Physiological Impact of Abnormal Lipoxin A 4

Lipoxin A4 has been described as a major signal for the resolution of inflammation and is abnormally produced in the lungs of patients with cystic fibrosis (CF). In CF, the loss of chloride transport caused by the mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel gene results in dehydration, mucus plugging, and reduction of the airway surface liquid layer (ASL) height which favour chronic lung infection and neutrophil based inflammation leading to progressive lung destruction and early death of people with CF. This review highlights the unique ability of LXA4 to restore airway surface hydration, to stimulate airway epithelial repair, and to antagonise the proinflammatory program of the CF airway, circumventing some of the most difficult aspects of CF pathophysiology. The report points out novel aspects of the cellular mechanism involved in the physiological response to LXA4, including release of ATP from airway epithelial cell via pannexin channel and subsequent activation of and P2Y11 purinoreceptor. Therefore, inadequate endogenous LXA4 biosynthesis reported in CF exacerbates the ion transport abnormality and defective mucociliary clearance, in addition to impairing the resolution of inflammation, thus amplifying the vicious circle of airway dehydration, chronic infection, and inflammation

Spatial patterns in the fruiting bodies of the cellular slime mold Polysphondylium pallidum

During morphogenesis in the slime mold Polysphondylium pallidum cell masses are periodically pinched off from the base of the developing sorogen. These masses round up and differentiate into secondary sorogens, which become radially ordered arrays of secondary fruiting bodies called whorls. Here we describe the morphogenesis of P. pallidum and characterize the spacing of whorls along the central stalk of the fruiting body and the spacing of soro-carps within whorls. We find both are highly regular. We propose that the linear spacing of whorls can be accounted for satisfactorily by a model that views the periodic release of cell masses from the base of the developing sorogen as the consequence of an imbalance between forces that orient amoebae toward the tip of the culminating sorogen, and cohesive forces between randomly moving cells in the basal region of the sorogen, which act as a retarding force. The orderly arrangement of fruiting bodies within whorls can be explained most easily by models that employ short-range activation and lateral inhibition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72498/1/j.1432-0436.1988.tb00200.x.pd

Technologies for restricting mould growth on baled silage

End of project reportSilage is made on approximately 86% of Irish farms, and 85% of these make some baled silage. Baled silage is particularly important as the primary silage making, storage and feeding system on many beef and smaller sized farms, but is also employed as a secondary system (often associated with facilitating grazing management during mid-summer) on many dairy and larger sized farms (O’Kiely et al., 2002). Previous surveys on farms indicated that the extent of visible fungal growth on baled silage was sometimes quite large, and could be a cause for concern. Whereas some improvements could come from applying existing knowledge and technologies, the circumstances surrounding the making and storage of baled silage suggested that environmental conditions within the bale differed from those in conventional silos, and that further knowledge was required in order to arrive at a secure set of recommendations for baled silage systems. This report deals with the final in a series (O’Kiely et al., 1999; O’Kiely et al., 2002) of three consecutive research projects investigating numerous aspect of the science and technology of baled silage. The success of each depended on extensive, integrated collaboration between the Teagasc research centres at Grange and Oak Park, and with University College Dublin. As the series progressed the multidisciplinary team needed to underpin the programme expanded, and this greatly improved the amount and detail of the research undertaken. The major objective of the project recorded in this report was to develop technologies to improve the “hygienic value” of baled silage

Physiological levels of lipoxin A4 inhibit ENaC and restore airway surface liquid height in cystic fibrosis bronchial epithelium.

