Simple model to explain effects of plasma protein binding and tissue binding on calculated volumes of distribution, apparent elimination rate constants and clearances

A simple pharmacokinetic model, incorporating linear plasma protein binding, linear tissue binding, and first order elimination of free (unbound) drug, was studied. If Cl p is the plasma clearance, V f is the “true” volume of distribution of free drug, β is the apparent elimination rate constant, σ is the fraction of the drug which is free in plasma, f is the fraction of the drug which is free in the entire body, k f is the intrinsic elimination rate constant for free drug, and A TB o is the initial amount of drug which is bound to tissues, then the model indicates that the following relationships hold: (1) Cl p = V f σ k f ; (2) β = f k f ; and V dext = (σ/f) V f . Only σ, and not f, can be measured experimentally . Dividing Cl p by σ provides an estimate of the intrinsic clearance of free drug, V f k f . A plot of V dext versus σ has an intercept equal to V f , and the ratio of the slope/intercept is an estimate of A TB o /A f o , where A f o is the initial amount of free drug (equal to V f times initial concentration of free drug in plasma). Thus, an estimate of A TB o may be obtained. Dividing the intrinsic clearance by V f provides an estimate of k f . Thus, theoretically, estimates of V f , k f , A TB o and f may be obtained. The variables are not separated when β is plotted versus σ, and curvature of such plots is expected; no useful information is obtained from such plots.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46634/1/228_2004_Article_BF00563079.pd

Subject-specific, multiscale simulation of electrophysiology: a software pipeline for image-based models and application examples

Many simulation studies in biomedicine are based on a similar sequence of processing steps, starting from images and running through geometric model generation, assignment of tissue properties, numerical simulation and visualization of the results—a process known as image-based geometric modelling and simulation. We present an overview of software systems for implementing such a sequence both within highly integrated problem-solving environments and in the form of loosely integrated pipelines. Loose integration in this case indicates that individual programs function largely independently but communicate through files of a common format and support simple scripting, so as to automate multiple executions wherever possible. We then describe three specific applications of such pipelines to translational biomedical research in electrophysiology

Wigner Functions on a Lattice

The Wigner functions on the one dimensional lattice are studied. Contrary to the previous claim in literature, Wigner functions exist on the lattice with any number of sites, whether it is even or odd. There are infinitely many solutions satisfying the conditions which reasonable Wigner functions should respect. After presenting a heuristic method to obtain Wigner functions, we give the general form of the solutions. Quantum mechanical expectation values in terms of Wigner functions are also discussed.Comment: 11 pages, no figures, REVTE

Self-Consistent Quasi-Particle RPA for the Description of Superfluid Fermi Systems

Self-Consistent Quasi-Particle RPA (SCQRPA) is for the first time applied to a more level pairing case. Various filling situations and values for the coupling constant are considered. Very encouraging results in comparison with the exact solution of the model are obtained. The nature of the low lying mode in SCQRPA is identified. The strong reduction of the number fluctuation in SCQRPA vs BCS is pointed out. The transition from superfluidity to the normal fluid case is carefully investigated.Comment: 23 pages, 18 figures and 1 table, submitted to Phys. Rev.

Linear response within the projection-based renormalization method: Many-body corrections beyond the random phase approximation

The explicit evaluation of linear response coefficients for interacting many-particle systems still poses a considerable challenge to theoreticians. In this work we use a novel many-particle renormalization technique, the so-called projector-based renormalization method, to show how such coefficients can systematically be evaluated. To demonstrate the prospects and power of our approach we consider the dynamical wave-vector dependent spin susceptibility of the two-dimensional Hubbard model and also determine the subsequent magnetic phase diagram close to half-filling. We show that the superior treatment of (Coulomb) correlation and fluctuation effects within the projector-based renormalization method significantly improves the standard random phase approximation results.Comment: 17 pages, 7 figures, revised versio

Observation of a Narrow Resonance of Mass 2.46 GeV/c^2 Decaying to D_s^*+ pi^0 and Confirmation of the D_sJ^* (2317) State

