10 resultados para Double mutant cycle analysis
em Aston University Research Archive
Resumo:
As an alternative fuel for compression ignition engines, plant oils are in principle renewable and carbon-neutral. However, their use raises technical, economic and environmental issues. A comprehensive and up-to-date technical review of using both edible and non-edible plant oils (either pure or as blends with fossil diesel) in CI engines, based on comparisons with standard diesel fuel, has been carried out. The properties of several plant oils, and the results of engine tests using them, are reviewed based on the literature. Findings regarding engine performance, exhaust emissions and engine durability are collated. The causes of technical problems arising from the use of various oils are discussed, as are the modifications to oil and engine employed to alleviate these problems. The review shows that a number of plant oils can be used satisfactorily in CI engines, without transesterification, by preheating the oil and/or modifying the engine parameters and the maintenance schedule. As regards life-cycle energy and greenhouse gas emission analyses, these reveal considerable advantages of raw plant oils over fossil diesel and biodiesel. Typical results show that the life-cycle output-to-input energy ratio of raw plant oil is around 6 times higher than fossil diesel. Depending on either primary energy or fossil energy requirements, the life-cycle energy ratio of raw plant oil is in the range of 2–6 times higher than corresponding biodiesel. Moreover, raw plant oil has the highest potential of reducing life-cycle GHG emissions as compared to biodiesel and fossil diesel.
Resumo:
The Saccharomyces cerevisiae MIP channel Fps1p plays an important role in yeast osmoregulation by exporting glycerol. Glycerol accumulates in the cell as a compatible osmolyte during hyperosmotic conditions and is exported once conditions become hypotonic. A gpd1 gpd2 mutant is unable to produce glycerol and is therefore very sensitive to high concentrations of polyols in the growth medium. The sensitivity to C3, C4 and C5, but not C6 polyols, is suppressed by expression of truncated, hyperactive Fps1p. This is because the polyols can then equilibrate over the membrane and hence the concentration gradient collapses. This experiments reveals the substrate spectrum of Fps1p. The system can be used in different ways. For instance, growth assays on different polyols elucidate the substrate range of heterologous channels such as that of the rat aquaglyceroporin AQP9. In addition, the same system is used to search for novel hyperactive mutants of Fps1p, which provide additional information on the mechanism underlying channel regulation. Finally we illustrate that the gpd1 gpd2 double mutant expressing hyperactive Fps1p can be used to manipulate activation and deactivation of the HOG pathway, contributing to our understanding of the control of this osmoregulatory system.
Resumo:
Eukaryotic initiation factor 2A (eIF2A) has been shown to direct binding of the initiator methionyl-tRNA (Met-tRNA(i)) to 40 S ribosomal subunits in a codon-dependent manner, in contrast to eIF2, which requires GTP but not the AUG codon to bind initiator tRNA to 40 S subunits. We show here that yeast eIF2A genetically interacts with initiation factor eIF4E, suggesting that both proteins function in the same pathway. The double eIF2A/eIF4E-ts mutant strain displays a severe slow growth phenotype, which correlated with the accumulation of 85% of the double mutant cells arrested at the G(2)/M border. These cells also exhibited a disorganized actin cytoskeleton and elevated actin levels, suggesting that eIF2A might be involved in controlling the expression of genes involved in morphogenic processes. Further insights into eIF2A function were gained from the studies of eIF2A distribution in ribosomal fractions obtained from either an eIF5BDelta (fun12Delta) strain or a eIF3b-ts (prt1-1) strain. It was found that the binding of eIF2A to 40 and 80 S ribosomes was not impaired in either strain. We also found that eIF2A functions as a suppressor of Ure2p internal ribosome entry site-mediated translation in yeast cells. The regulation of expression from the URE2 internal ribosome entry site appears to be through the levels of eIF2A protein, which has been found to be inherently unstable with a half-life of approximately 17 min. It was hypothesized that this instability allows for translational control through the level of eIF2A protein in yeast cells.
