Quantum mechanics allows for many-particle wavefunctions that cannot be factorized into a product of single-particle wavefunctions, even when the constituent particles are entirely distinct. Such 'entangled' states explicitly demonstrate the non-local character of quantum theory, having potential applications in high-precision spectroscopy, quantum communication, cryptography and computation. In general, the more particles that can be entangled, the more clearly nonclassical effects are exhibited--and the more useful the states are for quantum applications. Here we implement a recently proposed entanglement technique to generate entangled states of two and four trapped ions. Coupling between the ions is provided through their collective motional degrees of freedom, but actual motional excitation is minimized. Entanglement is achieved using a single laser pulse, and the method can in principle be applied to any number of ions.

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abstract:The origin and divergence of the three living orders of amphibians (Anura, Caudata, Gymnophiona) and their main lineages are one of the most hotly debated topics in vertebrate evolution. Here, we present a robust molecular phylogeny based on the nuclear RAG1 gene as well as results from a variety of alternative independent molecular clock calibrations. Our analyses suggest that the origin and early divergence of the three living amphibian orders dates back to the Palaeozoic or early Mesozoic, before the breakup of Pangaea, and soon after the divergence from lobe-finned fishes. The resulting new biogeographic scenario, age estimate, and the inferred rapid divergence of the three lissamphibian orders may account for the lack of fossils that represent plausible ancestors or immediate sister taxa of all three orders and the heretofore paradoxical distribution of some amphibian fossil taxa. Furthermore, the ancient and rapid radiation of the three lissamphibian orders likely explains why branch lengths connecting their early nodes are particularly short, thus rendering phylogenetic inference of implicated relationships especially difficult.* E-mail: diegos@mncn.csic.es. † E-mail: vences@science.uva.nl. ‡ E-mail: marina@mncn.csic.es. § E-mail: rafaz@mncn.csic.es. Keywords: amphibian evolution, Pangaea breakup, molecular phylogeny, molecular clock, multiple calibrations, RAG1.Living amphibians (Lissamphibia) are a successful and highly diversified group of vertebrates that includes thousands of forms (5,770 species; AmphibiaWeb, January 26, 2005; http://www.amphibiaweb.org/) distributed throughout most habitats in all continents except Antarctica (Duellman and Trueb 1994). They experienced a long evolutionary history dating back at least to the early Triassic, the earliest known fossils being Triadobatrachus from Madagascar (Rage and Rocek 1989) and Czatkobatrachus from Poland (Evans and Borsuk-Bialynicka 1998). The Lissamphibia are widely thought to be a monophyletic group, constituted by three monophyletic orders (Anura, Caudata, and Gymnophiona) whose origin and interrelationships remain hotly debated (see Meyer and Zardoya 2003 for a recent review). The poor fossil record of some major lissamphibian groups and the fact that the three living amphibian orders possibly acquired their specialized morphology very early in their evolutionary histories (Zardoya and Meyer 2001) have left many questions unresolved regarding the origins, relationships, and historical distribution of the Lissamphibia.A recent molecular phylogeny of lissamphibians based on mitochondrial rRNA genes grouped salamanders and caecilians to the exclusion of frogs and suggested that the early evolutionary history of living amphibians was associated with the Mesozoic continental fragmentation of the supercontinent Pangaea (Feller and Hedges 1998). Paradoxically, some distributional patterns and some data from the fossil record (Estes and Wake 1972;Estes and Reig 1973;Rage and Rocek 1989;Jenkins and Walsh 1993;Duellman and Trueb 1994;Evans et ...

Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid). Coadministration of tenofovir with myrcludex B revealed no relevant changes in tenofovir pharmacokinetics. CYP3A activity slightly but significantly decreased by 29% during combination therapy. Myrcludex B caused an asymptomatic but distinct rise in plasma bile acid concentrations and had no relevant impact on tenofovir pharmacokinetics. Changes in CYP3A activity might be due to alterations in bile acid signaling. Long-term effects of elevated bile acids will require critical evaluation.