363 research outputs found

    Modelling long-term trends in lunar exposure to the Earth's plasmasheet

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    The progestin-only contraceptive medroxyprogesterone acetate, but not norethisterone acetate, enhances HIV-1 Vpr-mediated apoptosis in human CD4+ T cells through the glucocorticoid receptor

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    The glucocorticoid receptor (GR) regulates several physiological functions, including immune function and apoptosis. The HIV-1 virus accessory protein, viral protein R (Vpr), can modulate the transcriptional response of the GR. Glucocorticoids (GCs) and Vpr have been reported to induce apoptosis in various cells, including T-cells. We have previously shown that the injectable contraceptive, medroxyprogesterone acetate (MPA) is a partial to full agonist for the GR, unlike norethisterone acetate (NET-A). We investigated the functional cross talk between the GR and Vpr in inducing apoptosis in CD4 + T-cells, in the absence and presence of GCs and these progestins, as well as progesterone. By using flow cytometry, we show that, in contrast to NET-A and progesterone, the synthetic GR ligand dexamethasone (Dex), cortisol and MPA induce apoptosis in primary CD4 + T-cells. Furthermore, the C-terminal part of the Vpr peptide, or HIV-1 pseudovirus, together with Dex or MPA further increased the apoptotic phenotype, unlike NET-A and progesterone. By a combination of Western blotting, PCR and the use of receptor- selective agonists, we provide evidence that the GR and the estrogen receptor are the only steroid receptors expressed in peripheral blood mononuclear cells. These results, together with the findings that RU486, a GR antagonist, prevents Dex-, MPA- and Vpr-mediated apoptosis, provide evidence for the first time that GR agonists or partial agonists increase apoptosis in primary CD4 + T-cells via the GR. We show that apoptotic induction involves differential expression of key apoptotic genes by both Vpr and GCs/MPA. This work suggests that contraceptive doses of MPA but not NET-A or physiological doses of progesterone could potentially accelerate depletion of CD4 + T-cells in a GR-dependent fashion in HIV-1 positive women, thereby contributing to immunodeficiency. The results imply that choice of progestin used in contraception may be critical to susceptibility and progression of diseases such as HIV-1

    Using Extreme Value Theory for Determining the Probability of Carrington-Like Solar Flares

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    Space weather events can negatively affect satellites, the electricity grid, satellite navigation systems and human health. As a consequence, extreme space weather has been added to the UK and other national risk registers. By their very nature, extreme space weather events occur rarely and, therefore, statistical methods are required to determine the probability of their occurrence. Space weather events can be characterised by a number of natural phenomena such as X-ray (solar) flares, solar energetic particle (SEP) fluxes, coronal mass ejections and various geophysical indices (Dst, Kp, F10.7). In this paper extreme value theory (EVT) is used to investigate the probability of extreme solar flares. Previous work has assumed that the distribution of solar flares follows a power law. However such an approach can lead to a poor estimation of the return times of such events due to uncertainties in the tails of the probability distribution function. Using EVT and GOES X-ray flux data it is shown that the expected 150-year return level is approximately an X60 flare whilst a Carrington-like flare is a one in a 100-year event. It is also shown that the EVT results are consistent with flare data from the Kepler space telescope mission.Comment: 13 pages, 4 figures; updated content following reviewer feedbac

    Kinetics of immersion nucleation driven by surface tension

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    Immersion nucleation is the nuclei formation mechanism for wet granulation systems where the liquid drops are large relative to the primary particles. The process of immersion nucleation has been examined in many studies, however the kinetics of nuclei formation are not well understood, and there is a distinct lack of experimentally validated models for this process. A kinetic model has been proposed by Hounslow et al. (2009) which describes surface tension driven immersion nucleation. This paper presents the results from a series of experiments measuring the kinetics of immersion nucleation, and these results are compared with the model predictions. Drops of model liquids (aqueous HPMC solution and silicone oil) are placed on static powder beds of zeolite and lactose. Nuclei granules are carefully excavated at different times and the change in granule mass with time is measured. As predicted by Hounslow et al.'s model, the granule mass increases with the square root of time to a maximum granule size at a time tmax after an initial adjustment period. The critical packing factor is shown to be a function of powder properties, and not dependent on the liquid properties. The model captures well the measured effects of liquid and powder properties. However, the kinetics of the nucleation process are much slower than predicted by the model. It is believed this is due to continued percolation of the liquid within the powder bed, after the liquid drop is fully immersed. This secondary liquid movement may have an important effect on granule growth kinetics, and influence final granule product properties

    High shear granulation: an investigation into the granule consolidation mechanism

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    The mechanisms of early granule growth are difficult to study and poorly understood. Consolidation and layering play a critical role in the growth process. However, little is known about the kinetics. In this work, a novel consolidation-only granulator (COG) was used to study dynamic consolidation and layering only, eliminating other granulation mechanisms. Prenucleated granule growth was studied over time. Based on experimental data and literature models, a mechanistic layering kernel for population balance modelling was developed. Granule growth kinetics were qualitatively predicted by a previously reported model; growth behaviour was linear with the square root of time to a certain critical size, after which growth stopped. X-ray computed tomography revealed that consolidation mainly occurred in the outer layers of the granules. The results greatly advance understanding of consolidation and layered growth, and the new model opens the way for improved predictive modelling and design of granulation processes and products
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