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Sample records for translation initiation sites

  1. Ribosome signatures aid bacterial translation initiation site identification.

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    Giess, Adam; Jonckheere, Veronique; Ndah, Elvis; Chyżyńska, Katarzyna; Van Damme, Petra; Valen, Eivind

    2017-08-30

    While methods for annotation of genes are increasingly reliable, the exact identification of translation initiation sites remains a challenging problem. Since the N-termini of proteins often contain regulatory and targeting information, developing a robust method for start site identification is crucial. Ribosome profiling reads show distinct patterns of read length distributions around translation initiation sites. These patterns are typically lost in standard ribosome profiling analysis pipelines, when reads from footprints are adjusted to determine the specific codon being translated. Utilising these signatures in combination with nucleotide sequence information, we build a model capable of predicting translation initiation sites and demonstrate its high accuracy using N-terminal proteomics. Applying this to prokaryotic translatomes, we re-annotate translation initiation sites and provide evidence of N-terminal truncations and extensions of previously annotated coding sequences. These re-annotations are supported by the presence of structural and sequence-based features next to N-terminal peptide evidence. Finally, our model identifies 61 novel genes previously undiscovered in the Salmonella enterica genome. Signatures within ribosome profiling read length distributions can be used in combination with nucleotide sequence information to provide accurate genome-wide identification of translation initiation sites.

  2. Identifying translation initiation sites in prokaryotes using support vector machine.

    Science.gov (United States)

    Gao, Tingting; Yang, Zhixia; Wang, Yong; Jing, Ling

    2010-02-21

    Gene identification in genomes has been a fundamental and long-standing task in bioinformatics and computational biology. Many computational methods have been developed to predict genes in prokaryote genomes by identifying translation initiation site (TIS) in transcript data. However, the pseudo-TISs at the genome level make these methods suffer from a high number of false positive predictions. In addition, most of the existing tools use an unsupervised learning framework, whose predictive accuracy may depend on the choice of specific organism. In this paper, we present a supervised learning method, support vector machine (SVM), to identify translation initiation site at the genome level. The features are extracted from the sequence data by modeling the sequence segment around predicted TISs as a position specific weight matrix (PSWM). We train the parameters of our SVM through well constructed positive and negative TIS datasets. Then we apply the method to recognize translation initiation sites in E. coli, B. subtilis, and validate our method on two GC-rich bacteria genomes: Pseudomonas aeruginosa and Burkholderia pseudomallei K96243. We show that translation initiation sites can be recognized accurately at the genome level by our method, irrespective of their GC content. Furthermore, we compare our method with four existing methods and demonstrate that our method outperform these methods by obtaining better performance in all the four organisms. (c) 2009. Published by Elsevier Ltd.

  3. Engineering support vector machine kernels that recognize translation initiation sites.

    Science.gov (United States)

    Zien, A; Rätsch, G; Mika, S; Schölkopf, B; Lengauer, T; Müller, K R

    2000-09-01

    In order to extract protein sequences from nucleotide sequences, it is an important step to recognize points at which regions start that code for proteins. These points are called translation initiation sites (TIS). The task of finding TIS can be modeled as a classification problem. We demonstrate the applicability of support vector machines for this task, and show how to incorporate prior biological knowledge by engineering an appropriate kernel function. With the described techniques the recognition performance can be improved by 26% over leading existing approaches. We provide evidence that existing related methods (e.g. ESTScan) could profit from advanced TIS recognition.

  4. MetWAMer: eukaryotic translation initiation site prediction

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    Brendel Volker

    2008-09-01

    Full Text Available Abstract Background Translation initiation site (TIS identification is an important aspect of the gene annotation process, requisite for the accurate delineation of protein sequences from transcript data. We have developed the MetWAMer package for TIS prediction in eukaryotic open reading frames of non-viral origin. MetWAMer can be used as a stand-alone, third-party tool for post-processing gene structure annotations generated by external computational programs and/or pipelines, or directly integrated into gene structure prediction software implementations. Results MetWAMer currently implements five distinct methods for TIS prediction, the most accurate of which is a routine that combines weighted, signal-based translation initiation site scores and the contrast in coding potential of sequences flanking TISs using a perceptron. Also, our program implements clustering capabilities through use of the k-medoids algorithm, thereby enabling cluster-specific TIS parameter utilization. In practice, our static weight array matrix-based indexing method for parameter set lookup can be used with good results in data sets exhibiting moderate levels of 5'-complete coverage. Conclusion We demonstrate that improvements in statistically-based models for TIS prediction can be achieved by taking the class of each potential start-methionine into account pending certain testing conditions, and that our perceptron-based model is suitable for the TIS identification task. MetWAMer represents a well-documented, extensible, and freely available software system that can be readily re-trained for differing target applications and/or extended with existing and novel TIS prediction methods, to support further research efforts in this area.

  5. Hon-yaku: a biology-driven Bayesian methodology for identifying translation initiation sites in prokaryotes

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    de Hoon Michiel JL

    2007-02-01

    Full Text Available Abstract Background Computational prediction methods are currently used to identify genes in prokaryote genomes. However, identification of the correct translation initiation sites remains a difficult task. Accurate translation initiation sites (TISs are important not only for the annotation of unknown proteins but also for the prediction of operons, promoters, and small non-coding RNA genes, as this typically makes use of the intergenic distance. A further problem is that most existing methods are optimized for Escherichia coli data sets; applying these methods to newly sequenced bacterial genomes may not result in an equivalent level of accuracy. Results Based on a biological representation of the translation process, we applied Bayesian statistics to create a score function for predicting translation initiation sites. In contrast to existing programs, our combination of methods uses supervised learning to optimally use the set of known translation initiation sites. We combined the Ribosome Binding Site (RBS sequence, the distance between the translation initiation site and the RBS sequence, the base composition of the start codon, the nucleotide composition (A-rich sequences following start codons, and the expected distribution of the protein length in a Bayesian scoring function. To further increase the prediction accuracy, we also took into account the operon orientation. The outcome of the procedure achieved a prediction accuracy of 93.2% in 858 E. coli genes from the EcoGene data set and 92.7% accuracy in a data set of 1243 Bacillus subtilis 'non-y' genes. We confirmed the performance in the GC-rich Gamma-Proteobacteria Herminiimonas arsenicoxydans, Pseudomonas aeruginosa, and Burkholderia pseudomallei K96243. Conclusion Hon-yaku, being based on a careful choice of elements important in translation, improved the prediction accuracy in B. subtilis data sets and other bacteria except for E. coli. We believe that most remaining

  6. A Novel Quality Measure and Correction Procedure for the Annotation of Microbial Translation Initiation Sites

    NARCIS (Netherlands)

    Overmars, L.; Siezen, R.J.; Francke, C.

    2015-01-01

    The identification of translation initiation sites (TISs) constitutes an important aspect of sequence-based genome analysis. An erroneous TIS annotation can impair the identification of regulatory elements and N-terminal signal peptides, and also may flaw the determination of descent, for any

  7. Dragon TIS Spotter: An Arabidopsis-derived predictor of translation initiation sites in plants

    KAUST Repository

    Magana-Mora, Arturo

    2012-10-30

    In higher eukaryotes, the identification of translation initiation sites (TISs) has been focused on finding these signals in cDNA or mRNA sequences. Using Arabidopsis thaliana (A.t.) information, we developed a prediction tool for signals within genomic sequences of plants that correspond to TISs. Our tool requires only genome sequence, not expressed sequences. Its sensitivity/specificity is for A.t. (90.75%/92.2%), for Vitis vinifera (66.8%/94.4%) and for Populus trichocarpa (81.6%/94.4%), which suggests that our tool can be used in annotation of different plant genomes. We provide a list of features used in our model. Further study of these features may improve our understanding of mechanisms of the translation initiation. The Author(s) 2012. Published by Oxford University Press.

  8. Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites.

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    Angela Re

    2016-12-01

    Full Text Available Transcript levels do not faithfully predict protein levels, due to post-transcriptional regulation of gene expression mediated by RNA binding proteins (RBPs and non-coding RNAs. We developed a multivariate linear regression model integrating RBP levels and predicted RBP-mRNA regulatory interactions from matched transcript and protein datasets. RBPs significantly improved the accuracy in predicting protein abundance of a portion of the total modeled mRNAs in three panels of tissues and cells and for different methods employed in the detection of mRNA and protein. The presence of upstream translation initiation sites (uTISs at the mRNA 5' untranslated regions was strongly associated with improvement in predictive accuracy. On the basis of these observations, we propose that the recently discovered widespread uTISs in the human genome can be a previously unappreciated substrate of translational control mediated by RBPs.

  9. Neural Network Prediction of Translation Initiation Sites in Eukaryotes: Perspectives for EST and Genome analysis

    DEFF Research Database (Denmark)

    Pedersen, Anders Gorm; Nielsen, Henrik

    1997-01-01

    Translation in eukaryotes does not always start at the first AUG in an mRNA, implying that context information also plays a role.This makes prediction of translation initiation sites a non-trivial task, especially when analysing EST and genome data where the entire mature mRNA sequence is not known....... In this paper, we employ artificial neural networks to predict which AUG triplet in an mRNA sequence is the start codon. The trained networks correctly classified 88% of Arabidopsis and 85% of vertebrate AUG triplets. We find that our trained neural networks use a combination of local start codon context...... and global sequence information. Furthermore, analysis of false predictions shows that AUGs in frame with the actual start codon are more frequently selected than out-of-frame AUGs, suggesting that our nteworks use reading frame detection. A number of conflicts between neural network predictions and database...

  10. Dragon TIS Spotter: an Arabidopsis-derived predictor of translation initiation sites in plants.

    Science.gov (United States)

    Magana-Mora, Arturo; Ashoor, Haitham; Jankovic, Boris R; Kamau, Allan; Awara, Karim; Chowdhary, Rajesh; Archer, John A C; Bajic, Vladimir B

    2013-01-01

    In higher eukaryotes, the identification of translation initiation sites (TISs) has been focused on finding these signals in cDNA or mRNA sequences. Using Arabidopsis thaliana (A.t.) information, we developed a prediction tool for signals within genomic sequences of plants that correspond to TISs. Our tool requires only genome sequence, not expressed sequences. Its sensitivity/specificity is for A.t. (90.75%/92.2%), for Vitis vinifera (66.8%/94.4%) and for Populus trichocarpa (81.6%/94.4%), which suggests that our tool can be used in annotation of different plant genomes. We provide a list of features used in our model. Further study of these features may improve our understanding of mechanisms of the translation initiation. Our tool is implemented as an artificial neural network. It is available as a web-based tool and, together with the source code, the list of features, and data used for model development, is accessible at http://cbrc.kaust.edu.sa/dts.

  11. Oligo kernels for datamining on biological sequences: a case study on prokaryotic translation initiation sites

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    Merkl Rainer

    2004-10-01

    Full Text Available Abstract Background Kernel-based learning algorithms are among the most advanced machine learning methods and have been successfully applied to a variety of sequence classification tasks within the field of bioinformatics. Conventional kernels utilized so far do not provide an easy interpretation of the learnt representations in terms of positional and compositional variability of the underlying biological signals. Results We propose a kernel-based approach to datamining on biological sequences. With our method it is possible to model and analyze positional variability of oligomers of any length in a natural way. On one hand this is achieved by mapping the sequences to an intuitive but high-dimensional feature space, well-suited for interpretation of the learnt models. On the other hand, by means of the kernel trick we can provide a general learning algorithm for that high-dimensional representation because all required statistics can be computed without performing an explicit feature space mapping of the sequences. By introducing a kernel parameter that controls the degree of position-dependency, our feature space representation can be tailored to the characteristics of the biological problem at hand. A regularized learning scheme enables application even to biological problems for which only small sets of example sequences are available. Our approach includes a visualization method for transparent representation of characteristic sequence features. Thereby importance of features can be measured in terms of discriminative strength with respect to classification of the underlying sequences. To demonstrate and validate our concept on a biochemically well-defined case, we analyze E. coli translation initiation sites in order to show that we can find biologically relevant signals. For that case, our results clearly show that the Shine-Dalgarno sequence is the most important signal upstream a start codon. The variability in position and composition

  12. A Novel Quality Measure and Correction Procedure for the Annotation of Microbial Translation Initiation Sites.

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    Lex Overmars

    Full Text Available The identification of translation initiation sites (TISs constitutes an important aspect of sequence-based genome analysis. An erroneous TIS annotation can impair the identification of regulatory elements and N-terminal signal peptides, and also may flaw the determination of descent, for any particular gene. We have formulated a reference-free method to score the TIS annotation quality. The method is based on a comparison of the observed and expected distribution of all TISs in a particular genome given prior gene-calling. We have assessed the TIS annotations for all available NCBI RefSeq microbial genomes and found that approximately 87% is of appropriate quality, whereas 13% needs substantial improvement. We have analyzed a number of factors that could affect TIS annotation quality such as GC-content, taxonomy, the fraction of genes with a Shine-Dalgarno sequence and the year of publication. The analysis showed that only the first factor has a clear effect. We have then formulated a straightforward Principle Component Analysis-based TIS identification strategy to self-organize and score potential TISs. The strategy is independent of reference data and a priori calculations. A representative set of 277 genomes was subjected to the analysis and we found a clear increase in TIS annotation quality for the genomes with a low quality score. The PCA-based annotation was also compared with annotation with the current tool of reference, Prodigal. The comparison for the model genome of Escherichia coli K12 showed that both methods supplement each other and that prediction agreement can be used as an indicator of a correct TIS annotation. Importantly, the data suggest that the addition of a PCA-based strategy to a Prodigal prediction can be used to 'flag' TIS annotations for re-evaluation and in addition can be used to evaluate a given annotation in case a Prodigal annotation is lacking.

  13. Genetic Algorithms for Models Optimization for Recognition of Translation Initiation Sites

    KAUST Repository

    Mora, Arturo Magana

    2011-06-01

    This work uses genetic algorithms (GA) to reduce the complexity of the artificial neural networks (ANNs) and decision trees (DTs) for the accurate recognition of translation initiation sites (TISs) in Arabidopsis Thaliana. The Arabidopsis data was extracted directly from genomic DNA sequences. Methods derived in this work resulted in both reduced complexity of the predictors, as well as in improvement in prediction accuracy (generalization). Optimization through use of GA is generally a computationally intensive task. One of the approaches to overcome this problem is to use parallelization of code that implements GA, thus allowing computation on multiprocessing infrastructure. However, further improvement in performance GA implementation could be achieved through modification done to GA basic operations such as selection, crossover and mutation. In this work we explored two such improvements, namely evolutive mutation and GA-Simplex crossover operation. In this thesis we studied the benefit of these modifications on the problem of TISs recognition. Compared to the non-modified GA approach, we reduced the number of weights in the resulting model\\'s neural network component by 51% and the number of nodes in the model\\'s DTs component by 97% whilst improving the model\\'s accuracy at the same time. Separately, we developed another methodology for reducing the complexity of prediction models by optimizing the composition of training data subsets in bootstrap aggregation (bagging) methodology. This optimization is achieved by applying a new GA-based bagging methodology in order to optimize the composition of each of the training data subsets. This approach has shown in our test cases to considerably enhance the accuracy of the TIS prediction model compared to the original bagging methodology. Although these methods are applied to the problem of accurate prediction of TISs we believe that these methodologies have a potential for wider scope of application.

  14. iTIS-PseKNC: Identification of Translation Initiation Site in human genes using pseudo k-tuple nucleotides composition.

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    Kabir, Muhammad; Iqbal, Muhammad; Ahmad, Saeed; Hayat, Maqsood

    2015-11-01

    Translation is an essential genetic process for understanding the mechanism of gene expression. Due to the large number of protein sequences generated in the post-genomic era, conventional methods are unable to identify Translation Initiation Site (TIS) in human genes timely and accurately. It is thus highly desirable to develop an automatic and accurate computational model for identification of TIS. Considerable improvements have been achieved in developing computational models; however, development of accurate and reliable automated systems for TIS identification in human genes is still a challenging task. In this connection, we propose iTIS-PseKNC, a novel protocol for identification of TIS. Three protein sequence representation methods including dinucleotide composition, pseudo-dinucleotide composition and Trinucleotide composition have been used in order to extract numerical descriptors. Support Vector Machine (SVM), K-nearest neighbor and Probabilistic Neural Network are assessed for their performance using the constructed descriptors. The proposed model iTIS-PseKNC has achieved 99.40% accuracy using jackknife test. The experimental results validated the superior performance of iTIS-PseKNC over the existing methods reported in the literature. It is highly anticipated that the iTIS-PseKNC predictor will be useful for basic research studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Integrated Features by Administering the Support Vector Machine (SVM of Translational Initiations Sites in Alternative Polymorphic Contex

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    Nurul Arneida Husin

    2012-04-01

    Full Text Available Many algorithms and methods have been proposed for classification problems in bioinformatics. In this study, the discriminative approach in particular support vector machines (SVM is employed to recognize the studied TIS patterns. The applied discriminative approach is used to learn about some discriminant functions of samples that have been labelled as positive or negative. After learning, the discriminant functions are employed to decide whether a new sample is true or false. In this study, support vector machines (SVM is employed to recognize the patterns for studied translational initiation sites in alternative weak context. The method has been optimized with the best parameters selected; c=100, E=10-6 and ex=2 for non linear kernel function. Results show that with top 5 features and non linear kernel, the best prediction accuracy achieved is 95.8%. J48 algorithm is applied to compare with SVM with top 15 features and the results show a good prediction accuracy of 95.8%. This indicates that the top 5 features selected by the IGR method and that are performed by SVM are sufficient to use in the prediction of TIS in weak contexts.

  16. Synaptic Plasticity and Translation Initiation

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    Klann, Eric; Antion, Marcia D.; Banko, Jessica L.; Hou, Lingfei

    2004-01-01

    It is widely accepted that protein synthesis, including local protein synthesis at synapses, is required for several forms of synaptic plasticity. Local protein synthesis enables synapses to control synaptic strength independent of the cell body via rapid protein production from pre-existing mRNA. Therefore, regulation of translation initiation is…

  17. A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

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    Wanjun Gu

    2010-02-01

    Full Text Available Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evidence for reduced mRNA stability near the start codon. The reduction in stability generally increases with increasing genomic GC content. In prokaryotes, the reduction also increases with decreasing optimal growth temperature. Within genomes, there is variation in the stability among genes, and this variation correlates with gene GC content, codon bias, and gene expression level. For birds and mammals, however, we do not find a genome-wide trend of reduced mRNA stability near the start codon. Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start codon by initiator-tRNA.

  18. Regulation of translation initiation at the Poliovirus IRES

    OpenAIRE

    Hirnet, Juliane

    2010-01-01

    Poliovirus (PV) translation and replication can occur in neuronal cells where it causes degeneration and lysis of cells leading to paralytic poliomyelitis. Other cell types are much less affected by PV infection and do not support translation and replication of the virus as well. Apart from the poliospecific receptor, the reasons for the tissue preference of poliovirus may be found in its translation initiation via an internal ribosome entry site (IRES), which in addition ...

  19. Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

    DEFF Research Database (Denmark)

    Friis, Martin Barfred; Rasmussen, Thomas Bruun; Belsham, Graham

    2012-01-01

    Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, cDNAs corresponding to the wild type (wt) or mutant forms of the IRES of CSFV strain Paderborn were...

  20. Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

    DEFF Research Database (Denmark)

    Friis, Martin Barfred; Rasmussen, Thomas Bruun; Belsham, Graham J.

    Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, the nucleotides 47 to 427, including the IRES region of the wt CSFV strain Paderborn, were amplified...

  1. Architecture of human translation initiation factor 3

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    Querol-Audi, Jordi; Sun, Chaomin; Vogan, Jacob M.; Smith, Duane; Gu, Yu; Cate, Jamie; Nogales, Eva

    2013-01-01

    SUMMARY Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans. PMID:23623729

  2. AUU-to-AUG mutation in the initiator codon of the translation initiation factor IF3 abolishes translational autocontrol of its own gene (infC) in vivo.

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    Butler, J S; Springer, M; Grunberg-Manago, M

    1987-06-01

    We previously showed that Escherichia coli translation initiation factor IF3 regulates the expression of its own gene infC at the translational level in vivo. Here we create two alterations in the infC gene and test their effects on translational autocontrol of infC expression in vivo by measuring beta-galactosidase activity expressed from infC-lacZ gene fusions under conditions of up to 4-fold derepression or 3-fold repression of infC expression. Replacement of the infC promoter with the trp promoter deletes 120 nucleotides of the infC mRNA 5' to the translation initiation site without affecting autogenous translational control. Mutation of the unusual AUU initiator codon of infC to the more common AUG initiator codon abolishes translation initiation factor IF3-dependent repression and derepression of infC expression in vivo. These results establish the AUU initiator codon of infC as an essential cis-acting element in autogenous translational control of translation initiation factor IF3 expression in vivo.

  3. Heterogeneous Pathways and Timing of Factor Departure during Translation Initiation

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    Tsai, Albert; Petrov, Alexey; Marshall, R. Andrew; Korlach, Jonas; Uemura, Sotaro; Puglisi, Joseph D.

