Application of oxygen-enriched combustion for locomotive diesel engines. Phase 1

A thermodynamic simulation is used to study the effects of oxygen-enriched intake air on the performance and nitrogen oxide (NO) emissions of a locomotive diesel engine. The parasitic power of the air separation membrane required to supply the oxygen-enriched air is also estimated. For a given constraint on peak cylinder pressure, the gross and net power outputs of an engine operating under different levels of oxygen enrichment are compared with those obtained when a high-boost turbocharged engine is used. A 4% increase in peak cylinder pressure can result in an increase in net engine power of approximately 13% when intake air with an oxygen content of 28% by volume is used and fuel injection timing is retarded by 4 degrees. When the engine is turbocharged to a higher inlet boost, the same increase in peak cylinder pressure improves power by only 4%. If part of the significantly higher exhaust enthalpies available as a result of oxygen enrichment are recovered, the power requirements of the air separator membrane can be met, resulting in substantial net power improvements. Oxygen enrichment reduces particulate and visible smoke emissions but increases NO emissions. However, a combination of retarded fuel injection timing and post-treatment of exhaust gases may be adequate to meet the locomotive diesel engine NO{sub x} standards. Exhaust gas after-treatment and heat recovery would be required to realize the full potential of oxygen enrichment. Economic analysis shows that oxygen-enrichment technology is economically feasible and provides high returns on investment. The study also indicates the strong influence of membrane parasitic requirements and exhaust energy recovery on economic benefits. To obtain an economic advantage while using a membrane with higher parasitic power requirements, it is necessary to recover a part of the exhaust energy

Study of using oxygen-enriched combustion air for locomotive diesel engines

A thermodynamic simulation is used to study effects of O2-enriched intake air on performance and NO emissions of a locomotive diesel engine. Parasitic power of the air separation membrane required to supply the O2-enriched air is also estimated. For a given constraint on peak cylinder pressure, gross and net power output of an engine operating under different levels of O2 enrichment are compared with those obtained when a high-boost turbocharged engine is used. A 4% increase in peak cylinder pressure can result in 13% increase in net engine power when intake air with 28 vol% O2 is used and fuel injection timing retarded by 4 degrees. When the engine is turbocharged to a higher inlet boost, the same increase in peak cylinder pressure can result in only 4% improvement in power. If part of the higher exhaust enthalpies from the O2 enrichment is recovered, the power requirements of the air separator membrane can be met. O2 enrichment with its higher combustion temperatures reduces emissions of particulates and visible smoke but increases NO emissions (by up to 3 times at 26% O2 content). Therefore, exhaust gas after-treatment and heat recovery would be required if the full potential of O2 enrichment for improving the performance of locomotive diesel engines is to be realized

Modeling the Effects of Late Cycle Oxygen Enrichment on Diesel Engine Combustion and Emissions

A multidimensional simulation of Auxiliary Gas Injection (AGI) for late cycle oxygen enrichment was exercised to assess the merits of AGI for reducing the emissions of soot from heavy duty diesel engines while not adversely affecting the NO{sub x} emissions of the engine. Here, AGI is the controlled enhancement of mixing within the diesel engine combustion chamber by high speed jets of air or another gas. The engine simulated was a Caterpillar 3401 engine. For a particular operating condition of this engine, the simulated soot emissions of the engine were reduced by 80% while not significantly affecting the engine-out NO{sub x} emissions compared to the engine operating without AGI. The effects of AGI duration, timing, and orientation are studied to confirm the window of opportunity for realizing lower engine-out soot while not increasing engine out NO{sub x} through controlled enhancement of in-cylinder mixing. These studies have shown that this window occurs during the late combustion cycle, from 20 to 60 crank angle degrees after top-dead-center. During this time, the combustion chamber temperatures are sufficiently high that soot oxidation increases in response in increased mixing, but the temperature is low enough that NO{sub x} reactions are quenched. The effect of the oxygen composition of the injected air is studied for the range of compositions between 21% and 30% oxygen by volume. This is the range of oxygen enrichment that is practical to produce from an air separation membrane. Simulations showed that this level of oxygen enrichment is insufficient to provide an additional benefit by either increasing the level of soot oxidation or prolonging the window of opportunity for increasing soot oxidation through enhanced mixing

Elevated Oestrogen Receptor Splice Variant ERαΔ5 Expression in Tumour-adjacent Hormone-responsive Tissue

Susceptibility to prostate or endometrial cancer is linked with obesity, a state of oestrogen excess. Oestrogen receptor (ER) splice variants may be responsible for the tissue-level of ER activity. Such micro-environmental regulation may modulate cancer initiation and/or progression mechanisms. Real-time reverse transcriptase (RT) polymerase chain reaction (PCR) was used to quantitatively assess the levels of four ER splice variants (ERαΔ3, ERαΔ5, ERβ2 and ERβ5), plus the full-length parent isoforms ERα and ERβ1, in high-risk [tumour-adjacent prostate (n = 10) or endometrial cancer (n = 9)] vs. low-risk [benign prostate (n = 12) or endometrium (n = 9)], as well as a comparison of UK (n = 12) vs. Indian (n = 15) benign prostate. All three tissue groups expressed the ER splice variants at similar levels, apart from ERαΔ5. This splice variant was markedly raised in all of the tumour-adjacent prostate samples compared to benign tissues. Immunofluorescence analysis for ERβ2 in prostate tissue demonstrated that such splice variants are present in comparable, if not greater, amounts as the parent full-length isoform. This small pilot study demonstrates the ubiquitous nature of ER splice variants in these tissue sites and suggests that ERαΔ5 may be involved in progression of prostate adenocarcinoma

