OPERA experiment

The OPERA long-baseline neutrino-oscillation experiment has observed the direct appearance of $\nu_\tau$ in the CNGS $\nu_\mu$ beam. Two large muon magnetic spectrometers are used to identify muons produced in the $\tau$ leptonic decay and in $\nu_\mu^{CC}$ interactions by measuring their charge and momentum. Besides the kinematic analysis of the $\tau$ decays, background resulting from the decay of charmed particles produced in $\nu_\mu^{CC}$ interactions is reduced by efficiently identifying the muon track. A new method for the charge sign determination has been applied, via a weighted angular matching of the straight track-segments reconstructed in the different parts of the dipole magnets. Results obtained for Monte Carlo and real data are presented. Comparison with a method where no matching is used shows a significant reduction of up to 40\% of the fraction of wrongly determined charges.Comment: 10 pages. Improvements in the tex

Procedure for short-lived particle detection in the OPERA experiment and its application to charm decays

The OPERA experiment, designed to perform the first observation of $\nu_\mu \rightarrow \nu_\tau$ oscillations in appearance mode through the detection of the $\tau$ leptons produced in $\nu_\tau$ charged current interactions, has collected data from 2008 to 2012. In the present paper, the procedure developed to detect $\tau$ particle decays, occurring over distances of the order of 1 mm from the neutrino interaction point, is described in detail. The results of its application to the search for charmed hadrons are then presented as a validation of the methods for $\nu_\tau$ appearance detection

Limits on muon-neutrino to tau-neutrino oscillations induced by a sterile neutrino state obtained by OPERA at the CNGS beam

The OPERA experiment, exposed to the CERN to Gran Sasso $\nu_\mu$ beam, collected data from 2008 to 2012. Four oscillated $\nu_\tau$ Charged Current interaction candidates have been detected in appearance mode, which are consistent with $\nu_\mu \to \nu_\tau$ oscillations at the atmospheric $\Delta m^2$ within the "standard" three-neutrino framework. In this paper, the OPERA $\nu_\tau$ appearance results are used to derive limits on the mixing parameters of a massive sterile neutrino.Comment: 11 pages, 4 figures; reference to Planck result updated in the Introduction. Submitted to JHE

Observation of nu_tau appearance in the CNGS beam with the OPERA experiment

The OPERA experiment is searching for nu_mu -> nu_tau oscillations in appearance mode i.e. via the direct detection of tau leptons in nu_tau charged current interactions. The evidence of nu_mu -> nu_tau appearance has been previously reported with three nu_tau candidate events using a sub-sample of data from the 2008-2012 runs. We report here a fourth nu_tau candidate event, with the tau decaying into a hadron, found after adding the 2012 run events without any muon in the final state to the data sample. Given the number of analysed events and the low background, nu_mu -> nu_tau oscillations are established with a significance of 4.2sigma.Comment: Submitted to Progress of Theoretical and Experimental Physics (PTEP