    2015-01-01

    Initiation of translation establishes the reading frame for protein synthesis and is a key point of regulation1. Initiation involves factor-driven assembly at a start codon of an mRNA of an elongation competent 70S ribosomal particle (in bacteria) from separated 30S and 50S subunits and initiator tRNA. Here we establish by direct single-molecule tracking the timing of initiator tRNA, initiation factor 2 (IF2), and 50S subunit joining during initiation. Our results show multiple pathways to initiation, with orders of arrival of tRNA and IF2 dependent on factor concentration and composition. IF2 accelerates 50S subunit joining, and stabilizes the assembled 70S complex. Transition to elongation is gated by the departure of IF2 after GTP hydrolysis, allowing efficient arrival of elongator tRNAs to the second codon presented in the aminoacyl-tRNA acceptor site. These experiments highlight the power of single-molecule approaches to delineate mechanism in complex multicomponent systems. PMID:22722848

  4. Starting the protein synthesis machine: eukaryotic translation initiation.

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    Preiss, Thomas; W Hentze, Matthias

    2003-12-01

    The final assembly of the protein synthesis machinery occurs during translation initiation. This delicate process involves both ends of eukaryotic messenger RNAs as well as multiple sequential protein-RNA and protein-protein interactions. As is expected from its critical position in the gene expression pathway between the transcriptome and the proteome, translation initiation is a selective and highly regulated process. This synopsis summarises the current status of the field and identifies intriguing open questions. Copyright 2003 Wiley Periodicals, Inc.

  5. Predicting Translation Initiation Rates for Designing Synthetic Biology

    Energy Technology Data Exchange (ETDEWEB)

    Reeve, Benjamin; Hargest, Thomas [Centre for Synthetic Biology and Innovation, Imperial College London, London (United Kingdom); Department of Bioengineering, Imperial College London, London (United Kingdom); Gilbert, Charlie [Centre for Synthetic Biology and Innovation, Imperial College London, London (United Kingdom); Ellis, Tom, E-mail: t.ellis@imperial.ac.uk [Centre for Synthetic Biology and Innovation, Imperial College London, London (United Kingdom); Department of Bioengineering, Imperial College London, London (United Kingdom)

    2014-01-20

    In synthetic biology, precise control over protein expression is required in order to construct functional biological systems. A core principle of the synthetic biology approach is a model-guided design and based on the biological understanding of the process, models of prokaryotic protein production have been described. Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5′-untranslated region and the start of the coding sequence. Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels. In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.

  6. Predicting Translation Initiation Rates for Designing Synthetic Biology

    International Nuclear Information System (INIS)

    Reeve, Benjamin; Hargest, Thomas; Gilbert, Charlie; Ellis, Tom

    2014-01-01

    In synthetic biology, precise control over protein expression is required in order to construct functional biological systems. A core principle of the synthetic biology approach is a model-guided design and based on the biological understanding of the process, models of prokaryotic protein production have been described. Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5′-untranslated region and the start of the coding sequence. Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels. In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.

  7. Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons.

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    Diaz de Arce, Alexander J; Noderer, William L; Wang, Clifford L

    2018-01-25

    The initiation of mRNA translation from start codons other than AUG was previously believed to be rare and of relatively low impact. More recently, evidence has suggested that as much as half of all translation initiation utilizes non-AUG start codons, codons that deviate from AUG by a single base. Furthermore, non-AUG start codons have been shown to be involved in regulation of expression and disease etiology. Yet the ability to gauge expression based on the sequence of a translation initiation site (start codon and its flanking bases) has been limited. Here we have performed a comprehensive analysis of translation initiation sites that utilize non-AUG start codons. By combining genetic-reporter, cell-sorting, and high-throughput sequencing technologies, we have analyzed the expression associated with all possible variants of the -4 to +4 positions of non-AUG translation initiation site motifs. This complete motif analysis revealed that 1) with the right sequence context, certain non-AUG start codons can generate expression comparable to that of AUG start codons, 2) sequence context affects each non-AUG start codon differently, and 3) initiation at non-AUG start codons is highly sensitive to changes in the flanking sequences. Complete motif analysis has the potential to be a key tool for experimental and diagnostic genomics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Translation initiation mediated by nuclear cap-binding protein complex.

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    Ryu, Incheol; Kim, Yoon Ki

    2017-04-01

    In mammals, cap-dependent translation of mRNAs is initiated by two distinct mechanisms: cap-binding complex (CBC; a heterodimer of CBP80 and 20)-dependent translation (CT) and eIF4E-dependent translation (ET). Both translation initiation mechanisms share common features in driving cap- dependent translation; nevertheless, they can be distinguished from each other based on their molecular features and biological roles. CT is largely associated with mRNA surveillance such as nonsense-mediated mRNA decay (NMD), whereas ET is predominantly involved in the bulk of protein synthesis. However, several recent studies have demonstrated that CT and ET have similar roles in protein synthesis and mRNA surveillance. In a subset of mRNAs, CT preferentially drives the cap-dependent translation, as ET does, and ET is responsible for mRNA surveillance, as CT does. In this review, we summarize and compare the molecular features of CT and ET with a focus on the emerging roles of CT in translation. [BMB Reports 2017; 50(4): 186-193].

  9. A minimum structure of aminoglycosides that causes an initiation shift of trans-translation.

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    Konno, Takayuki; Takahashi, Toshiharu; Kurita, Daisuke; Muto, Akira; Himeno, Hyouta

    2004-01-01

    Trans-translation is an unusual translation in which transfer-messenger RNA plays a dual function--as a tRNA and an mRNA--to relieve the stalled translation on the ribosome. It has been shown that paromomycin, a typical member of a 4,5-disubstituted class of aminoglycosides, causes a shift of the translation-resuming point on the tmRNA by -1 during trans-translation. To address the molecular basis of this novel effect, we examined the effects of various aminoglycosides that can bind around the A site of the small subunit of the ribosome on trans-translation in vitro. Tobramycin and gentamicin, belonging to the 4,6-disubstituted class of aminoglycosides having rings I and II similar to those in the 4,5-disubstituted class, possess similar effects. Neamine, which has only rings I and II, a common structure shared by 4,5- and 4,6-disubstituted classes of aminoglycosides, was sufficient to cause an initiation shift of trans-translation. In contrast, streptomycin or hygromycin B, lacking ring I, did not cause an initiation shift. The effect of each aminoglycoside on trans-translation coincides with that on conformational change in the A site of the small subunit of the ribosome revealed by recent structural studies: paromomycin, tobramycin and geneticin which is categorized into the gentamicin subclass, but not streptomycin and hygromycin B, flip out two conserved adenine bases at 1492 and 1493 from the A site helix. The pattern of initiation shifts by paromomycin fluctuates with variation of mutations introduced into a region upstream of the initiation point.

  10. Supporting knowledge translation through collaborative translational research initiatives: ‘Bridging’ versus ‘blurring’ boundary-spanning approaches in the UK CLAHRC initiative

    Science.gov (United States)

    Evans, Sarah; Scarbrough, Harry

    2014-01-01

    Recent policy initiatives in the UK and internationally have sought to promote knowledge translation between the ‘producers’ and ‘users’ of research. Within this paper we explore how boundary-spanning interventions used within such initiatives can support knowledge translation between diverse groups. Using qualitative data from a 3-year research study conducted from January 2010 to December 2012 of two case-sites drawn from the CLAHRC initiative in the UK, we distinguish two different approaches to supporting knowledge translation; a ‘bridging’ approach that involves designated roles, discrete events and activities to span the boundaries between communities, and a ‘blurring’ approach that de-emphasises the boundaries between groups, enabling a more continuous process of knowledge translation as part of day-to-day work-practices. In this paper, we identify and differentiate these boundary-spanning approaches and describe how they emerged from the context defined by the wider CLAHRC networks. This highlights the need to develop a more contextualised analysis of the boundary-spanning that underpins knowledge translation processes, relating this to the distinctive features of a particular case. PMID:24561773

  11. Hanford Site sustainable development initiatives

    International Nuclear Information System (INIS)

    Sullivan, C.T.

    1994-05-01

    Since the days of the Manhattan Project of World War II, the economic well being of the Tri-Cities (Pasco, Kennewick, and Richland) of Washington State has been tied to the US Department of Energy missions at the nearby Hanford Site. As missions at the Site changed, so did the economic vitality of the region. The Hanford Site is now poised to complete its final mission, that of environmental restoration. When restoration is completed, the Site may be closed and the effect on the local economy will be devastating if action is not taken now. To that end, economic diversification and transition are being planned. To facilitate the process, the Hanford Site will become a sustainable development demonstration project

  12. Development and characterization of a reconstituted yeast translation initiation system.

    Science.gov (United States)

    Algire, Mikkel A; Maag, David; Savio, Peter; Acker, Michael G; Tarun, Salvador Z; Sachs, Alan B; Asano, Katsura; Nielsen, Klaus H; Olsen, Deanne S; Phan, Lon; Hinnebusch, Alan G; Lorsch, Jon R

    2002-03-01

    To provide a bridge between in vivo and in vitro studies of eukaryotic translation initiation, we have developed a reconstituted translation initiation system using components from the yeast Saccharomyces cerevisiae. We have purified a minimal set of initiation factors (elFs) that, together with yeast 80S ribosomes, GTP, and initiator methionyl-tRNA, are sufficient to assemble active initiation complexes on a minimal mRNA template. The kinetics of various steps in the pathway of initiation complex assembly and the formation of the first peptide bond in vitro have been explored. The formation of active initiation complexes in this system is dependent on ribosomes, mRNA, Met-tRNAi, GTP hydrolysis, elF1, elF1A, elF2, elF5, and elF5B. Our data indicate that elF1 and elF1A both facilitate the binding of the elF2 x GTP x Met-tRNAi complex to the 40S ribosomal subunit to form the 43S complex. elF5 stimulates a step after 43S complex formation, consistent with its proposed role in activating GTP hydrolysis by elF2 upon initiation codon recognition. The presence of elF5B is required for the joining of the 40S and 60S subunits to form the 80S initiation complex. The step at which each of these factors acts in this reconstituted system is in agreement with previous data from in vivo studies and work using reconstituted mammalian systems, indicating that the system recapitulates fundamental events in translation initiation in eukaryotic cells. This system should allow us to couple powerful yeast genetic and molecular biological experiments with in vitro kinetic and biophysical experiments, yielding a better understanding of the molecular mechanics of this central, complex process.

  13. The translation initiation factor DAP5 promotes IRES-driven translation of p53 mRNA.

    Science.gov (United States)

    Weingarten-Gabbay, S; Khan, D; Liberman, N; Yoffe, Y; Bialik, S; Das, S; Oren, M; Kimchi, A

    2014-01-30

    Translational regulation of the p53 mRNA can determine the ratio between p53 and its N-terminal truncated isoforms and therefore has a significant role in determining p53-regulated signaling pathways. Although its importance in cell fate decisions has been demonstrated repeatedly, little is known about the regulatory mechanisms that determine this ratio. Two internal ribosome entry sites (IRESs) residing within the 5'UTR and the coding sequence of p53 mRNA drive the translation of full-length p53 and Δ40p53 isoform, respectively. Here, we report that DAP5, a translation initiation factor shown to positively regulate the translation of various IRES containing mRNAs, promotes IRES-driven translation of p53 mRNA. Upon DAP5 depletion, p53 and Δ40p53 protein levels were decreased, with a greater effect on the N-terminal truncated isoform. Functional analysis using bicistronic vectors driving the expression of a reporter gene from each of these two IRESs indicated that DAP5 preferentially promotes translation from the second IRES residing in the coding sequence. Furthermore, p53 mRNA expressed from a plasmid carrying this second IRES was selectively shifted to lighter polysomes upon DAP5 knockdown. Consequently, Δ40p53 protein levels and the subsequent transcriptional activation of the 14-3-3σ gene, a known target of Δ40p53, were strongly reduced. In addition, we show here that DAP5 interacts with p53 IRES elements in in vitro and in vivo binding studies, proving for the first time that DAP5 directly binds a target mRNA. Thus, through its ability to regulate IRES-dependent translation of the p53 mRNA, DAP5 may control the ratio between different p53 isoforms encoded by a single mRNA.

  14. Designing Course An Initial Approach To Translation Teaching

    Directory of Open Access Journals (Sweden)

    Roswani Siregar

    2017-09-01

    Full Text Available Along with the human history translation is the sustainable communication tool among the cultures to preserve this knowledge from generation to generations. Undoubtedly both translation plays a very important role in an increasingly globalized world and translators have the prominent roles in the development of countries. Many translators really enjoy their work but hesitated to teach a course due to their lack of pedagogical knowledge and believe that the translation skill is gained by personal experiences and talents. Thus this paper attempt to promote the translation teaching in classroom by set the preliminary approach to teach translation. The sequences of teaching design are described by propose the brief definition to the nature of translation the importance translation teaching the translator competence and design of translation course. This paper is the preliminary approach to translation teaching for beginners in university setting.

  15. Machine Assisted Translation of Health Materials to Chinese: An Initial Evaluation.

    Science.gov (United States)

    Turner, Anne M; Desai, Loma; Dew, Kristin; Martin, Nathalie; Kirchhoff, Katrin

    2015-01-01

    There is an unmet need for Chinese language health materials in the USA. We investigated the use of machine translation (MT) plus human post-editing (PE) to produce Chinese translations of public health materials. We collected 60 documents that had been manually translated from English to traditional Chinese. The English versions were translated to Chinese using MT and assessed for errors and time required to correct via PE. Results suggest poor initial translation may explain the lack of quality translations despite PE.

  16. Environmental Research Translation: Enhancing Interactions with Communities at Contaminated Sites

    Science.gov (United States)

    Ramirez-Andreotta, Monica D.; Brusseau, Mark L.; Artiola, Janick F.; Maier, Raina M.; Gandolfi, A. Jay

    2014-01-01

    The characterization and remediation of contaminated sites are complex endeavors fraught with numerous challenges. One particular challenge that is receiving increased attention is the development and encouragement of full participation by communities and community members affected by a given site in all facets of decision-making. Many disciplines have been grappling with the challenges associated with environmental and risk communication, public participation in environmental data generation, and decision-making and increasing community capacity. The concepts and methods developed by these disciplines are reviewed, with a focus on their relevance to the specific dynamics associated with environmental contamination sites. The contributions of these disciplines are then synthesized and integrated to help develop Environmental Research Translation (ERT), a proposed framework for environmental scientists to promote interaction and communication among involved parties at contaminated sites. This holistic approach is rooted in public participation approaches to science, which includes: a transdisciplinary team, effective collaboration, information transfer, public participation in environmental projects, and a cultural model of risk communication. Although there are challenges associated with the implementation of ERT, it is anticipated that application of this proposed translational science method could promote more robust community participation at contaminated sites. PMID:25173762

  17. microRNAs stimulate translation initiation mediated by HCV-like IRESes

    Science.gov (United States)

    Mengardi, Chloé; Limousin, Taran; Ricci, Emiliano P.; Soto-Rifo, Ricardo; Decimo, Didier

    2017-01-01

    Abstract MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by recognizing and hybridizing to a specific sequence generally located in the 3΄ untranslated region (UTR) of targeted mRNAs. miRNA-induced inhibition of translation occurs during the initiation step, most probably at the level of ribosome scanning. In this process, the RNA-induced silencing complex interacts both with PABP and the 43S pre-initiation complex to disrupt scanning of the 40S ribosome. However, in some specific cases, miRNAs can stimulate translation. Although the mechanism of miRNA-mediated upregulation is unknown, it appears that the poly(A) tail and the lack of availability of the TNRC6 proteins are amongst major determinants. The genomic RNA of the Hepatitis C Virus is uncapped, non-polyadenylated and harbors a peculiar internal ribosome entry site (IRES) that binds the ribosome directly to the AUG codon. Thus, we have exploited the unique properties of the HCV IRES and other related IRESes (HCV-like) to study how translation initiation can be modulated by miRNAs on these elements. Here, we report that miRNA binding to the 3΄ UTR can stimulate translation of a reporter gene given that its expression is driven by an HCV-like IRES and that it lacks a poly(A) tail at its 3΄ extremity. PMID:28077561

  18. The UK's National Electronic Site Licencing Initiative.

    OpenAIRE

    Woodward, Hazel

    2001-01-01

    In 1998 the UK created the National Electronic Site Licensing Initiative (NESLI) to increase and improve access to electronic journals and to negotiate license agreements on behalf of academic libraries. The use of a model license agreement and the success of site licensing is discussed. Highlights from an interim evaluation by the Joint Information Systems Committee (JISC) are noted and key issues and questions arising from the evaluation are identified

  19. A translational silencing function of MCPIP1/Regnase-1 specified by the target site context.

    Science.gov (United States)

    Behrens, Gesine; Winzen, Reinhard; Rehage, Nina; Dörrie, Anneke; Barsch, Monika; Hoffmann, Anne; Hackermüller, Jörg; Tiedje, Christopher; Heissmeyer, Vigo; Holtmann, Helmut

    2018-02-19

    The expression of proteins during inflammatory and immune reactions is coordinated by post-transcriptional mechanisms. A particularly strong suppression of protein expression is exerted by a conserved translational silencing element (TSE) identified in the 3' UTR of NFKBIZ mRNA, which is among the targets of the RNA-binding proteins Roquin-1/2 and MCPIP1/Regnase-1. We present evidence that in the context of the TSE MCPIP1, so far known for its endonuclease activity toward mRNAs specified by distinct stem-loop (SL) structures, also suppresses translation. Overexpression of MCPIP1 silenced translation in a TSE-dependent manner and reduced ribosome occupancy of the mRNA. Correspondingly, MCPIP1 depletion alleviated silencing and increased polysomal association of the mRNA. Translationally silenced NFKBIZ or reporter mRNAs were mostly capped, polyadenylated and ribosome associated. Furthermore, MCPIP1 silenced also cap-independent, CrPV-IRES-dependent translation. This suggests that MCPIP1 suppresses a post-initiation step. The TSE is predicted to form five SL structures. SL4 and 5 resemble target structures reported for MCPIP1 and together were sufficient for MCPIP1 binding and mRNA destabilization. Translational silencing, however, required SL1-3 in addition. Thus the NFKBIZ TSE functions as an RNA element in which sequences adjacent to the site of interaction with MCPIP1 and dispensable for accelerated mRNA degradation extend the functional repertoire of MCPIP1 to translational silencing.

  20. Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2.

    Science.gov (United States)

    Khan, Mohammad Farhan; Spurgeon, Sarah; von der Haar, Tobias

    2018-05-14

    Phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is one of the best studied and most widely used means for regulating protein synthesis activity in eukaryotic cells. This pathway regulates protein synthesis in response to stresses, viral infections, and nutrient depletion, among others. We present analyses of an ordinary differential equation-based model of this pathway, which aim to identify its principal robustness-conferring features. Our analyses indicate that robustness is a distributed property, rather than arising from the properties of any one individual pathway species. However, robustness-conferring properties are unevenly distributed between the different species, and we identify a guanine nucleotide dissociation inhibitor (GDI) complex as a species that likely contributes strongly to the robustness of the pathway. Our analyses make further predictions on the dynamic response to different types of kinases that impinge on eIF2. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Eukaryotic Initiation Factor 6, an evolutionarily conserved regulator of ribosome biogenesis and protein translation

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jianjun [Harvard University; Jin, Zhaoqing [ORNL; Yang, Xiaohan [ORNL; Li, Jian-Feng [Harvard University; Chen, Jay [ORNL

    2011-01-01

    We recently identified Receptor for Activated C Kinase 1 (RACK1) as one of the molecular links between abscisic acid (ABA) signaling and its regulation on protein translation. Moreover, we identified Eukaryotic Initiation Factor 6 (eIF6) as an interacting partner of RACK1. Because the interaction between RACK1 and eIF6 in mammalian cells is known to regulate the ribosome assembly step of protein translation initiation, it was hypothesized that the same process of protein translation in Arabidopsis is also regulated by RACK1 and eIF6. In this article, we analyzed the amino acid sequences of eIF6 in different species from different lineages and discovered some intriguing differences in protein phosphorylation sites that may contribute to its action in ribosome assembly and biogenesis. In addition, we discovered that, distinct from non-plant organisms in which eIF6 is encoded by a single gene, all sequenced plant genomes contain two or more copies of eIF6 genes. While one copy of plant eIF6 is expressed ubiquitously and might possess the conserved function in ribosome biogenesis and protein translation, the other copy seems to be only expressed in specific organs and therefore may have gained some new functions. We proposed some important studies that may help us better understand the function of eIF6 in plants.

