Isoscalar off-shell effects in threshold pion production from pd collisions

We test the presence of pion-nucleon isoscalar off-shell effects in the $pd\to \pi^+ t$ reaction around the threshold region. We find that these effects significantly modify the production cross section and that they may provide the missing strength needed to reproduce the data at threshold.Comment: 6 pages, REVTeX, twocolumn, including 3 figures (Postscript), uses psfig, updated and extended versio

Faddeev Calculations of Proton-Deuteron Radiative Capture with Exchange Currents

pd capture processes at various energies have been analyzed based on solutions of 3N-Faddeev equations and using modern NN forces. The application of the Siegert theorem is compared to the explicit use of $\pi$- and $\rho$-like exchange currents connected to the AV18 NN interaction. Overall good agreement with cross sections and spin observables has been obtained but leaving room for improvement in some cases. Feasibility studies for 3NF's consistently included in the 3N continuum and the 3N bound state have been performed as well.Comment: Minor changes in notation, ps files for figure

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

Observation of the Charge Symmetry Breaking d + d -> 4He + pi0 Reaction Near Threshold

We report the first observation of the charge symmetry breaking d + d -> 4He + pi0 reaction near threshold at the Indiana University Cyclotron Facility. Kinematic reconstruction permitted the separation of 4He + pi0 events from double radiative capture 4He + gamma + gamma events. We measured total cross sections for neutron pion production of 12.7 +- 2.2 pb at 228.5 MeV and 15.1 +- 3.1 pb at 231.8 MeV. The uncertainty is dominated by statistical errors.Comment: 7 pages, 2 figures, plain Te

The pd <--> pi+ t reaction around the Delta resonance

The pd pi+ t process has been calculated in the energy region around the Delta-resonance with elementary production/absorption mechanisms involving one and two nucleons. The isobar degrees of freedom have been explicitly included in the two-nucleon mechanism via pi-- and rho-exchange diagrams. No free parameters have been employed in the analysis since all the parameters have been fixed in previous studies on the simpler pp pi+ d process. The treatment of the few-nucleon dynamics entailed a Faddeev-based calculation of the reaction, with continuum calculations for the initial p-d state and accurate solutions of the three-nucleon bound-state equation. The integral cross-section was found to be quite sensitive to the NN interaction employed while the angular dependence showed less sensitivity. Approximately a 4% effect was found for the one-body mechanism, for the three-nucleon dynamics in the p-d channel, and for the inclusion of a large, possibly converged, number of three-body partial states, indicating that these different aspects are of comparable importance in the calculation of the spin-averaged observables.Comment: 40 Pages, RevTex, plus 5 PostScript figure

Studies of Pi° Production Near Threshold

Supported by the National Science Foundation and Indiana Universit

Proton-deuteron radiative capture cross sections at intermediate energies

Differential cross sections of the reaction $p(d,^3{\rm He})\gamma$ have been measured at deuteron laboratory energies of 110, 133 and 180 MeV. The data were obtained with a coincidence setup measuring both the outgoing $^3$He and the photon. The data are compared with modern calculations including all possible meson-exchange currents and two- and three- nucleon forces in the potential. The data clearly show a preference for one of the models, although the shape of the angular distribution cannot be reproduced by any of the presented models.Comment: 6 pages, 6 figures, accepted for publication in EPJ

Mechanism-based pharmacokinetic-pharmacodynamic modeling of the dopamine D-2 receptor occupancy of olanzapine in rats

A mechanism-based PK-PD model was developed to predict the time course of dopamine D-2 receptor occupancy (D2RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of olanzapine in rats using the exposure (plasma and brain concentration) and D2RO profile obtained experimentally at various doses (0.01-40 mg/kg) administered by different routes. A two-compartment pharmacokinetic model was used to describe the plasma pharmacokinetic profile. A hybrid physiology- and mechanism-based model was developed to characterize the D-2 receptor binding in the striatum and was fitted sequentially to the data. The parameters were estimated using nonlinear mixed-effects modeling . Plasma, brain concentration profiles and time course of D2RO were well described by the model; validity of the proposed model is supported by good agreement between estimated association and dissociation rate constants and in vitro values from literature. This model includes both receptor binding kinetics and pharmacokinetics as the basis for the prediction of the D2RO in rats. Moreover, this modeling framework can be applied to scale the in vitro and preclinical information to clinical receptor occupancy

Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis

In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K+ ingestion or rest after exercise. Force can be restored by muscle work or treatment with β2-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na+ channel (Nav1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K+]o. In resting mutant soleus, tetrodotoxin (TTX)-suppressible 22Na uptake and [Na+]i were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P < 0.0001) and repolarized by TTX. Na+,K+ pump–mediated 86Rb uptake was 83% larger than in WT. Salbutamol stimulated 86Rb uptake and reduced [Na+]i both in mutant and WT soleus. Stimulating Na+,K+ pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na+]i with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na+,K+ pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na+]i on the synthesis of Na+,K+ pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na+ influx and show that contractility can be restored by acute stimulation of the Na+,K+ pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in 86Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated muscles. These observations may explain how mild exercise helps locally to prevent severe weakness during an attack of HyperKPP