Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44HI/CD24lO/-stem cell phenotype in human breast cancer

We review here the recently emerging relationship between epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSC), and provide analyses of published data on human breast cancer cell lines, supporting their utility as a model for the EMT/BCSC state. Genome-wide transcriptional profiling of these cell lines has confirmed the existence of a subgroup with mesenchymal tendencies and enhanced invasive properties ('Basal B'/Mesenchymal), distinct from subgroups with either predominantly luminal ('Luminal') or mixed basal/luminal ('Basal A') features (Neve et al. Cancer Cell, 2006). A literature-derived EMT gene signature has shown specific enrichment within the Basal B subgroup of cell lines, consistent with their over-expression of various EMT transcriptional drivers. Basal B cell lines are found to resemble BCSC, being CD44highCD24low. Moreover, gene products that distinguish Basal B from Basal A and Luminal cell lines (Basal B Discriminators) showed close concordance with those that define BCSC isolated from clinical material, as reported by Shipitsin et al. (Cancer Cell, 2007). CD24 mRNA levels varied across Basal B cell lines, correlating with other Basal B Discriminators. Many gene products correlating with CD24 status in Basal B cell lines were also differentially expressed in isolated BCSC. These findings confirm and extend the importance of the cellular product of the EMT with Basal B cell lines, and illustrate the value of analysing these cell lines for new leads that may improve breast cancer outcomes. Gene products specific to Basal B cell lines may serve as tools for the detection, quantification, and analysis of BCSC/EMT attributes.

Association of MMP-2 activation potential with metastatic progression in human breast cancer cell lines independent of MMP-2 production

Background: Expression of matrix metalloproteinase-2 (MMP-2), the 72-kd type IV collagenase/gelatinase, by cancer cells has been implicated in metastasis through cancer cell invasion of basement membranes mediated by degradation of collagen IV. However, the abundance of this latent proenzyme in normal tissues and fluids suggests that MMP-2 proenzyme utilization is limited by its physiological activation rather than expression alone. We previously reported activation of this proenzyme by normal and malignant fibroblastoid cells cultured on collagen I (vitrogen) gels. Purpose: Our purposes in this study were 1) to determine whether MMP-2 activation is restricted to the more invasive human breast cancer cell lines and 2) to localize the activating mechanism. Methods: Zymography was used to monitor MMP-2 activation through detection of latent MMP-2 (72 kd) and mature species of smaller molecular weight (59 or 62 kd). Human breast cancer cell lines cultured on plastic, vitrogen, and other matrices were thus screened for MMP- 2 activation. Collagen I-cultured cells were exposed to cycloheximide, a protein synthesis inhibitor, or to protease inhibitors to determine the nature of the MMP-2-activating mechanism. Triton X-114 (TX-114) detergent extracts from cells cultured on collagen I or plastic were incubated with latent MMP-2 and analyzed by zymography to localize the MMP-2 activator. Results: MMP-2 activation was only induced by collagen I culture in the more aggressive, highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines (Hs578T, MDA-MB-436, BT549, MDA-MB-231, MDA- MB-435, MCF-7(ADR)) and was independent of MMP-2 production. MMP-2 activation was detected in cells cultured on collagen I gels but not in those cultured on gelatin gels, Matrigel, or thin layers of collagen I or IV, gelatin, or fibronectin. Collagen-induced activation was specific for the enzyme species MMP-2, since MMP-9, the 92-kd type IV collagenase/gelatinase, was not activatable under similar conditions. MMP-2 activation was inhibited by cycloheximide and was sensitive to a metalloproteinase inhibitor but not to aspartyl, serine, or cysteinyl protease inhibitors. MMP-2 activation was detected in the hydrophobic, plasma membrane-enriched, TX-114 extracts from invasive collagen I-cultured cells. Conclusion: Collagen I-induced MMP-2 activation is restricted to highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines, is independent of MMP-2 production, and is associated with metastatic potential. Our findings are consistent with plasma membrane localization of the activator. Implications: The MMP-2 activation mechanism may represent a new target for diagnosis, prognosis, and treatment of human breast cancer.

A natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer : a phase III double-blind randomised controlled trial

Purpose To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation induced skin reactions (RISR). Methods and Materials A total of 174 patients were randomised and participated in the study. Patients either received Cream 1 (the natural oil-based emulsion containing allantoin) or Cream 2 (aqueous cream). Skin toxicity, pain, itching and skin-related quality of life scores were collected for up to four weeks after radiation treatment. Results Patients who received Cream 1 had a significantly lower average level of Common Toxicity Criteria at week 3 (p<0.05), but had statistically higher average levels of skin toxicity at weeks 7, 8 and 9 (all p<0.001). Similar results were observed when skin toxicity was analysed by grades. With regards to pain, patients in the Cream 2 group had a significantly higher average level of worst pain (p<0.05) and itching (p=0.046) compared to the Cream 1 group at week 3, however these differences were not observed at other weeks. In addition, there was a strong trend for Cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison to Cream 1 (p=0.056). Overall, more participants in the Cream 1 group were required to use another topical treatment at weeks 8 (p=0.049) and 9 (p=0.01). Conclusion The natural oil-based emulsion containing allantoin appears to have similar effects for managing skin toxicity compared to aqueous cream up to week 5, however, it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion (week 6 and beyond). There were no major differences in pain, itching and skin-related quality of life. In light of these results, clinicians and patients can base their decision on costs and preferences. Overall, aqueous cream appears to be a more preferred option.

Plasma-enabled, catalyst-free growth of carbon nanotubes on mechanically-written Si features with arbitrary shape

Simple, rapid, catalyst-free synthesis of complex patterns of long, vertically aligned multiwalled carbon nanotubes, strictly confined within mechanically-written features on a Si(1 0 0) surface is reported. It is shown that dense arrays of the nanotubes can nucleate and fully fill the features when the low-temperature microwave plasma is in a direct contact with the surface. This eliminates additional nanofabrication steps and inevitable contact losses in applications associated with carbon nanotube patterns. Using metal catalyst has long been considered essential for the nucleation and growth of surface-supported carbon nanotubes (CNTs) [1] and [2]. Only very recently, the possibility of CNT growth using non-metallic (e.g., oxide [3] and SiC [4]) catalysts or artificially created carbon-enriched surface layers [5] has been demonstrated. However, successful integration of carbon nanostructures into Si-based nanodevice platforms requires catalyst-free growth, as the catalyst nanoparticles introduce contact losses, and their catalytic activity is very difficult to control during the growth [6]. Furthermore, in many applications in microfluidics, biological and molecular filters, electronic, sensor, and energy conversion nanodevices, the CNTs need to be arranged in specific complex patterns [7] and [8]. These patterns need to contain the basic features (e.g., lines and dots) written using simple procedures and fully filled with dense arrays of high-quality, straight, yet separated nanotubes. In this paper, we report on a completely metal or oxide catalyst-free plasma-based approach for the direct and rapid growth of dense arrays of long vertically-aligned multi-walled carbon nanotubes arranged into complex patterns made of various combinations of basic features on a Si(1 0 0) surface written using simple mechanical techniques. The process was conducted in a plasma environment [9] and [10] produced by a microwave discharge which typically generates the low-temperature plasmas at the discharge power below 1 kW [11]. Our process starts from mechanical writing (scribing) a pattern of arbitrary features on pre-treated Si(1 0 0) wafers. Before and after the mechanical feature writing, the Si(1 0 0) substrates were cleaned in an aqueous solution of hydrofluoric acid for 2 min to remove any possible contaminations (such as oil traces which could decompose to free carbon at elevated temperatures) from the substrate surface. A piece of another silicon wafer cleaned in the same way as the substrate, or a diamond scriber were used to produce the growth patterns by a simple arbitrary mechanical writing, i.e., by making linear scratches or dot punctures on the Si wafer surface. The results were the same in both cases, i.e., when scratching the surface by Si or a diamond scriber. The procedure for preparation of the substrates did not involve any possibility of external metallic contaminations on the substrate surface. After the preparation, the substrates were loaded into an ASTeX model 5200 chemical vapour deposition (CVD) reactor, which was very carefully conditioned to remove any residue contamination. The samples were heated to at least 800 °C to remove any oxide that could have formed during the sample loading [12]. After loading the substrates into the reactor chamber, N2 gas was supplied into the chamber at the pressure of 7 Torr to ignite and sustain the discharge at the total power of 200 W. Then, a mixture of CH4 and 60% of N2 gases were supplied at 20 Torr, and the discharge power was increased to 700 W (power density of approximately 1.49 W/cm3). During the process, the microwave plasma was in a direct contact with the substrate. During the plasma exposure, no external heating source was used, and the substrate temperature (∼850 °C) was maintained merely due to the plasma heating. The features were exposed to a microwave plasma for 3–5 min. A photograph of the reactor and the plasma discharge is shown in Fig. 1a and b.