  2. Report of Committee for JAEA Internationalization Initiative (Translated document)

    International Nuclear Information System (INIS)

    2013-07-01

    In global circumstances surrounding nuclear energy, the role expected by the Japan Atomic Energy Agency (JAEA) is becoming increasingly important. JAEA has promoted an initiative for an international hub in order to increase the scientific competitiveness of Japan and make international contributions, by gathering excellent researchers from the entire world with the latest facilities. Also, JAEA has established the 'Committee for JAEA Internationalization Initiative', which will discuss issues such as environmental improvement for accepted foreigners, direction of efforts for internationalization initiative and strategies to improve the current situation. This report mentions the results of the committee's discussion including current issues for the initiative and recommendations for their solution, as well as issues to be discussed in order to enhance international awareness of JAEA staff. The following is the summary of the recommendations for the initiative: Set up local teams that focus on the situation of each site in order to provide detailed support for foreigners from diversified backgrounds. Develop systems for emergency situations to provide information for safety swiftly for foreigners and confirm their safety, in addition to preparing emergency goods. Prepare bilingual documents and systems that foreigners need to use for their work based on importance and frequency of use of such systems and documents. (author)

  3. Multiple Parallel Pathways of Translation Initiation on the CrPV IRES.

    Science.gov (United States)

    Petrov, Alexey; Grosely, Rosslyn; Chen, Jin; O'Leary, Seán E; Puglisi, Joseph D

    2016-04-07

    The complexity of eukaryotic translation allows fine-tuned regulation of protein synthesis. Viruses use internal ribosome entry sites (IRESs) to minimize or, like the CrPV IRES, eliminate the need for initiation factors. Here, by exploiting the CrPV IRES, we observed the entire process of initiation and transition to elongation in real time. We directly tracked the CrPV IRES, 40S and 60S ribosomal subunits, and tRNA using single-molecule fluorescence spectroscopy and identified multiple parallel initiation pathways within the system. Our results distinguished two pathways of 80S:CrPV IRES complex assembly that produce elongation-competent complexes. Following 80S assembly, the requisite eEF2-mediated translocation results in an unstable intermediate that is captured by binding of the elongator tRNA. Whereas initiation can occur in the 0 and +1 frames, the arrival of the first tRNA defines the reading frame and strongly favors 0 frame initiation. Overall, even in the simplest system, an intricate reaction network regulates translation initiation. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. N-terminal Proteomics Assisted Profiling of the Unexplored Translation Initiation Landscape in Arabidopsis thaliana.

    Science.gov (United States)

    Willems, Patrick; Ndah, Elvis; Jonckheere, Veronique; Stael, Simon; Sticker, Adriaan; Martens, Lennart; Van Breusegem, Frank; Gevaert, Kris; Van Damme, Petra

    2017-06-01

    Proteogenomics is an emerging research field yet lacking a uniform method of analysis. Proteogenomic studies in which N-terminal proteomics and ribosome profiling are combined, suggest that a high number of protein start sites are currently missing in genome annotations. We constructed a proteogenomic pipeline specific for the analysis of N-terminal proteomics data, with the aim of discovering novel translational start sites outside annotated protein coding regions. In summary, unidentified MS/MS spectra were matched to a specific N-terminal peptide library encompassing protein N termini encoded in the Arabidopsis thaliana genome. After a stringent false discovery rate filtering, 117 protein N termini compliant with N-terminal methionine excision specificity and indicative of translation initiation were found. These include N-terminal protein extensions and translation from transposable elements and pseudogenes. Gene prediction provided supporting protein-coding models for approximately half of the protein N termini. Besides the prediction of functional domains (partially) contained within the newly predicted ORFs, further supporting evidence of translation was found in the recently released Araport11 genome re-annotation of Arabidopsis and computational translations of sequences stored in public repositories. Most interestingly, complementary evidence by ribosome profiling was found for 23 protein N termini. Finally, by analyzing protein N-terminal peptides, an in silico analysis demonstrates the applicability of our N-terminal proteogenomics strategy in revealing protein-coding potential in species with well- and poorly-annotated genomes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Model of cap-dependent translation initiation in sea urchin: a step towards the eukaryotic translation regulation network.

    Science.gov (United States)

    Bellé, Robert; Prigent, Sylvain; Siegel, Anne; Cormier, Patrick

    2010-03-01

    The large and rapid increase in the rate of protein synthesis following fertilization of the sea urchin egg has long been a paradigm of translational control, an important component of the regulation of gene expression in cells. This translational up-regulation is linked to physiological changes that occur upon fertilization and is necessary for entry into first cell division cycle. Accumulated knowledge on cap-dependent initiation of translation makes it suited and timely to start integrating the data into a system view of biological functions. Using a programming environment for system biology coupled with model validation (named Biocham), we have built an integrative model for cap-dependent initiation of translation. The model is described by abstract rules. It contains 51 reactions involved in 74 molecular complexes. The model proved to be coherent with existing knowledge by using queries based on computational tree logic (CTL) as well as Boolean simulations. The model could simulate the change in translation occurring at fertilization in the sea urchin model. It could also be coupled with an existing model designed for cell-cycle control. Therefore, the cap-dependent translation initiation model can be considered a first step towards the eukaryotic translation regulation network.

  6. Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide.

    Science.gov (United States)

    Tang, Leiming; Morris, Jacob; Wan, Ji; Moore, Chelsea; Fujita, Yoshihiko; Gillaspie, Sarah; Aube, Eric; Nanda, Jagpreet; Marques, Maud; Jangal, Maika; Anderson, Abbey; Cox, Christian; Hiraishi, Hiroyuki; Dong, Leiming; Saito, Hirohide; Singh, Chingakham Ranjit; Witcher, Michael; Topisirovic, Ivan; Qian, Shu-Bing; Asano, Katsura

    2017-11-16

    In the human genome, translation initiation from non-AUG codons plays an important role in various gene regulation programs. However, mechanisms regulating the non-AUG initiation rate remain poorly understood. Here, we show that the non-AUG initiation rate is nearly consistent under a fixed nucleotide context in various human and insect cells. Yet, it ranges from <1% to nearly 100% compared to AUG translation, depending on surrounding sequences, including Kozak, and possibly additional nucleotide contexts. Mechanistically, this range of non-AUG initiation is controlled in part, by the eIF5-mimic protein (5MP). 5MP represses non-AUG translation by competing with eIF5 for the Met-tRNAi-binding factor eIF2. Consistently, eIF5 increases, whereas 5MP decreases translation of NAT1/EIF4G2/DAP5, whose sole start codon is GUG. By modulating eIF5 and 5MP1 expression in combination with ribosome profiling we identified a handful of previously unknown non-AUG initiation sites, some of which serve as the exclusive start codons. If the initiation rate for these codons is low, then an AUG-initiated downstream ORF prevents the generation of shorter, AUG-initiated isoforms. We propose that the homeostasis of the non-AUG translatome is maintained through balanced expression of eIF5 and 5MP. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Binding of eukaryotic translation initiation factor 4E (eIF4E) to eIF4G represses translation of uncapped mRNA.

    Science.gov (United States)

    Tarun, S Z; Sachs, A B

    1997-12-01

    mRNA translation in crude extracts from the yeast Saccharomyces cerevisiae is stimulated by the cap structure and the poly(A) tail through the binding of the cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) and the poly(A) tail-binding protein Pab1p. These proteins also bind to the translation initiation factor eIF4G and thereby link the mRNA to the general translational apparatus. In contrast, uncapped, poly(A)-deficient mRNA is translated poorly in yeast extracts, in part because of the absence of eIF4E and Pab1p binding sites on the mRNA. Here, we report that uncapped-mRNA translation is also repressed in yeast extracts due to the binding of eIF4E to eIF4G. Specifically, we find that mutations which weaken the eIF4E binding site on the yeast eIF4G proteins Tif4631p and Tif4632p lead to temperature-sensitive growth in vivo and the stimulation of uncapped-mRNA translation in vitro. A mutation in eIF4E which disturbs its ability to interact with eIF4G also leads to a stimulation of uncapped-mRNA translation in vitro. Finally, overexpression of eIF4E in vivo or the addition of excess eIF4E in vitro reverses these effects of the mutations. These data support the hypothesis that the eIF4G protein can efficiently stimulate translation of exogenous uncapped mRNA in extracts but is prevented from doing so as a result of its association with eIF4E. They also suggest that some mRNAs may be translationally regulated in vivo in response to the amount of free eIF4G in the cell.

  8. Predictive design of mRNA translation initiation region to control prokaryotic translation efficiency.

    Science.gov (United States)

    Seo, Sang Woo; Yang, Jae-Seong; Kim, Inhae; Yang, Jina; Min, Byung Eun; Kim, Sanguk; Jung, Gyoo Yeol

    2013-01-01

    Precise prediction of prokaryotic translation efficiency can provide valuable information for optimizing bacterial host for the production of biochemical compounds or recombinant proteins. However, dynamic changes in mRNA folding throughout translation make it difficult to assess translation efficiency. Here, we systematically determined the universal folding regions that significantly affect the efficiency of translation in Escherichia coli. By assessing the specific regions for mRNA folding, we could construct a predictive design method, UTR Designer, and demonstrate that proper codon optimization around the 5'-proximal coding sequence is necessary to achieve a broad range of expression levels. Finally, we applied our method to control the threshold value of input signals switching on a genetic circuit. This should increase our understanding of the processes underlying gene expression and provide an efficient design principle for optimizing various biological systems, thereby facilitating future efforts in metabolic engineering and synthetic biology. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Translation initiation factor eIF4G mediates in vitro poly(A) tail-dependent translation

    Science.gov (United States)

    Tarun, Salvador Z.; Wells, Sandra E.; Deardorff, Julie A.; Sachs, Alan B.

    1997-01-01

    The yeast translation factor eIF4G associates with both the cap-binding protein eIF4E and the poly(A)-binding protein Pab1p. Here we report that the two yeast eIF4G homologs, Tif4631p and Tif4632p, share a conserved Pab1p-binding site. This site is required for Pab1p and poly(A) tails to stimulate the in vitro translation of uncapped polyadenylylated mRNA, and the region encompassing it is required for the cap and the poly(A) tail to synergistically stimulate translation. This region on Tif4631p becomes essential for cell growth when the eIF4E binding site on Tif4631p is mutated. Pab1p mutations also show synthetic lethal interactions with eIF4E mutations. These data suggest that eIF4G mediates poly(A) tail stimulated translation in vitro, and that Pab1p and the domain encompassing the Pab1p-binding site on eIF4G can compensate for partial loss of eIF4E function in vivo. PMID:9256432

  10. Translation initiation factor eIF4G mediates in vitro poly(A) tail-dependent translation.

    Science.gov (United States)

    Tarun, S Z; Wells, S E; Deardorff, J A; Sachs, A B

    1997-08-19

    The yeast translation factor eIF4G associates with both the cap-binding protein eIF4E and the poly(A)-binding protein Pab1p. Here we report that the two yeast eIF4G homologs, Tif4631p and Tif4632p, share a conserved Pab1p-binding site. This site is required for Pab1p and poly(A) tails to stimulate the in vitro translation of uncapped polyadenylylated mRNA, and the region encompassing it is required for the cap and the poly(A) tail to synergistically stimulate translation. This region on Tif4631p becomes essential for cell growth when the eIF4E binding site on Tif4631p is mutated. Pab1p mutations also show synthetic lethal interactions with eIF4E mutations. These data suggest that eIF4G mediates poly(A) tail stimulated translation in vitro, and that Pab1p and the domain encompassing the Pab1p-binding site on eIF4G can compensate for partial loss of eIF4E function in vivo.

  11. A distinct translation initiation mechanism generates cryptic peptides for immune surveillance.

    Directory of Open Access Journals (Sweden)

    Shelley R Starck

    Full Text Available MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexes assemble at non-AUG codons but differ from canonical AUG initiation in response to specific inhibitors acting within the peptidyl transferase and decoding centers of the ribosome. Thus, cryptic translation at non-AUG start codons can utilize a distinct initiation mechanism which could be differentially regulated to provide peptides for immune surveillance.

  12. Initial results from MARmara SuperSITE

    Science.gov (United States)

    Meral Ozel, Nurcan; Necmioglu, Ocal; Favali, Paolo; Douglas, John; Mathieu, Pierre-Philippe; Geli, Louis; Ergintav, Semih; Oguz Ozel, Asım; Tan, Onur; Gurbuz, Cemil; Erdik, Mustafa

    2014-05-01

    shaking measurements, has been prepared by INERIS to be set up on the field to be also set up as an early warning system prototype to be progressively parameterized and tested on near to real time condition. Slip rate on the Main Marmara Fault from 3D seismic data has been estimated and extremely young age of the North Anatolian Fault in the Sea of Marmara has been determined. Seismic risk study for IGDAS Natural Gas Network including pipelines and its components has been carried out with several earthquake scenarios in Marmara Sea. An automatic shut-off algorithm has been developed for the automatic shut-off of the gas flow at the IGDAS district regulators during an extreme event. All the European and international initiatives and projects that could have links with MARsite were identified as the initial step for the integration of data management practices and coordination with ongoing research infrastructures. EPOS and EMSO are considered to be crucial links that could provide sustainability of MARsite's developments beyond the project's lifetime. Concerning EMSO, Marmara is one of the nodes of the research infrastructure, in which a permanent installation at sea is being integrated with land-based networks. In the context of EPOS, MARsite will be a thematic core service. In addition, the data collection and dissemination in MARsite is carried out according to the data management principles of EMSO and EPOS. Dissemination activities reached a certain level of maturity through the relesea of Public Annual Report, quarterly newsletter, ID card and poster, social media interaction, dedicated web sites, videos and several conferences and workhops participated, such as GEO European Projects' Workshop, Supersites Coordination Workshop and GEO-X Plenary & Geneva Ministerial Summit .

  13. A guide to the translation of the Global Initiative for Asthma (GINA) strategy into improved care

    DEFF Research Database (Denmark)

    Boulet, Louis-Philippe; FitzGerald, J Mark; Levy, Mark L

    2012-01-01

    published. This report is intended to draw on this experience and assist with the translation of asthma guideline recommendations into quality programmes for patients with asthma using current knowledge translation principles. It also provides examples of successful initiatives in various socioeconomic...

  14. The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon

    Directory of Open Access Journals (Sweden)

    Moes Lorin

    2007-11-01

    Full Text Available Abstract Background Bovine viral diarrhea virus (BVDV is the prototype representative of the pestivirus genus in the Flaviviridae family. It has been shown that the initiation of translation of BVDV RNA occurs by an internal ribosome entry mechanism mediated by the 5' untranslated region of the viral RNA 1. The 5' and 3' boundaries of the IRES of the cytopathic BVDV NADL have been mapped and it has been suggested that the IRES extends into the coding of the BVDV polyprotein 2. A putative pseudoknot structure has been recognized in the BVDV 5'UTR in close proximity to the AUG start codon. A pseudoknot structure is characteristic for flavivirus IRESes and in the case of the closely related classical swine fever virus (CSFV and the more distantly related Hepatitis C virus (HCV pseudoknot function in translation has been demonstrated. Results To characterize the BVDV IRESes in detail, we studied the BVDV translational initiation by transfection of dicistronic expression plasmids into mammalian cells. A region coding for the amino terminus of the BVDV SD-1 polyprotein contributes considerably to efficient initiation of translation. The translation efficiency mediated by the IRES of BVDV strains NADL and SD-1 approximates the poliovirus type I IRES directed translation in BHK cells. Compared to the poliovirus IRES increased expression levels are mediated by the BVDV IRES of strain SD-1 in murine cell lines, while lower levels are observed in human cell lines. Site directed mutagenesis revealed that a RNA pseudoknot upstream of the initiator AUG is an important structural element for IRES function. Mutants with impaired ability to base pair in stem I or II lost their translational activity. In mutants with repaired base pairing either in stem 1 or in stem 2 full translational activity was restored. Thus, the BVDV IRES translation is dependent on the pseudoknot integrity. These features of the pestivirus IRES are reminiscent of those of the classical

  15. Cap- and initiator tRNA-dependent initiation of TYMV polyprotein synthesis by ribosomes: evaluation of the Trojan horse model for TYMV RNA translation.

    Science.gov (United States)

    Matsuda, Daiki; Dreher, Theo W

    2007-01-01

    Turnip yellow mosaic virus (TYMV) RNA directs the translation of two overlapping open reading frames. Competing models have been previously published to explain ribosome access to the downstream polyprotein cistron. The Trojan horse model, based on cell-free experiments, proposes noncanonical cap-independent initiation in which the 3'-terminal tRNA-like structure (TLS) functionally replaces initiator tRNA, and the valine bound to the TLS becomes cis-incorporated into viral protein. The initiation coupling model, based on in vivo expression and ribosome toe-printing studies, proposes a variation of canonical leaky scanning. Here, we have re-examined the wheat germ extract experiments that led to the Trojan horse model, incorporating a variety of controls. We report that (1) translation in vitro from the polyprotein AUG of TYMV RNA is unchanged after removal of the 3' TLS but is stimulated by the presence of a 5'-cap; (2) the presence of free cap analog or edeine (which interferes with initiation at the ribosomal P site and its tRNA(i) (Met) involvement) inhibits translation from the polyprotein AUG; (3) the toe-prints of immediately post-initiation ribosomes on TYMV RNA are similar with and without an intact TLS; and (4) significant deacylation of valyl-TYMV RNA in wheat germ extract can complicate the detection of cis-incorporation. These results favor the initiation coupling model.

  16. Identifying intrinsic and extrinsic determinants that regulate internal initiation of translation mediated by the FMR1 5' leader

    Directory of Open Access Journals (Sweden)

    Timmerman Stephanie

    2008-10-01

    Full Text Available Abstract Background Regulating synthesis of the Fragile X gene (FMR1 product, FMRP alters neural plasticity potentially through its role in the microRNA pathway. Cap-dependent translation of the FMR1 mRNA, a process requiring ribosomal scanning through the 5' leader, is likely impeded by the extensive secondary structure generated by the high guanosine/cytosine nucleotide content including the CGG triplet nucleotide repeats in the 5' leader. An alternative mechanism to initiate translation – internal initiation often utilizes secondary structure to recruit the translational machinery. Consequently, studies were undertaken to confirm and extend a previous observation that the FMR1 5' leader contains an internal ribosomal entry site (IRES. Results Cellular transfection of a dicistronic DNA construct containing the FMR1 5' leader inserted into the intercistronic region yielded significant translation of the second cistron, but the FMR1 5' leader was also found to contain a cryptic promoter possibly confounding interpretation of these results. However, transfection of dicistronic and monocistronic RNA ex vivo or in vitro confirmed that the FMR1 5' leader contains an IRES. Moreover, inhibiting cap-dependent translation ex vivo did not affect the expression level of endogenous FMRP indicating a role for IRES-dependent translation of FMR1 mRNA. Analysis of the FMR1 5' leader revealed that the CGG repeats and the 5' end of the leader were vital for internal initiation. Functionally, exposure to potassium chloride or intracellular acidification and addition of polyinosinic:polycytidylic acid as mimics of neural activity and double stranded RNA, respectively, differentially affected FMR1 IRES activity. Conclusion Our results indicate that multiple stimuli influence IRES-dependent translation of the FMR1 mRNA and suggest a functional role for the CGG nucleotide repeats.

  17. A common function for mRNA 5' and 3' ends in translation initiation in yeast.

    Science.gov (United States)

    Tarun, S Z; Sachs, A B

    1995-12-01

    The mRNA poly(A) tail and its associated poly(A) binding protein (Pab1p) are ubiquitous in eukaryotes. The function of the poly(A) tail is to stabilize mRNA and to stimulate its translation. The development of a poly(A)- and cap-dependent yeast in vitro translation system has allowed us to understand how poly(A) stimulates translation. We find that Pab1p but not the cap binding protein eIF-4E is required for poly(A) tail-dependent translation, and that the Pab1p-poly(A) tail complex functions to recruit the 40S ribosomal subunit to the mRNA. These data introduce a new step into the pathway of translation initiation and merge the translational functions of the two ends of mRNA.

  18. Eukaryotic initiation factor 5A dephosphorylation is required for translational arrest in stationary phase cells.

    Science.gov (United States)

    Chung, Janete; Rocha, Antonio A; Tonelli, Renata R; Castilho, Beatriz A; Schenkman, Sergio

    2013-04-15

    The protein known as eIF5A (eukaryotic initiation factor 5A) has an elusive role in translation. It has a unique and essential hypusine modification at a conserved lysine residue in most eukaryotes. In addition, this protein is modified by phosphorylation with unknown functions. In the present study we show that a phosphorylated state of eIF5A predominates in exponentially growing Trypanosoma cruzi cells, and extensive dephosphorylation occurs in cells in stationary phase. Phosphorylation occurs mainly at Ser(2), as shown in yeast eIF5A. In addition, a novel phosphorylation site was identified at Tyr(21). In exponential cells, T. cruzi eIF5A is partially associated with polysomes, compatible with a proposed function as an elongation factor, and becomes relatively enriched in polysomal fractions in stationary phase. Overexpression of the wild-type eIF5A, or eIF5A with Ser(2) replaced by an aspartate residue, but not by alanine, increases the rate of cell proliferation and protein synthesis. However, the presence of an aspartate residue instead of Ser(2) is toxic for cells reaching the stationary phase, which show a less-pronounced protein synthesis arrest and a decreased amount of eIF5A in dense fractions of sucrose gradients. We conclude that eIF5A phosphorylation and dephosphorylation cycles regulate translation according to the growth conditions.

  19. Translating Kuzguncuk: A Site of Tolerance and Solidarity

    Directory of Open Access Journals (Sweden)

    Harika KARAVİN

    2015-08-01

    Full Text Available This study has aims to explore the relationship between cities and texts. Benefiting from Jakobson’s notion of “intersemiotic translation”, some literary works on cities has been considered target texts of the nonverbal signs of cities. In other words, these narratives are analy zed as a translation process, underlining the interdisciplinary relationship between Urban Studies and Translation Studies. Cities are assumed to be translated into cultural texts with a specific discourse. As a methodological tool, Tymoczko’s notions of “ translation” and “metonymics” have been adopted and Kuzguncuk has been chosen to present a partial representation of the city of İstanbul. After selecting some fiction and non - fiction works, these texts are analyzed in three different categories, namely tr anslation of Kuzguncuk in prose, short stories and poetry, with an aim to reveal the various discourses reflected in the “translations”.

