Buying a Green Image or Investing in a Green Future?

This paper examines the business motives of integrated oil and gas firms with regard to investing in renewable energy research and development. In doing so, five distinct methodologies are employed in examining five distinct facets of the topic. Precedent research is reviewed to determine if consumers are drawn to renewables. Oil industry advertisements are reviewed to ascertain whether renewables are a specific focus. Industry research is used to determine the expected points at which various technologies would reach commercial viability. Annual reports of integrated oil and gas companies are searched for mentions of renewables and related technologies. Finally, patent data is analyzed for patent quality specifically as it relates to renewable energy patents. This paper finds that there is evidence to support the conclusion that integrated oil and gas companies invest in renewable energy on the basis of developing their offerings and maintaining their viability in an increasingly green future

Investigation into the nature of complexes formed between organic acids and bases in aprotic solvents

The work described in this thesis consists of an investigation into the nature of the complexes formed between organic acids and bases in aprotic solvents. The physical techniques employed were dielectric constant measurement and nuclear magnetic resonance (n.m.r) respectively.The first section of the thesis consists of a summary of the properties of hydrogen-bonded systems and of the theories concerning the nature of the hydrogen bond.The second section deals firstly with the methods based on dielectric constant determination which have been used for the simultaneous determination of association constant and dipole moment of these complexes. This is followed by an account of the determination of both association constant and dipole moment of several complexes of acetic acid with heterocyclic bases. This work was carried out with the object of establishing: (i) Whether or not there exists a valid method for the simultaneous determination of association constant and dipole moment from dielectric constants. (ii) Whether or not the dipole moment change in the components on complex formation can be found with sufficient accuracy to throw light on the nature of the bonding between acid and base. Computer programs were developed to assist the determination of both association constant and dipole moment. This technique is particularly helpful in cases where one of the components of the mixture is strongly self-associated, but should be of general use. The results suggested that little charge transfer accompanied hydrogen bond format ion.The third section consists of an account of the n.m.r. spectra of acetic acid dissolved in benzene, cyclo-hexane and several heterocyclic bases. The results were consistent with the view that little charge transfer is associated with the hydrogen bonding between acetic acid and those bases.<p

Suberanilohydroxamic acid prevents TGF-β1-induced COX-2 repression in human lung fibroblasts post-transcriptionally by TIA-1 downregulation

Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE, is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE have been shown to contribute to the activation of lung fibroblasts and excessive deposition of collagen in pulmonary fibrosis. We have previously demonstrated that COX-2 expression in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) is epigenetically silenced and can be restored by epigenetic inhibitors. This study aimed to investigate whether COX-2 downregulation induced by the profibrotic cytokine transforming growth factor-β1 (TGF-β1) in normal lung fibroblasts could be prevented by epigenetic inhibitors. We found that COX-2 protein expression and PGE production were markedly reduced by TGF-β1 and this was prevented by the pan-histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) and to a lesser extent by the DNA demethylating agent Decitabine (DAC), but not by the G9a histone methyltransferase (HMT) inhibitor BIX01294 or the EZH2 HMT inhibitor 3-deazaneplanocin A (DZNep). However, chromatin immunoprecipitation assay revealed that the effect of SAHA was unlikely mediated by histone modifications. Instead 3'-untranslated region (3'-UTR) luciferase reporter assay indicated the involvement of post-transcriptional mechanisms. This was supported by the downregulation by SAHA of the 3'-UTR mRNA binding protein TIA-1 (T-cell intracellular antigen-1), a negative regulator of COX-2 translation. Furthermore, TIA-1 knockdown by siRNA mimicked the effect of SAHA on COX-2 expression. These findings suggest SAHA can prevent TGF-β1-induced COX-2 repression in lung fibroblasts post-transcriptionally through a novel TIA-1-dependent mechanism and provide new insights into the mechanisms underlying its potential antifibrotic activity

Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis

Introduction and objectives: Idiopathic Pulmonary Fibrosis (IFP) is a fatal interstitial lung disease with unknown aetiology. Lung myofibroblasts (activated fibrobalsts) are the major effector cells in the pathogenesis of IPF. Transforming growth factor-β (TGF-β1) is a potent activator of fibroblasts. Lack of effective treatment options necessitates novel therapeutic approaches. Epigenetic drugs, by inhibiting chromatin modifying enzymes involved in gene expression control, represent promising agents capable of modulating the cellular phenotype. We previously demonstrated that the cyclooxygenase-2 (COX-2) gene is epigenetically silenced in lung fibroblasts from IPF patients (F-IPF)[1] and epigenetic inhibitors and restore COX-2 expression. However, whether epigenetic inhibitors can alter fibroblast phenotype remains unknown. This study aimed to investigate the effect of four different epigenetic enzyme inhibitors on fibroblast phenotype change in IPF. Methods: F-IPF and fibroblasts from non-fibrotic lung (F-NL) treated with TGF-β1 were cultured to test the effects of the epigenetic inhibitors BIX01294 (BIX, G9a histone methyltransferase inhibitor), 3- deazaneplanocin A (DZNep, EZH2 histone methyltransferase inhibitor), SAHA (histone deacetylases inhibitor) and Decitabine (DAC, DNA demethylating agent), in comparison with the COX-2 products prostaglandin E2 (PGE2). The expression of COX-2 and myofibroblast markers collagen 1 (COL1) and α- smooth muscle actin (α-SMA) was assessed. The COX-2 DNA promoter methylation level was analysed by bisulfite sequencing. Results: TGF-β1 induced a myofibroblast phenotype in F-NL characterised by COL1 and α-SMA upregulation and COX-2 downregulation, similar to F-IPF. PGE2 and SAHA were able to maintain/restore COX-2 expression in TGF-β1-induced myofibroblasts and F-IPF. DAC demonstrated similar effect in TGF-β1 treated F-NL only. SAHA also reduced COL1 and α-SMA expression. But DZNep and BIX showed no effect. No differences in the COX-2 promoter methylation was detected between F-NL and F-IPF. Conclusions: Among the epigenetic inhibitors tested, SAHA shows a promising antifibrotic effect by inhibiting fibroblast activation and the underlying molecular mechanisms are currently under investigation

S52 Suberanilohydroxamic acid (SAHA) inhibits collagen deposition in a transforming growth factor β1-driven precision cut lung slice (PCLS) model of pulmonary fibrosis

Introduction and objectives Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease that is refractory to current treatment options. Transforming growth factor (TGF)-β1 is a key pro-fibrotic cytokine that plays a crucial role in IPF pathogenesis. Our group previously demonstrated distinct epigenetic modifications involved in repression of the antifibrotic gene cyclooxygenase-2 (COX-2) in fibroblasts from IPF (F-IPF) lungs compared with fibroblasts from non-fibrotic lungs (F-NL). Epigenetic drugs capable of inhibiting DNA and histone modifications may, therefore, represent a putative novel therapy. The aim of this study was to investigate the ability of 4 epigenetic inhibitors to regulate TGF-β-driven fibrosis in ex vivo mouse lung. Methods A precision-cut lung slice (PCLS) model of fibrosis was established using the previously described1 CC10-tTS-rtTA-TGFβ1 transgenic (tgTGF-β1) mouse. The model was first assessed by investigating PCLS overexpression of TGF-β1 in response to stimulation of the transgene by doxycycline treatment. Gene expression of COX-2 and fibrotic markers including collagen were assessed after 4 days of treatment. The anti-fibrotic potential of 4 epigenetic inhibitors; BIX01294 (BIX, inhibitor of G9a histone methyltransferase), 3-deazaneplanocin A (DZNep, inhibitor of EZH2 histone methyltransferase), SAHA (inhibitor of histone deacetylases, HDACs) and Decitabine (DAC, DNA demethylating agent) was investigated. Viability of PCLS was assessed by MTT and Prestoblue® assay. Results Treatment of PCLS from tgTGF-β1 mice with doxycycline induced a concentration-dependent increase in global TGF-β1, pro-fibrotic markers including collagen and pro-inflammatory COX-2, which was comparable to recombinant TGF-β1 treatment. Treatment with three of the epigenetic inhibitors BIX01294, DZNep and DAC did not reduce the pro-fibrotic response following doxycycline treatment. However SAHA demonstrated a significant suppressive effect on COX-2 and collagen expression, while not directly affecting TGF-β1 transgene expression. Conclusions The data suggests that SAHA has the potential to reduce fibrosis in a TGF-β1 driven model of pulmonary fibrosis. Further work is currently underway to assess the anti-fibrotic potential of this drug in tgTGF-β1 animals

Comparative Effects of the Sorghum \u3ci\u3ebmr\u3c/i\u3e-6 and \u3ci\u3ebmr\u3c/i\u3e-12 Genes: II. Grain Yield, Stover Yield, and Stover Quality in Grain Sorghum

