Dexamethasone and RU24858 induce survival and growth factor receptor bound protein 2, leukotriene B4 receptor 1 and annexin-1 expression in primary human neutrophils

Glucocorticoids are widely used anti-inflammatory medication in diseases like asthma and chronic obstructive pulmonary disease. Glucocorticoids can either activate (transactivation) or inhibit (transrepression) transcription. RU24858 was introduced as a dissociated glucocorticoid and it has been reported to transrepress but not to transactivate. The aim of this study was to compare the effects of RU24858 and dexamethasone in human neutrophils. RU24858 delayed spontaneous neutrophil apoptosis and further enhanced GM-CSF- induced neutrophil survival to a similar extent as dexamethasone. Like dexamethasone RU24858 also reduced CXCL8 and MIP-1α. Unexpectedly however, RU24858 increased the expression of the glucocorticoid-inducible genes BLT-1, Annexin-1 and Grb-2 in neutrophils to a similar level as seen with dexamethasone. We have shown here that dexamethasone and RU24858 both increase Grb-2, BLT1 and Annexin-1 expression and inhibit CXCL8 and MIP-1α production. This suggests that RU24858 was not able to dissociate between transactivation and transrepression in human neutrophils but enhanced neutrophil survival. © the author(s), publisher and licensee Libertas Academica Ltd

Sparse approximation of multivariate functions from small datasets via weighted orthogonal matching pursuit

We show the potential of greedy recovery strategies for the sparse approximation of multivariate functions from a small dataset of pointwise evaluations by considering an extension of the orthogonal matching pursuit to the setting of weighted sparsity. The proposed recovery strategy is based on a formal derivation of the greedy index selection rule. Numerical experiments show that the proposed weighted orthogonal matching pursuit algorithm is able to reach accuracy levels similar to those of weighted $\ell^1$ minimization programs while considerably improving the computational efficiency for small values of the sparsity level

Performance of an ideal turbine in an inviscid shear flow

Although wind and tidal turbines operate in turbulent shear flow, most theoretical results concerning turbine performance, such as the well-known Betz limit, assume the upstream velocity profile is uniform. To improve on these existing results we extend the classical actuator disc model in this paper to investigate the performance of an ideal turbine in steady, inviscid shear flow. The model is developed on the assumption that there is negligible lateral interaction in the flow passing through the disc and that the actuator applies a uniform resistance across its area. With these assumptions, solution of the model leads to two key results. First, for laterally unbounded shear flow, it is shown that the normalised power extracted is the same as that for an ideal turbine in uniform flow, if the average of the cube of the upstream velocity of the fluid passing through the turbine is used in the normalisation. Second, for a laterally bounded shear flow, it is shown that the same normalisation can be applied, but allowance must also be made for the fact that non-uniform flow bypassing the turbine alters the background pressure gradient and, in turn, the turbines ‘effective blockage’ (so that it may be greater or less than the geometric blockage, defined as the ratio of turbine disc area to cross-sectional area of the flow). Predictions based on the extended model agree well with numerical simulations approximating the incompressible Euler equations. The model may be used to improve interpretation of model-scale results for wind and tidal turbines in tunnels/flumes, to investigate the variation in force across a turbine and to update existing theoretical models of arrays of tidal turbines

Reduced Phagocytic Capacity of Blood Monocyte/Macrophages in Tuberculosis Patients Is Further Reduced by Smoking.

Tuberculosis (TB) and tobacco use are two major alarming global health issues posing immense threats to human populations. Mycobacterium tuberculosis (MTB) by activation of macrophages could induce the sequences of cells activation and releases of inflammatory cytokines such as CXCL-8, Il-12 and TNF-α which in turn induces the immune system network. However no information is available on other activity of cells by MTB and smoking. In the current study we aimed to investigate the serum levels TNF-a, CXCL-8 and phagocytosis capacity in tuberculosis patients with and without smoking. 103 subjects entered the study including 61 new diagnosed pulmonary TB patients (23 smokers and 38 nonsmokers) and 42 control healthy subjects. The phagocytosis of fluorescein isothiocyanate dextran (FITC-dextran) in blood monocytes/macrophages through flowcytometry was assessed. Serum levels of TNF-a and CXCL-8 were analyzed by ELISA methods. A lower percentage of cells from TB patients who smoked [50.29% (43.4-57.2), p<0.01] took up FITC-dextran after 2h compared to non-smoking TB subjects [71.62% (69.2-74.1)] and healthy cases [97.45% (95.9-99.1). Phagocytic capacity was inversely correlated with cigarette smoking as measured by pack years (r=-0.73, p<0.001). The serum levels of TNF-a and CXCL-8 were significantly higher in the TB patients who smoked compared to the TB non-smoker group (p<0.001, p<0.01 respectively). Blood monocytes/macrophages from TB patients have reduced phagocytic capacity which is further reduced in TB patients who smoke. Smoking enhanced serum levels of TNF-a and CXCL-8 suggesting a greater imbalance between the proinflammatory and anti-inflammatory factors in these patients

