612 research outputs found

    Fe(III)2O3 Nanoparticle Mediated Molecular Growth and Soot Particle Inception from the Oxidative Pyrolysis of 1-Methylnaphthalene

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    The potential for Fe(III)2O3 nanoparticles to participate in the molecular growth and particle inception of soot from 1-methylnapthalene (1-MN) was studied in a dual-zone, high-temperature flow reactor. An iron substituted, dendrimer template was oxidized in the Zone 1 reactor to generate ~5nm Fe(III)2O3 nanoparticles, that were continually seeded to a high sooting 1-MN fuel under oxidative pyrolysis conditions. The Fe(III)2O3 nanoparticles could then influence the otherwise gas-phase reactions of 1-MN. Increased PAH formation, soot number density, soot mass yield, and soot radical intensity were observed as a result of Fe(III)2O3 nanoparticle introduction prior to soot inception. Low Temperature Matrix Isolation-Electron Paramagnetic Resonance (LTMI-EPR) spectroscopy was used to determine the superimposed signal of particulate from the oxidative pyrolysis of 1-MN. The EPR spectrum of particulate was found to be a mixture of organic carbon-centered radicals, oxygen-centered radicals, and soot. The carbon-centered radicals were identified through simulation of the hyperfine structure to be the resonance-stabilized indenyl, cyclopentadienyl, and naphthalene 1-methylene radicals. The species of iron oxide nanoparticles generated from the iron substituted dendrimer was also determined with the LTMI-EPR technique to be Fe(III)2O3 nanoparticles clusters and superoxide anion-radicals, O2•- adsorbed on nanoparticle surfaces in form of Fe (IV)-O2•-. Superoxide anion-radicals initiate radical chain reactions through abstraction of hydrogen whereas Fe(III)2O3 nanoparticles are capable of the stabilization of the initially formed radicals species. Subsequent formation of soot also resulted in a partial reduction of the Fe(III)2O3 nanoparticles. These studies contained herein suggest Fe(III)2O3 nanoparticles can mediate the formation and stabilization of resonance stabilized radicals and subsequent reactions can result in the molecular growth of PAHs into soot. At the high concentrations in the flow reactor, these resonance–stabilized free radicals can undergo surface-mediated, radical-radical, molecular growth reactions and contribute to molecular growth and soot particle inception

    The function of the 130kDa MLCK in regulating in vivo vascular permeability and angiogenesis

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    poster abstractDisruption of endothelial integrity is an essential component of vascular inflammation, angiogenesis, atherosclerosis, and tumor metastasis. Many studies have shown that activation of myosin light chain kinase (MLCK) in endothelial cell is correlated with increase in vascular permeability. Currently, most research in endothelial cells has focused on the 220kDa MLCK isoform which is the predominant isoform present in cultured endothelial cells. However, in freshly isolated uncultured endothelial cells, the 130kDa MLCK predominates. Yet nothing is known about the roles of the 130kDa MLCK isoform in endothelial cells. Therefore, our goal is to determine the role of the 130kDa MLCK in regulating vascular permeability and angiogenesis in vivo. To do this we will generate an endothelial cell-specific 130kDa MLCK knockout mice. As transcripts encoding the 130 and 220kDa MLCK isoforms are produced by independent promoters within the same mylk1 gene, I will selectively knockout the 130kDa MLCK by deleting unique cis-acting gene regulatory elements required for the expression of this transcript. A key element identified within the intron following the first exon of the 130kDa MLCK transcript has been flanked by LoxP sites such that Cre recombinase (Cre) mediated recombination will delete the element and attenuate expression of the 130kDa MLCK. By crossing these floxed mice with Tie2-Cre mice which express Cre specifically in endothelial cells, I will obtain endothelial cellspecific 130kDa MLCK knockout mice. In vivo vascular permeability and angiogenesis assays on these mice will allow me to determine the role played by the 130kDa MLCK in these processes. This study will not only help to identify specific functions of the 130kDa MLCK isoform, but also determine if this is a drug target for developing novel treatments of vascular diseases and cancer

    The role of Brahma-related gene 1 in regulating the expression of microRNAs in colonic smooth muscle cells

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    poster abstractPrevious work by our group has shown that mice harboring null mutation of Brahma-related gene 1 (Brg1)-an ATPase subunit of SWI/SNF (SWItch/Sucrose NonFermentable) chromatin remodeling complex have reduced smooth muscle contractility and disorganized smooth muscle cells (SMCs) in colon, which are similar defects to those of microRNA maturation enzyme Dicer-deficient mice. Recently microRNAs (miRs) such as miR-143/145 have been implicated in the regulation of gene expression essential for smooth muscle cell proliferation and differentiation. Thus we aimed to identify the microRNAs that were involved in regulating the phenotypic changes in Brg1-deficient colonic smooth muscle cells and determine how Brg1 regulated them. The microRNA array screens of colonic smooth muscle and quantitative reverse transcription-polymerase chain reaction assays identified 6 miRs were down-regulated and 6 were up-regulated in smooth muscle specific Brg1 knockout tissue compared with control. Inactivation of endogenous Brg1 by introducing dominant negative Brg1 into wild type SMCs in vitro decreased miR-143/145 expression in smooth muscle cells. In Brg1 null SW13 cells, miR-143/145 were dramatically induced by myogenic transcriptional co-factor myocardin only in the presence of Brg1. Chromatin immunoprecipitation assays demonstrated that myocardin together with Brg1 increased the binding of transcription factor serum response factor (SRF) to the promoter region of miR-143/145 gene cluster. In conclusion, Brg1 together with myocardin can induce the transcription of miR-143/145 through enhancing the binding of SRF to the promoter region in SMCs. Together this suggests that SWI/SNF mediated chromatin remodeling regulates the phenotype of colonic smooth muscle by regulating expression of microRNAs that further modulate expression of their targets