  20. Viral and chloroplastic signals essential for initiation and efficiency of translation in Agrobacterium tumefaciens.

    Science.gov (United States)

    Ahmad, Tauqeer; Venkataraman, Srividhya; Hefferon, Kathleen; AbouHaidar, Mounir G

    2014-09-12

    The construction of high-level protein expression vectors using the CaMV 35S promoter in concert with highly efficient translation initiation signals for Agrobacterium tumefaciens is a relatively less explored field compared to that of Escherichia coli. In the current study, we experimentally investigated the capacity of the CaMV 35S promoter to direct GFP gene expression in A. tumefaciens in the context of different viral and chloroplastic translation initiation signals. GFP expression and concomitant translational efficiency was monitored by confocal microscopy and Western blot analysis. Among all of the constructs, the highest level of translation was observed for the construct containing the phage T7 translation initiation region followed by the chloroplastic Rubisco Large Subunit (rbcL) 58-nucleotide 5' leader region including its SD-like sequence (GGGAGGG). Replacing the SD-like (GGGAGGG) with non SD-like (TTTATTT) or replacing the remaining 52 nucleotides of rbcL with nonspecific sequence completely abolished translation. In addition, this 58 nucleotide region of rbcL serves as a translational enhancer in plants when located within the 5' UTR of mRNA corresponding to GFP. Other constructs, including those containing sequences upstream of the coat proteins of Alfalfa Mosaic Virus, or the GAGG sequence of T4 phage or the chloroplastic atpI and/or PsbA 5' UTR sequence, supported low levels of GFP expression or none at all. From these studies, we propose that we have created high expression vectors in A. tumefaciens and/or plants which contain the CaMV 35S promoter, followed by the translationally strong T7 SD plus RBS translation initiation region or the rbcL 58-nucleotide 5' leader region upstream of the gene of interest. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Engineering bacterial translation initiation - Do we have all the tools we need?

    Science.gov (United States)

    Vigar, Justin R J; Wieden, Hans-Joachim

    2017-11-01

    Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts. Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals. Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools. Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier

  2. Mixed messages: Re-initiation factors regulate translation of animal mRNAs

    OpenAIRE

    Obermayer, Benedikt; Rajewsky, Nikolaus

    2014-01-01

    When ribosomes encounter upstream open reading frames (uORFs) during scanning of the 5' untranslated region (5' UTR), translation of the downstream ORF requires re-initiation. In a recent paper in Nature, Schleich et al. describe metazoan factors which specifically promote re-initiation.

  3. BIOREMEDIATION FIELD INITIATIVE SITE PROFILE: ESCAMBIA WOOD PRESERVING SITE - BROOKHAVEN

    Science.gov (United States)

    The Escambia Wood Preserving Site—Brookhaven in Brookhaven, Mississippi, is a former wood preserving facility that used pentachlo- rophenol (PCP) and creosote to treat wooden poles. The site contains two pressure treatment cylinders, a wastewater treatment system, five bulk pr...

  4. Role of helix 44 of 16S rRNA in the fidelity of translation initiation.

    Science.gov (United States)

    Qin, Daoming; Liu, Qi; Devaraj, Aishwarya; Fredrick, Kurt

    2012-03-01

    The molecular mechanisms that govern translation initiation to ensure accuracy remain unclear. Here, we provide evidence that the subunit-joining step of initiation is controlled in part by a conformational change in the 1408 region of helix h44. First, chemical probing of 30S initiation complexes formed with either a cognate (AUG) or near-cognate (AUC) start codon shows that an IF1-dependent enhancement at A1408 is reduced in the presence of AUG. This change in reactivity is due to a conformational change rather than loss of IF1, because other portions of the IF1 footprint are unchanged and high concentrations of IF1 fail to diminish the reactivity difference seen at A1408. Second, mutations in h44 such as A1413C stimulate 50S docking and cause reduced reactivity at A1408. Third, streptomycin, which has been shown by Rodnina and coworkers to stimulate 50S docking by reversing the inhibitory effects of IF1, also causes reduced reactivity at A1408. Collectively, these data support a model in which IF1 alters the A1408 region of h44 in a way that makes 50S docking unfavorable, and canonical codon-anticodon pairing in the P site restores h44 to a docking-favorable conformation. We also find that, in the absence of factors, the cognate 30S•AUG•fMet-tRNA ternary complex is >1000-fold more stable than the near-cognate 30S•AUC•fMet-tRNA complex. Hence, the selectivity of ternary complex formation is inherently high, exceeding that of initiation in vivo by more than 10-fold.

  5. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    International Nuclear Information System (INIS)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan; Li, Qiuping; Yang, Zhiyuan; Wu, Guoqiang; Sun, Shuhui; Gu, Jianxin; Wei, Yuanyan; Jiang, Jianhai

    2010-01-01

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  6. Hanford tank initiative test facility site selection study

    International Nuclear Information System (INIS)

    Staehr, T.W.

    1997-01-01

    The Hanford Tanks Initiative (HTI) project is developing equipment for the removal of hard heel waste from the Hanford Site underground single-shell waste storage tanks. The HTI equipment will initially be installed in the 241-C-106 tank where its operation will be demonstrated. This study evaluates existing Hanford Site facilities and other sites for functional testing of the HTI equipment before it is installed into the 241-C-106 tank

  7. Human DDX3 functions in translation and interacts with the translation initiation factor eIF3.

    Science.gov (United States)

    Lee, Chung-Sheng; Dias, Anusha P; Jedrychowski, Mark; Patel, Arvind H; Hsu, Jeanne L; Reed, Robin

    2008-08-01

    The conserved RNA helicase DDX3 is of major medical importance due to its involvement in numerous cancers, human hepatitis C virus (HCV) and HIV. Although DDX3 has been reported to have a wide variety of cellular functions, its precise role remains obscure. Here, we raised a new antibody to DDX3 and used it to show that DDX3 is evenly distributed throughout the cytoplasm at steady state. Consistent with this observation, HA-tagged DDX3 also localizes to the cytoplasm. RNAi of DDX3 in both human and Drosophila cells shows that DDX3 is required for cell viability. Moreover, using RNAi, we show that DDX3 is required for expression of protein from reporter constructs. In contrast, we did not detect a role for DDX3 in nuclear steps in gene expression. Further insight into the function of DDX3 came from the observation that its major interaction partner is the multi-component translation initiation factor eIF3. We conclude that a primary function for DDX3 is in protein translation, via an interaction with eIF3.

  8. Translation initiation factors eIF3 and HCR1 control translation termination and stop codon read-through in yeast cells

    Czech Academy of Sciences Publication Activity Database

    Beznosková, P.; Cuchalová, Lucie; Wagner, S.; Shoemaker, Ch. J.; Gunišová, S.; von der Haar, T.; Valášek, L. S.

    2013-01-01

    Roč. 9, č. 11 (2013), e1003962_1-e1003962_17 ISSN 1553-7404 Institutional support: RVO:61389013 Keywords : translation initiation * translation termination * eIF3 Subject RIV: CD - Macromolecular Chemistry Impact factor: 8.167, year: 2013

  9. Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity.

    Science.gov (United States)

    Ivanov, Ivaylo P; Wei, Jiajie; Caster, Stephen Z; Smith, Kristina M; Michel, Audrey M; Zhang, Ying; Firth, Andrew E; Freitag, Michael; Dunlap, Jay C; Bell-Pedersen, Deborah; Atkins, John F; Sachs, Matthew S

    2017-06-27

    Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs) in its >700-nucleotide (nt) 5' leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation. We also found that the 5' region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5' conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs) in the CPC1 reading frame upstream of uORF2, some deeply conserved, could potentially initiate translation. At least four NCCs initiated translation in vitro In vivo data were consistent with initiation at NCCs to produce N-terminally extended N. crassa CPC1 isoforms. The pivotal role played by CPC1, combined with its translational regulation by uORFs and NCC utilization, underscores the emerging significance of noncanonical initiation events in controlling gene expression. IMPORTANCE There is a deepening and widening appreciation of the diverse roles of translation in controlling gene expression. A central fungal transcription factor, the best-studied example of which is Saccharomyces cerevisiae GCN4, is crucial for the response to amino acid limitation. Two upstream open reading frames (uORFs) in the GCN4 mRNA are critical for controlling GCN4 synthesis. We observed that two uORFs in the corresponding Neurospora crassa cpc-1 mRNA appear functionally analogous to the GCN4 uORFs. We also discovered that, surprisingly, unlike GCN4, the CPC1 coding sequence extends far

  10. Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity

    Directory of Open Access Journals (Sweden)

    Ivaylo P. Ivanov

    2017-06-01

    Full Text Available Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs in its >700-nucleotide (nt 5′ leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation. We also found that the 5′ region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5′ conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs in the CPC1 reading frame upstream of uORF2, some deeply conserved, could potentially initiate translation. At least four NCCs initiated translation in vitro. In vivo data were consistent with initiation at NCCs to produce N-terminally extended N. crassa CPC1 isoforms. The pivotal role played by CPC1, combined with its translational regulation by uORFs and NCC utilization, underscores the emerging significance of noncanonical initiation events in controlling gene expression.

  11. PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism.

    Science.gov (United States)

    Liang, Hui; He, Shiming; Yang, Jingyi; Jia, Xinying; Wang, Pan; Chen, Xi; Zhang, Zhong; Zou, Xiajuan; McNutt, Michael A; Shen, Wen Hong; Yin, Yuxin

    2014-05-06

    PTEN is one of the most frequently mutated genes in human cancer. It is known that PTEN has a wide range of biological functions beyond tumor suppression. Here, we report that PTENα, an N-terminally extended form of PTEN, functions in mitochondrial metabolism. Translation of PTENα is initiated from a CUG codon upstream of and in-frame with the coding region of canonical PTEN. Eukaryotic translation initiation factor 2A (eIF2A) controls PTENα translation, which requires a CUG-centered palindromic motif. We show that PTENα induces cytochrome c oxidase activity and ATP production in mitochondria. TALEN-mediated somatic deletion of PTENα impairs mitochondrial respiratory chain function. PTENα interacts with canonical PTEN to increase PINK1 protein levels and promote energy production. Our studies demonstrate the importance of eIF2A-mediated alternative translation for generation of protein diversity in eukaryotic systems and provide insights into the mechanism by which the PTEN family is involved in multiple cellular processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Molecular Architecture of the 40S⋅eIF1⋅eIF3 Translation Initiation Complex

    Science.gov (United States)

    Erzberger, Jan P.; Stengel, Florian; Pellarin, Riccardo; Zhang, Suyang; Schaefer, Tanja; Aylett, Christopher H.S.; Cimermančič, Peter; Boehringer, Daniel; Sali, Andrej; Aebersold, Ruedi; Ban, Nenad

    2014-01-01

    Summary Eukaryotic translation initiation requires the recruitment of the large, multiprotein eIF3 complex to the 40S ribosomal subunit. We present X-ray structures of all major components of the minimal, six-subunit Saccharomyces cerevisiae eIF3 core. These structures, together with electron microscopy reconstructions, cross-linking coupled to mass spectrometry, and integrative structure modeling, allowed us to position and orient all eIF3 components on the 40S⋅eIF1 complex, revealing an extended, modular arrangement of eIF3 subunits. Yeast eIF3 engages 40S in a clamp-like manner, fully encircling 40S to position key initiation factors on opposite ends of the mRNA channel, providing a platform for the recruitment, assembly, and regulation of the translation initiation machinery. The structures of eIF3 components reported here also have implications for understanding the architecture of the mammalian 43S preinitiation complex and the complex of eIF3, 40S, and the hepatitis C internal ribosomal entry site RNA. PMID:25171412

  13. Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.

    Science.gov (United States)

    Chung, Liliane; Bailey, Dalan; Leen, Eoin N; Emmott, Edward P; Chaudhry, Yasmin; Roberts, Lisa O; Curry, Stephen; Locker, Nicolas; Goodfellow, Ian G

    2014-08-01

    Viruses have evolved a variety of mechanisms to usurp the host cell translation machinery to enable translation of the viral genome in the presence of high levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man, have evolved a mechanism that relies on the interaction of translation initiation factors with the virus-encoded VPg protein covalently linked to the 5' end of the viral RNA. To further characterize this novel mechanism of translation initiation, we have used proteomics to identify the components of the norovirus translation initiation factor complex. This approach revealed that VPg binds directly to the eIF4F complex, with a high affinity interaction occurring between VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is important for the VPg-eIF4G interaction; viruses with mutations that alter or disrupt this interaction are debilitated or non-viable. Our results shed new light on the unusual mechanisms of protein-directed translation initiation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Harmonization in preclinical epilepsy research: A joint AES/ILAE translational initiative.

    Science.gov (United States)

    Galanopoulou, Aristea S; French, Jacqueline A; O'Brien, Terence; Simonato, Michele

    2017-11-01

    Among the priority next steps outlined during the first translational epilepsy research workshop in London, United Kingdom (2012), jointly organized by the American Epilepsy Society (AES) and the International League Against Epilepsy (ILAE), are the harmonization of research practices used in preclinical studies and the development of infrastructure that facilitates multicenter preclinical studies. The AES/ILAE Translational Task Force of the ILAE has been pursuing initiatives that advance these goals. In this supplement, we present the first reports of the working groups of the Task Force that aim to improve practices of performing rodent video-electroencephalography (vEEG) studies in experimental controls, generate systematic reviews of preclinical research data, and develop preclinical common data elements (CDEs) for epilepsy research in animals. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. Young Adult Capacity Initiative Cross-Site Analysis

    Science.gov (United States)

    Academy for Educational Development, 2012

    2012-01-01

    This cross-site analysis presents findings about the implementation, impact, and outcomes of the Young Adult Capacity Initiative (YACI), at 13 community-based organizations in New York City. These agencies received technical assistance and small incentive grants from the Fund for the City of New York Youth Development Institute (YDI) to build…

  16. ABCD1 translation-initiator mutation demonstrates genotype-phenotype correlation for AMN.

    Science.gov (United States)

    O'Neill, G N; Aoki, M; Brown, R H

    2001-12-11

    Inherited mutations of the X-linked adrenoleukodystrophy (X-ALD) gene (ABCD1) cause two neuropathologically distinct disorders: cerebral adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN). The biochemical hallmark of these disorders is a reduction of very long chain fatty acid (VLCFA) beta-oxidation with accumulation of VLCFA esters in neural white matter. More than 300 mutations of the ABCD1 gene have been described. Genotype-phenotype correlation in X-ALD has not been demonstrated; indeed, the two disorders coexist in individual pedigrees and in homozygotic twin pairs. The authors have identified one large kindred with a highly concordant AMN phenotype resembling an X-linked dominant hereditary spastic paraparesis. All obligate female carriers are clinically affected. The ABCD1 gene was examined by direct sequencing of genomic DNA and full-length cDNA. Mutant gene transcription was analyzed by reverse transcriptase PCR. ALD protein (ALDP) expression was tested by Western blotting and indirect immunofluorescence. VLCFA beta-oxidation was examined by in vitro assay. The authors have identified a novel deletion of the ABCD1 gene ATG translation initiation codon. The authors have demonstrated that an N-terminal truncated ALDP, missing the first 65 amino acids, is expressed by internal initiation of translation and is correctly trafficked to peroxisomes. They have documented complete penetrance of this mutant in all female carriers. They have also shown that VLCFA beta-oxidation is reduced to 20% of normal in association with this mutant ALDP. It appears that initiation of translation at an internal AUG codon generates a truncated ALDP that uniformly leads to an AMN phenotype in this family. Possible models for action of this truncated ALDP and full disease penetrance in heterozygotes are reviewed.

  17. Dynamic and static tibial translation in patients with anterior cruciate ligament deficiency initially treated with a structured rehabilitation protocol.

    Science.gov (United States)

    Sonesson, Sofi; Kvist, Joanna

    2017-08-01

    To compare dynamic and static tibial translation, in patients with anterior cruciate ligament deficiency, at 2- to 5-year follow-up, with the tibial translation after 4 months of rehabilitation initiated early after the injury. Secondarily, to compare tibial translation in the injured knee and non-injured knee and explore correlations between dynamic and static tibial translation. Twelve patients with ACL rupture were assessed at 3-8 weeks after ACL injury, after 4 months of structured rehabilitation, and 2-5 years after ACL injury. Sagittal tibial translation was measured during the Lachman test (static translation) and during gait (dynamic translation) using a CA-4000 electrogoniometer. Static tibial translation was increased bilateral 2-5 years after ACL injury, whereas the dynamic tibial translation was unchanged. Tibial translation was greater in the injured knee compared with the non-injured knee (Lachman test 134 N 9.1 ± 1.0 vs. 7.0 ± 1.7 mm, P = 0.001, gait 5.6 ± 2.1 vs. 4.7 ± 1.8 mm, P = 0.011). There were no correlations between dynamic and static tibial translation. Dynamic tibial translation was unchanged in spite of increased static tibial translation in the ACL-deficient knee at 2- to 5-year follow-up compared to directly after rehabilitation. Dynamic tibial translation did not correlate with the static tibial translation. A more normal gait kinematics may be maintained from completion of a rehabilitation programme to mid-term follow-up in patients with ACL deficiency treated with rehabilitation only. IV.

  18. Execution programme for the initial site investigations at Simpevarp

    International Nuclear Information System (INIS)

    2002-10-01

    In the feasibility studies that were completed in 2001, eight sites were identified as potentially suitable for hosting a repository. All the identified sites meet the safety requirements with respect to bedrock conditions that could be checked at that time. The feasibility studies have revealed good potential when it comes to the technical and environmental aspects as well. Based on an integrated evaluation SKB proposed to start site investigations with test drillings at three sites; Simpevarp, Forsmark, and Tierp north. The site investigations have started at Simpevarp and Forsmark. The municipal council of Tierp rejected a site investigation in April 2002. The site investigations are divided into two main phases; initial and complete investigations. Initial Site Investigation is performed to identify the site within a specified area that is deemed to be most suitable for a deep repository and to determine whether the feasibility study's judgement of the suitability of the area holds up in the light of borehole data from repository depth. The Initial Site Investigation is expected to take about 3 years. If the assessment shows that the site has good potential to host a repository, Complete Site Investigation will follow for an expected duration of another 3 years. The purpose of the Complete Site Investigation is to gather all information required to select one of the sites as the main alternative and to apply for a permit for construction of the deep repository at that site. The site-specific programme gives an overview of the whole site investigation phase as well as a detailed description of the initial stage. The results of the initial investigations will determine whether Simpevarp is appropriate for further investigation, i.e. the Complete Site Investigation. This document summarizes the investigations that will be carried out at Simpevarp during the Initial Site Investigations. The document is a working document, which will be successively updated as

  19. Execution programme for the initial site investigations at Simpevarp

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-10-01

    In the feasibility studies that were completed in 2001, eight sites were identified as potentially suitable for hosting a repository. All the identified sites meet the safety requirements with respect to bedrock conditions that could be checked at that time. The feasibility studies have revealed good potential when it comes to the technical and environmental aspects as well. Based on an integrated evaluation SKB proposed to start site investigations with test drillings at three sites; Simpevarp, Forsmark, and Tierp north. The site investigations have started at Simpevarp and Forsmark. The municipal council of Tierp rejected a site investigation in April 2002. The site investigations are divided into two main phases; initial and complete investigations. Initial Site Investigation is performed to identify the site within a specified area that is deemed to be most suitable for a deep repository and to determine whether the feasibility study's judgement of the suitability of the area holds up in the light of borehole data from repository depth. The Initial Site Investigation is expected to take about 3 years. If the assessment shows that the site has good potential to host a repository, Complete Site Investigation will follow for an expected duration of another 3 years. The purpose of the Complete Site Investigation is to gather all information required to select one of the sites as the main alternative and to apply for a permit for construction of the deep repository at that site. The site-specific programme gives an overview of the whole site investigation phase as well as a detailed description of the initial stage. The results of the initial investigations will determine whether Simpevarp is appropriate for further investigation, i.e. the Complete Site Investigation. This document summarizes the investigations that will be carried out at Simpevarp during the Initial Site Investigations. The document is a working document, which will be successively updated as

  20. Translation initiation requires cell division cycle 123 (Cdc123) to facilitate biogenesis of the eukaryotic initiation factor 2 (eIF2).

    Science.gov (United States)

    Perzlmaier, Angelika F; Richter, Frank; Seufert, Wolfgang

    2013-07-26

    The eukaryotic translation initiation factor 2 (eIF2) is central to the onset of protein synthesis and its modulation in response to physiological demands. eIF2, a heterotrimeric G-protein, is activated by guanine nucleotide exchange to deliver the initiator methionyl-tRNA to the ribosome. Here we report that assembly of the eIF2 complex in vivo depends on Cdc123, a cell proliferation protein conserved among eukaryotes. Mutations of CDC123 in budding yeast reduced the association of eIF2 subunits, diminished polysome levels, and increased GCN4 expression indicating that Cdc123 is critical for eIF2 activity. Cdc123 bound the unassembled eIF2γ subunit, but not the eIF2 complex, and the C-terminal domain III region of eIF2γ was both necessary and sufficient for Cdc123 binding. Alterations of the binding site revealed a strict correlation between Cdc123 binding, the biological function of eIF2γ, and its ability to assemble with eIF2α and eIF2β. Interestingly, high levels of Cdc123 neutralized the assembly defect and restored the biological function of an eIF2γ mutant. Moreover, the combined overexpression of eIF2 subunits rescued an otherwise inviable cdc123 deletion mutant. Thus, Cdc123 is a specific eIF2 assembly factor indispensable for the onset of protein synthesis. Human Cdc123 is encoded by a disease risk locus, and, therefore, eIF2 biogenesis control by Cdc123 may prove relevant for normal cell physiology and human health. This work identifies a novel step in the eukaryotic translation initiation pathway and assigns a biochemical function to a protein that is essential for growth and viability of eukaryotic cells.

