723 research outputs found

    Exoplanet phase curves: observations and theory

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    Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation

    Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

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    DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity

    Using keystroke logging to understand writers’ processes on a reading-into-writing test

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    Background Integrated reading-into-writing tasks are increasingly used in large-scale language proficiency tests. Such tasks are said to possess higher authenticity as they reflect real-life writing conditions better than independent, writing-only tasks. However, to effectively define the reading-into-writing construct, more empirical evidence regarding how writers compose from sources both in real-life and under test conditions is urgently needed. Most previous process studies used think aloud or questionnaire to collect evidence. These methods rely on participants’ perceptions of their processes, as well as their ability to report them. Findings This paper reports on a small-scale experimental study to explore writers’ processes on a reading-into-writing test by employing keystroke logging. Two L2 postgraduates completed an argumentative essay on computer. Their text production processes were captured by a keystroke logging programme. Students were also interviewed to provide additional information. Keystroke logging like most computing tools provides a range of measures. The study examined the students’ reading-into-writing processes by analysing a selection of the keystroke logging measures in conjunction with students’ final texts and interview protocols. Conclusions The results suggest that the nature of the writers’ reading-into-writing processes might have a major influence on the writer’s final performance. Recommendations for future process studies are provided

    Soil organic matter and litter chemistry response to experimental N deposition in northern temperate deciduous forest ecosystems

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    The effects of atmospheric nitrogen (N) deposition on organic matter decomposition vary with the biochemical characteristics of plant litter. At the ecosystem-scale, net effects are difficult to predict because various soil organic matter (SOM) fractions may respond differentially. We investigated the relationship between SOM chemistry and microbial activity in three northern deciduous forest ecosystems that have been subjected to experimental N addition for 2 years. Extractable dissolved organic carbon (DOC), DOC aromaticity, C : N ratio, and functional group distribution, measured by Fourier transform infrared spectra (FTIR), were analyzed for litter and SOM. The largest biochemical changes were found in the sugar maple–basswood (SMBW) and black oak–white oak (BOWO) ecosystems. SMBW litter from the N addition treatment had less aromaticity, higher C : N ratios, and lower saturated carbon, lower carbonyl carbon, and higher carboxylates than controls; BOWO litter showed opposite trends, except for carbonyl and carboxylate contents. Litter from the sugar maple–red oak (SMRO) ecosystem had a lower C : N ratio, but no change in DOC aromaticity. For SOM, the C : N ratio increased with N addition in SMBW and SMRO ecosystems, but decreased in BOWO; N addition did not affect the aromaticity of DOC extracted from mineral soil. All ecosystems showed increases in extractable DOC from both litter and soil in response to N treatment. The biochemical changes are consistent with the divergent microbial responses observed in these systems. Extracellular oxidative enzyme activity has declined in the BOWO and SMRO ecosystems while activity in the SMBW ecosystem, particularly in the litter horizon, has increased. In all systems, enzyme activities associated with the hydrolysis and oxidation of polysaccharides have increased. At the ecosystem scale, the biochemical characteristics of the dominant litter appear to modulate the effects of N deposition on organic matter dynamics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72320/1/j.1365-2486.2005.01001.x.pd

    Disorder Effects on Exciton-Polariton Condensates

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    The impact of a random disorder potential on the dynamical properties of Bose Einstein condensates is a very wide research field. In microcavities, these studies are even more crucial than in the condensates of cold atoms, since random disorder is naturally present in the semiconductor structures. In this chapter, we consider a stable condensate, defined by a chemical potential, propagating in a random disorder potential, like a liquid flowing through a capillary. We analyze the interplay between the kinetic energy, the localization energy, and the interaction between particles in 1D and 2D polariton condensates. The finite life time of polaritons is taken into account as well. In the first part, we remind the results of [G. Malpuech et al. Phys. Rev. Lett. 98, 206402 (2007).] where we considered the case of a static condensate. In that case, the condensate forms either a glassy insulating phase at low polariton density (strong localization), or a superfluid phase above the percolation threshold. We also show the calculation of the first order spatial coherence of the condensate versus the condensate density. In the second part, we consider the case of a propagating non-interacting condensate which is always localized because of Anderson localization. The localization length is calculated in the Born approximation. The impact of the finite polariton life time is taken into account as well. In the last section we consider the case of a propagating interacting condensate where the three regimes of strong localization, Anderson localization, and superfluid behavior are accessible. The localization length is calculated versus the system parameters. The localization length is strongly modified with respect to the non-interacting case. It is infinite in the superfluid regime whereas it is strongly reduced if the fluid flows with a supersonic velocity.Comment: chapter for a book "Exciton Polaritons in Microcavities: New Frontiers" by Springer (2012), the original publication is available at http://www.springerlink.co

    Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

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    Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

    Modelling the Cost Effectiveness of Interventions for Osteoporosis: Issues to Consider

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    Expenditure on treating osteoporotic fractures and on preventative intervention is considerable and is likely to rise in forthcoming years due to the association between fracture risk and age. With funders such as the National Institute for Health and Care Excellence and the Pharmaceutical Benefits Advisory Committee explicitly considering cost-effectiveness analyses within the process of producing guidance, it is imperative that economic models are as robust as possible. This article details issues that need to be considered specifically related to health technology assessments of interventions for osteoporosis, and highlights limitations within the current evidence base. A likely direction of impact on cost effectiveness of addressing the key issues has been included alongside a tentative categorization of the level of these impacts. It is likely that cost-effectiveness ratios presented in previous models that did not address the identified issues were favourable to interventions

    Phenylpropanoid Glycoside Analogues: Enzymatic Synthesis, Antioxidant Activity and Theoretical Study of Their Free Radical Scavenger Mechanism

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    Phenylpropanoid glycosides (PPGs) are natural compounds present in several medicinal plants that have high antioxidant power and diverse biological activities. Because of their low content in plants (less than 5% w/w), several chemical synthetic routes to produce PPGs have been developed, but their synthesis is a time consuming process and the achieved yields are often low. In this study, an alternative and efficient two-step biosynthetic route to obtain natural PPG analogues is reported for the first time. Two galactosides were initially synthesized from vanillyl alcohol and homovanillyl alcohol by a transgalactosylation reaction catalyzed by Kluyveromyces lactis β-galactosidase in saturated lactose solutions with a 30%–35% yield. To synthesize PPGs, the galactoconjugates were esterified with saturated and unsaturated hydroxycinnamic acid derivatives using Candida antarctica Lipase B (CaL-B) as a biocatalyst with 40%–60% yields. The scavenging ability of the phenolic raw materials, intermediates and PPGs was evaluated by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) method. It was found that the biosynthesized PPGs had higher scavenging abilities when compared to ascorbic acid, the reference compound, while their antioxidant activities were found similar to that of natural PPGs. Moreover, density functional theory (DFT) calculations were used to determine that the PPGs antioxidant mechanism proceeds through a sequential proton loss single electron transfer (SPLET). The enzymatic process reported in this study is an efficient and versatile route to obtain PPGs from different phenylpropanoid acids, sugars and phenolic alcohols
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