    The alcohol improvement programme: evaluation of an initiative to address alcohol-related health harm in England

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    Aims: The evaluation aimed to assess the impact of The Alcohol Improvement Programme (AIP). This was a UK Department of Health initiative (April 2008–March 2011) aiming to contribute to the reduction of alcohol-related harm as measured by a reduction in the rate of increase in alcohol-related hospital admissions (ARHAs). Methods: The evaluation (March 2010–September 2011) used a mix of qualitative and quantitative methods to assess the impact of the AIP on ARHAs, to describe and assess the process of implementation, and to identify elements of the programme which might serve as a ‘legacy’ for the future. Results: There was no evidence that the AIP had an impact on reducing the rise in the rate of ARHAs. The AIP was successfully delivered, increased the priority given to alcohol-related harm on local policy agendas and strengthened the infrastructure for the delivery of interventions. Conclusion: Although there was no measurable short-term impact on the rise in the rate of ARHAs, the AIP helped to set up a strategic response and a delivery infrastructure as a first, necessary step in working towards that goal. There are a number of valuable elements in the AIP which should be retained and repackaged to fit into new policy contexts

    Giant magnetoelectric effect in pure manganite-manganite heterostructures

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    Obtaining strong magnetoelectric couplings in bulk materials and heterostructures is an ongoing challenge. We demonstrate that manganite heterostructures of the form (Insulator)/(LaMnO3)n/(CaMnO3)n/(Insulator){\rm (Insulator)/(LaMnO_3)_n/(CaMnO_3)_n/(Insulator)} show strong multiferroicity in magnetic manganites where ferroelectric polarization is realized by charges leaking from LaMnO3{\rm LaMnO_3} to CaMnO3{\rm CaMnO_3} due to repulsion. Here, an effective nearest-neighbor electron-electron (electron-hole) repulsion (attraction) is generated by cooperative electron-phonon interaction. Double exchange, when a particle virtually hops to its unoccupied neighboring site and back, produces magnetic polarons that polarize antiferromagnetic regions. Thus a striking giant magnetoelectric effect ensues when an external electrical field enhances the electron leakage across the interface.Comment: 13 page

    Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis

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    BACKGROUND: Gastric emptying is impaired in patients with gastroparesis whereas it is either unchanged or accelerated in obese individuals. The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in idiopathic gastroparesis and obesity. METHODS: Quantitative real time RT-PCR and whole transcriptome sequencing were used to compare the transcriptomes of lean individuals, obese individuals and either lean or obese individuals with idiopathic gastroparesis. RESULTS: Obesity leads to an increase in mRNAs associated with muscle contractility whereas idiopathic gastroparesis leads to a decrease in mRNAs associated with PDGF BB signaling. Both obesity and idiopathic gastroparesis were also associated with similar alterations in pathways associated with inflammation. CONCLUSIONS: Our findings show that obesity and idiopathic gastroparesis result in overlapping but distinct changes in the gastric muscularis transcriptome. Increased expression of mRNAs encoding smooth muscle contractile proteins may be contributing to the increased gastric motility observed in obese subjects, whereas decreased PDGF BB signaling may be contributing to the impaired motility seen in subjects with idiopathic gastroparesis

    Previously differentiated medial vascular smooth muscle cells contribute to neointima formation following vascular injury

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    Background The origins of neointimal smooth muscle cells that arise following vascular injury remains controversial. Studies have suggested that these cells may arise from previously differentiated medial vascular smooth muscle cells, resident stem cells or blood born progenitors. In the current study we examined the contribution of the previously differentiated vascular smooth muscle cells to the neointima that forms following carotid artery ligation. Methods We utilized transgenic mice harboring a cre recombinase-dependent reporter gene (mTmG). These mice express membrane targeted tandem dimer Tomato (mTomato) prior to cre-mediated excision and membrane targeted EGFP (mEGFP) following excision. The mTmG mice were crossed with transgenic mice expressing either smooth muscle myosin heavy chain (Myh11) or smooth muscle α-actin (Acta2) driven tamoxifen regulated cre recombinase. Following treatment of adult mice with tamoxifen these mice express mEGFP exclusively in differentiated smooth muscle cells. Subsequently vascular injury was induced in the mice by carotid artery ligation and the contribution of mEGFP positive cells to the neointima determined. Results Analysis of the cellular composition of the neointima that forms following injury revealed that mEGFP positive cells derived from either Mhy11 or Acta2 tagged medial vascular smooth muscle cells contribute to the majority of neointima formation (79 ± 17% and 81 ± 12%, respectively). Conclusion These data demonstrate that the majority of the neointima that forms following carotid ligation is derived from previously differentiated medial vascular smooth muscle cells
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