  1. The long non-coding RNA GAS5 cooperates with the eukaryotic translation initiation factor 4E to regulate c-Myc translation.

    Directory of Open Access Journals (Sweden)

    Guangzhen Hu

    Full Text Available Long noncoding RNAs (lncRNAs are important regulators of transcription; however, their involvement in protein translation is not well known. Here we explored whether the lncRNA GAS5 is associated with translation initiation machinery and regulates translation. GAS5 was enriched with eukaryotic translation initiation factor-4E (eIF4E in an RNA-immunoprecipitation assay using lymphoma cell lines. We identified two RNA binding motifs within eIF4E protein and the deletion of each motif inhibited the binding of GAS5 with eIF4E. To confirm the role of GAS5 in translation regulation, GAS5 siRNA and in vitro transcribed GAS5 RNA were used to knock down or overexpress GAS5, respectively. GAS5 siRNA had no effect on global protein translation but did specifically increase c-Myc protein level without an effect on c-Myc mRNA. The mechanism of this increase in c-Myc protein was enhanced association of c-Myc mRNA with the polysome without any effect on protein stability. In contrast, overexpression of in vitro transcribed GAS5 RNA suppressed c-Myc protein without affecting c-Myc mRNA. Interestingly, GAS5 was found to be bound with c-Myc mRNA, suggesting that GAS5 regulates c-Myc translation through lncRNA-mRNA interaction. Our findings have uncovered a role of GAS5 lncRNA in translation regulation through its interactions with eIF4E and c-Myc mRNA.

  2. HSV usurps eukaryotic initiation factor 3 subunit M for viral protein translation: novel prevention target.

    Directory of Open Access Journals (Sweden)

    Natalia Cheshenko

    2010-07-01

    Full Text Available Prevention of genital herpes is a global health priority. B5, a recently identified ubiquitous human protein, was proposed as a candidate HSV entry receptor. The current studies explored its role in HSV infection. Viral plaque formation was reduced by approximately 90% in human cells transfected with small interfering RNA targeting B5 or nectin-1, an established entry receptor. However, the mechanisms were distinct. Silencing of nectin-1 prevented intracellular delivery of viral capsids, nuclear transport of a viral tegument protein, and release of calcium stores required for entry. In contrast, B5 silencing had no effect on these markers of entry, but inhibited viral protein translation. Specifically, viral immediate early genes, ICP0 and ICP4, were transcribed, polyadenylated and transported from the nucleus to the cytoplasm, but the viral transcripts did not associate with ribosomes or polysomes in B5-silenced cells. In contrast, immediate early gene viral transcripts were detected in polysome fractions isolated from control cells. These findings are consistent with sequencing studies demonstrating that B5 is eukaryotic initiation factor 3 subunit m (eIF3m. Although B5 silencing altered the polysome profile of cells, silencing had little effect on cellular RNA or protein expression and was not cytotoxic, suggesting that this subunit is not essential for host cellular protein synthesis. Together these results demonstrate that B5 plays a major role in the initiation of HSV protein translation and could provide a novel target for strategies to prevent primary and recurrent herpetic disease.

  3. Novel role of c-jun N-terminal kinase in regulating the initiation of cap-dependent translation.

    Science.gov (United States)

    Patel, Manish R; Sadiq, Ahad A; Jay-Dixon, Joe; Jirakulaporn, Tanawat; Jacobson, Blake A; Farassati, Faris; Bitterman, Peter B; Kratzke, Robert A

    2012-02-01

    Initiation of protein translation by the 5' mRNA cap is a tightly regulated step in cell growth and proliferation. Aberrant activation of cap-dependent translation is a hallmark of many cancers including non-small cell lung cancer. The canonical signaling mechanisms leading to translation initiation include activation of the Akt/mTOR pathway in response to the presence of nutrients and growth factors. We have previously observed that inhibition of c-jun N-terminal kinase (JNK) leads to inactivation of cap-dependent translation in mesothelioma cells. Since JNK is involved in the genesis of non-small cell lung cancer (NSCLC), we hypothesized that JNK could also be involved in activating cap-dependent translation in NSCLC cells and could represent an alternative pathway regulating translation. In a series of NSCLC cell lines, inhibition of JNK using SP600125 resulted in inhibition of 4E-BP1 phosphorylation and a decrease in formation of the cap-dependent translation complex, eIF4F. Furthermore, we show that JNK-mediated inhibition of translation is independent of mTOR. Our data provide evidence that JNK is involved in the regulation of translation and has potential as a therapeutic target in NSCLC.

  4. Tuning of Recombinant Protein Expression in Escherichia coli by Manipulating Transcription, Translation Initiation Rates, and Incorporation of Noncanonical Amino Acids.

    Science.gov (United States)

    Schlesinger, Orr; Chemla, Yonatan; Heltberg, Mathias; Ozer, Eden; Marshall, Ryan; Noireaux, Vincent; Jensen, Mogens Høgh; Alfonta, Lital

    2017-06-16

    Protein synthesis in cells has been thoroughly investigated and characterized over the past 60 years. However, some fundamental issues remain unresolved, including the reasons for genetic code redundancy and codon bias. In this study, we changed the kinetics of the Eschrichia coli transcription and translation processes by mutating the promoter and ribosome binding domains and by using genetic code expansion. The results expose a counterintuitive phenomenon, whereby an increase in the initiation rates of transcription and translation lead to a decrease in protein expression. This effect can be rescued by introducing slow translating codons into the beginning of the gene, by shortening gene length or by reducing initiation rates. On the basis of the results, we developed a biophysical model, which suggests that the density of co-transcriptional-translation plays a role in bacterial protein synthesis. These findings indicate how cells use codon bias to tune translation speed and protein synthesis.

  5. Site Specific Advisory Board initiative, evaluation survey results supplementary appendix: Summary of individual site results

    International Nuclear Information System (INIS)

    1996-08-01

    This Appendix presents results of the Site-Specific Advisory Board (SSAB) Initiative for each of the 11 sites that participated in the survey. These individual results are a supplement to the June 1996 Summary Report which presented overall survey results. Results are presented in 11 sections, arranged alphabetically by site. Each section includes a series of figures and tables that parallel those presented in the Summary Report. To facilitate comparison, figures are presented both for the individual site and for the overall long survey. The sequence of sections is: Fernald, Hanford, Idaho, Los Alamos, Monticello, Nevada, Pantex, Rocky Flats, St. Louis, Sandia, and Savannah River

  6. The 3′ cap-independent translation element of Barley yellow dwarf virus binds eIF4F via the eIF4G subunit to initiate translation

    Science.gov (United States)

    Treder, Krzysztof; Pettit Kneller, Elizabeth L.; Allen, Edwards M.; Wang, Zhaohui; Browning, Karen S.; Miller, W. Allen

    2008-01-01

    The 3′ cap-independent translation element (BTE) of Barley yellow dwarf virus RNA confers efficient translation initiation at the 5′ end via long-distance base pairing with the 5′-untranslated region (UTR). Here we provide evidence that the BTE functions by recruiting translation initiation factor eIF4F. We show that the BTE interacts specifically with the cap-binding initiation factor complexes eIF4F and eIFiso4F in a wheat germ extract (wge). In wge depleted of cap-interacting factors, addition of eIF4F (and to a lesser extent, eIFiso4F) allowed efficient translation of an uncapped reporter construct (BLucB) containing the BTE in its 3′ UTR. Translation of BLucB required much lower levels of eIF4F or eIFiso4F than did a capped, nonviral mRNA. Both full-length eIF4G and the carboxy-terminal half of eIF4G lacking the eIF4E binding site stimulated translation to 70% of the level obtained with eIF4F, indicating a minor role for the cap-binding protein, eIF4E. In wge inhibited by either BTE in trans or cap analog, eIF4G alone restored translation nearly as much as eIF4F, while addition of eIF4E alone had no effect. The BTE bound eIF4G (Kd = 177 nm) and eIF4F (Kd = 37 nm) with high affinity, but very weakly to eIF4E. These interactions correlate with the ability of the factors to facilitate BTE-mediated translation. These results and previous observations are consistent with a model in which eIF4F is delivered to the 5′ UTR by the BTE, and they show that eIF4G, but not eIF4E, plays a major role in this novel mechanism of cap-independent translation. PMID:18025255

  7. The 3' cap-independent translation element of Barley yellow dwarf virus binds eIF4F via the eIF4G subunit to initiate translation.

    Science.gov (United States)

    Treder, Krzysztof; Kneller, Elizabeth L Pettit; Allen, Edwards M; Wang, Zhaohui; Browning, Karen S; Miller, W Allen

    2008-01-01

    The 3' cap-independent translation element (BTE) of Barley yellow dwarf virus RNA confers efficient translation initiation at the 5' end via long-distance base pairing with the 5'-untranslated region (UTR). Here we provide evidence that the BTE functions by recruiting translation initiation factor eIF4F. We show that the BTE interacts specifically with the cap-binding initiation factor complexes eIF4F and eIFiso4F in a wheat germ extract (wge). In wge depleted of cap-interacting factors, addition of eIF4F (and to a lesser extent, eIFiso4F) allowed efficient translation of an uncapped reporter construct (BLucB) containing the BTE in its 3' UTR. Translation of BLucB required much lower levels of eIF4F or eIFiso4F than did a capped, nonviral mRNA. Both full-length eIF4G and the carboxy-terminal half of eIF4G lacking the eIF4E binding site stimulated translation to 70% of the level obtained with eIF4F, indicating a minor role for the cap-binding protein, eIF4E. In wge inhibited by either BTE in trans or cap analog, eIF4G alone restored translation nearly as much as eIF4F, while addition of eIF4E alone had no effect. The BTE bound eIF4G (Kd = 177 nm) and eIF4F (Kd = 37 nm) with high affinity, but very weakly to eIF4E. These interactions correlate with the ability of the factors to facilitate BTE-mediated translation. These results and previous observations are consistent with a model in which eIF4F is delivered to the 5' UTR by the BTE, and they show that eIF4G, but not eIF4E, plays a major role in this novel mechanism of cap-independent translation.

  8. Translational initiation in Leishmania tarentolae and Phytomonas serpens (Kinetoplastida) is strongly influenced by pre-ATG triplet and its 5' sequence context.

    Science.gov (United States)

    Lukes, Julius; Paris, Zdenek; Regmi, Sandesh; Breitling, Reinhard; Mureev, Sergey; Kushnir, Susanna; Pyatkov, Konstantin; Jirků, Milan; Alexandrov, Kirill A

    2006-08-01

    To investigate the influence of sequence context of translation initiation codon on translation efficiency in Kinetoplastida, we constructed a library of expression plasmids randomized in the three nucleotides prefacing ATG of a reporter gene encoding enhanced green fluorescent protein (EGFP). All 64 possible combinations of pre-ATG triplets were individually stably integrated into the rDNA locus of Leishmania tarentolae and the resulting cell lines were assessed for EGFP expression. The expression levels were quantified directly by measuring the fluorescence of EGFP protein in living cells and confirmed by Western blotting. We observed a strong influence of the pre-ATG triplet on the level of protein expression over a 20-fold range. To understand the degree of evolutionary conservation of the observed effect, we transformed Phytomonas serpens, a trypanosomatid parasite of plants, with a subset of the constructs. The pattern of translational efficiency mediated by individual pre-ATG triplets in this species was similar to that observed in L. tarentolae. However, the pattern of translational efficiency of two other proteins (red fluorescent protein and tetracycline repressor) containing selected pre-ATG triplets did not correlate with either EGFP or each other. Thus, we conclude that a conserved mechanism of translation initiation site selection exists in kinetoplastids that is strongly influenced not only by the pre-ATG sequences but also by the coding region of the gene.

  9. Eukaryotic Translation Initiation Factor 4E Is a Feed-Forward Translational Coactivator of Transforming Growth Factor β Early Protransforming Events in Breast Epithelial Cells.

    Science.gov (United States)

    Decarlo, Lindsey; Mestel, Celine; Barcellos-Hoff, Mary-Helen; Schneider, Robert J

    2015-08-01

    Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in breast cancers in association with disease progression and reduced survival. Much remains to be understood regarding the role of eIF4E in human cancer. We determined, using immortalized human breast epithelial cells, that elevated expression of eIF4E translationally activates the transforming growth factor β (TGF-β) pathway, promoting cell invasion, a loss of cell polarity, increased cell survival, and other hallmarks of early neoplasia. Overexpression of eIF4E is shown to facilitate the selective translation of integrin β1 mRNA, which drives the translationally controlled assembly of a TGF-β receptor signaling complex containing α3β1 integrins, β-catenin, TGF-β receptor I, E-cadherin, and phosphorylated Smad2/3. This receptor complex acutely sensitizes nonmalignant breast epithelial cells to activation by typically substimulatory levels of activated TGF-β. TGF-β can promote cellular differentiation or invasion and transformation. As a translational coactivator of TGF-β, eIF4E confers selective mRNA translation, reprogramming nonmalignant cells to an invasive phenotype by reducing the set point for stimulation by activated TGF-β. Overexpression of eIF4E may be a proinvasive facilitator of TGF-β activity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Researching for sustained translation from site cluster permeability into building courtyard and interior atrium

    Science.gov (United States)

    Teddy Badai Samodra, FX; Defiana, Ima; Setyawan, Wahyu

    2018-03-01

    Many previous types of research have discussed the permeability of site cluster. Because of interaction and interconnected attribute, it will be better that there is its translation into lower context such as building and interior scale. In this paper, the sustainability design performance of both similar designs of courtyard and atrium are investigated continuing the recommendation of site space permeability. By researching related literature review and study through Ecotect Analysis and Ansys Fluent simulations, the pattern transformation and optimum courtyard and atrium design could comply the requirement. The results highlighted that the air movement from the site could be translated at the minimum of 50% higher to the building and indoor environment. Thus, it has potency for energy efficiency when grid, loop, and cul-de-sac site clusters, with 25% of ground coverage, have connectivity with building courtyard compared to the atrium. Energy saving is higher when using low thermal transmittance of transparent material and its lower area percentages for the courtyard walls. In general, it was more energy efficient option as part of a low rise building, while the courtyard building performed better with increasing irregular building height more than 90% of the difference.

  11. HIV-1 transcripts use IRES-initiation under conditions where Cap-dependent translation is restricted by poliovirus 2A protease.

    Directory of Open Access Journals (Sweden)

    Raquel Amorim

    Full Text Available The 30 different species of mRNAs synthesized during the HIV-1 replication cycle are all capped and polyadenilated. Internal ribosome entry sites have been recognized in the 5' untranslated region of some mRNA species of HIV-1, which would contribute to an alternative mechanism of initiation of mRNA translation. However, the Cap-dependent translation is assumed to be the main mechanism driving the initiation of HIV-1 protein synthesis. In this work, we describe a cell system in which lower to higher levels of transient expression of the poliovirus 2A protease strongly inhibited cellular Cap-dependent translation with no toxic effect to the cells during a 72-hour time frame. In this system, the synthesis of HIV-1 proteins was inhibited in a temporal dose-dependent way. Higher levels of 2A protease expression severely inhibited HIV-1 protein synthesis during the first 24 hours of infection consequently inhibiting viral production and infectivity. Intermediate to lower levels of 2A Protease expression caused the inhibition of viral protein synthesis only during the first 48 hours of viral replication. After this period both protein synthesis and viral release were recovered to the control levels. However, the infectivity of viral progeny was still partially inhibited. These results indicate that two mechanisms of mRNA translation initiation contribute to the synthesis of HIV-1 proteins; during the first 24-48 hours of viral replication HIV-1 protein synthesis is strongly dependent on Cap-initiation, while at later time points IRES-driven translation initiation is sufficient to produce high amounts of viral particles.

  12. Comparative genomic analysis of translation initiation mechanisms for genes lacking the Shine–Dalgarno sequence in prokaryotes

    KAUST Repository

    Nakagawa, So

    2017-02-15

    In prokaryotes, translation initiation is believed to occur through an interaction between the 3\\' tail of a 16S rRNA and a corresponding Shine-Dalgarno (SD) sequence in the 5\\' untranslated region (UTR) of an mRNA. However, some genes lack SD sequences (non-SD genes), and the fraction of non-SD genes in a genome varies depending on the prokaryotic species. To elucidate non-SD translation initiation mechanisms in prokaryotes from an evolutionary perspective, we statistically examined the nucleotide frequencies around the initiation codons in non-SD genes from 260 prokaryotes (235 bacteria and 25 archaea). We identified distinct nucleotide frequency biases upstream of the initiation codon in bacteria and archaea, likely because of the presence of leaderless mRNAs lacking a 5\\' UTR. Moreover, we observed overall similarities in the nucleotide patterns between upstream and downstream regions of the initiation codon in all examined phyla. Symmetric nucleotide frequency biases might facilitate translation initiation by preventing the formation of secondary structures around the initiation codon. These features are more prominent in species\\' genomes that harbor large fractions of non-SD sequences, suggesting that a reduced stability around the initiation codon is important for efficient translation initiation in prokaryotes.

  13. Androgen signaling promotes translation of TMEFF2 in prostate cancer cells via phosphorylation of the α subunit of the translation initiation factor 2.

    Directory of Open Access Journals (Sweden)

    Ryan F Overcash

    Full Text Available The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2, is expressed mainly in brain and prostate. Expression of TMEFF2 is deregulated in prostate cancer, suggesting a role in this disease, but the molecular mechanism(s involved in this effect are not clear. Although androgens promote tmeff2 transcription, androgen delivery to castrated animals carrying CWR22 xenografts increases TMEFF2 protein levels in the absence of mRNA changes, suggesting that TMEFF2 may also be post-transcriptionally regulated. Here we show that translation of TMEFF2 is regulated by androgens. Addition of physiological concentrations of dihydrotestosterone (DHT to prostate cancer cell lines increases translation of endogenous TMEFF2 or transfected TMEFF2-Luciferase fusions, and this effect requires the presence of upstream open reading frames (uORFs in the 5'-untranslated region (5'-UTR of TMEFF2. Using chemical and siRNA inhibition of the androgen receptor (AR, we show that the androgen effect on TMEFF2 translation is mediated by the AR. Importantly, DHT also promotes phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α in an AR-dependent manner, paralleling the effect on TMEFF2 translation. Moreover, endoplasmic reticulum (ER stress conditions, which promote eIF2α phosphorylation, also stimulate TMEFF2 translation. These results indicate that androgen signaling promotes eIF2α phosphorylation and subsequent translation of TMEFF2 via a mechanism that requires uORFs in the 5'-UTR of TMEFF2.

  14. AtLa1 protein initiates IRES-dependent translation of WUSCHEL mRNA and regulates the stem cell homeostasis of Arabidopsis in response to environmental hazards.

    Science.gov (United States)

    Cui, Yuchao; Rao, Shaofei; Chang, Beibei; Wang, Xiaoshuang; Zhang, Kaidian; Hou, Xueliang; Zhu, Xueyi; Wu, Haijun; Tian, Zhaoxia; Zhao, Zhong; Yang, Chengwei; Huang, Tao

    2015-10-01

    Plant stem cells are hypersensitive to environmental hazards throughout their life cycle, but the mechanism by which plants safeguard stem cell homeostasis in response to environmental hazards is largely unknown. The homeodomain transcription factor WUSCHEL (WUS) protein maintains the stem cell pool in the shoot apical meristem of Arabidopsis. Here, we demonstrate that the translation of WUS mRNA is directed by an internal ribosomal entry site (IRES) located in the 5'-untranslated region. The AtLa1 protein, an RNA-binding factor, binds to the 5'-untranslated region and initiates the IRES-dependent translation of WUS mRNA. Knockdown of AtLa1 expression represses the WUS IRES-dependent translation and leads to the arrest of growth and development. The AtLa1 protein is mainly located in the nucleoplasm. However, environmental hazards promote the nuclear-to-cytoplasmic translocation of the AtLa1 protein, which further enhances the IRES-dependent translation of WUS mRNA. Genetic evidence indicates that the WUS protein increases the tolerance of the shoot apical meristem to environmental hazards. Based on these results, we conclude that the stem cell niche in Arabidopsis copes with environmental hazards by enhancing the IRES-dependent translation of WUS mRNA under the control of the AtLa1 protein. © 2015 John Wiley & Sons Ltd.

  15. A minimum structure of aminoglycosides that causes an initiation shift of trans-translation

    OpenAIRE

    Konno, Takayuki; Takahashi, Toshiharu; Kurita, Daisuke; Muto, Akira; Himeno, Hyouta

    2004-01-01

    Trans-translation is an unusual translation in which transfer-messenger RNA plays a dual function—as a tRNA and an mRNA—to relieve the stalled translation on the ribosome. It has been shown that paromomycin, a typical member of a 4,5-disubstituted class of aminoglycosides, causes a shift of the translation-resuming point on the tmRNA by −1 during trans-translation. To address the molecular basis of this novel effect, we examined the effects of various aminoglycosides that can bind around the ...

