Impact pressures generated by spherical particle hypervelocity impact on Yorkshire Sandstone

Hypervelocity impact tests were carried out at 4.8 km/s using the Open University's All Axis Light Gas Gun (AALGG) in the Planetary and Space Sciences Research Institute (PSSRI)'s Hypervelocity Impact Laboratory. A first estimate of the peak loading pressures was made using preliminary hydrocode simulations, supported by calculations. Following a review of existing published quartz and sandstone data, our previously published plate impact data were combined with high pressure quartz data to produce a synthetic Hugoniot. This will form the basis of future hydrocode modelling, as a linear Us-Up relationship does not adequately represent the behaviour of sandstone over the pressure range of interest, as indicated by experimental data on Coconino sandstone. This work is a precursor to investigating the biological effects of shock on microorganisms in sandstone targets. This paper also contains the first presentation of results of ultra high speed imaging of hypervelocity impact at the Open University. © 2007 American Institute of Physics

Evaluation of mTOR-regulated mRNA translation.

mTOR, the mammalian target of rapamycin, regulates protein synthesis (mRNA translation) by affecting the phosphorylation or activity of several translation factors. Here, we describe methods for studying the impact of mTOR signalling on protein synthesis, using inhibitors of mTOR such as rapamycin (which impairs some of its functions) or mTOR kinase inhibitors (which probably block all functions).To assess effects of mTOR inhibition on general protein synthesis in cells, the incorporation of radiolabelled amino acids into protein is measured. This does not yield information on the effects of mTOR on the synthesis of specific proteins. To do this, two methods are described. In one, stable-isotope labelled amino acids are used, and their incorporation into new proteins is determined using mass spectrometric methods. The proportions of labelled vs. unlabeled versions of each peptide from a given protein provide quantitative information about the rate of that protein's synthesis under different conditions. Actively translated mRNAs are associated with ribosomes in polyribosomes (polysomes); thus, examining which mRNAs are found in polysomes under different conditions provides information on the translation of specific mRNAs under different conditions. A method for the separation of polysomes from non-polysomal mRNAs is describe

Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells - Activation of protein kinase B by wortmannin-sensitive and -insensittve mechanisms

Previous studies using L6 myotubes have suggested that glycogen synthase kinase-3 (GSK-3) is phosphoryl ated and inactivated in response to insulin by protein kinase B (PKB, also known as Akt or RAG) (Cross, D, A, E., Alessi, D, R., Cohen, P., Andjelkovic, M., and Hemmings, B, A. (1995) Nature 378, 785-789), In the present study, marked increases in the activity of PKB have been shown to occur in insulin-treated rat epididymal fat cells with a time course compatible with the observed decrease in GSK-3 activity, Isoproterenol, acting primarily through beta(3)-adrenoreceptors, was found to decrease GSK-3 activity to a similar extent (approximately 50%) to insulin, However, unlike the effect of insulin, the inhibition of GSK by isoproterenol was not found to be sensitive to inhibition by the phosphatidylinositol 3'-kinase inhibitors, wortmannin or LY 294002, The change in GSK-3 activity brought about by isoproterenol could not be mimicked by the addition of permeant cyclic AMP analogues or forskolin to the cells, although at the concentrations used, these agents were able to stimulate lipolysis. Isoproterenol, but again not the cyclic AMP analogues, was found to increase the activity of PKB, although to a lesser extent than insulin. While wortmannin abolished the stimulation of PKB activity by insulin, it was without effect on the activation seen in response to isoproterenol, The activation of PKB by isoproterenol was not accompanied by any detectable change in the electrophoretic mobility of the protein on SDS-polyacrylamide gel electrophoresis. It would therefore appear that distinct mechanisms exist for the stimulation of PKB by insulin and isoproterenol in rat fat cells

Multilayer perceptron neural networks model for meteosat second generation SEVIRI daytime cloud masking

