170 research outputs found

    Rigorous 3D inversion of marine CSEM data based on the integral equation method

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    Journal ArticleMarine controlled-source electromagnetic (MCSEM) surveys have become an important part of offshore petroleum exploration. However, due to enormous computational difficulties with full 3D inversion, practical interpretation of MCSEM data is still a very challenging problem. We present a new approach to 3D inversion of MCSEM data based on rigorous integral-equation (IE) forward modeling and a new IE representation of the sensitivity (Fréchet derivative matrix) of observed data to variations in sea-bottom conductivity. We develop a new form of the quasi-analytical approximation for models with variable background conductivity (QAVB) and apply this form for more efficient Fréchet derivative calculations. This approach requires just one forward modeling on every iteration of the regularized gradient-type inversion algorithm, which speeds up the computations significantly. We also use a regularized focusing inversion method, which provides a sharp boundary image of the petroleum reservoir. The methodology is tested on a 3D inversion of the synthetic EM data representing a typical MCSEM survey conducted for offshore petroleum exploration

    РОЛЬ МИСТЕЦЬКО-ПЕДАГОГІЧНОЇ ОСВІТИ У ПРОФЕСІЙНОМУ СТАНОВЛЕННІ ПЕДАГОГА

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    In the article describes of the contemporary trends ofperfection o f the art-pedagogical education

    ПРОБЛЕМИ ФОРМУВАННЯ ІНДИВІДУАЛЬНОГО СТИЛЮ ПЕДАГОГІЧНОГО СПІЛКУВАННЯ МАЙБУТНІХ ВЧИТЕЛІВ

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    In the article describes essence of the democratic style of the pedagogical intercourse, and also ways of forming of the individual style of intercourse of future teachers.В статті розглянуто сутність демократичного стилю педагогічного спілкування, а також шляхи формування індивідуального стилю спілкування майбутніх вчителів

    ПЕДАГОГІЧНІ УМОВИ ФОРМУВАННЯ ТВОРЧОЇ ОСОБИСТОСТІ МАЙБУТНЬОГО ПЕДАГОГА

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    The article describes objective and subjective conditions of student’s creative personality development in teaching and educational process of higher pedagogical education.B статті розглядаються об'єктивні та суб’єктивні умови розвитку творчої особистості студента в навчально-виховному процесі вищої педагогічної освіти

    Activation of tissue plasminogen activator by metastasis-inducing S100P protein

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    S100P protein in human breast cancer cells is associated with reduced patient survival and, in a model system of metastasis, it confers a metastatic phenotype upon benign mammary tumour cells. S100P protein possesses a C-terminal lysine residue. Using a multiwell in vitro assay, S100P is now shown for the first time to exhibit a strong, C-terminal lysine-dependent activation of tissue plasminogen activator (tPA), but not of urokinase-catalysed plasminogen activation. The presence of 10 μM calcium ions stimulates tPA activation of plasminogen 2-fold in an S100P-dependent manner. S100P physically interacts with both plasminogen and tPA in vitro, but not with urokinase. Cells constitutively expressing S100P exhibit detectable S100P protein on the cell surface, and S100P-containing cells show enhanced activation of plasminogen compared with S100P-negative control cells. S100P shows C-terminal lysine-dependent enhancement of cell invasion. An S100P antibody, when added to the culture medium, reduced the rate of invasion of wild-type S100P-expressing cells, but not of cells expressing mutant S100P proteins lacking the C-terminal lysine, suggesting that S100P functions outside the cell. The protease inhibitors, aprotinin or α-2-antiplasmin, reduced the invasion of S100P-expressing cells, but not of S100P-negative control cells, nor cells expressing S100P protein lacking the C-terminal lysine. It is proposed that activation of tPA via the C-terminal lysine of S100P contributes to the enhancement of cell invasion by S100P and thus potentially to its metastasis-promoting activity

    3D inversion of towed streamer EM data: a model study of the Harding field with comparison to CSEM

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    provide an early study of the challenges involved in validating offshore electromagnetic (EM) data acquired using a towed streamer receiver (currently under development) and compare the results with existing seabed-based marine controlled source electromagnetic (CSEM) technology. T he premise of the various marine controlled source electromagnetic (CSEM) methods is sensitivity to the lateral extents and thicknesses of resistive bodies embedded in conductive hosts. Over the past decade, CSEM surveys have been characterized by arrays of fixed ocean bottom receivers and towed transmitters, and applied to de-risking exploration and appraisal projects with direct hydrocarbon indication. The most successful applications of CSEM to date have been in complement to those seismic interpretations where lithological or fluid variations cannot be adequately discriminated by seismic methods alone (e.g., Hesthammer et al., 2010). However, relatively high acquisition costs have represented a significant obstacle to widespread adoption of conventional CSEM technology, particularly in frontier basins. To this end, a towed streamer system capable of simultaneous seismic and electromagnetic (EM) data acquisition has recently been developed and tested in the North Sea In exploration, hydrocarbon reserves and resources are estimated with varying confidence from volumetrics that are predicted from different 3D earth models and scenarios. Quantitative interpretation of EM data is inherently reliant upon 3D earth models derived from inversion since EM data cannot simply be separated or transformed with linear operators as per seismic methods. However, methods for inverting CSEM data are complicated by the very small, nonunique and non-linear responses of hydrocarbon-bearing reservoir units when compared to the measured total fields. Moreover, 3D inversion of towed streamer EM data poses a significant challenge because of the increased scale of the surveys, the requirement for high resolution models, and the significantly increased number of transmitter-receiver pairs. Inverting towed streamer EM data Large-scale conventional CSEM surveys may have in the order of hundreds of fixed receivers, and in the order of thousands of transmitter positions. Reciprocity is routinely exploited in 3D conventional CSEM modelling and inversion to minimize the number of source terms that need to be solved (e.g.