  16. The involvement of eukaryotic translation initiation factor 4E in extravillous trophoblast cell function.

    Science.gov (United States)

    Kitroser, E; Pomeranz, M; Epstein Shochet, G; Fishman, A; Drucker, L; Sadeh-Mestechkin, D; Lishner, M; Tartakover-Matalon, S

    2012-09-01

    Extravillous trophoblast cells (EVT) are major players in placental implantation. They differentiate in the villous cell column, invade to the uterus and remodel the uterine spiral arteries. Trophoblast and tumor cells have similar invasion mechanisms, share similar biochemical mediators (e.g. c-myc, MMP9) and growth-factors (e.g. VEGF). The mRNA of these proteins has extremely structured 5-UTR and their translation is highly dependent on eukaryotic-translation-initiation-factor-4E (eIF4E). Cancer cells have elevated eIF4E and are more vulnerable to its silencing than normal cells. We speculated that like cancer, trophoblast function is highly eIF4E dependent. Analyze eIF4E involvement in EVT differentiation and function. EIF4E levels were assessed in first-trimester human placentae and in placental explants before and after EVT differentiation. The effect of eIF4E knockdown (siRNA, ribavirin) on the phenotype of placental explant and EVT cell lines (HTR-8/SVNEO) was evaluated. Tested parameters included eIF4E and its target levels, migration, invasion, cell death, cell cycle and cell count. High eIF4E levels were found in cytotrophoblast and especially EVT cells during their differentiation in the villi, compared to other placental cell types. EIF4E silencing increased cell death and cell cycle arrest in placental explants and HTR-8/SVNEO cells. Although it induced EVT outgrowth in the placental explants, it reduced HTR-8/SVNEO motility, reflecting the importance of using ex vivo models that include an intact placental microenvironment in its original architecture. Our results suggest that eIF4E prevents final EVT differentiation and supports placental cell proliferation and survival. A balance between cell proliferation and differentiation is crucial for placental development and implantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Repeat associated non-ATG translation initiation: one DNA, two transcripts, seven reading frames, potentially nine toxic entities!

    Science.gov (United States)

    Pearson, Christopher E

    2011-03-01

    Diseases associated with unstable repetitive elements in the DNA, RNA, and amino acids have consistently revealed scientific surprises. Most diseases are caused by expansions of trinucleotide repeats, which ultimately lead to diseases like Huntington's disease, myotonic dystrophy, fragile X syndrome, and a series of spinocerebellar ataxias. These repeat mutations are dynamic, changing through generations and within an individual, and the repeats can be bi-directionally transcribed. Unsuspected modes of pathogenesis involve aberrant loss of protein expression; aberrant over-expression of non-mutant proteins; toxic-gain-of-protein function through expanded polyglutamine tracts that are encoded by expanded CAG tracts; and RNA-toxic-gain-of-function caused by transcripts harboring expanded CUG, CAG, or CGG tracts. A recent advance reveals that RNA transcripts with expanded CAG repeats can be translated in the complete absence of a starting ATG, and this Repeat Associated Non-ATG translation (RAN-translation) occurs across expanded CAG repeats in all reading frames (CAG, AGC, and GCA) to produce homopolymeric proteins of long polyglutamine, polyserine, and polyalanine tracts. Expanded CTG tracts expressing CUG transcripts also show RAN-translation occurring in all three frames (CUG, UGC, and GCU), to produce polyleucine, polycysteine, and polyalanine. These RAN-translation products can be toxic. Thus, one unstable (CAG)•(CTG) DNA can produce two expanded repeat transcripts and homopolymeric proteins with reading frames (the AUG-directed polyGln and six RAN-translation proteins), yielding a total of potentially nine toxic entities. The occurrence of RAN-translation in patient tissues expands our horizons of modes of disease pathogenesis. Moreover, since RAN-translation counters the canonical requirements of translation initiation, many new questions are now posed that must be addressed. This review covers RAN-translation and some of the pertinent questions.

  18. Repeat associated non-ATG translation initiation: one DNA, two transcripts, seven reading frames, potentially nine toxic entities!

    Directory of Open Access Journals (Sweden)

    Christopher E Pearson

    2011-03-01

    Full Text Available Diseases associated with unstable repetitive elements in the DNA, RNA, and amino acids have consistently revealed scientific surprises. Most diseases are caused by expansions of trinucleotide repeats, which ultimately lead to diseases like Huntington's disease, myotonic dystrophy, fragile X syndrome, and a series of spinocerebellar ataxias. These repeat mutations are dynamic, changing through generations and within an individual, and the repeats can be bi-directionally transcribed. Unsuspected modes of pathogenesis involve aberrant loss of protein expression; aberrant over-expression of non-mutant proteins; toxic-gain-of-protein function through expanded polyglutamine tracts that are encoded by expanded CAG tracts; and RNA-toxic-gain-of-function caused by transcripts harboring expanded CUG, CAG, or CGG tracts. A recent advance reveals that RNA transcripts with expanded CAG repeats can be translated in the complete absence of a starting ATG, and this Repeat Associated Non-ATG translation (RAN-translation occurs across expanded CAG repeats in all reading frames (CAG, AGC, and GCA to produce homopolymeric proteins of long polyglutamine, polyserine, and polyalanine tracts. Expanded CTG tracts expressing CUG transcripts also show RAN-translation occurring in all three frames (CUG, UGC, and GCU, to produce polyleucine, polycysteine, and polyalanine. These RAN-translation products can be toxic. Thus, one unstable (CAG•(CTG DNA can produce two expanded repeat transcripts and homopolymeric proteins with reading frames (the AUG-directed polyGln and six RAN-translation proteins, yielding a total of potentially nine toxic entities. The occurrence of RAN-translation in patient tissues expands our horizons of modes of disease pathogenesis. Moreover, since RAN-translation counters the canonical requirements of translation initiation, many new questions are now posed that must be addressed. This review covers RAN-translation and some of the pertinent

  19. Cap- and initiator tRNA-dependent initiation of TYMV polyprotein synthesis by ribosomes: Evaluation of the Trojan horse model for TYMV RNA translation

    OpenAIRE

    Matsuda, Daiki; Dreher, Theo W.

    2007-01-01

    Turnip yellow mosaic virus (TYMV) RNA directs the translation of two overlapping open reading frames. Competing models have been previously published to explain ribosome access to the downstream polyprotein cistron. The Trojan horse model, based on cell-free experiments, proposes noncanonical cap-independent initiation in which the 3′-terminal tRNA-like structure (TLS) functionally replaces initiator tRNA, and the valine bound to the TLS becomes cis-incorporated into viral protein. The initia...

  20. NATIONAL FRAMEWORK FOR THE SUSTAINABILITY OF HEALTH KNOWLEDGE TRANSLATION INITIATIVES IN UGANDA.

    Science.gov (United States)

    Basaza, Robert; Kinegyere, Alison; Mutatina, Boniface; Sewankambo, Nelson

    2018-01-01

    The aim of this study was to provide evidence about the design and implementation of policies for advancing the sustainability of knowledge translation (KT) initiatives and policies in Uganda's health system. We searched for and reviewed evidence about KT sustainability issues in Uganda, the impacts of options, barriers to implementing these options, and implementation strategies to address such barriers. In instances where the systematic reviews provided limited evidence, these were supplemented with relevant primary studies. Documents such as the government reports and unpublished literature were also included in the search. Key informant interviews and a policy dialogue were conducted, and an expert working group guided the study. The KT sustainability issues identified were: the absence of a specific unit within the health sector to coordinate and synthesize research; health worker not familiar with KT activities and not often used. Furthermore, Uganda lacks a mechanism to sustain its current national health frameworks or platforms, and does not have a system to ensure the sustained coordination of existing national health KT platforms. The policy options proposed include: (i) the identification of a KT champion; (ii) the establishment of an operational KT framework; (iii) KT capacity building for researchers and research users, as well as policy and decision makers. The sustainability of KT will be influenced by the prevailing context and concerns within healthcare both in Uganda and internationally. Furthermore, the availability of resources for KT advocacy, communication, and program design will impact on the sustainability of Uganda's KT activities.

  1. Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

    Directory of Open Access Journals (Sweden)

    Masayoshi Hashimoto

    2016-10-01

    Full Text Available The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant’s resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable. Moreover, recessive resistance may be acquired by a deficiency in a negative regulator of plant defense responses, possibly due to the autoactivation of defense signaling. Eukaryotic translation initiation factor (eIF 4E and eIF4G and their isoforms are the most widely exploited recessive resistance genes in several crop species, and they are effective against a subset of viral species. However, the establishment of efficient, recessive resistance-type antiviral control strategies against a wider range of plant viral diseases requires genetic resources other than eIF4Es. In this review, we focus on recent advances related to antiviral recessive resistance genes evaluated in model plants and several crop species. We also address the roles of next-generation sequencing and genome editing technologies in improving plant genetic resources for recessive resistance-based antiviral breeding in various crop species.

  2. The NS1 Protein from Influenza Virus Stimulates Translation Initiation by Enhancing Ribosome Recruitment to mRNAs.

    Science.gov (United States)

    Panthu, Baptiste; Terrier, Olivier; Carron, Coralie; Traversier, Aurélien; Corbin, Antoine; Balvay, Laurent; Lina, Bruno; Rosa-Calatrava, Manuel; Ohlmann, Théophile

    2017-10-27

    The non-structural protein NS1 of influenza A viruses exerts pleiotropic functions during infection. Among these functions, NS1 was shown to be involved in the control of both viral and cellular translation; however, the mechanism by which this occurs remains to be determined. Thus, we have revisited the role of NS1 in translation by using a combination of influenza infection, mRNA reporter transfection, and in vitro functional and biochemical assays. Our data show that the NS1 protein is able to enhance the translation of virtually all tested mRNAs with the exception of constructs bearing the Dicistroviruses Internal ribosome entry segment (IRESes) (DCV and CrPV), suggesting a role at the level of translation initiation. The domain of NS1 required for translation stimulation was mapped to the RNA binding amino-terminal motif of the protein with residues R38 and K41 being critical for activity. Although we show that NS1 can bind directly to mRNAs, it does not correlate with its ability to stimulate translation. This activity rather relies on the property of NS1 to associate with ribosomes and to recruit them to target mRNAs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Viral Genome-Linked Protein (VPg Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV.

    Directory of Open Access Journals (Sweden)

    Jie Zhu

    Full Text Available Rabbit hemorrhagic disease virus (RHDV, the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.

  4. Diffusion is capable of translating anisotropic apoptosis initiation into a homogeneous execution of cell death.

    LENUS (Irish Health Repository)

    Huber, Heinrich J

    2010-01-01

    ABSTRACT: BACKGROUND: Apoptosis is an essential cell death process throughout the entire life span of all metazoans and its deregulation in humans has been implicated in many proliferative and degenerative diseases. Mitochondrial outer membrane permeabilisation (MOMP) and activation of effector caspases are key processes during apoptosis signalling. MOMP can be subject to spatial coordination in human cancer cells, resulting in intracellular waves of cytochrome-c release. To investigate the consequences of these spatial anisotropies in mitochondrial permeabilisation on subsequent effector caspase activation, we devised a mathematical reaction-diffusion model building on a set of partial differential equations. RESULTS: Reaction-diffusion modelling suggested that even if strong spatial anisotropies existed during mitochondrial cytochrome c release, these would be eliminated by free diffusion of the cytosolic proteins that instantiate the apoptosis execution network. Experimentally, rapid sampling of mitochondrial permeabilisation and effector caspase activity in individual HeLa cervical cancer cells confirmed predictions of the reaction-diffusion model and demonstrated that the signalling network of apoptosis execution could efficiently translate spatial anisotropies in mitochondrial permeabilisation into a homogeneous effector caspase response throughout the cytosol. Further systems modelling suggested that a more than 10,000-fold impaired diffusivity would be required to maintain spatial anisotropies as observed during mitochondrial permeabilisation until the time effector caspases become activated. CONCLUSIONS: Multi-protein diffusion efficiently contributes to eliminating spatial asynchronies which are present during the initiation of apoptosis execution and thereby ensures homogeneous apoptosis execution throughout the entire cell body. For previously reported biological scenarios in which effector caspase activity was shown to be targeted selectively to

  5. Role of eukaryotic translation initiation factor 3a in bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Li, Xian-Wei; Wu, Yue-Han; Li, Xiao-Hui; Li, Dai; Du, Jie; Hu, Chang-Ping; Li, Yuan-Jian

    2015-02-15

    Eukaryotic translation initiation factor 3a (eIF3a) is a multifunctional protein and plays an important role in regulation of cellular function including proliferation and differentiation. In the present study, we tested the function of eIF3a in pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5mg/kg) in rats. Primary pulmonary fibroblasts were cultured for proliferation investigation by BrdU incorporation method and flow cytometry. The expression/level of eIF3a, TGF-β1, ERK1/2 and α-SMA were analyzed by ELISA, real-time PCR or western blot. Results showed that the expression of eIF3a was obviously increased in lungs of pulmonary fibrosis rats accompanied by up-regulation of α-SMA and collagens. In cultured pulmonary fibroblasts, application of exogenous TGF-β1 induced cell proliferation and differentiation concomitantly with up-regulation of eIF3a expression and ERK1/2 phosphorylation. The effects of TGF-β1-induced proliferation of fibroblasts and up-regulation of α-SMA were abolished by eIF3a siRNA. TGF-β1-induced eIF3a expression was reversed in the presence of PD98059, an inhibitor of ERK1/2. These findings suggest that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis by regulating pulmonary fibroblasts׳ function, and up-regulation of eIF3a induced by TGF-β1 is mediated via the ERK1/2 pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Eukaryotic translation initiation factor 5A2 promotes metabolic reprogramming in hepatocellular carcinoma cells.

    Science.gov (United States)

    Cao, Ting-Ting; Lin, Shu-Hai; Fu, Li; Tang, Zhi; Che, Chi-Ming; Zhang, Li-Yi; Ming, Xiao-Yan; Liu, Teng-Fei; Tang, Xu-Ming; Tan, Bin-Bin; Xiang, Di; Li, Feng; Chan, On-Yee; Xie, Dan; Cai, Zongwei; Guan, Xin-Yuan

    2017-01-01

    Reprogramming of intracellular metabolism is common in liver cancer cells. Understanding the mechanisms of cell metabolic reprogramming may present a new basis for liver cancer treatment. In our previous study, we reported that a novel oncogene eukaryotic translation initiation factor 5A2 (EIF5A2) promotes tumorigenesis under hypoxic condition. Here, we aim to investigate the role of EIF5A2 in cell metabolic reprogramming during hepatocellular carcinoma (HCC) development. In this study, we reported that the messenger RNA (mRNA) level of EIF5A2 was upregulated in 59 of 105 (56.2%) HCC clinical samples (P = 0.015), and EIF5A2 overexpression was significantly associated with shorter survival time of patients with HCC (P = 0.021). Ectopic expression of EIF5A2 in HCC cell lines significantly promoted cell growth and accelerated glucose utilization and lipogenesis rates. The high rates of glucose uptake and lactate secretion conferred by EIF5A2 revealed an abnormal activity of aerobic glycolysis in HCC cells. Several key enzymes involved in glycolysis including glucose transporter type 1 and 2, hexokinase 2, phosphofructokinase liver type, glyceraldehyde 3-phosphate dehydrogenase, pyruvate kinase M2 isoform, phosphoglycerate mutase 1 and lactate dehydrogenase A were upregulated by overexpression of EIF5A2. Moreover, EIF5A2 showed positive correlations with FASN and ACSS2, two key enzymes involved in the fatty acid de novo biosynthetic pathway, at both protein and mRNA levels in HCC. These results indicated that EIF5A2 may regulate fatty acid de novo biosynthesis by increasing the uptake of acetate. In conclusion, our findings demonstrate that EIF5A2 has a critical role in HCC cell metabolic reprogramming and may serve as a prominent novel therapeutic target for liver cancer treatment. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Innate immune evasion mediated by the Ambystoma tigrinum virus eukaryotic translation initiation factor 2alpha homologue.

    Science.gov (United States)

    Jancovich, James K; Jacobs, Bertram L

    2011-05-01

    Ranaviruses (family Iridoviridae, genus Ranavirus) are large, double-stranded DNA (dsDNA) viruses whose replication is restricted to ectothermic vertebrates. Many highly pathogenic members of the genus Ranavirus encode a homologue of the eukaryotic translation initiation factor 2α (eIF2α). Data in a heterologous vaccinia virus system suggest that the Ambystoma tigrinum virus (ATV) eIF2α homologue (vIF2αH; open reading frame [ORF] 57R) is involved in evading the host innate immune response by degrading the interferon-inducible, dsRNA-activated protein kinase, PKR. To test this hypothesis directly, the ATV vIF2αH gene (ORF 57R) was deleted by homologous recombination, and a selectable marker was inserted in its place. The ATVΔ57R virus has a small plaque phenotype and is 8-fold more sensitive to interferon than wild-type ATV (wtATV). Infection of fish cells with the ATVΔ57R virus leads to eIF2α phosphorylation, in contrast to infection with wtATV, which actively inhibits eIF2α phosphorylation. The inability of ATVΔ57R to prevent phosphorylation of eIF2α correlates with degradation of fish PKZ, an interferon-inducible enzyme that is closely related to mammalian PKR. In addition, salamanders infected with ATVΔ57R displayed an increased time to death compared to that of wtATV-infected salamanders. Therefore, in a biologically relevant system, the ATV vIF2αH gene acts as an innate immune evasion factor, thereby enhancing virus pathogenesis.

  8. Safeguards First Principles Initiative at the Nevada Test Site

    International Nuclear Information System (INIS)

    Johnson, Geneva

    2007-01-01

    The Material Control and Accountability (MC and A) program at the Nevada Test Site (NTS) was selected as a test bed for the Safeguards First Principles Initiative (SFPI). The implementation of the SFPI is evaluated using the system effectiveness model and the program is managed under an approved MC and A Plan. The effectiveness model consists of an evaluation of the critical elements necessary to detect, deter, and/or prevent the theft or diversion of Special Nuclear Material (SNM). The modeled results indicate that the MC and A program established under this variance is still effective, without creating unacceptable risk. Extensive performance testing is conducted through the duration of the pilot to ensure the protection system is effective and no material is at an unacceptable risk. The pilot was conducted from January 1, 2007, through May 30, 2007. This paper will discuss the following activities in association with SFPI: (1) Development of Timeline; (2) Crosswalk of DOE Order and SFPI; (3) Peer Review; (4) Deviation; (5) MC and A Plan and Procedure changes; (6) Changes implemented at NTS; (7) Training; and (8) Performance Test

  9. HuR and Ago2 Bind the Internal Ribosome Entry Site of Enterovirus 71 and Promote Virus Translation and Replication.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lin

    Full Text Available EV71 (enterovirus 71 RNA contains an internal ribosomal entry site (IRES that directs cap-independent initiation of translation. IRES-dependent translation requires the host's translation initiation factors and IRES-associated trans-acting factors (ITAFs. We reported recently that mRNA decay factor AUF1 is a negative-acting ITAF that binds IRES stem-loop II. We also reported that the small RNA-processing enzyme Dicer produces at least four small RNAs (vsRNAs from the EV71 IRES. One of these, vsRNA1, derived from IRES stem-loop II, reduces IRES activity and virus replication. Since its mechanism of action is unknown, we hypothesized that it might control association of ITAFs with the IRES. Here, we identified the mRNA stability factor HuR and the RISC subunit Argonaute 2 (Ago2 as two ITAFs that bind stem-loop II. In contrast to AUF1, HuR and Ago2 promote EV71 IRES activity and virus replication. In vitro RNA-binding assays revealed that vsRNA1 can alter association of Ago2, HuR, and AUF1 with stem-loop II. This presents a possible mechanism by which vsRNA1 could control viral translation and replication.

  10. Translation initiation factor AteIF(iso4E is involved in selective mRNA translation in Arabidopsis thaliana seedlings.

    Directory of Open Access Journals (Sweden)

    Ana Valeria Martínez-Silva

    Full Text Available One of the most regulated steps of translation initiation is the recruitment of mRNA by the translation machinery. In eukaryotes, this step is mediated by the 5'end cap-binding factor eIF4E bound to the bridge protein eIF4G and forming the eIF4F complex. In plants, different isoforms of eIF4E and eIF4G form the antigenically distinct eIF4F and eIF(iso4F complexes proposed to mediate selective translation. Using a microarray analysis of polyribosome- and non-polyribosome-purified mRNAs from 15 day-old Arabidopsis thaliana wild type [WT] and eIF(iso4E knockout mutant [(iso4E-1] seedlings we found 79 transcripts shifted from polyribosomes toward non-polyribosomes, and 47 mRNAs with the opposite behavior in the knockout mutant. The translationally decreased mRNAs were overrepresented in root-preferentially expressed genes and proteins from the endomembrane system, including several transporters such as the phosphate transporter PHOSPHATE1 (PHO1, Sucrose transporter 3 (SUC3, ABC transporter-like with ATPase activity (MRP11 and five electron transporters, as well as signal transduction-, protein modification- and transcription-related proteins. Under normal growth conditions, eIF(iso4E expression under the constitutive promoter 35 S enhanced the polyribosomal recruitment of PHO1 supporting its translational preference for eIF(iso4E. Furthermore, under phosphate deficiency, the PHO1 protein increased in the eIF(iso4E overexpressing plants and decreased in the knockout mutant as compared to wild type. In addition, the knockout mutant had larger root, whereas the 35 S directed expression of eIF(iso4E caused shorter root under normal growth conditions, but not under phosphate deficiency. These results indicate that selective translation mediated by eIF(iso4E is relevant for Arabidopsis root development under normal growth conditions.

