Precision measurement of the weak mixing angle in Møller scattering.

We report on a precision measurement of the parity-violating asymmetry in fixed target electron-electron (Møller) scattering: A(PV) = [-131 +/- 14(stat) +/- 10(syst)] x 10(-9), leading to the determination of the weak mixing angle sin2(thetaW(eff) = 0.2397 +/- 0.0010(stat) +/- 0.0008(syst), evaluated at Q2 = 0.026 GeV2. Combining this result with the measurements of sin2(thetaW(eff) at the Z0 pole, the running of the weak mixing angle is observed with over 6sigma significance. The measurement sets constraints on new physics effects at the TeV scale.

Observation of parity nonconservation in møller scattering.

We report a measurement of the parity-violating asymmetry in fixed target electron-electron (Møller) scattering: A(PV)=[-175+/-30(stat)+/-20(syst)] x 10(-9). This first direct observation of parity nonconservation in Møller scattering leads to a measurement of the electron's weak charge at low energy Q(e)(W)=-0.053+/-0.011. This is consistent with the standard model expectation at the current level of precision: sin((2)theta(W)(M(Z))((-)MS)=0.2293+/-0.0024(stat)+/-0.0016(syst)+/-0.0006(theory).

Dynamical relativistic effects in quasielastic 1p-shell proton knockout from 16O

We have measured the cross section for quasielastic 1p-shell proton knockout in the 16O(e,e(')p) reaction at omega = 0.439 GeV and Q2 = 0.8 (GeV/c)(2) for missing momentum P(miss)

Preclinical pharmacokinetics and interspecies scaling of a novel vitronectin receptor antagonist.

Allometric scaling may be used in drug development to predict the pharmacokinetics of xenobiotics in humans from animal data. Although allometry may be successful for compounds that are excreted unchanged or that are oxidatively metabolized (with corrections for metabolic capacity), it has been more challenging for compounds excreted primarily as conjugates in bile. (S)-10, 11-Dihydro-3-[3-(pyridin-2-ylamino)-1-propyloxy]-5H-dibenzo[ a, d]cycloheptene-10-acetic acid (SB-265123) is a novel alphavbeta3 ("vitronectin receptor") antagonist. In this study, the in vivo pharmacokinetics and in vitro plasma protein binding of SB-265123 were examined in four species: mice, rats, dogs, and monkeys. In monkeys and dogs, SB-265123 exhibited moderate clearance, whereas low clearance (<20% hepatic blood flow) was observed in the rat, and high clearance (>70% hepatic blood flow) was seen in the mouse. The concentration-time profiles indicated the possibility of enterohepatic recirculation; subsequent studies in bile duct-cannulated rats demonstrated extensive biliary excretion of an acyl-glucuronide of SB-265123. In allometric scaling to predict the disposition of SB-265123 in humans, various standard correction factors were applied, including protein binding, maximum lifespan potential, and brain weight; each failed to produce adequate interspecies scaling of clearance (r(2) < 0.72). Consequently, a novel correction factor incorporating bile flow and microsomal UDP-glucuronosyltransferase activity in each species was applied, demonstrating substantial improvement in the correlation of the allometric plot (r(2) = 0.96). This study demonstrates a novel allometric correction that may be applicable to compounds that undergo conjugation and biliary excretion.

High-performance liquid chromatographic determination of cilastatin in biological fluids.

Cilastatin, a dehydropeptidase-I inhibitor, is coadministered with the beta-lactam antibiotic imipenem. The described procedure was developed for quantification of cilastatin in human plasma and urine. The assay involved sample purification on a C18 extraction cartridge, reversed-phase high-performance liquid chromatography with post-column derivatization and fluorescence detection. Standard curves were linear from 0.75 to 75.0 micrograms/ml in plasma and from 2.5 to 200.0 micrograms/ml in urine. Intra-day mean coefficients of variation at concentrations within the standard curve range were 4.2 +/- 2.4% and 3.1 +/- 1.7% in plasma and urine, respectively. The inter-day coefficients of variation for analyses of cilastatin in plasma (1.0 and 50.5 micrograms/ml) were less than 10% after 31 days of analysis while those for urine (5.0 and 74.1 micrograms/ml) were less than 11% after 44 days of analysis. The limits of reliable detection were 0.75 and 2.5 micrograms/ml in plasma and urine, respectively. This procedure met the sensitivity and specificity requirements for the analysis of samples from clinical pharmacokinetic studies.