A multilayer perceptron neural network cloud mask for Meteosat Second Generation SEVIRI (Spinning Enhanced Visible and Infrared Imager) images is introduced and evaluated. The model is trained for cloud detection on MSG SEVIRI daytime data. It consists of a multi-layer perceptron with one hidden sigmoid layer, trained with the error back-propagation algorithm. The model is fed by six bands of MSG data (0.6, 0.8, 1.6, 3.9, 6.2 and 10.8 μm) with 10 hidden nodes. The multiple-layer perceptrons lead to a cloud detection accuracy of 88.96%, when trained to map two predefined values that classify cloud and clear sky. The network was further evaluated using sixty MSG images taken at different dates. The network detected not only bright thick clouds but also thin or less bright clouds. The analysis demonstrated the feasibility of using machine learning models of cloud detection in MSG SEVIRI imagery

Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology.

Tuberculosis remains a global pandemic and drives lung matrix destruction to transmit. Whilst pathways driving inflammatory responses in macrophages have been relatively well described, negative regulatory pathways are less well defined. We hypothesised that Mycobacterium tuberculosis (Mtb) specifically targets negative regulatory pathways to augment immunopathology. Inhibition of signalling through the PI3K/AKT/mTORC1 pathway increased matrix metalloproteinase-1 (MMP-1) gene expression and secretion, a collagenase central to TB pathogenesis, and multiple pro-inflammatory cytokines. In patients with confirmed pulmonary TB, PI3Kδ expression was absent within granulomas. Furthermore, Mtb infection suppressed PI3Kδ gene expression in macrophages. Interestingly, inhibition of the MNK pathway, downstream of pro-inflammatory p38 and ERK MAPKs, also increased MMP-1 secretion, whilst suppressing secretion of TH1 cytokines. Cross-talk between the PI3K and MNK pathways was demonstrated at the level of eIF4E phosphorylation. Mtb globally suppressed the MMP-inhibitory pathways in macrophages, reducing levels of mRNAs encoding PI3Kδ, mTORC-1 and MNK-1 via upregulation of miRNAs. Therefore, Mtb disrupts negative regulatory pathways at multiple levels in macrophages to drive a tissue-destructive phenotype that facilitates transmission

Examining the role of wine brand love on brand loyalty: a multi-country comparison

This study develops and tests a model through a multi-country study that considers consumer wine knowledge and wine experience, wine brand trust and wine brand satisfaction as antecedents of wine brand love, and wine brand loyalty as a consequence of wine brand love. Data were collected in five wine-producing countries (Australia, Chile, France, Mexico and Portugal) with a final sample of 3462 completed surveys. Hypotheses were tested with structural equation modeling and the findings confirm the importance of brand love as both a mediator and direct influence on brand loyalty for wine consumers. Furthermore, brand satisfaction was positively and significantly related to brand love. In addition, wine experience, rather than wine knowledge, positively influenced brand trust and satisfaction. Finally, results also identify differences between countries thereby providing insights into how companies should focus their marketing strategies internationally.info:eu-repo/semantics/acceptedVersio

Human rhinovirus infection up-regulates MMP-9 production in airway epithelial cells via NF-{kappa}B

Human rhinovirus (HRV) infections up-regulate proinflammatory mediators and growth factors that are associated with exacerbations of inflammatory airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Matrix metalloproteinase (MMP)-9 was shown to be increased in the airways of patients with asthma and COPD. We sought to determine whether HRV infection modulated the expression of MMP-9 and its highest-affinity inhibitor, the tissue inhibitor of metalloproteinase (TIMP)-1, and we explored the mechanism by which this modulation occurs. In vitro studies, using RT-PCR, ELISA, zymography, and a fluorescent activity assay, demonstrated that MMP-9 mRNA, protein, and activity were increased upon infection with HRV, whereas TIMP-1 mRNA and protein remained unchanged. These results were verified in vivo, using nasal lavage samples obtained from subjects with confirmed rhinovirus infections. Human rhinovirus infections were shown to up-regulate NF-kappaB, and NF-kappaB has also been reported to play a role in the expression of MMP-9. We therefore investigated the role of NF-kappaB in HRV-induced MMP-9 expression. Using two inhibitors of IkappaBalpha kinase beta, we observed a concentration-dependent decrease in HRV-induced MMP-9 expression. The role of NF-kappaB in HRV-induced MMP-9 expression was further confirmed using MMP-9 promoter luciferase constructs, which demonstrated that an NF-kappaB site at -620/-607 base pairs was necessary for HRV-induced MMP-9 expression. Electrophoretic mobility shift assays and supershift assays confirmed the nuclear translocation and binding of p50/p65 NF-kappaB subunits to an MMP-9-specific NF-kappaB oligonucleotide. This increase in MMP-9 may be a mechanism by which rhinovirus infections contribute to airway inflammation and, potentially, to airway remodeling