  11. From what we know to what we do: lessons learned from the translational CLAHRC initiative in England.

    Science.gov (United States)

    Currie, Graeme; Lockett, Andy; El Enany, Nellie

    2013-10-01

    There exists a translation gap between academic research and clinical practice in health care systems. One policy-driven initiative to address the translation gap in England are the Collaborations for Leadership in Applied Health Research and Care (CLAHRCs), funded by the National Institute of Health Research (NIHR). These aim to bring together NHS organizations and universities to accelerate the translation of evidence-based innovation into clinical practice. Our aim was to draw out lessons for policy-makers regarding the mobilization of such initiatives. Qualitative semi-structured interviews with 174 participants across nine CLAHRCs plus in-depth case studies across four CLAHRCs. Those interviewed were staff who were central to the CLAHRCs including senior managers and directors, junior and senior academics, and health care practitioners. Social positions of the CLAHRC leaders, conceived as institutional entrepreneurs, together with the antecedent conditions for CLAHRC bids, had an impact on the vision for a CLAHRC. The process of envisioning encompassed diagnostic and prognostic framing. Within the envisioning process, the utilization of existing activities and established relationships in the CLAHRC bid influenced early mobilization. However, in some cases, it led to a translational 'lock in' towards established models regarding applied research. The CLAHRC experiment in England holds important lessons for policy-makers regarding how to address the translation gap. First, policy makers need to consider whether they set out a defined template for translational initiatives or whether variation is encouraged. We might expect a degree of learning from pilot activities within a CLAHRC that allows for greater clarity in the design of subsequent translational initiatives. Second, policy makers and practitioners need to understand the importance of both antecedent conditions and the social position of senior members of a CLAHRC (institutional entrepreneurs) leading

  12. Beyond initiation-limited translational bursting: the effects of burst size distributions on the stability of gene expression

    KAUST Repository

    Kuwahara, Hiroyuki

    2015-11-04

    A main source of gene expression noise in prokaryotes is translational bursting. It arises from efficient translation of mRNAs with low copy numbers, which makes the production of protein copies highly variable and pulsatile. To obtain analytical solutions, previous models to capture this noise source had to assume translation to be initiation-limited, representing the burst size by a specific type of a long-tail distribution. However, there is increasing evidence suggesting that the initiation is not the rate-limiting step in certain settings, for example, under stress conditions. Here, to overcome the limitations imposed by the initiation-limited assumption, we present a new analytical approach that can evaluate biological consequences of the protein burst size with a general distribution. Since our new model can capture the contribution of other factors to the translational noise, it can be used to analyze the effects of gene expression noise in more general settings. We used this new model to analytically analyze the connection between the burst size and the stability of gene expression processes in various settings. We found that the burst size with different distributions can lead to quantitatively and qualitatively different stability characteristics of protein abundance and can have non-intuitive effects. By allowing analysis of how the stability of gene expression processes changes based on various distributions of translational noise, our analytical approach is expected to enable deeper insights into the control of cell fate decision-making, the evolution of cryptic genetic variations, and fine-tuning of gene circuits.

  13. Evolutionary Conservation and Diversification of the Translation Initiation Apparatus in Trypanosomatids

    Directory of Open Access Journals (Sweden)

    Alexandra Zinoviev

    2012-01-01

    Full Text Available Trypanosomatids are ancient eukaryotic parasites that migrate between insect vectors and mammalian hosts, causing a range of diseases in humans and domestic animals. Trypanosomatids feature a multitude of unusual molecular features, including polycistronic transcription and subsequent processing by trans-splicing and polyadenylation. Regulation of protein coding genes is posttranscriptional and thus, translation regulation is fundamental for activating the developmental program of gene expression. The spliced-leader RNA is attached to all mRNAs. It contains an unusual hypermethylated cap-4 structure in its 5 end. The cap-binding complex, eIF4F, has gone through evolutionary changes in accordance with the requirement to bind cap-4. The eIF4F components in trypanosomatids are highly diverged from their orthologs in higher eukaryotes, and their potential functions are discussed. The cap-binding activity in all eukaryotes is a target for regulation and plays a similar role in trypanosomatids. Recent studies revealed a novel eIF4E-interacting protein, involved in directing stage-specific and stress-induced translation pathways. Translation regulation during stress also follows unusual regulatory cues, as the increased translation of Hsp83 following heat stress is driven by a defined element in the 3 UTR, unlike higher eukaryotes. Overall, the environmental switches experienced by trypanosomatids during their life cycle seem to affect their translational machinery in unique ways.

  14. Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma

    Science.gov (United States)

    Stenson, Mary J.; Maurer, Matthew J.; Wellik, Linda E.; Link, Brian; Hege, Kristen; Dogan, Ahmet; Sotomayor, Eduardo; Witzig, Thomas; Gupta, Mamta

    2015-01-01

    Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4EWT) but not cap-mutant eIF4E (eIF4Ecap mutant) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor CC214-1 reduced the level of the eIF4F complex by decreasing the cap bound fraction of eIF4G and increasing the levels of 4E-BP1. CC214-1 inhibited both the cap dependent and global protein translation. CC214-1 inhibited c-Myc, and cyclin D3 translation by decreasing polysomal fractions from lymphoma cells. Inhibition of eIF4E with shRNA further decreased the CC214-1 induced inhibition of the eIF4F complex, c-Myc, cyclin D3 translation, and colony formation. These studies demonstrate that the eIF4F complex is deregulated in aggressive lymphoma and that dual mTOR therapy has therapeutic potential in these patients. PMID:25839159

  15. Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma.

    Science.gov (United States)

    Demosthenous, Christos; Han, Jing Jing; Stenson, Mary J; Maurer, Matthew J; Wellik, Linda E; Link, Brian; Hege, Kristen; Dogan, Ahmet; Sotomayor, Eduardo; Witzig, Thomas; Gupta, Mamta

    2015-04-20

    Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4E(WT)) but not cap-mutant eIF4E (eIF4E(cap mutant)) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor CC214-1 reduced the level of the eIF4F complex by decreasing the cap bound fraction of eIF4G and increasing the levels of 4E-BP1. CC214-1 inhibited both the cap dependent and global protein translation. CC214-1 inhibited c-Myc, and cyclin D3 translation by decreasing polysomal fractions from lymphoma cells. Inhibition of eIF4E with shRNA further decreased the CC214-1 induced inhibition of the eIF4F complex, c-Myc, cyclin D3 translation, and colony formation. These studies demonstrate that the eIF4F complex is deregulated in aggressive lymphoma and that dual mTOR therapy has therapeutic potential in these patients.

  16. Found in Translation: International initiatives pursuing interleukin-1 blockade for treatment of acute Kawasaki Disease

    Science.gov (United States)

    Burns, Jane C.; Koné-Paut, Isabelle; Kuijpers, Taco; Shimizu, Chisato; Tremoulet, Adriana; Arditi, Moshe

    2016-01-01

    The decision to move forward with three clinical trials of IL-1 blockade for treatment of acute Kawasaki disease is a case study in translational science. These trials were born on the one hand from transcriptome studies of host response during the acute disease coupled with animal model investigations of key immune signaling pathways and, on the other hand, out of clinical desperation to intervene in patients with severe inflammation in the setting of acute Kawasaki disease. The convergence of laboratory science and clinical observations led to the clinical trials described here and serves as a model for how such observations can be translated into new therapies. PMID:27792871

  17. Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5 ' untranslated regions are efficiently translated in cells by a cap-dependent mechanism

    DEFF Research Database (Denmark)

    Belsham, Graham; Nielsen, Inge; Normann, Preben

    2008-01-01

    The initiation of protein synthesis on mRNAs within eukaryotic cells is achieved either by a 5' cap-dependent mechanism or through internal initiation directed by an internal ribosome entry site (IRES). Picornavirus IRES elements, located in the 59 untranslated region (5'UTR), contain extensive...... secondary structure and multiple upstream AUG codons. These features can be expected to inhibit cap-dependent initiation of translation. However, we have now shown that certain mutant hepatitis C virus-like picornavirus IRES elements (from porcine teschovirus-1 and avian encephalomyelitis virus), which...... are unable to direct internal initiation, are not significant barriers to efficient translation of capped monocistronic mRNAs that contain these defective elements within their 5'UTRs. Moreover, the translation of these mRNAs is highly sensitive to the expression of an enterovirus 2A protease (which induces...

  18. Determine the Impact of Novel BRCA1 Translation Start Sites on Therapy Resistance in Ovarian Cancer

    Science.gov (United States)

    2016-07-01

    loading control. (E) CRISPR /Cas9 targeting sg_GFP, sg_exon 2 (E2), or sg_exon 11 (E11) in MDA-MB-231 and SUM1315MO2 RR1 cells. Western blot analyses...exogenous BRCA1–Met-297 cells (Figure 2D). To confirm that Met-297 was the initiating start site, we used CRISPR /Cas9 gene editing to disrupt the BRCA1...analyzed using FlowJo software. CRISPR /Cas9 gene editing. The CRISPR /Cas9 system was a gift of Christoph Seeger (Fox Chase Cancer Center) (57). MDA-MB

  19. Site initialization, recovery, and back-up in a distributed database system

    International Nuclear Information System (INIS)

    Attar, R.; Bernstein, P.A.; Goodman, N.

    1982-01-01

    Site initialization is the problem of integrating a new site into a running distributed database system (DDBS). Site recovery is the problem of integrating an old site into a DDBS when the site recovers from failure. Site backup is the problem of creating a static backup copy of a database for archival or query purposes. We present an algorithm that solves the site initialization problem. By modifying the algorithm slightly, we get solutions to the other two problems as well. Our algorithm exploits the fact that a correct DDBS must run a serializable concurrency control algorithm. Our algorithm relies on the concurrency control algorithm to handle all inter-site synchronization

  20. La Autoantigen Induces Ribosome Binding Protein 1 (RRBP1 Expression through Internal Ribosome Entry Site (IRES-Mediated Translation during Cellular Stress Condition

    Directory of Open Access Journals (Sweden)

    Wenqing Gao

    2016-07-01

    Full Text Available The function of ribosome binding protein 1 (RRBP1 is regulating the transportation and secretion of some intracellular proteins in mammalian cells. Transcription of RRBP1 is induced by various cytokines. However, few studies focused on the process of RRPB1 mRNA translation. The RRBP1 mRNA has a long 5′ untranslated region that potentially formed a stable secondary structure. In this study, we show that the 5′ UTR of RRBP1 mRNA contains an internal ribosome entry site (IRES. Moreover, the RRBP1 expression is induced by chemotherapeutic drug paclitaxel or adriamycin in human hepatocellular carcinoma cells and accompanied with the increased expression of La autoantigen (La, which binds to RRBP1 IRES element and facilitates translation initiation. Interestingly, we found IRES-mediated RRBP1 translation is also activated during serum-starvation condition which can induce cytoplasmic localization of La. After mapping the entire RRBP1 5′ UTR, we determine the core IRES activity is located between nt-237 and -58. Furthermore, two apical GARR loops within the functional RRBP1 IRES elements may be important for La binding. These results strongly suggest an important role for IRES-dependent translation of RRBP1 mRNA in hepatocellular carcinoma cells during cellular stress conditions.

  1. Eukaryotic translation initiation factor 4G (eIF4G) coordinates interactions with eIF4A, eIF4B, and eIF4E in binding and translation of the barley yellow dwarf virus 3' cap-independent translation element (BTE).

    Science.gov (United States)

    Zhao, Pei; Liu, Qiao; Miller, W Allen; Goss, Dixie J

    2017-04-07

    Barley yellow dwarf virus RNA, lacking a 5' cap and a 3' poly(A) tail, contains a cap-independent translation element (BTE) in the 3'-untranslated region that interacts with host translation initiation factor eIF4G. To determine how eIF4G recruits the mRNA, three eIF4G deletion mutants were constructed: (i) eIF4G601-1196, containing amino acids 601-1196, including the putative BTE-binding region, and binding domains for eIF4E, eIF4A, and eIF4B; (ii) eIF4G601-1488, which contains an additional C-terminal eIF4A-binding domain; and (iii) eIF4G742-1196, which lacks the eIF4E-binding site. eIF4G601-1196 binds BTE tightly and supports efficient translation. The helicase complex, consisting of eIF4A, eIF4B, and ATP, stimulated BTE binding with eIF4G601-1196 but not eIF4G601-1488, suggesting that the eIF4A binding domains may serve a regulatory role, with the C-terminal binding site having negative effects. eIF4E binding to eIF4G601-1196 induced a conformational change, significantly increasing the binding affinity to BTE. A comparison of the binding of eIF4G deletion mutants with BTEs containing mutations showed a general correlation between binding affinity and ability to facilitate translation. In summary, these results reveal a new role for the helicase complex in 3' cap-independent translation element-mediated translation and show that the functional core domain of eIF4G plus an adjacent probable RNA-binding domain mediate translation initiation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Instrument translation and initial psychometric evaluation of the Danish Body Image Quality of Life Inventory

    DEFF Research Database (Denmark)

    Rasmussen, Trine Bernholdt; Berg, Selina Kikkenborg; Dixon, Jane

    2016-01-01

    RATIONALE AND OBJECTIVES: Negative body perception has been reported in a number of patient populations. No instrument in Danish for measuring body image-related concerns has been available. Without such an instrument, understanding of the phenomenon in Danish-speaking populations is limited....... The purpose of the study was thus to translate and validate a Danish version of the Body Image Quality of Life Inventory (BIQLI), in order to obtain a valid instrument applicable for healthcare research. METHODS: The study consisted of two phases: (i) instrument adaptation, including forward and back...... translation, expert committee comparisons and cognitive interviewing, and (ii) empirical testing of the Danish version (BIQLI-DA) with subsequent psychometric evaluation. Hypothesised correlations to other measures, including body mass index (BMI), Medical Outcome Short Form-8 (SF-8), Patient Health...

  3. Tunable translational control using site-specific unnatural amino acid incorporation in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Yusuke Kato

    2015-04-01

    Full Text Available Translation of target gene transcripts in Escherichia coli harboring UAG amber stop codons can be switched on by the amber-codon-specific incorporation of an exogenously supplied unnatural amino acid, 3-iodo-L-tyrosine. Here, we report that this translational switch can control the translational efficiency at any intermediate magnitude by adjustment of the 3-iodo-L-tyrosine concentration in the medium, as a tunable translational controller. The translational efficiency of a target gene reached maximum levels with 10−5 M 3-iodo-L-tyrosine, and intermediate levels were observed with suboptimal concentrations (approximately spanning a 2-log10 concentration range, 10−7–10−5 M. Such intermediate-level expression was also confirmed in individual bacteria.

  4. In vivo deletion analysis of the architecture of a multiprotein complex of translation initiation factors

    Czech Academy of Sciences Publication Activity Database

    Nielsen, K. H.; Valášek, Leoš

    2007-01-01

    Roč. 431, - (2007), s. 15-32 ISSN 0076-6879 Grant - others:US(US) Wellcome Trust Grant 076456/Z/05/Z; US(US) R01 TW007271 Institutional research plan: CEZ:AV0Z50200510 Source of funding: N - neverejné zdroje ; N - neverejné zdroje Keywords : translation * multiprotein complex * eif3 Subject RIV: EE - Microbiology, Virology Impact factor: 2.122, year: 2007

  5. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    International Nuclear Information System (INIS)

    Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio; Hazemann, Isabelle; Jenner, Lasse; Urzhumtsev, Alexandre; Gualerzi, Claudio O.; Klaholz, Bruno P.

    2013-01-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue

  6. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    Energy Technology Data Exchange (ETDEWEB)

    Simonetti, Angelita [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Marzi, Stefano [Architecture et Réactivité de l’ARN, UPR 9002 CNRS, IBMC (Institute of Molecular and Cellular Biology), 15 Rue R. Descartes, 67084 Strasbourg, France, Université de Strasbourg, 67000 Strasbourg (France); Fabbretti, Attilio [University of Camerino, 62032 Camerino (Monaco) (Italy); Hazemann, Isabelle; Jenner, Lasse [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale -INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Urzhumtsev, Alexandre [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Gualerzi, Claudio O. [University of Camerino, 62032 Camerino (Monaco) (Italy); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France)

    2013-06-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.

  7. Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation

    Directory of Open Access Journals (Sweden)

    Miller Eric S

    2010-12-01

    Full Text Available Abstract Over 50 years of biological research with bacteriophage T4 includes notable discoveries in post-transcriptional control, including the genetic code, mRNA, and tRNA; the very foundations of molecular biology. In this review we compile the past 10 - 15 year literature on RNA-protein interactions with T4 and some of its related phages, with particular focus on advances in mRNA decay and processing, and on translational repression. Binding of T4 proteins RegB, RegA, gp32 and gp43 to their cognate target RNAs has been characterized. For several of these, further study is needed for an atomic-level perspective, where resolved structures of RNA-protein complexes are awaiting investigation. Other features of post-transcriptional control are also summarized. These include: RNA structure at translation initiation regions that either inhibit or promote translation initiation; programmed translational bypassing, where T4 orchestrates ribosome bypass of a 50 nucleotide mRNA sequence; phage exclusion systems that involve T4-mediated activation of a latent endoribonuclease (PrrC and cofactor-assisted activation of EF-Tu proteolysis (Gol-Lit; and potentially important findings on ADP-ribosylation (by Alt and Mod enzymes of ribosome-associated proteins that might broadly impact protein synthesis in the infected cell. Many of these problems can continue to be addressed with T4, whereas the growing database of T4-related phage genome sequences provides new resources and potentially new phage-host systems to extend the work into a broader biological, evolutionary context.

  8. Initiating Events for Multi-Reactor Plant Sites

    Energy Technology Data Exchange (ETDEWEB)

    Muhlheim, Michael David [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Flanagan, George F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Poore, III, Willis P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-09-01

    Inherent in the design of modular reactors is the increased likelihood of events that initiate at a single reactor affecting another reactor. Because of the increased level of interactions between reactors, it is apparent that the Probabilistic Risk Assessments (PRAs) for modular reactor designs need to specifically address the increased interactions and dependencies.

  9. Deep Proteome Coverage Based on Ribosome Profiling Aids Mass Spectrometry-based Protein and Peptide Discovery and Provides Evidence of Alternative Translation Products and Near-cognate Translation Initiation Events*

    Science.gov (United States)

    Menschaert, Gerben; Van Criekinge, Wim; Notelaers, Tineke; Koch, Alexander; Crappé, Jeroen; Gevaert, Kris; Van Damme, Petra

    2013-01-01

    An increasing number of studies involve integrative analysis of gene and protein expression data, taking advantage of new technologies such as next-generation transcriptome sequencing and highly sensitive mass spectrometry (MS) instrumentation. Recently, a strategy, termed ribosome profiling (or RIBO-seq), based on deep sequencing of ribosome-protected mRNA fragments, indirectly monitoring protein synthesis, has been described. We devised a proteogenomic approach constructing a custom protein sequence search space, built from both Swiss-Prot- and RIBO-seq-derived translation products, applicable for MS/MS spectrum identification. To record the impact of using the constructed deep proteome database, we performed two alternative MS-based proteomic strategies as follows: (i) a regular shotgun proteomic and (ii) an N-terminal combined fractional diagonal chromatography (COFRADIC) approach. Although the former technique gives an overall assessment on the protein and peptide level, the latter technique, specifically enabling the isolation of N-terminal peptides, is very appropriate in validating the RIBO-seq-derived (alternative) translation initiation site profile. We demonstrate that this proteogenomic approach increases the overall protein identification rate 2.5% (e.g. new protein products, new protein splice variants, single nucleotide polymorphism variant proteins, and N-terminally extended forms of known proteins) as compared with only searching UniProtKB-SwissProt. Furthermore, using this custom database, identification of N-terminal COFRADIC data resulted in detection of 16 alternative start sites giving rise to N-terminally extended protein variants besides the identification of four translated upstream ORFs. Notably, the characterization of these new translation products revealed the use of multiple near-cognate (non-AUG) start codons. As deep sequencing techniques are becoming more standard, less expensive, and widespread, we anticipate that mRNA sequencing

  10. Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative

    Directory of Open Access Journals (Sweden)

    Straus Sharon E

    2011-12-01

    Full Text Available Abstract Background Globally, healthcare systems are attempting to optimize quality of care. This challenge has resulted in the development of implementation science or knowledge translation (KT and the resulting need to build capacity in both the science and practice of KT. Findings We are attempting to meet these challenges through the creation of a national training initiative in KT. We have identified core competencies in this field and have developed a series of educational courses and materials for three training streams. We report the outline for this approach and the progress to date. Conclusions We have prepared a strategy to develop, implement, and evaluate a national training initiative to build capacity in the science and practice of KT. Ultimately through this initiative, we hope to meet the capacity demand for KT researchers and practitioners in Canada that will lead to improved care and a strengthened healthcare system.

  11. Novel RNA-binding protein P311 binds eukaryotic translation initiation factor 3 subunit b (eIF3b) to promote translation of transforming growth factor β1-3 (TGF-β1-3).