Seed phosphorus in wheat and lupins

Trial 90NO119 Seed P in wheat. Location: Greenhills. Design: 2 applied P x 3 seed P x 4 replicates, sowing wheat (cv. Aroona) seed from 89N33 at 70 kg/ha on May 15, 1990. Trial 90NO120 Seed P in wheat. Location: York Design: 2 applied from P x 3 seed P x 4 replicates, 89N33 at 70 kg/ha on May 25, 1990. Trial 90NO117 Seed P in lupins Location: Greenhills. Design: 2 applied P x 3 seed P x 4 replicates, sowing lupins (cv. Gungurru) from 85BA35 at 100 kg/ha on May 15, 1990. Trial 90NO118 Seed P in lupins. Location: York Design: 3 applied P x 3 seed P x 4 replicates, sowing lupins (cv. Gungurru) from 85BA35 at 100 kg/ha on May 25, 1990. Trial 90MD9 Phosphorus placement and seed P. Aim: To measure the effects of phosphate fertilizer placement on the response of lupins to varying seed P levels

Measuring portfolio performance using a modified measure of risk

This paper reports the results of an investigation into the properties of a theoretical modification of beta proposed by Leland (1999) and based on earlier work of Rubinstein (1976). It is shown that when returns are elliptically symmetric, beta is the appropriate measure of risk and that there are other situations in which the modified beta will be similar to the traditional measure based on the capital asset pricing model. For the case where returns have a normal distribution, it is shown that the criterion either does not exist or reduces exactly to the conventional beta. It is therefore conjectured that the modified measure will only be useful for portfolios that have nonstandard return distributions which incorporate skewness. For such situations, it is shown how to estimate the measure using regression and how to compare the resulting statistic with a traditional estimated beta using Hotelling's test. An empirical study based on stocks from the FTSE350 does not find evidence to support the use of the new measure even in the presence of skewness.Journal of Asset Management (2007) 7, 388-403. doi:10.1057/palgrave.jam.225005

On testing global optimization algorithms for space trajectory design

In this paper we discuss the procedures to test a global search algorithm applied to a space trajectory design problem. Then, we present some performance indexes that can be used to evaluate the effectiveness of global optimization algorithms. The performance indexes are then compared highlighting the actual significance of each one of them. A number of global optimization algorithms are tested on four typical space trajectory design problems. From the results of the proposed testing procedure we infer for each pair algorithm-problem the relation between the heuristics implemented in the solution algorithm and the main characteristics of the problem under investigation. From this analysis we derive a novel interpretation of some evolutionary heuristics, based on dynamical system theory and we significantly improve the performance of one of the tested algorithms

Anti-Inflammatory Effects of Lactobacillus Rahmnosus and Bifidobacterium Breve on Cigarette Smoke Activated Human Macrophages

Chronic obstructive pulmonary disease (COPD) is a major global health problem with cigarette smoke (CS) as the main risk factor for its development. Airway inflammation in COPD involves the increased expression of inflammatory mediators such as CXCL-8 and IL-1β which are important mediators for neutrophil recruitment. Macrophages are an important source of these mediators in COPD. Lactobacillus rhamnosus (L. rhamnosus) and Befidobacterium breve (B. breve) attenuate the development of 'allergic asthma' in animals but their effects in COPD are unknown.To determine the anti-inflammatory effects of L. rhamnosus and B. breve on CS and Toll-like receptor (TLR) activation.We stimulated the human macrophage cell line THP-1 with CS extract in the presence and absence of L. rhamnosus and B. breve and measured the expression and release of inflammatory mediators by RT-qPCR and ELISA respectively. An activity assay and Western blotting were used to examine NF-κB activation.Both L. rhamnosus and B. breve were efficiently phagocytized by human macrophages. L. rhamnosus and B. breve significantly suppressed the ability of CS to induce the expression of IL-1β, IL-6, IL-10, IL-23, TNFα, CXCL-8 and HMGB1 release (all p<0.05) in human THP-1 macrophages. Similar suppression of TLR4- and TLR9-induced CXCL8 expression was also observed (p<0.05). The effect of L. rhamnosus and B. breve on inflammatory mediator release was associated with the suppression of CS-induced NF-κB activation (p<0.05).This data indicate that these probiotics may be useful anti-inflammatory agents in CS-associated disease such as COPD