Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Population based models of cortical drug response: insights from anaesthesia

A great explanatory gap lies between the molecular pharmacology of psychoactive agents and the neurophysiological changes they induce, as recorded by neuroimaging modalities. Causally relating the cellular actions of psychoactive compounds to their influence on population activity is experimentally challenging. Recent developments in the dynamical modelling of neural tissue have attempted to span this explanatory gap between microscopic targets and their macroscopic neurophysiological effects via a range of biologically plausible dynamical models of cortical tissue. Such theoretical models allow exploration of neural dynamics, in particular their modification by drug action. The ability to theoretically bridge scales is due to a biologically plausible averaging of cortical tissue properties. In the resulting macroscopic neural field, individual neurons need not be explicitly represented (as in neural networks). The following paper aims to provide a non-technical introduction to the mean field population modelling of drug action and its recent successes in modelling anaesthesia

Measurement of B-0 -> D-s(*)D+*(-) branching fractions and B-0 -> D-s*D+*(-) polarization with a partial reconstruction technique

We present a study of the decays B-0 --> D-s((*)) D*-, using 20.8 fb(-1) of e(+)e(-) annihilation data recorded with the BABAR detector. The analysis is conducted with a partial reconstruction technique, in which only the D-s((*)+) and the soft pion from the D*- decay are reconstructed. We measure the branching fractions B(B-0 --> Ds+D*-) = (1.03 +/- 0.14 +/- 0.13 +/- 0.26)% and B(B-0 --> D-s(*+) D*-) = (1.97 +/- 0.15 +/- 0.30+/- 0.49)%, where the first error is statistical, the second is systematic, and the third is the error due to the D-s(+) --> phipi(+) branching fraction uncertainty. From the B-0 --> D-s(*+) D*- angular distributions, we measure the fraction of longitudinal polarization Gamma(L)/Gamma = (51.9 +/- 5.0 +/- 2.8)%, which is consistent with theoretical predictions based on factorization

Lead optimization studies, synthesis and biological evaluation of new isonipecotamide-based orally active thrombin inhibitors

Current anticoagulant therapy of venous thromboembolism (VTE) is based on parenterally administered heparins and orally administered vitamin K antagonists (e.g., warfarin), but narrow therapeutic window and side effects, such as bleeding, diet and genetic makeup influence, are associated with their use [1]. Recently, key serine proteases of the blood coagulation cascade, such as thrombin (thr) and factor Xa (fXa), have emerged as promising targets for anticoagulants, and indeed several direct inhibitors of thr (e.g., argatroban, dabigatran) and fXa (e.g., rivaroxaban, apixaban) have been introduced in therapy or in advanced clinical trials [2,3]. Some years ago we investigated the isonipecotanilide scaffold for new thr/fXa inhibitors [4]. Further optimization studies led us to develop new benzyloxy derivatives of N-(phenyl)-1-(pyridin-4-yl)piperidine-4-carboxamide, one of them (i.e., the 3-F analog, see below) showing low nanomolar Ki (thr) value, high selectivity against other serine proteases and good anticoagulant activity as measured by the activated partial thromboplastin time (aPTT) test. Physicochemical profiles of the newly synthesized compounds were assessed and their potential oral bioavailability estimated, by measuring effective permeability coefficients using PAMPA (Parallel Artificial Membrane Permeability Assay)

Adaptor protein ARH is recruited to the plasma membrane by low density lipoprotein (LDL) binding and modulates endocytosis of the LDL/LDL receptor complex in hepatocytes

ARH is a newly discovered adaptor protein required for the efficient activity of low density lipoprotein receptor ( LDLR) in selected tissues. Individuals lacking ARH have severe hypercholesterolemia due to an impaired hepatic clearance of LDL. It has been demonstrated that ARH is required for the efficient internalization of the LDL-LDLR complex and to stabilize the association of the receptor with LDL in Epstein-Barr virus-immortalized B lymphocytes. However, little information is available on the role of ARH in liver cells. Here we provide evidence that ARH is codistributed with LDLR on the basolateral area in confluent HepG2-polarized cells. This distribution is not modified by the overexpression of LDLR. Conversely, the activation of the LDLR-mediated endocytosis, but not the binding of LDL to LDLR, promotes a significant colocalization of ARH with LDL-LDLR complex that peaked at 2 min at 37 degrees C. To further assess the role of ARH in LDL-LDLR complex internalization, we depleted ARH protein using the RNA interference technique. Twenty-four hours after transfection with ARH-specific RNA interference, ARH protein was depleted in HepG2 cells by more than 70%. Quantitative immunofluorescence analysis revealed that the depletion of ARH caused about 80% reduction in LDL internalization. Moreover, our findings indicate that ARH is associated with other proteins of the endocytic machinery. We suggest that ARH is an endocytic sorting adaptor that actively participates in the internalization of the LDL-LDLR complex, possibly enhancing the efficiency of its packaging into the endocytic vesicles