The synthesis and CRF receptor binding affinities of several new series of N-aryltriazolo- and -imidazopyrimidines and -pyridines are described. These cyclized systems were prepared from ...appropriately substituted diaminopyrimidines or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations of amino (ether) pendants and aromatic substituents have defined the structure−activity relationships of these series and resulted in the identification of a variety of high-affinity agents (K i's < 10 nM). On the basis of this property and lipophilicity differences, six of these compounds (4d,i,n,x, 8k, 9a) were initially chosen for rat pharmacokinetic (PK) studies. Good oral bioavailability, high plasma levels, and duration of four of these compounds (4d,i,n,x) prompted further PK studies in the dog following both iv and oral routes of administration. Results from this work indicated 4i,x had properties we believe necessary for a potential therapeutic agent, and 4i has been selected for further pharmacological studies that will be reported in due course.
The Evidence Base for Public Health Thacker, Stephen B.; Ikeda, Robin M.; Gieseker, Karen E. ...
American journal of preventive medicine,
10/2005, Letnik:
29, Številka:
3
Journal Article
Recenzirano
As part of a major re-examination of its organization, in 2004, the Centers for Disease Control and Prevention (CDC) assessed the evidence base for the effectiveness of population-based public health ...intervention programs.
For the leading causes of disease, injury, and disability, evidence was systematically reviewed for modifiable risk factors and their attributable fractions, and for public health interventions and their preventable fractions.
For 31 conditions, 194 modifiable risk factors were identified, and attributable fractions were found for 65 (33.5%). For 137 (70.6%) of the risk factors, 702 population-based interventions were found. Preventable fractions were found for 31 (4.4%) of the interventions.
Despite considerable information about both modifiable risk factors and interventions designed to reduce the risks of the major causes of disease, injury, and disability, the evidence base that describes the effectiveness of these interventions is limited. The CDC is committed to support research that will set priorities for program development and identify effective public health interventions.
We present an observation of B → η ′ K ∗ . The data sample corresponds to 232 × 10 6 B ¯¯¯ B pairs collected with the BABAR detector at the PEP-II asymmetric-energy B factory at the Stanford Linear ...Accelerator Center. We measure the branching fractions (in units of 10 − 6 ) B ( B 0 → η ′ K * 0 ) = 3.8 ± 1.1 ± 0.5 and B ( B + → η ′ K * + ) = 4.9 + 1.9 − 1.7 ± 0.8 , where the first error is statistical and the second systematic. A simultaneous fit results in the observation of B → η ′ K ∗ with B ( B → η ′ K ∗ ) = 4.1 + 1.0 − 0.9 ± 0.5 . We also search for B → η ′ ρ and η ′ f 0 ( 980 ) ( f 0 → π + π − ) with results and 90% confidence level upper limits B ( B + → η ′ ρ + ) = 8.7 + 3.1 + 2.3 − 2.8 − 1.3 ( < 14 ), B ( B 0 → η ′ ρ 0 ) < 3.7 , and B ( B 0 → η ′ f 0 ( 980 ) ( f 0 → π + π − ) ) < 1.5 . Charge asymmetries in the channels with significant yields are consistent with zero.
Using 226 million $B\bar{B}$ events recorded on the $\Upsilon(4S)$ resonance with the BABAR detector at the SLAC $e^+e^-$ PEPII storage rings, we reconstruct $B^- \to D^{*0} e^-\bar{\nu}_e$ decays ...using the decay chain $D^{*0} \to D^0\pi^0$ and $D^0 \to K^-\pi^+$. From the $w$ dependence of their differential rate, and using the form factor description by Caprini et al., we obtain the results $\rho_{A_1}^2 = 1.16\pm 0.06 \pm 0.08$, $F(1)\cdot|V_{cb}| =(35.9\pm 0.6 \pm 1.4)\cdot 10^{-3}$, and ${\cal{B}}(B^- \to D^{*0}e^-\bar{\nu}_e) = (5.56\pm 0.08\pm 0.41)%$.