Oestrogen receptor β and neoadjuvant therapy with tamoxifen: prediction of response and effects of treatment

In order to elucidate the relative importance of oestrogen receptor (ER)α, ERβ and an ERβ variant (ERβ2/βcx) in the response of breast cancers to tamoxifen, tumour levels of each receptor were assessed in 36 patients before and after 3 months of neoadjuvant treatment with tamoxifen (20 mg daily). All patients were postmenopausal women presenting with large ERα-positive breast cancers. Clinical response to treatment was assessed by tumour volume changes as determined from sequential ultrasounds and pathological response by comparison of the tumour morphology before and after treatment. Of 33 cases, 23 (70%) were classified as having a clinical response and 16 (48%) as having a response pathologically. All tumours stained positively for ERα and ERβ and 15 out of 33 (45%) for ERβ2/βcx. There were no significant differences in quantitative expression of any receptor between tumours that subsequently responded and that did not, whether response was assessed clinically or pathologically. Tamoxifen treatment was associated with a decrease in ERα, but an increase was the most frequent change (17 out of 33) in ERβ, and no consistent change was evident in staining of the ERβ2/βcx variant. In summary, ERβ1 and ERβ2/βcx variant protein are detected in ERα-positive breast tumours but their expression is not associated with a response to tamoxifen. Differential changes in ERα and ERβ were seen with treatment

Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features

Background Increased understanding of the variability in normal breast biology will enable us to identify mechanisms of breast cancer initiation and the origin of different subtypes, and to better predict breast cancer risk. Methods Gene expression patterns in breast biopsies from 79 healthy women referred to breast diagnostic centers in Norway were explored by unsupervised hierarchical clustering and supervised analyses, such as gene set enrichment analysis and gene ontology analysis and comparison with previously published genelists and independent datasets. Results Unsupervised hierarchical clustering identified two separate clusters of normal breast tissue based on gene-expression profiling, regardless of clustering algorithm and gene filtering used. Comparison of the expression profile of the two clusters with several published gene lists describing breast cells revealed that the samples in cluster 1 share characteristics with stromal cells and stem cells, and to a certain degree with mesenchymal cells and myoepithelial cells. The samples in cluster 1 also share many features with the newly identified claudin-low breast cancer intrinsic subtype, which also shows characteristics of stromal and stem cells. More women belonging to cluster 1 have a family history of breast cancer and there is a slight overrepresentation of nulliparous women in cluster 1. Similar findings were seen in a separate dataset consisting of histologically normal tissue from both breasts harboring breast cancer and from mammoplasty reductions. Conclusion This is the first study to explore the variability of gene expression patterns in whole biopsies from normal breasts and identified distinct subtypes of normal breast tissue. Further studies are needed to determine the specific cell contribution to the variation in the biology of normal breasts, how the clusters identified relate to breast cancer risk and their possible link to the origin of the different molecular subtypes of breast cancer

Membrane estrogen receptor-α levels predict estrogen-induced ERK1/2 activation in MCF-7 cells

INTRODUCTION: We examined the participation of a membrane form of estrogen receptor (mER)-α in the activation of mitogen-activated protein kinases (extracellular signal-regulated kinase [ERK]1 and ERK2) related to cell growth responses in MCF-7 cells. METHODS: We immunopanned and subsequently separated MCF-7 cells (using fluorescence-activated cell sorting) into mER-α-enriched (mER(high)) and mER-α-depleted (mER(low)) populations. We then measured the expression levels of mER-α on the surface of these separated cell populations by immunocytochemical analysis and by a quantitative 96-well plate immunoassay that distinguished between mER-α and intracellular ER-α. Western analysis was used to determine colocalized estrogen receptor (ER)-α and caveolins in membrane subfractions. The levels of activated ERK1 and ERK2 were determined using a fixed cell-based enzyme-linked immunosorbent assay developed in our laboratory. RESULTS: Immunocytochemical studies revealed punctate ER-α antibody staining of the surface of nonpermeabilized mER(high )cells, whereas the majority of mER(low )cells exhibited little or no staining. Western analysis demonstrated that mER(high )cells expressed caveolin-1 and caveolin-2, and that ER-α was contained in the same gradient-separated membrane fractions. The quantitative immunoassay for ER-α detected a significant difference in mER-α levels between mER(high )and mER(low )cells when cells were grown at a sufficiently low cell density, but equivalent levels of total ER-α (membrane plus intracellular receptors). These two separated cell subpopulations also exhibited different kinetics of ERK1/2 activation with 1 pmol/l 17β-estradiol (E(2)), as well as different patterns of E(2 )dose-dependent responsiveness. The maximal kinase activation was achieved after 10 min versus 6 min in mER(high )versus mER(low )cells, respectively. After a decline in the level of phosphorylated ERKs, a reactivation was seen at 60 min in mER(high )cells but not in mER(low )cells. Both 1A and 2B protein phosphatases participated in dephosphorylation of ERKs, as demonstrated by efficient reversal of ERK1/2 inactivation with okadaic acid and cyclosporin A. CONCLUSION: Our results suggest that the levels of mER-α play a role in the temporal coordination of phosphorylation/dephosphorylation events for the ERKs in breast cancer cells, and that these signaling differences can be correlated to previously demonstrated differences in E(2)-induced cell proliferation outcomes in these cell types