Redox control of multidrug resistance and Its possible modulation by antioxidants

Clinical efficacy of anticancer chemotherapies is dramatically hampered by multidrug resistance (MDR) dependent on inherited traits, acquired defence against toxins, and adaptive mechanisms mounting in tumours. There is overwhelming evidence that molecular events leading to MDR are regulated by redox mechanisms. For example, chemotherapeutics which overrun the first obstacle of redox-regulated cellular uptake channels (MDR1, MDR2, and MDR3) induce a concerted action of phase I/II metabolic enzymes with a temporal redox-regulated axis. This results in rapid metabolic transformation and elimination of a toxin. This metabolic axis is tightly interconnected with the inducible Nrf2-linked pathway, a key switch-on mechanism for upregulation of endogenous antioxidant enzymes and detoxifying systems. As a result, chemotherapeutics and cytotoxic by-products of their metabolism (ROS, hydroperoxides, and aldehydes) are inactivated and MDR occurs. On the other hand, tumour cells are capable of mounting an adaptive antioxidant response against ROS produced by chemotherapeutics and host immune cells. The multiple redox-dependent mechanisms involved in MDR prompted suggesting redox-active drugs (antioxidants and prooxidants) or inhibitors of inducible antioxidant defence as a novel approach to diminish MDR. Pitfalls and progress in this direction are discussed

Sensitive Search for a Permanent Muon Electric Dipole Moment

We are proposing a new method to carry out a dedicated search for a permanent electric dipole moment (EDM) of the muon with a sensitivity at a level of 10^{-24} e cm. The experimental design exploits the strong motional electric field sensed by relativistic particles in a magnetic storage ring. As a key feature, a novel technique has been invented in which the g-2 precession is compensated with radial electric field. This technique will benefit greatly when the intense muon sources advocated by the developers of the muon storage rings and the muon colliders become available.Comment: 16 pages, 3 figures. Submitted for publication in Proceedings of the International Workshop on High Intensity Muon Sources (HIMUS99), KEK, Japan, December 1-4 199

Improved Measurement of the Positive Muon Lifetime and Determination of the Fermi Constant

The mean life of the positive muon has been measured to a precision of 11 ppm using a low-energy, pulsed muon beam stopped in a ferromagnetic target, which was surrounded by a scintillator detector array. The result, tau_mu = 2.197013(24) us, is in excellent agreement with the previous world average. The new world average tau_mu = 2.197019(21) us determines the Fermi constant G_F = 1.166371(6) x 10^-5 GeV^-2 (5 ppm). Additionally, the precision measurement of the positive muon lifetime is needed to determine the nucleon pseudoscalar coupling g_P.Comment: As published version (PRL, July 2007

An Improved Limit on the Muon Electric Dipole Moment

Three independent searches for an electric dipole moment (EDM) of the positive and negative muons have been performed, using spin precession data from the muon g-2 storage ring at Brookhaven National Laboratory. Details on the experimental apparatus and the three analyses are presented. Since the individual results on the positive and negative muon, as well as the combined result, d=-0.1(0.9)E-19 e-cm, are all consistent with zero, we set a new muon EDM limit, |d| < 1.9E-19 e-cm (95% C.L.). This represents a factor of 5 improvement over the previous best limit on the muon EDM.Comment: 19 pages, 15 figures, 7 table

Polarised Quark Distributions in the Nucleon from Semi-Inclusive Spin Asymmetries

We present a measurement of semi-inclusive spin asymmetries for positively and negatively charged hadrons from deep inelastic scattering of polarised muons on polarised protons and deuterons in the range $0.003$1 GeV$^2$. Compared to our previous publication on this subject, with the new data the statistical errors have been reduced by nearly a factor of two. From these asymmetries and our inclusive spin asymmetries we determine the polarised quark distributions of valence quarks and non-strange sea quarks at $Q^2$=10 GeV$^2$. The polarised $u$ valence quark distribution, $\Delta u_v(x)$, is positive and the polarisation increases with $x$. The polarised $d$ valence quark distribution, $\Delta d_v(x)$, is negative and the non-strange sea distribution, $\Delta \bar q(x)$, is consistent with zero over the measured range of $x$. We find for the first moments $\int_0^1 \Delta u_v(x) dx = 0.77 \pm 0.10 \pm 0.08$, $\int_0^1 \Delta d_v(x) dx = -0.52 \pm 0.14 \pm 0.09$ and $\int_0^1 \Delta \bar q(x) dx= 0.01 \pm 0.04 \pm 0.03$, where we assumed $\Delta \bar u(x) = \Delta \bar d(x)$. We also determine for the first time the second moments of the valence distributions $\int_0^1 x \Delta q_v(x) dx$.Comment: 17 page

Spin Structure of the Proton from Polarized Inclusive Deep-Inelastic Muon-Proton Scattering

We have measured the spin-dependent structure function $g_1^p$ in inclusive deep-inelastic scattering of polarized muons off polarized protons, in the kinematic range $0.003 < x < 0.7$ and $1 GeV^2 < Q^2 < 60 GeV^2$. A next-to-leading order QCD analysis is used to evolve the measured $g_1^p(x,Q^2)$ to a fixed $Q^2_0$. The first moment of $g_1^p$ at $Q^2_0 = 10 GeV^2$ is $\Gamma^p = 0.136\pm 0.013(stat.) \pm 0.009(syst.)\pm 0.005(evol.)$. This result is below the prediction of the Ellis-Jaffe sum rule by more than two standard deviations. The singlet axial charge $a_0$ is found to be $0.28 \pm 0.16$. In the Adler-Bardeen factorization scheme, $\Delta g \simeq 2$ is required to bring $\Delta \Sigma$ in agreement with the Quark-Parton Model. A combined analysis of all available proton and deuteron data confirms the Bjorken sum rule.Comment: 33 pages, 22 figures, uses ReVTex and smc.sty. submitted to Physical Review