219 research outputs found

    Measuring ultrafine aerosols by direct photoionization and charge capture in continuous flow

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    Direct ultraviolet (UV) photoionization enables electrical charging of aerosol nanoparticles with- out relying on the collision of particles and ions. In this work, a low-strength electric field is applied during particle photoionization to capture charge as it is photoemitted from the par- ticles in continuous flow, yielding a novel electrical current measurement. As in conventional photocharging-based measurement devices, a distinct electrical current from the remaining pho- tocharged particles is also measured downstream. The two distinct measured currents are proportional to the total photoelectrically active area of the particles. A three dimensional numerical model for particle and ion (dis)charging and transport is evaluated by comparing simulations of integrated electric currents with those from charged soot particles and ions in an experimental photoionization chamber. The model and experiment show good quantitative agreement for a single empirical constant, KcI, over a range of particle sizes and concentrations providing confidence in the theoretical equations and numerical method used

    Inhibition of SOC/Ca2+/NFAT pathway is involved in the anti-proliferative effect of sildenafil on pulmonary artery smooth muscle cells

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    <p>Abstract</p> <p>Background</p> <p>Sildenafil, a potent phosphodiesterase type 5 (PDE5) inhibitor, has been proposed as a treatment for pulmonary arterial hypertension (PAH). The mechanism of its anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC) is unclear. Nuclear translocation of nuclear factor of activated T-cells (NFAT) is thought to be involved in PASMC proliferation and PAH. Increase in cytosolic free [Ca<sup>2+</sup>] ([Ca<sup>2+</sup>]<sub>i</sub>) is a prerequisite for NFAT nuclear translocation. Elevated [Ca<sup>2+</sup>]<sub>i </sub>in PASMC of PAH patients has been demonstrated through up-regulation of store-operated Ca<sup>2+ </sup>channels (SOC) which is encoded by the transient receptor potential (TRP) channel protein. Thus we investigated if: 1) up-regulation of TRPC1 channel expression which induces enhancement of SOC-mediated Ca<sup>2+ </sup>influx and increase in [Ca<sup>2+</sup>]<sub>i </sub>is involved in hypoxia-induced PASMC proliferation; 2) hypoxia-induced promotion of [Ca<sup>2+</sup>]<sub>i </sub>leads to nuclear translocation of NFAT and regulates PASMC proliferation and TRPC1 expression; 3) the anti-proliferative effect of sildenafil is mediated by inhibition of this SOC/Ca<sup>2+</sup>/NFAT pathway.</p> <p>Methods</p> <p>Human PASMC were cultured under hypoxia (3% O<sub>2</sub>) with or without sildenafil treatment for 72 h. Cell number and cell viability were determined with a hemocytometer and MTT assay respectively. [Ca<sup>2+</sup>]<sub>i </sub>was measured with a dynamic digital Ca<sup>2+ </sup>imaging system by loading PASMC with fura 2-AM. TRPC1 mRNA and protein level were detected by RT-PCR and Western blotting respectively. Nuclear translocation of NFAT was determined by immunofluoresence microscopy.</p> <p>Results</p> <p>Hypoxia induced PASMC proliferation with increases in basal [Ca<sup>2+</sup>]<sub>i </sub>and Ca<sup>2+ </sup>entry via SOC (SOCE). These were accompanied by up-regulation of TRPC1 gene and protein expression in PASMC. NFAT nuclear translocation was significantly enhanced by hypoxia, which was dependent on SOCE and sensitive to SOC inhibitor SKF96365 (SKF), as well as cGMP analogue, 8-brom-cGMP. Hypoxia-induced PASMC proliferation and TRPC1 up-regulation were inhibited by SKF and NFAT blocker (VIVIT and Cyclosporin A). Sildenafil treatment ameliorated hypoxia-induced PASMC proliferation and attenuated hypoxia-induced enhancement of basal [Ca<sup>2+</sup>]<sub>i</sub>, SOCE, up-regulation of TRPC1 expression, and NFAT nuclear translocation.</p> <p>Conclusion</p> <p>The SOC/Ca<sup>2+</sup>/NFAT pathway is, at least in part, a downstream mediator for the anti-proliferative effect of sildenafil, and may have therapeutic potential for PAH treatment.</p