Resumo:
Bedrock geochemical analysis, coupled with detailed data analysis, was carried out on some 260 samples taken from two areas of 'the Harlech Dome, near Dolgellau, North Wales. This was done to determine if rocks from mineralised and non-mineralised areas could be distinguished, and to determine mineralisation types and wall rock alterations. The Northern Area, near Talsarnau, has no recorded mineralisation, while the Southern Area, near Bontddu, has been exploited for gold. The rocks sampled, in both areas, were from the Cambrian Gamlan Flags, Clogau Shales, Vigra Flags, later vein materials, and igneous intrusions. All samples were analysed, using a new rapid, atomic absorption spectrophotometric technique, for Si, AI, Fe, Cu, Ni, Zn, Pb, Sr, Hg, and Ba. In addition 60 samples were analysed by X-ray fluorescence for Mn, Ti, Ca, K, Na, P, Cr, Ce, La, S, Y , Rh, and Th. Total CO2 was determined, on selected samples, using a combustion technique. Elemental distributions, for each rock type, in each area, were· plotted, and means, standard deviations, and enrichment indices were calculated. Multivariate statistical analysis on the results distinguished a Cu-type mineralisation in the Northern area, and both Cu and Pb/Zn types in the Southern Area. It also showed the Northern Area to be less strongly mineralised than the Southern one in which both mineralisation types are associated with wall rock alteration. Elemental associations and trends due to sedimentary processes were distinguished from those related to mineralisation. Hg is related to mineralisation, and plots of factor scores, on the sampling grid, produced clusters of mineralisation related factors in areas of known mineralisation. A double Fourier Trend Analysis program, with a wavelength search routine, was developed and used to recognise sedimentary trends for Sr. Y., Rb, and Th. These trends were interpreted to represent areas of low pH and reducing conditions. They also indicate that the supply of sediment remained constant over Gamlan, Clogau, and Vigra times. The trend surface of Hg showed no association with rock type. It is shown that analysis of a small number of samples, for a carefully selected number of elements, with detailed data analysis, can provide more useful information than analysis of a large number of samples for many elements. The mineralisation is suggested to have been the result of water solutions leaching ore metals from the sedimentary rocks and redepositing them in veins.
Resumo:
This paper proposes a more profound discussion of the philosophical underpins of sustainability than currently exists in the MOT literature and considers their influence on the construction of the theories on green operations and technology management. Ultimately, it also debates the link between theory and practice on this subject area. The paper is derived from insights gained in three research projects completed during the past twelve years, primarily involving the first author. From 2000 to 2002, an investigation using scenario analysis, aimed at reducing atmospheric pollution in urban centres by substituting natural gas for petrol and diesel, provided the first set of insights about public policy, environmental impacts, investment analysis, and technological feasibility. The second research project, from 2003 to 2005, using a survey questionnaire, was aimed at improving environmental performance in livestock farming and explored the issues of green supply chain scope, environmental strategy and priorities. Finally, the third project, from 2006 to 2011, investigated environmental decisions in manufacturing organisations through case study research and examined the underlying sustainability drivers and decision-making processes. By integrating the findings and conclusions from these projects, the link between philosophy, theory, and practice of green operations and technology management is debated. The findings from all these studies show that the philosophical debate seems to have little influence on theory building so far. For instance, although ‘sustainable development’ emphasises ‘meeting the needs of current and future generation’, no theory links essentiality and environmental impacts. Likewise, there is a weak link between theory and the practical issues of green operations and technology management. For example, the well-known ‘life-cycle analysis’ has little application in many cases because the life cycle of products these days is dispersed within global production and consumption systems and there are different stakeholders for each life cycle stage. The results from this paper are relevant to public policy making and corporate environmental strategy and decision making. Most of the past and current studies in the subject of green operations and sustainability management deal with only a single sustainability dimension at any one time. Here the value and originality of this paper lies in its integration between philosophy, theory, and practice of green technology and operations management.
Resumo:
The influence of IT investment on hospital efficiency and quality are of great interest to healthcare executives as well as insurers. Few studies have examined how IT investments influence both efficiency and quality or whether there is an optimal IT investment level that influences both in the desired direction. Decision makers in healthcare wonder if there are tradeoffs between their pursuit of hospital operational efficiency and quality. Our study involving a 2-stage double bootstrap DEA analysis of 187 US hospitals over 2. years found direct effects of IT investment upon service quality and a moderating effect of quality upon operational efficiency. Further, our findings indicate a U-shaped relationship between IT investments and operational efficiency suggesting that IT investments have diminishing returns beyond a certain point.