Investigation of corona sources in high voltage power lines

This paper describes the results of experiments made in the vicinity of EHV overhead lines to investigate sources of clouds of charged particles using simultaneously-recording arrays of electric field meters to measure direct electric fields produced under ion clouds. E-field measurements, made at one metre above ground level, are correlated with wind speed and direction, and with measurements from ionisation counters and audible corona effects to identify possible positions of sources of corona on adjacent power lines. Measurements made in dry conditions on EHV lines in flat remote locations with no adjacent buildings or large vegetation indicate the presence of discrete ion sources associated with high stress points on some types of line hardware such as connectors and conductor spacers. Faulty line components such as insulators and line fittings are also found to be a possible source of ion clouds.

Air ion concentrations under overhead power lines

Corona discharge is responsible for the flux of small ions from overhead power lines, and is capable of modifying the ambient electrical environment, such as the air ion concentrations at ground level. Once produced, small ions quickly attach to aerosol particles in the air, producing ‘large ions’, approximately 1 nm to 1 µm in diameter. However, very few studies have measured air ion concentrations directly near high voltage transmission lines. The present study involved the simultaneously measurement of small ion concentration and net large ion concentration using air ion counters and an aerosol electrometer at four power line sites. Both positive and negative small ion concentration (<1.6nm), net large ion concentration (2nm-5μm) and particle number concentration (10nm-2μm) were measured using air ion counters and an aerosol electrometer at four power line sites. Measurements at sites 1 and 2 were conducted at both upwind and downwind sides. The results showed that total ion concentrations on the downwind side were 3-5 times higher than on the upwind side, while particle number concentrations did not show a significant difference. This result also shows that a large number of ions were emitted from the power lines at sites 1 and 2. Furthermore, both positive and negative ions were observed at different power line sites. Dominant positive ions were observed at site 1, with a concentration of 4.4 x 103 ions cm-3, which was 10 times higher than on the upwind side. Contrary to site 1, sites 2 to 4 showed negative ion emissions, with concentrations of -1.2 x 103, -460 and -410 ions cm-3, respectively. These values were higher than the background urban negative ion concentration of 400 cm-3. At site 1 and site 2, the net ion concentration and net particle charge concentration on downwind side of the lines showed same polarities. Further investigations were also conducted into the correlation between net ion concentration and net charge particle concentration 20 m downwind of the power lines at site 2. The two parameters showed a correlation coefficient of 0.72, indicating that a substantial number of ions could attach to particles and affect the particle charge status within a short distance from the source.

Biodiesel production from non-edible beauty leaf (Calophyllum Inophyllum) oil : process optimization using response surface methodology (RSM)