In cystic fibrosis (CF), the airway surface liquid (ASL) is depleted. We previously demonstrated that lipoxin A4 (LXA4) can modulate ASL height (ASLh) through actions on Cl(-) transport. Here, we report novel effects of lipoxin on the epithelial Na(+) channel ENaC in this response. ASL dynamics and ion transport were studied using live-cell confocal microscopy and short-circuit current measurements in CF (CuFi-1) and non-CF (NuLi-1) cell cultures. Low physiological concentrations of LXA4 in the picomolar range produced an increase in ASLh which was dependent on inhibition of an amiloride-sensitive Na(+) current and stimulation of a bumetanide-sensitive Cl(-) current. These ion transport and ASLh responses to LXA4 were blocked by Boc-2 an inhibitor of the specific LXA4 receptor ALX/FPR2. LXA4 affected the subcellular localization of its receptor and enhanced the localization of ALX/FPR2 at the apical membrane of CF cells. Our results provide evidence for a novel effect of low physiological concentrations of LXA4 to inhibit airway epithelial Na(+) absorption that results in an ASL height increase in CF airway epithelia

Indice Generale

Melt viscosity is a key indicator of product quality in polymer extrusion processes. However, real time monitoring and control of viscosity is difficult to achieve. In this article, a novel “soft sensor” approach based on dynamic gray-box modeling is proposed. The soft sensor involves a nonlinear finite impulse response model with adaptable linear parameters for real-time prediction of the melt viscosity based on the process inputs; the model output is then used as an input of a model with a simple-fixed structure to predict the barrel pressure which can be measured online. Finally, the predicted pressure is compared to the measured value and the corresponding error is used as a feedback signal to correct the viscosity estimate. This novel feedback structure enables the online adaptability of the viscosity model in response to modeling errors and disturbances, hence producing a reliable viscosity estimate. The experimental results on different material/die/extruder confirm the effectiveness of the proposed “soft sensor” method based on dynamic gray-box modeling for real-time monitoring and control of polymer extrusion processes

Ultrashort laser sintering of printed silver nanoparticles on thin, flexible, and porous substrates

The fabrication of low-cost and mechanically robust flexible electronic patterns has increasingly gained attention due to their growing applications in flexible displays, touch screen panels, medical devices, and solar cells. Such applications require cost-effective deposition of metals in a well-controlled manner potentially using nanoparticles (NPs). The presence of solvent and precursors in NP based inks impacts the electrical conductivity of the printed pattern and a post-processing heating step is typically performed to restore the electrical properties and structure of the material. We report printing with picolitre droplet volumes of silver (Ag) NPs on flexible substrates using an acoustic microdroplet dispenser. The low-cost, controlled deposition of Ag ink is performed at room temperature on photopaper, polyimide and clear polyimide substrates. A localized, ultrashort pulsed laser with minimal heat affected zone is employed to sinter printed Ag patterns. For comparison, oven sintering is performed, and the results are analysed with scanning electron microscopy, four-point probe and Hall measurements. The femtosecond laser sintering revealed highly organized, connected nanostructure that is not achievable with oven heating. A significant decrease in sheet resistance, up to 93% in Ag NPs on clear polyimide confirms the laser sintering improves the connectivity of the printed film and as a result, the electrical properties are enhanced. The surface morphology attained by the laser sintering process is interpreted to be due to a joining of NPs as a result of a solid-state diffusion process in the near surface region of NPs

miR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production.

Interleukin (IL)-8 levels are higher than normal in cystic fibrosis (CF) airways, causing neutrophil infiltration and non-resolving inflammation. Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis. IL-8 protein and mRNA were measured in cystic fibrosis and non-cystic fibrosis bronchoalveolar lavage fluid and bronchial brushings (n=20 per group). miRNAs decreased in the cystic fibrosis lung and predicted to target IL-8 mRNA were quantified in βENaC-transgenic, cystic fibrosis transmembrane conductance regulator (Cftr)-/- and wild-type mice, primary cystic fibrosis and non-cystic fibrosis bronchial epithelial cells and a range of cystic fibrosis versus non-cystic fibrosis airway epithelial cell lines or cells stimulated with lipopolysaccharide, Pseudomonas-conditioned medium or cystic fibrosis bronchoalveolar lavage fluid. The effect of miRNA overexpression on IL-8 protein production was measured. miR-17 regulates IL-8 and its expression was decreased in adult cystic fibrosis bronchial brushings, βENaC-transgenic mice and bronchial epithelial cells chronically stimulated with Pseudomonas-conditioned medium. Overexpression of miR-17 inhibited basal and agonist-induced IL-8 protein production in F508del-CFTR homozygous CFTE29o(-) tracheal, CFBE41o(-) and/or IB3 bronchial epithelial cells. These results implicate defective CFTR, inflammation, neutrophilia and mucus overproduction in regulation of miR-17. Modulating miR-17 expression in cystic fibrosis bronchial epithelial cells may be a novel anti-inflammatory strategy for cystic fibrosis and other chronic inflammatory airway diseases