Using 13.5 inverse fb of e+e- annihilation data collected with the CLEO II detector we have observed a narrow resonance in the Ds*+pi0 final state, with a mass near 2.46 GeV. The search for such a state was motivated by the recent discovery by the BaBar Collaboration of a narrow state at 2.32 GeV, the DsJ*(2317)+ that decays to Ds+pi0. Reconstructing the Ds+pi0 and Ds*+pi0 final states in CLEO data, we observe peaks in both of the corresponding reconstructed mass difference distributions, dM(Dspi0)=M(Dspi0)-M(Ds) and dM(Ds*pi0)=M(Ds*pi0)-M(Ds*), both of them at values near 350 MeV. We interpret these peaks as signatures of two distinct states, the DsJ*(2317)+ plus a new state, designated as the DsJ(2463)+. Because of the similar dM values, each of these states represents a source of background for the other if photons are lost, ignored or added. A quantitative accounting of these reflections confirms that both states exist. We have measured the mean mass differences = 350.0 +/- 1.2 [stat] +/- 1.0 [syst] MeV for the DsJ*(2317) state, and = 351.2 +/- 1.7 [stat] +/- 1.0 [syst] MeV for the new DsJ(2463)+ state. We have also searched, but find no evidence, for decays of the two states via the channels Ds*+gamma, Ds+gamma, and Ds+pi+pi-. The observations of the two states at 2.32 and 2.46 GeV, in the Ds+pi0 and Ds*+pi0 decay channels respectively, are consistent with their interpretations as (c anti-strange) mesons with orbital angular momentum L=1, and spin-parities of 0+ and 1+.Comment: 16 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, version to be published in Physical Review D; minor modifications and fixes to typographical errors, plus an added section on production properties. The main results are unchanged; they supersede those reported in hep-ex/030501

Measurement of the Charge Asymmetry in B→K∗(892)±π∓B\to K^* (892)^{\pm}\pi^{\mp}

We report on a search for a CP-violating asymmetry in the charmless hadronic decay B -> K*(892)+- pi-+, using 9.12 fb^-1 of integrated luminosity produced at \sqrt{s}=10.58 GeV and collected with the CLEO detector. We find A_{CP}(B -> K*(892)+- pi-+) = 0.26+0.33-0.34(stat.)+0.10-0.08(syst.), giving an allowed interval of [-0.31,0.78] at the 90% confidence level.Comment: 7 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Study of the q^2-Dependence of B --> pi ell nu and B --> rho(omega)ell nu Decay and Extraction of |V_ub|

We report on determinations of |Vub| resulting from studies of the branching fraction and q^2 distributions in exclusive semileptonic B decays that proceed via the b->u transition. Our data set consists of the 9.7x10^6 BBbar meson pairs collected at the Y(4S) resonance with the CLEO II detector. We measure B(B0 -> pi- l+ nu) = (1.33 +- 0.18 +- 0.11 +- 0.01 +- 0.07)x10^{-4} and B(B0 -> rho- l+ nu) = (2.17 +- 0.34 +0.47/-0.54 +- 0.41 +- 0.01)x10^{-4}, where the errors are statistical, experimental systematic, systematic due to residual form-factor uncertainties in the signal, and systematic due to residual form-factor uncertainties in the cross-feed modes, respectively. We also find B(B+ -> eta l+ nu) = (0.84 +- 0.31 +- 0.16 +- 0.09)x10^{-4}, consistent with what is expected from the B -> pi l nu mode and quark model symmetries. We extract |Vub| using Light-Cone Sum Rules (LCSR) for 0<= q^2<16 GeV^2 and Lattice QCD (LQCD) for 16 GeV^2 <= q^2 < q^2_max. Combining both intervals yields |Vub| = (3.24 +- 0.22 +- 0.13 +0.55/-0.39 +- 0.09)x10^{-3}$ for pi l nu, and |Vub| = (3.00 +- 0.21 +0.29/-0.35 +0.49/-0.38 +-0.28)x10^{-3} for rho l nu, where the errors are statistical, experimental systematic, theoretical, and signal form-factor shape, respectively. Our combined value from both decay modes is |Vub| = (3.17 +- 0.17 +0.16/-0.17 +0.53/-0.39 +-0.03)x10^{-3}.Comment: 45 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Further Experimental Studies of Two-Body Radiative \Upsilon Decays

Continuing our studies of radiative Upsilon(1S) decays, we report on a search for Upsilon to gamma eta and Upsilon to gamma f_{J}(2220) in 61.3 pb^{-1} of e^{+}e^{-} data taken with the CLEO II detector at the Cornell Electron Storage Ring. For the gamma eta search the three decays of the eta meson to pi^{+}pi^{-}pi^{0}, pi^{0}pi^{0}pi^{0}, and gamma gamma were investigated. We found no candidate events in the two (3\pi)^{0} modes and no significant excess over expected backgrounds in the gamma gamma mode to set a limit on the branching fraction of B(Upsilon to gamma eta) < 2.1 x 10^{-5} at 90% C.L. The three charged two-body final states h h-bar (h = pi^{+}, K^{+}, p) were investigated for f_{J}(2220) production, with one, one, and two events found, respectively. Limits at 90% C.L. of B(\Upsilon to gamma f_{J}) x B(f_{J} to h h-bar) ~ 1.5 x 10^{-5} have been set for each of these modes. We compare our results to measurements of other radiative Upsilon decays, to measurements of radiative J/psi decays, and to theoretical predictions.Comment: 19 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to Physical Review