In recent years, the beauty leaf plant (Calophyllum Inophyllum) is being considered as a potential 2nd generation biodiesel source due to high seed oil content, high fruit production rate, simple cultivation and ability to grow in a wide range of climate conditions. However, however, due to the high free fatty acid (FFA) content in this oil, the potential of this biodiesel feedstock is still unrealized, and little research has been undertaken on it. In this study, transesterification of beauty leaf oil to produce biodiesel has been investigated. A two-step biodiesel conversion method consisting of acid catalysed pre-esterification and alkali catalysed transesterification has been utilized. The three main factors that drive the biodiesel (fatty acid methyl ester (FAME)) conversion from vegetable oil (triglycerides) were studied using response surface methodology (RSM) based on a Box-Behnken experimental design. The factors considered in this study were catalyst concentration, methanol to oil molar ratio and reaction temperature. Linear and full quadratic regression models were developed to predict FFA and FAME concentration and to optimize the reaction conditions. The significance of these factors and their interaction in both stages was determined using analysis of variance (ANOVA). The reaction conditions for the largest reduction in FFA concentration for acid catalysed pre-esterification was 30:1 methanol to oil molar ratio, 10% (w/w) sulfuric acid catalyst loading and 75 °C reaction temperature. In the alkali catalysed transesterification process 7.5:1 methanol to oil molar ratio, 1% (w/w) sodium methoxide catalyst loading and 55 °C reaction temperature were found to result in the highest FAME conversion. The good agreement between model outputs and experimental results demonstrated that this methodology may be useful for industrial process optimization for biodiesel production from beauty leaf oil and possibly other industrial processes as well.

Does the price of oil interact with clean energy prices in the stock market?

In this paper, we analyze the relationships among oil prices, clean energy stock prices, and technology stock prices, endogenously controlling for structural changes in the market. To this end, we apply Markov-switching vector autoregressive models to the economic system consisting of oil prices, clean energy and technology stock prices, and interest rates. The results indicate that there was a structural change in late 2007, a period in which there was a significant increase in the price of oil. In contrast to the previous studies, we find a positive relationship between oil prices and clean energy prices after structural breaks. There also appears to be a similarity in terms of the market response to both clean energy stock prices and technology stock prices. © 2013 Elsevier B.V.

Effect of Oil Price on Emissions Trading Market: VAR Analysis

In this study, we investigated the relationship of European Union carbon dioxide CO2 allowances EUAs prices and oil prices by employing a VAR analysis, Granger causality test and impulse response function. If oil price continues increasing, companies will decrease dependency on fossil fuels because of an increase in energy costs. Therefore, the price of EUAs may be affected by variations in oil prices if the greenhouse gases discharged by the consumption of alternative energy are less than that of fossil fuels. There are no previous studies that investigated these relationships. In this study, we analyzed eight types of EUAs EUA05 to EUA12 with a time series daily data set during 2005-2007 collected from a European Climate Exchange time series data set. Differentiations in these eight types were redemption period. We used the New York Mercantile Exchange light sweet crude price as an oil price. From our examination, we found that only the EUA06 and EUA07 types of EUAs Granger-cause oil prices and vice versa and other six types of EUAs do not Granger-cause oil price. These results imply that the earlier redemption period types of EUAs are more sensitive to oil price. In employing the impulse response function, the results showed that a shock to oil price has a slightly positive effect on all types of EUAs for a very short period. On the other hand, we found that a shock to price of EUA has a slightly negative effect on oil price following a positive effect in only EUA06 and EUA07 types. Therefore, these results imply that fluctuations in EUAs prices and oil prices have little effect on each other. Lastly, we did not consider the substitute energy prices in this study, so we plan to include the prices of coal and natural gas in future analyses.

Stock prices of clean energy firms, oil and carbon markets : a vector autoregressive analysis

Recent discussions of energy security and climate change have attracted significant attention to clean energy. We hypothesize that rising prices of conventional energy and/or placement of a price on carbon emissions would encourage investments in clean energy firms. The data from three clean energy indices show that oil prices and technology stock prices separately affect the stock prices of clean energy firms. However, the data fail to demonstrate a significant relationship between carbon prices and the stock prices of the firms.

Productivity assessment of Angola's oil blocks

This paper analyzes the change in productivity as a result of Angola oil policy from 2001 to 2007. Angola oil blocks are the main source of tax receipts and, therefore, strategically important for public finances. A Malmquist index with the input technological bias is applied to measure productivity change. Oil blocks on average became both more efficient and experienced technological progress. Our results indicate that the traditional growth accounting method, which assumes Hicks neutral technological change, is not appropriate for analyzing changes in productivity for Angola oil blocks. Policy implications are derived.