We report measurements of branching fractions for the decays B --> P l nu, where P are the pseudoscalar charmless mesons pi-, pi0, eta and eta', based on 348 fb-1 of data collected with the BABAR ...detector, using B0 and B+ mesons found in the recoil of a second B meson decaying as B --> D(*) l nu. Assuming isospin symmetry, we combine pionic branching fractions to obtain B(B0 --> pi- l+ nu) = (1.54 +/- 0.17(stat) +/- 0.09(syst)) x 10-4; we find 3.2 sigma evidence of the decay B+ --> eta l+ nu and measure its branching fraction to be (0.64 +/- 0.20 (stat) +/- 0.03 (syst)) x 10-4, and determine B(B+ --> eta' l+ nu) < 0.47 x 10-4 to 90% confidence level. Using partial branching fractions for the pionic decays in ranges of the momentum transfer and a recent form factor calculation, we obtain the magnitude of the Cabibbo-Kobayashi-Maskawa matrix element |Vub| = (4.0 +/- 0.5(stat) +/- 0.2(syst) +0.7-0.5(theory)) x 10-3.
We report the results of a study of the exclusive charmless semileptonic decay, B --> pi l nu, undertaken with approximately 227 million BBbar pairs collected at the Upsilon(4S) resonance with the ...BaBar detector. The analysis uses events in which the signal B decays are reconstructed with an innovative loose neutrino reconstruction technique. We obtain partial branching fractions in 12 bins of q2, the momentum transfer squared, from which we extract the f+(q2) form-factor shape and the total branching fraction BF(B0 --> pi l nu) = (1.46 +- 0.07(stat) +- 0.08(syst)) x 10^-4. Based on a recent unquenched lattice QCD calculation of the form factor in the range q2 > 16 GeV^2, we find the magnitude of the CKM matrix element |Vub| to be (4.1 +- 0.2(stat) +- 0.2(syst) +0.6-0.4(FF)) x 10^-3, where the last uncertainty is due to the normalization of the form factor.
Using 230.2 fb^(-1) of e+e- annihilation data collected with the BABAR detector at and near the peak of the Y(4S) resonance, 489 +/- 55 events containing the pure leptonic decay D_s^+ --> mu^+ nu_mu ...have been isolated in charm-tagged events. The ratio of partial widths Gamma(D_s^+ --> mu^+ nu_mu)/Gamma(D_s^+ --> phi pi^+) is measured to be 0.143 +/- 0.018 +/- 0.006 allowing a determination of the pseudoscalar decay constant f_{D_s} = (283 +/- 17 +/- 7 +/- 14) MeV. The errors are statistical, systematic, and from the D_s^+ --> phi pi^+ branching ratio, respectively.
We present a measurement of the branching fraction and time-dependent CP asymmetry of B^0 to rho^0 K^0. The results are obtained from a data sample of 227 10^6 Y4S to BB_ decays collected with the ...BaBar detector at the PEP2 asymmetric-energy B Factory at SLAC. From a time-dependent maximum likelihood fit yielding 111+/-19 signal events we find B(B^0 to rho^0 K^0)=(4.9+/-0.8+/-0.9) 10^-6, where the first error is statistical and the second systematic. We report the measurement of the CP parameters S=0.20+/-0.52+/-0.24 and C=0.64+/-0.41+/-0.20.
We present measurements of the time-dependent CP-violation parameters S and C in B^0 --> eta' K^0 decays. The data sample corresponds to 384 million B Bar pairs produced by e^+ e^- annihilation at ...the Y(4S). The results are S = 0.58 +- 0.10 +- 0.03 and C = -0.16 +- 0.07 +- 0.03. We observe mixing-induced CP violation with a significance of 5.5 standard deviations in this b -> s penguin dominated mode.
PDF
