Heterologous Expression,Biosynthetic Studies,and Ecological Function of the Selective Gq‐Signaling Inhibitor FR900359

The cyclic depsipeptide FR900359 (FR), isolated from the tropical plant Ardisia crenata, is a strong and selective inhibitor of Gq proteins, making it an indispensable pharmacological tool to study Gq‐related processes, as well as a promising drug candidate. Gq inhibition is a novel mode of action for defense chemicals and crucial for the ecological function of FR, as shown by in vivo experiments in mice, its affinity to insect Gq proteins, and insect toxicity studies. The uncultured endosymbiont of A. crenata was sequenced, revealing the FR nonribosomal peptide synthetase (frs) gene cluster. We here provide a detailed model of FR biosynthesis, supported by in vitro enzymatic and bioinformatic studies, and the novel analogue AC‐1, which demonstrates the flexibility of the FR starter condensation domains. Finally, expression of the frs genes in E. coli led to heterologous FR production in a cultivable, bacterial host for the first time.     

An ESCA investigation of the inductively coupled RF plasma polymerization of fluoronaphthalene and fluoronaphthalene/hydrogen mixtures

1-Fluoronaphthalene was plasma polymerized and its composition and structure, as a function of position, power, and temperature, were examined by ESCA. The F:C ratio of the deposited film was lower than that of the starting monomer both at room temperature and at 150°C. An asymmetry of the main C_1s photoionization peak was noted. Plasmas were also excited in fluoronaphthalene/hydrogen mixtures where extensive fluorine elimination and hydrogen incorporation occurred. This gave direct evidence that the height of step function or asymmetry of the main C_1s peak is related to the degree of saturation in the compound.     

Repeated price competition with increasing marginal costs

We consider a repeated price setting game with firms facing increasing marginal costs and positive fixed costs. Besides setting prices, firms may decide to be not active. Since it is well known that there is no Nash-equilibrium in pure strategies in the stage game, we look for pure strategy equilibria in the repeated game and give a full characterization of all stationary symmetric equilibrium outcomes, supported by optimal penal codes (in pure strategies). [JEL-classification: D43, L13]     

ESCA and optical emission study of the inductively coupled RF plasma copolymerization of naphthalene and octafluoronaphthalene mixtures

Plasma polymerization of octafluoronaphthalene, naphthalene, and 1 : 1 mixtures of the two yielded thin films which were then analyzed by ESCA. Optical emission was recorded during deposition and the resultant spectra are shown. Deposition of the copolymer at 150°C resulted in a film whose composition was different from that deposited at room temperature and from the single plasma polymers. Copolymerization resulted in a lowering of CF₂ functionalities and an increased retention of the aromatic nature of the monomers. Optical emission of CF₂ during copolymerization was greatly reduced as was a peak at about 510 nm.     

Purification and characterization of commercial NADH and accompanying dehydrogenase inhibitors.

The anion-exchange chromatography of commercial NADH using a potassium bicarbonate solution as eluent yields highly pure NADH with good stability. Twelve compounds are also separated which act as dehydrogenase inhibitors. The main impurities are further characterized. The compound mainly responsible for residual optical density in commercial NADH preparations is probably a stereoisomer of NADH which is in reversible equilibrium with NADH at pH values in the range 5-7. A method of thin-layer chromatography, to check commercial NADH preparations for impurities, is described.     

Imaging of trapped ions with a microfabricated optic for quantum information processing

Trapped ions are a leading system for realizing quantum information processing (QIP). Most of the technologies required for implementing large-scale trapped-ion QIP have been demonstrated, with one key exception: a massively parallel ion-photon interconnect. Arrays of microfabricated phase Fresnel lenses (PFL) are a promising interconnect solution that is readily integrated with ion trap arrays for large-scale QIP. Here we show the first imaging of trapped ions with a microfabricated in-vacuum PFL, demonstrating performance suitable for scalable QIP. A single ion fluorescence collection efficiency of 4.2±1.5% was observed. The depth of focus for the imaging system was 19.4±2.4 μm and the field of view was 140±20 μm. Our approach also provides an integrated solution for high-efficiency optical coupling in neutral atom and solid-state QIP architectures.     

Floating carpets and the delamination of elastic sheets

We investigate the deformation of a thin elastic sheet floating on a liquid surface and subject to a uniaxial compression. We show that at a critical compression the sheet delaminates from the liquid over a finite region forming a delamination "blister." This blistering regime adds to the wrinkling and localized folding regimes that have been studied previously. The transition from wrinkled to blistered states occurs when delamination becomes energetically favorable compared with wrinkling. We determine the initial blister size and the evolution of blister size with continuing compression before verifying our theoretical results with experiments at a macroscopic scale.     

What is a Logic Translation?

We study logic translations from an abstract perspective, without any commitment to the structure of sentences and the nature of logical entailment, which also means that we cover both proof- theoretic and model-theoretic entailment. We show how logic translations induce notions of logical expressiveness, consistency strength and sublogic, leading to an explanation of paradoxes that have been described in the literature. Connectives and quantifiers, although not present in the definition of logic and logic translation, can be recovered by their abstract properties and are preserved and reflected by translations under suitable conditions. In memoriam Joseph Goguen     

On the complexity of SNP block partitioning under the perfect phylogeny model

Recent technologies for typing single nucleotide polymorphisms (SNPs) across a population are producing genome-wide genotype data for tens of thousands of SNP sites. The emergence of such large data sets underscores the importance of algorithms for large-scale haplotyping. Common haplotyping approaches first partition the SNPs into blocks of high linkage-disequilibrium, and then infer haplotypes for each block separately. We investigate an integrated haplotyping approach where a partition of the SNPs into a minimum number of non-contiguous subsets is sought, such that each subset can be haplotyped under the perfect phylogeny model. We show that finding an optimum partition is -hard even if we are guaranteed that two subsets suffice. On the positive side, we show that a variant of the problem, in which each subset is required to admit a perfect path phylogeny haplotyping, is solvable in polynomial time.     

Fast DNA and protein microarray tests for the diagnosis of hepatitis C virus infection on a single platform

Hepatitis C virus (HCV) is a major cause of chronic liver disease and liver cancer, and remains a large health care burden to the world. In this study we developed a DNA microarray test to detect HCV RNA and a protein microarray to detect human anti-HCV antibodies on a single platform. A main focus of this study was to evaluate possibilities to reduce the assay time, as a short time-to-result (TTR) is a prerequisite for a point-of-care test. Significantly reducing hybridisation and washing times did not impair the assay performance. This was confirmed first using artificial targets and subsequently using clinical samples from an HCV seroconversion panel derived from a HCV-infected patient. We were able to reduce the time required for the detection of human anti-HCV antibodies to only 14 min, achieving nanomolar sensitivity. The protein microarray exhibited an analytical sensitivity comparable to that of commercial systems. Similar results were obtained with the DNA microarray using a universal probe which covered all different HCV genotypes. It was possible to reduce the assay time after PCR from 150 min to 16 min without any loss of sensitivity. Taken together, these results constitute a significant step forward in the design of rapid, microarray-based diagnostics for human infectious disease, and show that the protein microarray is currently the most favourable candidate to fill this role.