Resumo:
Eukaryotic initiation factor 5A (eIF5A) is the only protein in nature that contains hypusine, an unusual amino acid derived from the modification of lysine by spermidine. Two genes, TIF51A and TIF51B, encode eIF5A in the yeast Saccharomyces cerevisiae. In an effort to understand the structure-function relationship of eIF5A, we have generated yeast mutants by introducing plasmid-borne tif51A into a double null strain where both TIF51A and TIF51B have been disrupted. One of the mutants, tsL102A strain (tif51A L102A tif51aDelta tif51bDelta) exhibits a strong temperature-sensitive growth phenotype. At the restrictive temperature, tsL102A strain also exhibits a cell shape change, a lack of volume change in response to temperature increase and becomes more sensitive to ethanol, a hallmark of defects in the PKC/WSC cell wall integrity pathway. In addition, a striking change in actin dynamics and a complete cell cycle arrest at G1 phase occur in tsL102A cells at restrictive temperature. The temperature-sensitivity of tsL102A strain is due to a rapid loss of mutant eIF5A with the half-life reduced from 6 h at permissive temperature to 20 min at restrictive temperature. Phenylmethyl sulfonylfluoride (PMSF), an irreversible inhibitor of serine protease, inhibited the degradation of mutant eIF5A and suppressed the temperature-sensitive growth arrest. Sorbitol, an osmotic stabilizer that complement defects in PKC/WSC pathways, stabilizes the mutant eIF5A and suppresses all the observed temperature-sensitive phenotypes.
Resumo:
Background - Plants have proved to be an important source of anti-cancer drugs. Here we have investigated the cytotoxic action of an aqueous extract of Fagonia cretica, used widely as a herbal tea-based treatment for breast cancer. Methodology/Principal Findings - Using flow cytometric analysis of cells labeled with cyclin A, annexin V and propidium iodide, we describe a time and dose-dependent arrest of the cell cycle in G0/G1 phase of the cell cycle and apoptosis following extract treatment in MCF-7 (WT-p53) and MDA-MB-231 (mutant-p53) human breast cancer cell lines with a markedly reduced effect on primary human mammary epithelial cells. Analysis of p53 protein expression and of its downstream transcription targets, p21 and BAX, revealed a p53 associated growth arrest within 5 hours of extract treatment and apoptosis within 24 hours. DNA double strand breaks measured as ?-H2AX were detected early in both MCF-7 and MDA-MB-231 cells. However, loss of cell viability was only partly due to a p53-driven response; as MDA-MB-231 and p53-knockdown MCF-7 cells both underwent cell cycle arrest and death following extract treatment. p53-independent growth arrest and cytotoxicity following DNA damage has been previously ascribed to FOXO3a expression. Here, in MCF-7 and MDA-MB-231 cells, FOXO3a expression was increased significantly within 3 hours of extract treatment and FOXO3 siRNA reduced the extract-induced loss of cell viability in both cell lines. Conclusions/Significance - Our results demonstrate for the first time that an aqueous extract of Fagonia cretica can induce cell cycle arrest and apoptosis via p53-dependent and independent mechanisms, with activation of the DNA damage response. We also show that FOXO3a is required for activity in the absence of p53. Our findings indicate that Fagonia cretica aqueous extract contains potential anti-cancer agents acting either singly or in combination against breast cancer cell proliferation via DNA damage-induced FOXO3a and p53 expression.
Resumo:
Energy price is related to more than half of the total life cycle cost of asphalt pavements. Furthermore, the fluctuation related to price of energy has been much higher than the general inflation and interest rate. This makes the energy price inflation an important variable that should be addressed when performing life cycle cost (LCC) studies re- garding asphalt pavements. The present value of future costs is highly sensitive to the selected discount rate. Therefore, the choice of the discount rate is the most critical element in LCC analysis during the life time of a project. The objective of the paper is to present a discount rate for asphalt pavement projects as a function of interest rate, general inflation and energy price inflation. The discount rate is defined based on the portion of the energy related costs during the life time of the pavement. Consequently, it can reflect the financial risks related to the energy price in asphalt pavement projects. It is suggested that a discount rate sensitivity analysis for asphalt pavements in Sweden should range between –20 and 30%.
Resumo:
Macroeconomic developments, such as the business cycle, have a remarkable influence on firms and their performance. In business-to-business (B-to-B) markets characterized by a strong emphasis on long-term customer relationships, market orientation (MO) provides a particularly important safeguard for firms against fluctuating market forces. Using panel data from an economic upturn and downturn, we examine the effectiveness of different forms of MO (i.e., customer orientation, competitor orientation, interfunctional coordination, and their combinations) on firm performance in B-to-B firms. Our findings suggest that the impact of MO increases especially during a downturn, with interfunctional coordination clearly boosting firm performance and, conversely, competitor orientation becoming even detrimental. The findings further indicate that both the role of MO and its most effective forms vary across industry sectors, MO having a particularly strong impact on performance among B-to-B service firms. The findings of our study provide guidelines for executives to better manage performance across the business cycle and tailor their investments in MO more effectively, according to the firm's specific industry sector.