    Two Vaccines for Staphylococcus aureus Induce a B-Cell- Mediated Immune Response

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    Staphylococcus aureus causes severe disease in humans for which no licensed vaccine exists. A novel S. aureus vaccine (SA4Ag) is in development, targeting the capsular polysaccharides (CPs) and two virulence-associated surface proteins. Vaccine-elicited antibody responses to CPs are efficacious against serious infection by other encapsulated bacteria. Studies of natural S. aureus infection have also shown a role for TH17 and/or TH1 responses in protection. Single-antigen vaccines, including CPs, have not been effective against S. aureus; a multiantigen vaccine approach is likely required. However, the impact of addition of protein antigens on the immune response to CPs has not been studied. Here, the immune response induced by a bivalent CP conjugate vaccine (to model the established mechanism of action of vaccine-induced protection against Gram-positive pathogens) was compared to the response induced by SA4Ag, which contains both CP conjugates and protein antigens, in cynomolgus macaques. Microengraving, flow cytometry, opsonophagocytic assays, and Luminex technology were used to analyze the B-cell, T-cell, functional antibody, and innate immune responses. Both the bivalent CP vaccine and SA4Ag induced cytokine production from naive cells and antigen-specific memory B-cell and functional antibody responses. Increases in levels of circulating, activated T cells were not apparent following vaccination, nor was a TH17 or TH1 response evident. However, our data are consistent with a vaccine-induced recruitment of T follicular helper (TFH) cells to lymph nodes. Collectively, these data suggest that the response to SA4Ag is primarily mediated by B cells and antibodies that abrogate important S. aureus virulence mechanisms.IMPORTANCEStaphylococcus aureus causes severe disease in humans for which no licensed vaccine exists. A novel vaccine is in development that targets multiple elements of the bacteria since single-component vaccines have not shown efficacy to date. How these multiple components alter the immune response raised by the vaccine is not well studied. We found that the addition of two protein components did not alter substantially the antibody responses raised with respect to function or mobilization of B cells. There was also not a substantial change in the activity of T cells, another part of the adaptive response. This study showed that protection by this vaccine may be mediated primarily by antibody protection.Pfizer Inc.National Cancer Institute (U.S.) (grant P30-CA14051

    Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

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    One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

    Expanding LAGLIDADG endonuclease scaffold diversity by rapidly surveying evolutionary sequence space

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    LAGLIDADG homing endonucleases (LHEs) are a family of highly specific DNA endonucleases capable of recognizing target sequences ∼20 bp in length, thus drawing intense interest for their potential academic, biotechnological and clinical applications. Methods for rational design of LHEs to cleave desired target sites are presently limited by a small number of high-quality native LHEs to serve as scaffolds for protein engineering—many are unsatisfactory for gene targeting applications. One strategy to address such limitations is to identify close homologs of existing LHEs possessing superior biophysical or catalytic properties. To test this concept, we searched public sequence databases to identify putative LHE open reading frames homologous to the LHE I-AniI and used a DNA binding and cleavage assay using yeast surface display to rapidly survey a subset of the predicted proteins. These proteins exhibited a range of capacities for surface expression and also displayed locally altered binding and cleavage specificities with a range of in vivo cleavage activities. Of these enzymes, I-HjeMI demonstrated the greatest activity in vivo and was readily crystallizable, allowing a comparative structural analysis. Taken together, our results suggest that even highly homologous LHEs offer a readily accessible resource of related scaffolds that display diverse biochemical properties for biotechnological applications

    Stabilization by Fusion to the C-terminus of Hyperthermophile Sulfolobus tokodaii RNase HI: A Possibility of Protein Stabilization Tag

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    RNase HI from the hyperthermophile Sulfolobus tokodaii (Sto-RNase HI) is stabilized by its C-terminal residues. In this work, the stabilization effect of the Sto-RNase HI C-terminal residues was investigated in detail by thermodynamic measurements of the stability of variants lacking the disulfide bond (C58/145A), or the six C-terminal residues (ΔC6) and by structural analysis of ΔC6. The results showed that the C-terminal does not affect overall structure and stabilization is caused by local interactions of the C-terminal, suggesting that the C-terminal residues could be used as a “stabilization tag.” The Sto-RNase HI C-terminal residues (-IGCIILT) were introduced as a tag on three proteins. Each chimeric protein was more stable than its wild-type protein. These results suggested the possibility of a simple stabilization technique using a stabilization tag such as Sto-RNase HI C-terminal residues
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