    Zinc finger protein ZBTB20 expression is increased in hepatocellular carcinoma and associated with poor prognosis

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    <p>Abstract</p> <p>Background</p> <p>Our previous studies showed that ZBTB20, a new BTB/POZ-domain gene, could negatively regulate α feto-protein and other liver-specific genes, concerning such as bio-transformation, glucose metabolism and the regulation of the somatotropic hormonal axis. The aim of this study is to determine the potential clinical implications of ZBTB20 in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>Quantitative real-time RT-PCR and Western blot analyses were used to detect expression levels of ZBTB20 in 50 paired HCC tumorous and nontumorous tissues and in 20 normal liver tissues. Moreover, expression of ZBTB20 was assessed by immunohistochemistry of paired tumor and peritumoral liver tissue from 102 patients who had undergone hepatectomy for histologically proven HCC. And its relationship with clinicopathological parameters and prognosis was investigated.</p> <p>Results</p> <p>Both messenger RNA and protein expression levels of ZBTB20 were elevated significantly in HCC tissues compared with the paired non-tumor tissues and normal liver tissues. Overexpressed ZBTB20 protein in HCC was significantly associated with vein invasion (<it>P </it>= 0.016). Importantly, the recurrence or metastasis rates of HCCs with higher ZBTB20 expression were markedly greater than those of HCCs with lower expression (<it>P </it>= 0.003, <it>P </it>= 0.00015, respectively). Univariate and multivariate analyses revealed that ZBTB20 overexpression was an independent prognostic factor for HCC. The disease-free survival period and over-all survival period in patients with overexpressed ZBTB20 in HCC was significantly reduced.</p> <p>Conclusions</p> <p>The expression of ZBTB20 is increased in HCC and associated with poor prognosis in patients with HCC, implicating ZBTB20 as a candidate prognostic marker in HCC.</p

    The Einstein-Vlasov System/Kinetic Theory

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    The main purpose of this article is to provide a guide to theorems on global properties of solutions to the Einstein--Vlasov system. This system couples Einstein's equations to a kinetic matter model. Kinetic theory has been an important field of research during several decades in which the main focus has been on non-relativistic and special relativistic physics, i.e., to model the dynamics of neutral gases, plasmas, and Newtonian self-gravitating systems. In 1990, Rendall and Rein initiated a mathematical study of the Einstein--Vlasov system. Since then many theorems on global properties of solutions to this system have been established.Comment: Published version http://www.livingreviews.org/lrr-2011-

    The chemical signatures underlying host plant discrimination by aphids

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    The diversity of phytophagous insects is largely attributable to speciation involving shifts between host plants. These shifts are mediated by the close interaction between insects and plant metabolites. However, there has been limited progress in understanding the chemical signatures that underlie host preferences. We use the pea aphid (Acyrthosiphon pisum) to address this problem. Host-associated races of pea aphid discriminate between plant species in race-specific ways. We combined metabolomic profiling of multiple plant species with behavioural tests on two A. pisum races, to identify metabolites that explain variation in either acceptance or discrimination. Candidate compounds were identified using tandem mass spectrometry. Our results reveal a small number of compounds that explain a large proportion of variation in the differential acceptability of plants to A. pisum races. Two of these were identified as L-phenylalanine and L-tyrosine but it may be that metabolically-related compounds directly influence insect behaviour. The compounds implicated in differential acceptability were not related to the set correlated with general acceptability of plants to aphids, regardless of host race. Small changes in response to common metabolites may underlie host shifts. This study opens new opportunities for understanding the mechanistic basis of host discrimination and host shifts in insects
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