Effect of temperature and moisture on high pressure lipid/oil extraction from microalgae

Commercially viable carbon–neutral biodiesel production from microalgae has potential for replacing depleting petroleum diesel. The process of biodiesel production from microalgae involves harvesting, drying and extraction of lipids which are energy- and cost-intensive processes. The development of effective large-scale lipid extraction processes which overcome the complexity of microalgae cell structure is considered one of the most vital requirements for commercial production. Thus the aim of this work was to investigate suitable extraction methods with optimised conditions to progress opportunities for sustainable microalgal biodiesel production. In this study, the green microalgal species consortium, Tarong polyculture was used to investigate lipid extraction with hexane (solvent) under high pressure and variable temperature and biomass moisture conditions using an Accelerated Solvent Extraction (ASE) method. The performance of high pressure solvent extraction was examined over a range of different process and sample conditions (dry biomass to water ratios (DBWRs): 100%, 75%, 50% and 25% and temperatures from 70 to 120 ºC, process time 5–15 min). Maximum total lipid yields were achieved at 50% and 75% sample dryness at temperatures of 90–120 ºC. We show that individual fatty acids (Palmitic acid C16:0; Stearic acid C18:0; Oleic acid C18:1; Linolenic acid C18:3) extraction optima are influenced by temperature and sample dryness, consequently affecting microalgal biodiesel quality parameters. Higher heating values and kinematic viscosity were compliant with biodiesel quality standards under all extraction conditions used. Our results indicate that biodiesel quality can be positively manipulated by selecting process extraction conditions that favour extraction of saturated and mono-unsaturated fatty acids over optimal extraction conditions for polyunsaturated fatty acids, yielding positive effects on cetane number and iodine values. Exceeding biodiesel standards for these two parameters opens blending opportunities with biodiesels that fall outside the minimal cetane and maximal iodine values.

2nd ESMO Consensus Conference on Lung Cancer : non-small-cell lung cancer first-line/second and further lines in advanced disease

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on 1st line / 2nd and further lines of treatment in advanced disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

How innovation and R&D happen in the upstream oil & gas industry : insights from a global survey

Few would disagree that the upstream oil & gas industry has become more technology-intensive over the years. But how does innovation happen in the industry? Specifically, what ideas and inputs flow from which parts of the sector׳s value network, and where do these inputs go? And how do firms and organizations from different countries contribute differently to this process? This paper puts forward the results of a survey designed to shed light on these questions. Carried out in collaboration with the Society of Petroleum Engineers (SPE), the survey was sent to 469 executives and senior managers who played a significant role with regard to R&D and/or technology deployment in their respective business units. A total of 199 responses were received from a broad range of organizations and countries around the world. Several interesting themes and trends emerge from the results, including: (1) service companies tend to file considerably more patents per innovation than other types of organization; (2) over 63% of the deployed innovations reported in the survey originated in service companies; (3) neither universities nor government-led research organizations were considered to be valuable sources of new information and knowledge in the industry׳s R&D initiatives, and; (4) despite the increasing degree of globalization in the marketplace, the USA still plays an extremely dominant role in the industry׳s overall R&D and technology deployment activities. By providing a detailed and objective snapshot of how innovation happens in the upstream oil & gas sector, this paper provides a valuable foundation for future investigations and discussions aimed at improving how R&D and technology deployment are managed within the industry. The methodology did result in a coverage bias within the survey, however, and the limitations arising from this are explored.

Experimental investigations of improved dielectric condition monitoring methods on transformer oil-paper insulation system

Frequency Domain Spectroscopy (FDS) is successfully being used to assess the insulation condition of oil filled power transformers. However, it has to date only been implemented on de-energized transformers, which requires the transformers to be shut down for an extended period which can result in significant costs. To solve this issue, a method of implementing FDS under energized condition is proposed here. A chirp excitation waveform is used to replace the conventional sinusoidal waveform to reduce the measurement time in this method. Investigation of the dielectric response under the influence of a high voltage stress at power frequency is reported based on experimental results. To further understand the insulation ageing process, the geometric capacitance effect is removed to enhance the detection of the ageing signature. This enhancement enables the imaginary part of admittance to be used as a new indicator to assess the ageing status of the insulation.