Femtosecond laser assisted crystallization of gold thin films.

We propose a novel low temperature annealing method for selective crystallization of gold thin films. Our method is based on a non-melt process using highly overlapped ultrashort laser pulses at a fluence below the damage threshold. Three different wavelengths of a femtosecond laser with the fundamental (1030 nm), second (515 nm) and third (343 nm) harmonic are used to crystallize 18-nm and 39-nm thick room temperature deposited gold thin films on a quartz substrate. Comparison of laser wavelengths confirms that improvements in electrical conductivity up to 40% are achievable for 18-nm gold film when treated with the 515-nm laser, and the 343-nm laser was found to be more effective in crystallizing 39-nm gold films with 29% improvement in the crystallinity. A two-temperature model provides an insight into ultrashort laser interactions with gold thin films and predicts that applied fluence was insufficient to cause melting of gold films. The simulation results suggest that non-equilibrium energy transfer between electrons and lattice leads to a solid-state and melt-free crystallization process. The proposed low fluence femtosecond laser processing method offers a possible solution for a melt-free thin film crystallization for wide industrial applications

c-Rel is required for the development of thymic Foxp3+ CD4 regulatory T cells

During thymopoiesis, a unique program of gene expression promotes the development of CD4 regulatory T (T reg) cells. Although Foxp3 maintains a pattern of gene expression necessary for T reg cell function, other transcription factors are emerging as important determinants of T reg cell development. We show that the NF-κB transcription factor c-Rel is highly expressed in thymic T reg cells and that in c-rel−/− mice, thymic T reg cell numbers are markedly reduced as a result of a T cell–intrinsic defect that is manifest during thymocyte development. Although c-Rel is not essential for TGF-β conversion of peripheral CD4+CD25− T cells into CD4+Foxp3+ cells, it is required for optimal homeostatic expansion of peripheral T reg cells. Despite a lower number of peripheral T reg cells in c-rel−/− mice, the residual peripheral c-rel−/− T reg cells express normal levels of Foxp3, display a pattern of cell surface markers and gene expression similar to those of wild-type T reg cells, and effectively suppress effector T cell function in culture and in vivo. Collectively, our results indicate that c-Rel is important for both the thymic development and peripheral homeostatic proliferation of T reg cells

Improvement of electrical properties of ITO thin films by melt-free ultra-short laser crystallization

We describe a novel solid state crystallisation method for optimising a thin film transparent conductive oxide when deposited on flexible polymer substrates. The method is based on ultra-short non-thermal laser sintering of indium tin oxide (ITO) thin films. In this study, we used commercial ITO thin films deposited on a flexible polyethylene terephthalate substrate with a relatively low melting temperature compared with ITO on glass. We demonstrate the use of laser scanning with high pulse overlapping at fluences seven times less than the threshold required for melting/damage of ITO. The results confirm greater than four times enhancement in the mobility of charge carriers of ITO thin films after laser scanning and sheet resistance can be reduced up to 25%. There is no reduction in optical transparency observed in laser treated samples. Surface morphology and x-ray diffraction analyses confirm the improvement in crystallite sizes by laser sintering, resulting in a greater than 37% increase in grain size due to enhanced crystallization. Comparison of experimental and simulation based on a delayed two temperature model confirms that ITO thin film crystallization occurred at about one-third of the melting temperature of ITO