Nearly 3 million hectares of grain sorghum [Sorghum bicolor (L). Moench] are harvested in the USA each year. It may be possible to add value to crop and animal systems by enhancing the digestibility of the stover residue by the use of brown midrib (bmr) genes if grain can be maintained. The objectives of this study were to evaluate the effect of bmr-6 and bmr-12 genes on grain yield of sorghum and to evaluate the effect of the bmr genes on stover yield and quality in these genetic backgrounds: ‘Wheatland’, ‘Redlan’, RTx430, Tx623, Tx630, Tx631, and the hybrid AWheatland X RTx430. Plant height, maturity, grain yield and test weight, stover neutral detergent fiber NDF), acid detergent fiber (ADF), acid detergent lignin (ADL), and in vitro NDF digestibility (IVNDFD) were measured in split-plot experiments replicated four times in each of four environments with lines being whole-plots and genotypes being subplots. Brown midrib genes reduced grain yield and residue yield in the lines; however, yield reduction was not observed in the bmr-12 AWheatland X RTx430 hybrid. The bmr-12 near-isolines generally had lowest stover lignin content and highest fiber digestibility, bmr-6 was intermediate, and wild-type counterparts had highest lignin content and lowest fiber digestibility. When all data are considered, the bmr-12 gene appears superior to the bmr-6 gene in terms of potentially adding value to the stover of grain sorghum for use in crop/animal systems. The variable expression of bmr-12 and bmr-6 in different lines indicates that selection of compatible genetic backgrounds will be critical in determining the realized impact on value

Suberanilohydroxamic acid (SAHA) inhibits collagen deposition in a transforming growth factor β1-driven precision cut lung slice (PCLS) model of pulmonary fibrosis

Introduction and Objectives: Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease that is refractory to current treatment options. Transforming growth factor (TGF)-β1 is a key pro-fibrotic cytokine that plays a crucial role in IPF pathogenesis. Our group previously demonstrated distinct epigenetic modifications involved in repression of the antifibrotic gene cyclooxygenase-2 (COX-2) in fibroblasts from IPF (F-IPF) lungs compared with fibroblasts from non-fibrotic lungs (F-NL). Epigenetic drugs capable of inhibiting DNA and histone modifications may, therefore, represent a putative novel therapy. The aim of this study was to investigate the ability of 4 epigenetic inhibitors to regulate TGF-β-driven fibrosis in ex vivo mouse lung. Methods: A precision-cut lung slice (PCLS) model of fibrosis was established using the previously described [1] CC10-tTS-rtTA-TGFβ1 transgenic (tgTGF-β1) mouse. The model was first assessed by investigating PCLS overexpression of TGF-β1 in response to stimulation of the transgene by doxycycline treatment. Gene expression of COX-2 and fibrotic markers including collagen were assessed after 4 days of treatment. The anti-fibrotic potential of 4 epigenetic inhibitors; BIX01294 (BIX, inhibitor of G9a histone methyltransferase), 3-deazaneplanocin A (DZNep, inhibitor of EZH2 histone methyltransferase), SAHA (inhibitor of histone deacetylases, HDACs) and Decitabine (DAC, DNA demethylating agent) was investigated. Viability of PCLS was assessed by MTT and Prestoblue® viability assay. Results: Treatment of PCLS from tgTGF-β1 mice with doxycycline induced a concentration-dependent increase in global TGF-β1, pro-fibrotic markers including collagen and pro-inflammatory COX-2, which was comparable to recombinant TGF-β1 treatment. Treatment with three of the epigenetic inhibitors BIX01294, DZNep and DAC did not reduce the pro-fibrotic response following doxycycline treatment. However SAHA demonstrated a significant suppressive effect on COX-2 and collagen expression, while not directly affecting TGF-β1 transgene expression. Conclusions: The data suggests that SAHA has the potential to reduce fibrosis in a TGF-β1 driven model of pulmonary fibrosis. Further work is currently underway to assess the anti-fibrotic potential of this drug in tgTGF-β1 animals

Development of a Large Field-of-View PIV System for Rotorcraft Testing in the 14- x 22-Foot Subsonic Tunnel

A Large Field-of-View Particle Image Velocimetry (LFPIV) system has been developed for rotor wake diagnostics in the 14-by 22-Foot Subsonic Tunnel. The system has been used to measure three components of velocity in a plane as large as 1.524 meters by 0.914 meters in both forward flight and hover tests. Overall, the system performance has exceeded design expectations in terms of accuracy and efficiency. Measurements synchronized with the rotor position during forward flight and hover tests have shown that the system is able to capture the complex interaction of the body and rotor wakes as well as basic details of the blade tip vortex at several wake ages. Measurements obtained with traditional techniques such as multi-hole pressure probes, Laser Doppler Velocimetry (LDV), and 2D Particle Image Velocimetry (PIV) show good agreement with LFPIV measurements

Immunocytochemical localization of AMPA selective glutamate receptor subunits in the rat cochlea

The localization of subunits of the [alpha]-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) selective glutamate receptor, termed Glutamate receptor (GluR) was examined in the rat cochlea using affinity purified polyclonal antibody to GluR subunits (GluR 1-4). GluR 2/3 and GluR 4 immunoreactive (IR) staining was observed in rat spiral ganglion cells, while GluR 1 IR was not. GluR 4 IR staining was also seen in puncta at inner and outer hair cell bases. These results suggest that GluR 2/3 and GluR 4 are components of excitatory amino acid synapses in the rat cochlea.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31208/1/0000110.pd