Corporate Financing in Great Britain

Background: The antifungal compound ketoconazole has, in addition to its ability to interfere with fungal ergosterol synthesis, effects upon other enzymes including human CYP3A4, CYP17, lipoxygenase and thromboxane synthetase. In the present study, we have investigated whether ketoconazole affects the cellular uptake and hydrolysis of the endogenous cannabinoid receptor ligand anandamide (AEA). Methodology/Principal Findings: The effects of ketoconazole upon endocannabinoid uptake were investigated using HepG2, CaCo2, PC-3 and C6 cell lines. Fatty acid amide hydrolase (FAAH) activity was measured in HepG2 cell lysates and in intact C6 cells. Ketoconazole inhibited the uptake of AEA by HepG2 cells and CaCo2 cells with IC50 values of 17 and 18 mu M, respectively. In contrast, it had modest effects upon AEA uptake in PC-3 cells, which have a low expression of FAAH. In cell-free HepG2 lysates, ketoconazole inhibited FAAH activity with an IC50 value (for the inhibitable component) of 34 mu M. Conclusions/Significance: The present study indicates that ketoconazole can inhibit the cellular uptake of AEA at pharmacologically relevant concentrations, primarily due to its effects upon FAAH. Ketoconazole may be useful as a template for the design of dual-action FAAH/CYP17 inhibitors as a novel strategy for the treatment of prostate cancer

New predictions for radiation-driven, steady-state mass-loss and wind-momentum from hot, massive stars II. A grid of O-type stars in the Galaxy and the Magellanic Clouds

Reliable predictions of mass-loss rates are important for massive-star evolution computations. We aim to provide predictions for mass-loss rates and wind-momentum rates of O-type stars, carefully studying the behaviour of these winds as functions of stellar parameters like luminosity and metallicity. We use newly developed steady-state models of radiation-driven winds to compute the global properties of a grid of O-stars. The self-consistent models are calculated by means of an iterative solution to the equation of motion using full NLTE radiative transfer in the co-moving frame to compute the radiative acceleration. In order to study winds in different galactic environments, the grid covers main-sequence stars, giants and supergiants in the Galaxy and both Magellanic Clouds. We find a strong dependence of mass-loss on both luminosity and metallicity. Mean values across the grid are $\dot{M}\sim L_{\ast}^{2.2}$ and $\dot{M}\sim Z_{\ast}^{0.95}$, however we also find a somewhat stronger dependence on metallicity for lower luminosities. Similarly, the mass loss-luminosity relation is somewhat steeper for the SMC than for the Galaxy. In addition, the computed rates are systematically lower (by a factor 2 and more) than those commonly used in stellar-evolution calculations. Overall, our results agree well with observations in the Galaxy that account properly for wind-clumping, with empirical $\dot{M}$ vs. $Z_\ast$ scaling relations, and with observations of O-dwarfs in the SMC. Our results provide simple fit relations for mass-loss rates and wind momenta of massive O-stars stars as functions of luminosity and metallicity, valid in the range $T_{\rm eff} = 28000 - 45000$\,K. Due to the systematically lower $\dot{M}$, our new models suggest that new rates might be needed in evolution simulations of massive stars.Comment: Accepted for publication in A&A. 16 pages, 13 figure

Eliminating Recursion from Monadic Datalog Programs on Trees

We study the problem of eliminating recursion from monadic datalog programs on trees with an infinite set of labels. We show that the boundedness problem, i.e., determining whether a datalog program is equivalent to some nonrecursive one is undecidable but the decidability is regained if the descendant relation is disallowed. Under similar restrictions we obtain decidability of the problem of equivalence to a given nonrecursive program. We investigate the connection between these two problems in more detail

Simultaneous laser-driven x-ray and two-photon fluorescence imaging of atomizing sprays

In this Letter, we report for the first time, to the best of our knowledge, the possibility of visualizing an atomizing spray by simultaneously recording x-ray absorption and two-photon laser-induced fluorescence imaging. This unique illumination/detection scheme is made possible due to the use of soft x rays emitted from a laser-driven x-ray source. An 800 mJ laser pulse of 38 fs duration is used to generate an x-ray beam with up to 4 × 108 photons ranging from 1 to 10 keV, allowing projection radiography of water jets generated by an automotive port fuel injector. In addition, a fraction of the laser pulse (∼10mJ) is employed to form a light sheet and to induce two-photon fluorescence in a dye added to the water. The resulting high-contrast fluorescence images provide fine details of the spray structure, with reduced blur from multiple light scattering, while the integrated liquid mass is extracted from the x-ray radiography. In this proof of principle, we show that the combination of these two highly complementary techniques, in both the visible and soft x-ray regimes, is very promising for future characterization of challenging spray, as well as for further understanding of the physics of liquid atomization

Symmetric Strategy Improvement

Symmetry is inherent in the definition of most of the two-player zero-sum games, including parity, mean-payoff, and discounted-payoff games. It is therefore quite surprising that no symmetric analysis techniques for these games exist. We develop a novel symmetric strategy improvement algorithm where, in each iteration, the strategies of both players are improved simultaneously. We show that symmetric strategy improvement defies Friedmann's traps, which shook the belief in the potential of classic strategy improvement to be polynomial

Separation of Oligosaccharides from Lotus Seeds via Medium-pressure Liquid Chromatography Coupled with ELSD and DAD

peer-reviewedLotus seeds were identified by the Ministry of Public Health of China as both food and medicine. One general function of lotus seeds is to improve intestinal health. However, to date, studies evaluating the relationship between bioactive compounds in lotus seeds and the physiological activity of the intestine are limited. In the present study, by using medium pressure liquid chromatography coupled with evaporative light-scattering detector and diode-array detector, five oligosaccharides were isolated and their structures were further characterized by electrospray ionization-mass spectrometry and gas chromatography-mass spectrometry. In vitro testing determined that LOS3-1 and LOS4 elicited relatively good proliferative effects on Lactobacillus delbrueckii subsp. bulgaricus. These results indicated a structure-function relationship between the physiological activity of oligosaccharides in lotus seeds and the number of probiotics applied, thus providing room for improvement of this particular feature. Intestinal probiotics may potentially become a new effective drug target for the regulation of immunity

Certain Query Answering on Compressed String Patterns: From Streams to Hyperstreams

International audienceWe study the problem of certain query answering (CQA) on compressed string patterns. These are incomplete singleton context-free grammars, that can model systems of multiple streams with references to others, called hyperstreams more recently. In order to capture regular path queries on strings, we consider nondeterministic finite automata (NFAs) for query definition. It turns out that CQA for Boolean NFA queries is equivalent to regular string pattern inclusion, i.e., whether all strings completing a compressed string pattern belong to a regular language. We prove that CQA on compressed string patterns is PSpace- complete for NFA queries. The PSpace-hardness even applies to Boolean queries defined by deterministic finite automata (DFAs) and without compression. We also show that CQA on compressed linear string patterns can be solved in PTime for DFA queries. The proofs of the results presented here can be found in the long version of this paper (https://hal.inria.fr/hal-01846016)

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

NQO2 is a reactive oxygen species generating off-target for acetaminophen

[Image: see text] The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity