Several nucleoside analogues (penciclovir, lobucavir, dioxalane guanine [DXG], 1-beta-2,6-diaminopurine dioxalane [DAPD], L-FMAU, lamivudine) and acyclic nucleoside phosphonate analogues (adefovir, tenofovir) that are in clinical use, in clinical trials or under preclinical development for the treatment of hepatitis B virus (HBV) infections, were evaluated for their inhibitory effect on the replication of a la- mivudine-resistant HBV variant containing the methionine --> valine substitution (M550V) in the polymerase nucleoside-binding domain. The antiviral activity was determined in the tetracycline-responsive HepAD38 and HepAD79 cells, which are stably transfected with either a cDNA copy of the wild-type pregenomic RNA or with cDNA containing the M550V mutation. As expected, lamivudine was much less ( approximately 200-fold) effective at inhibiting replication of the M550V mutant virus than the wild-type virus. In contrast, adefovir, tenofovir, lobucavir, L-FMAU, DXG and DAPD proved almost equally effective against both viruses. A second objective of this study was to directly compare the antiviral potency of the anti-HBV agents in HepG2 2.2.15 cells (which are routinely used for anti-HBV drug-screening purposes) with that in HepAD38 cells. HepAD38 cells produce much larger quantities of HBV than HepG2 2.2.15 cells, and thus allow drug screening in a multiwell plate format. All compounds were found to be almost equally effective at inhibiting HBV replication in HepAD38 cells (as in HepG2 2.2.15 cells), except for penciclovir, which was clearly less effective in HepAD38 cells.
We provide a detailed description of a model and its computational algorithm for the secondary electron emission process. The model is based on a broad phenomenological fit to data for the secondary emission yield (SEY) and the emitted-energy spectrum. We provide two sets of values for the parameters by fitting our model to two particular data sets, one for copper and the other one for stainless steel. We also present details of the electron-cloud simulation code POSINST that are relevant to the secondary emission process. This note expands on our previously published article [1].
Electron cloud instabilities in the Los Alamos Proton Storage Ring and those foreseen for the Oak Ridge Spallation Neutron Source are examined theoretically, numerically, and experimentally.
While there is widespread agreement among economists and management scholars that knowledge spillovers exist and have important economic consequences, researchers know substantially less about the "micro mechanisms" of spillovers-about the degree to which they are geographically localized, for example, or about the degree to which spillovers from public institutions are qualitatively different from those from privately owned firms (Jaffe, 1986; Krugman, 1991; Jaffe et al., 1993; Porter, 1990). In this paper we make use of the geographic distribution of the research activities of major global pharmaceutical firms to explore the extent to which knowledge spills over from proximate private and public institutions. Our data and empirical approach allow us to make advances on two dimensions. First, by focusing on spillovers in research productivity (as opposed to manufacturing productivity), we build closely on the theoretical literature on spillovers that suggests that knowledge externalities are likely to have the most immediate impact on the production of ideas (Romer, 1986; Aghion & Howitt, 1997). Second, our data allow us to distinguish spillovers from public research from spillovers from private, or competitively funded research, and to more deeply explore the role that institutions and geographic proximity play in driving knowledge spillovers.
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