Ribosomal stress activates eEF2K-eEF2 pathway causing translation elongation inhibition and recruitment of Terminal Oligopyrimidine (TOP) mRNAs on polysomes

The synthesis of adequate amounts of ribosomes is an essential task for the cell. It is therefore not surprising that regulatory circuits exist to organize the synthesis of ribosomal components. It has been shown that defect in ribosome biogenesis (ribosomal stress) induces apoptosis or cell cycle arrest through activation of the tumor suppressor p53. This mechanism is thought to be implicated in the pathophysiology of a group of genetic diseases such as Diamond Blackfan Anemia which are called ribosomopathies. We have identified an additional response to ribosomal stress that includes the activation of eukaryotic translation elongation factor 2 kinase with a consequent inhibition of translation elongation. This leads to a translational reprogramming in the cell that involves the structurally defined group of messengers called terminal oligopyrimidine (TOP) mRNAs which encode ribosomal proteins and translation factors. In fact, while general protein synthesis is decreased by the impairment of elongation, TOP mRNAs are recruited on polysomes causing a relative increase in the synthesis of TOP mRNA-encoded proteins compared to other proteins. Therefore, in response to ribosomal stress, there is a change in the translation pattern of the cell which may help restore a sufficient level of ribosomes

MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways

The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis. Here we show that mice in which the expression of either MNK1 or MNK2 has been knocked out (KO) are protected against adverse effects of high-fat feeding, and in distinct ways. High-fat diet (HFD)-fed MNK2-KO show less weight gain than wild-type animals, and improved glucose tolerance, better insulin sensitivity and markedly diminished adipose tissue inflammation. This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology. MNK1-KO/HFD mice show better glucose tolerance and insulin sensitivity, but gain weight and show similar adipose inflammation to WT animals. These data suggest MNK1 participates in mediating HFD-induced insulin resistance. Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease

Collective Modes in the Microshear Ensemble as a Mechanism of the Failure Wave

Results of theoretical and experimental study of failure wave phenomena are presented. A description ofthefailure wavephenomenon wasproposed in terms ofa self-similar solutionfor the microshear density. The mechanisms offailure wave generation andpropagation were classified as a delayedfailure with the delay time corresponding to the time ofexcitation ofself-similar blow-up collective modes in a microshear ensemble. Experimental study of the mechanism of the failure wave generation andpropagation was carried out using afused quartz rod and included the Taylor test with high-speed framing. The results obtained confirmed the "delayed” mechanism of the failure wave generation and propagation.Представлены результаты теоретических и экспериментальных исследований явления волны разрушения. Предложено описание явления волны разрушения на основе авто­модельного решения для плотности микро­сдвигов. Механизмы возникновения и рас­пространения волны разрушения классифи­цировали как замедленное разрушение, при­ чем время задержки соответствовало времени возбуждения автомодельных взрывных коллективных колебаний во множестве микросдвигов. Экспериментальное исследо­вание механизма возникновения и распро­странения волны разрушения проводилось с использованием расплавленного кварцевого стержня и включало испытание по методу Тейлора с высокоскоростным фотографированием. Полученные результаты подтверди­ ли “замедленный” механизм возникновения и распространения волны разрушения