    Science.gov (United States)

    Yue, Michael M; Lv, Kaosheng; Meredith, Stephen C; Martindale, Jennifer L; Gorospe, Myriam; Schuger, Lucia

    2014-12-05

    P311, a conserved 8-kDa intracellular protein expressed in brain, smooth muscle, regenerating tissues, and malignant glioblastomas, represents the first documented stimulator of TGF-β1-3 translation in vitro and in vivo. Here we initiated efforts to define the mechanism underlying P311 function. PONDR® (Predictor Of Naturally Disordered Regions) analysis suggested and CD confirmed that P311 is an intrinsically disordered protein, therefore requiring an interacting partner to acquire tertiary structure and function. Immunoprecipitation coupled with mass spectroscopy identified eIF3 subunit b (eIF3b) as a novel P311 binding partner. Immunohistochemical colocalization, GST pulldown, and surface plasmon resonance studies revealed that P311-eIF3b interaction is direct and has a Kd of 1.26 μm. Binding sites were mapped to the non-canonical RNA recognition motif of eIF3b and a central 11-amino acid-long region of P311, here referred to as eIF3b binding motif. Disruption of P311-eIF3b binding inhibited translation of TGF-β1, 2, and 3, as indicated by luciferase reporter assays, polysome fractionation studies, and Western blot analysis. RNA precipitation assays after UV cross-linking and RNA-protein EMSA demonstrated that P311 binds directly to TGF-β 5'UTRs mRNAs through a previously unidentified RNA recognition motif-like motif. Our results demonstrate that P311 is a novel RNA-binding protein that, by interacting with TGF-βs 5'UTRs and eIF3b, stimulates the translation of TGF-β1, 2, and 3. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Core Promoter Plasticity Between Maize Tissues and Genotypes Contrasts with Predominance of Sharp Transcription Initiation Sites.

    Science.gov (United States)

    Mejía-Guerra, María Katherine; Li, Wei; Galeano, Narmer F; Vidal, Mabel; Gray, John; Doseff, Andrea I; Grotewold, Erich

    2015-12-01

    Core promoters are crucial for gene regulation, providing blueprints for the assembly of transcriptional machinery at transcription start sites (TSSs). Empirically, TSSs define the coordinates of core promoters and other regulatory sequences. Thus, experimental TSS identification provides an essential step in the characterization of promoters and their features. Here, we describe the application of CAGE (cap analysis of gene expression) to identify genome-wide TSSs used in root and shoot tissues of two maize (Zea mays) inbred lines (B73 and Mo17). Our studies indicate that most TSS clusters are sharp in maize, similar to mice, but distinct from Arabidopsis thaliana, Drosophila melanogaster, or zebra fish, in which a majority of genes have broad-shaped TSS clusters. We established that ∼38% of maize promoters are characterized by a broader TATA-motif consensus, and this motif is significantly enriched in genes with sharp TSSs. A noteworthy plasticity in TSS usage between tissues and inbreds was uncovered, with ∼1500 genes showing significantly different dominant TSSs, sometimes affecting protein sequence by providing alternate translation initiation codons. We experimentally characterized instances in which this differential TSS utilization results in protein isoforms with additional domains or targeted to distinct subcellular compartments. These results provide important insights into TSS selection and gene expression in an agronomically important crop. © 2015 American Society of Plant Biologists. All rights reserved.

  13. Breaking Down Silos: Mapping Growth of Cross‐Disciplinary Collaboration in a Translational Science Initiative

    Science.gov (United States)

    Luke, Douglas A.; Carothers, Bobbi J.; Dhand, Amar; Bell, Ryan A.; Moreland‐Russell, Sarah; Sarli, Cathy C.; Evanoff, Bradley A.

    2014-01-01

    Abstract The importance of transdisciplinary collaboration is growing, though not much is known about how to measure collaboration patterns. The purpose of this paper is to present multiple ways of mapping and evaluating the growth of cross‐disciplinary partnerships over time. Social network analysis was used to examine the impact of a Clinical and Translational Science Award (CTSA) on collaboration patterns. Grant submissions from 2007 through 2010 and publications from 2007 through 2011 of Institute of Clinical and Translational Sciences (ICTS) members were examined. A Cohort Model examining the first‐year ICTS members demonstrated an overall increase in collaborations on grants and publications, as well as an increase in cross‐discipline collaboration as compared to within‐discipline. A Growth Model that included additional members over time demonstrated the same pattern for grant submissions, but a decrease in cross‐discipline collaboration as compared to within‐discipline collaboration for publications. ICTS members generally became more cross‐disciplinary in their collaborations during the CTSA. The exception of publications for the Growth Model may be due to the time lag between funding and publication, as well as pressure for younger scientists to publish in their own fields. Network analysis serves as a valuable tool for evaluating changes in scientific collaboration. PMID:25472908

  14. The Ezrin Metastatic Phenotype Is Associated with the Initiation of Protein Translation

    Directory of Open Access Journals (Sweden)

    Joseph W. Briggs

    2012-04-01

    Full Text Available We previously associated the cytoskeleton linker protein, Ezrin, with the metastatic phenotype of pediatric sarcomas, including osteosarcoma and rhabdomyosarcoma. These studies have suggested that Ezrin contributes to the survival of cancer cells after their arrival at secondary metastatic locations. To better understand this role in metastasis, we undertook two noncandidate analyses of Ezrin function including a microarray subtraction of high-and low-Ezrin-expressing cells and a proteomic approach to identify proteins that bound the N-terminus of Ezrin in tumor lysates. Functional analyses of these data led to a novel and unifying hypothesis that Ezrin contributes to the efficiency of metastasis through regulation of protein translation. In support of this hypothesis, we found Ezrin to be part of the ribonucleoprotein complex to facilitate the expression of complex messenger RNA in cells and to bind with poly A binding protein 1 (PABP1; PABPC1. The relevance of these findings was supported by our identification of Ezrin and components of the translational machinery in pseudopodia of highly metastatic cells during the process of cell invasion. Finally, two small molecule inhibitors recently shown to inhibit the Ezrin metastatic phenotype disrupted the Ezrin/PABP1 association. Taken together, these results provide a novel mechanistic basis by which Ezrin may contribute to metastasis.

  15. Sepsis and mechnaical ventilation restrain translation initiation in skeletal muscle by inducing AMPK-associated TSC[2] restriction of mTOR signaling in pigs

    Science.gov (United States)

    In skeletal muscle, AMP-activated protein kinase (AMPK) acts as a cellular energy sensor of AMP: ATP and modulates translation by repressing mammalian target of rapamycin (mTOR) activation. Endotoxin (LPS)-induced sepsis reduces muscle protein synthesis by blunting translation initiation. We hypothe...

  16. Mars Science Laboratory: Mission, Landing Site, and Initial Results

    Science.gov (United States)

    Grotzinger, John; Blake, D.; Crisp, J.; Edgett, K.; Gellert, R.; Gomez-Elvira, J.; Hassler, D.; Mahaffy, P.; Malin, M.; Meyer, M.; Mitrofanov, I.; Vasavada, A.; Wiens, R.

    2012-10-01

    Scheduled to land on August 5, 2012, the Mars Science Laboratory rover, Curiosity, will conduct an investigation of modern and ancient environments. Recent mission results will be discussed. Curiosity has a lifetime of at least one Mars year ( 23 months), and drive capability of at least 20 km. The MSL science payload was specifically assembled to assess habitability and includes a gas chromatograph-mass spectrometer and gas analyzer that will search for organic carbon in rocks, regolith fines, and the atmosphere; an x-ray diffractometer that will determine mineralogical diversity; focusable cameras that can image landscapes and rock/regolith textures in natural color; an alpha-particle x-ray spectrometer for in situ determination of rock and soil chemistry; a laser-induced breakdown spectrometer to remotely sense the chemical composition of rocks and minerals; an active neutron spectrometer designed to search for water in rocks/regolith; a weather station to measure modern-day environmental variables; and a sensor designed for continuous monitoring of background solar and cosmic radiation. The 155-km diameter Gale Crater was chosen as Curiosity’s field site based on several attributes: an interior mound of ancient flat-lying strata extending almost 5 km above the elevation of the landing site; the lower few hundred meters of the mound show a progression with relative age from clay-bearing to sulfate-bearing strata, separated by an unconformity from overlying likely anhydrous strata; the landing ellipse is characterized by a mixture of alluvial fan and high thermal inertia/high albedo stratified deposits; and a number of stratigraphically/geomorphically distinct fluvial features. Gale’s regional context and strong evidence for a progression through multiple potentially habitable environments, represented by a stratigraphic record of extraordinary extent, insure preservation of a rich record of the environmental history of early Mars.

  17. [Molecular mechanisms of protein biosynthesis initiation--biochemical and biomedical implications of a new model of translation enhanced by the RNA hypoxia response element (rHRE)].

    Science.gov (United States)

    Master, Adam; Nauman, Alicja

    2014-01-01

    Translation initiation is a key rate-limiting step in cellular protein synthesis. A cap-dependent initiation is the most effective mechanism of the translation. However, some physiological (mitosis) and pathological (oxidative stress) processes may switch the classic mechanism to an alternative one that is regulated by an mRNA element such as IRES, uORF, IRE, CPE, DICE, AURE or CITE. A recently discovered mechanism of RNA hypoxia response element (rHRE)-dependent translation initiation, may change the view of oxygen-regulated translation and give a new insight into unexplained biochemical processes. Hypoxia is one of the better-known factors that may trigger an alternative mechanism of the translation initiation. Temporal events of oxygen deficiency within tissues and organs may activate processes such as angiogenesis, myogenesis, regeneration, wound healing, and may promote an adaptive response in cardiovascular and neurodegenerative diseases. On the other hand, growth of solid tumors may be accompanied by cyclic hypoxia, allowing for synthesis of proteins required for further progression of cancer cells. This paper provides a review of current knowledge on translational control in the context of alternative models of translation initiation.

  18. Public health implications: translation into diabetes prevention initiatives--four-level public health concept.

    Science.gov (United States)

    Schwarz, Peter E H

    2011-03-01

    Many countries are struggling to meet the health care needs of a rapidly growing number of individuals with common chronic illnesses, especially diabetes mellitus. Incorporating the evidence from prevention trials into clinical practice represents one of the major challenges for public health, and the medical community is still learning how this can best be achieved at a population level. A 4-level public health initiative has been initiated that provides guidance for establishing milestones and strategies for such a program. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Neural Network Prediction of Translation Initiation Sites in Eukaryotes: Perspectives for EST and Genome analysis

    DEFF Research Database (Denmark)

    Pedersen, Anders Gorm; Nielsen, Henrik

    1997-01-01

    . In this paper, we employ artificial neural networks to predict which AUG triplet in an mRNA sequence is the start codon. The trained networks correctly classified 88% of Arabidopsis and 85% of vertebrate AUG triplets. We find that our trained neural networks use a combination of local start codon context...... and global sequence information. Furthermore, analysis of false predictions shows that AUGs in frame with the actual start codon are more frequently selected than out-of-frame AUGs, suggesting that our nteworks use reading frame detection. A number of conflicts between neural network predictions and database...

  20. Alternative DFN model based on initial site investigations at Simpevarp

    Energy Technology Data Exchange (ETDEWEB)

    Darcel, C. [Itasca Consultants, Ecully (France); Davy, S.A.P.; Bour, O.; Dreuzy, J.R. de [Geosciences, Rennes (France)

    2004-12-01

    In this report, we provide a first-order analysis of the fracture network at the Simpevarp site. The first order model is the fracture distribution function, noted, fdf, which provides the number of fractures having a given orientation and length, and belonging to a given volume of observation. The first-order distribution model does not describe higher-order correlation between fracture parameters, such as a possible dependency of fracture length distribution with orientations. We also check that most of the information is contained in this 1st-order distribution model, and that dividing the fracture networks into different sets do not bring a better statistical description. The fracture distribution function contains 3 main distributions: the probability distribution of fracture orientations, the dependency on the size of the sampling domain that may exhibit non-trivial scaling in case of fractal correlations, and the fracture-length density distribution, which appears to be well fitted by a power law. The main scaling parameters are the fractal dimension and the power-law exponent of the fracture length distribution. The former was found to be about equal to the embedding dimension, meaning that fractal correlations are weak and can be neglected in the DFN model. The latter depends on geology, that is either lithology or grain size, with values that ranges from 3.2 for granite-like outcrops to 4 for diorite or monzodiorite outcrops, as well as for the large-scale lineament maps. When analyzing the consistency of the different datasets (boreholes, outcrops, lineament maps), we found that two different DFNs can be described: the first one is derived from the fdf of the outcrop with fine-grained size lithology, and is valid across all scales investigated in this study, from the highly-fractured cores to large-scale maps; the second one is derived from the fdf of the outcrops with coarse-grained size lithology, and is found consistent with cores that present the

  1. P1 plasmid replication: initiator sequestration is inadequate to explain control by initiator-binding sites.

    OpenAIRE

    Pal, S K; Chattoraj, D K

    1988-01-01

    The unit-copy plasmid replicon mini-P1 consists of an origin, a gene for an initiator protein, RepA, and a control locus, incA. Both the origin and the incA locus contain repeat sequences that bind RepA. It has been proposed that the incA repeats control replication by sequestering the rate-limiting RepA initiator protein. Here we show that when the concentration of RepA was increased about fourfold beyond its normal physiological level from an inducible source in trans, the copy number of a ...

  2. Heat shock protein 70 promotes coxsackievirus B3 translation initiation and elongation via Akt-mTORC1 pathway depending on activation of p70S6K and Cdc2.

    Science.gov (United States)

    Wang, Fengping; Qiu, Ye; Zhang, Huifang M; Hanson, Paul; Ye, Xin; Zhao, Guangze; Xie, Ronald; Tong, Lei; Yang, Decheng

    2017-07-01

    We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of internal ribosome entry site trans-acting factor lupus autoantigen protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor. Second, we found that Hsp70 increased CVB3 VP1 translation by enhancing translation elongation. This was mediated by the Akt-mammalian target of rapamycin complex 1 signal cascade, which led to the activation of eukaryotic elongation factor 2 via p70S6K- and cell division cycle protein 2 homolog (Cdc2)-mediated phosphorylation and inactivation of eukaryotic elongation factor 2 kinase. We also determined the position of Cdc2 in this signal pathway, indicating that Cdc2 is regulated by mammalian target of rapamycin complex 1. This signal transduction pathway was validated using a number of specific pharmacological inhibitors, short interfering RNAs (siRNAs) and a dominant negative Akt plasmid. Because Hsp70 is a central component of the cellular network of molecular chaperones enhancing viral replication, these data may provide new strategies to limit this viral infection. © 2017 John Wiley & Sons Ltd.

  3. A blended knowledge translation initiative to improve colorectal cancer staging [ISRCTN56824239

    Directory of Open Access Journals (Sweden)

    Ryan David P

    2006-01-01

    Full Text Available Abstract Background A significant gap has been documented between best practice and the actual practice of surgery. Our group identified that colorectal cancer staging in Ontario was suboptimal and subsequently developed a knowledge translation strategy using the principles of social marketing and the influence of expert and local opinion leaders for colorectal cancer. Methods/Design Opinion leaders were identified using the Hiss methodology. Hospitals in Ontario were cluster-randomized to one of two intervention arms. Both groups were exposed to a formal continuing medical education session given by the expert opinion leader for colorectal cancer. In the treatment group the local Opinion Leader for colorectal cancer was detailed by the expert opinion leader for colorectal cancer and received a toolkit. Forty-two centres agreed to have the expert opinion leader for colorectal cancer come and give a formal continuing medical education session that lasted between 50 minutes and 4 hours. No centres refused the intervention. These sessions were generally well attended by most surgeons, pathologists and other health care professionals at each centre. In addition all but one of the local opinion leaders for colorectal cancer met with the expert opinion leader for colorectal cancer for the academic detailing session that lasted between 15 and 30 minutes. Discussion We have enacted a unique study that has attempted to induce practice change among surgeons and pathologists using an adapted social marketing model that utilized the influence of both expert and local opinion leaders for colorectal cancer in a large geographic area with diverse practice settings.

  4. GUG is an efficient initiation codon to translate the human mitochondrial ATP6 gene

    Czech Academy of Sciences Publication Activity Database

    Dubot, A.; Godinot, C.; Dumur, V.; Sablonniere, B.; Stojkovic, T.; Cuisset, J. M.; Vojtíšková, Alena; Pecina, Petr; Ješina, Pavel; Houštěk, Josef

    2004-01-01

    Roč. 313, č. 3 (2004), s. 687-693 ISSN 0006-291X R&D Projects: GA MŠk LN00A079; GA MZd NE6533 Grant - others:Fondation Jerome LeJeune(XE) Grant project; GA-(FR) CNRS; GA-(FR) Rhone Alpes Region Institutional research plan: CEZ:AV0Z5011922 Keywords : GUG initiation codon * ATP6 gene * mitochondrial diseases Subject RIV: CE - Biochemistry Impact factor: 2.904, year: 2004

  5. Site Characteristics Influencing the Translation of Clinical Research Into Clinical Practice

    DEFF Research Database (Denmark)

    Smed, Marie; Getz, Kenneth A.

    2014-01-01

    Investigative sites participating in clinical trials play an instrumental role in aiding market adoption. Site experiences in clinical research help physician investigators and research professionals gain familiarity with and exposure to investigational treatments. This knowledge may be passed...... on to sponsor companies and may ultimately assist in positioning new products and driving commercialization success. This study evaluates site characteristics that influence the acquisition and sharing of knowledge gained through clinical trial experience. The impact of 2 central site characteristics...

  6. Lentivirus-mediated knockdown of eukaryotic translation initiation factor 3 subunit D inhibits proliferation of HCT116 colon cancer cells.

    Science.gov (United States)

    Yu, Xiaojun; Zheng, Bo'an; Chai, Rui

    2014-12-12

    Dysregulation of protein synthesis is emerging as a major contributory factor in cancer development. eIF3D (eukaryotic translation initiation factor 3 subunit D) is one member of the eIF3 (eukaryotic translation initiation factor 3) family, which is essential for initiation of protein synthesis in eukaryotic cells. Acquaintance with eIF3D is little since it has been identified as a dispensable subunit of eIF3 complex. Recently, eIF3D was found to embed somatic mutations in human colorectal cancers, indicating its importance for tumour progression. To further probe into its action in colon cancer, we utilized lentivirus-mediated RNA interference to knock down eIF3D expression in one colon cancer cell line HCT116. Knockdown of eIF3D in HCT116 cells significantly inhibited cell proliferation and colony formation in vitro. Flow cytometry analysis indicated that depletion of eIF3D led to cell-cycle arrest in the G2/M phase, and induced an excess accumulation of HCT116 cells in the sub-G1 phase representing apoptotic cells. Signalling pathways responsible for cell growth and apoptosis have also been found altered after eIF3D silencing, such as AMPKα (AMP-activated protein kinase alpha), Bad, PRAS40 [proline-rich Akt (PKB) substrate of 40 kDa], SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase), GSK3β and PARP [poly(ADP-ribose) polymerase]. Taken together, these findings suggest that eIF3D might play an important role in colon cancer progression.

  7. Translating Inclusion

    DEFF Research Database (Denmark)

    Fallov, Mia Arp; Birk, Rasmus

    2018-01-01

    The purpose of this paper is to explore how practices of translation shape particular paths of inclusion for people living in marginalized residential areas in Denmark. Inclusion, we argue, is not an end-state, but rather something which must be constantly performed. Active citizenship, today......, is not merely a question of participation, but of learning to become active in all spheres of life. The paper draws on empirical examples from a multi-sited field work in 6 different sites of local community work in Denmark, to demonstrate how different dimensions of translation are involved in shaping active...... citizenship. We propose the following different dimensions of translation: translating authority, translating language, translating social problems. The paper takes its theoretical point of departure from assemblage urbanism, arguing that cities are heterogeneous assemblages of socio-material interactions...

  8. Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation.

    Science.gov (United States)

    Zhang, Hua; Song, Lei; Cong, Haolong; Tien, Po

    2015-10-01

    Enterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds specifically to the EV71 5' untranslated region (5'UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation. The nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially

  9. Exploring the Role of Social Capital in the Conduct of Initial Site Assessments of Polluted Sites in the Philippines

    OpenAIRE

    Jennifer Marie S. Amparo, MA; Marlo D. Mendoza, MDM; Maria Emilinda T. Mendoza, MA; Emilia S. Visco, PhD; Carla Edith G. Jimena, MDM

    2011-01-01

    Background. A number of studies have shown how enhanced social capital can improve environmental outcomes through decreased transaction costs, increased knowledge and information flow, and improved monitoring and enforcement. Objectives. Social capital plays an important role in reducing adversarial perceptions of initial site assessments of toxic hotspots. It also mobilizes stakeholders to work together to come up with a holistic and comprehensive site assessment. This paper explains the ...

  10. Eukaryotic translation initiation factor 3, subunit C is overexpressed and promotes cell proliferation in human glioma U-87 MG cells.

    Science.gov (United States)

    Hao, Jinmin; Liang, Chaohui; Jiao, Baohua

    2015-06-01

    Disrupted protein translation is prevalent in tumours. Eukaryotic translation initiation factors (eIFs) were found to play an important role in various tumours. However, the involvement of eIFs in glioma remains to be elucidated. The present study explored the expression and the role of eIF 3, subunit C (eIF3c) in human glioma. The expression of eIF3c in glioma tissues was evaluated by immunohistochemistry. The impact of eIF3c inhibition on U-87 MG was explored in vitro and in vivo by lentivirus-mediated siRNA targeting eIF3c. The results revealed that overexpression of eIF3c was present in glioma tissues. Knockdown of eIF3c significantly impaired cell proliferation and colony formation, further induced cell cycle arrest and apoptosis in the U-87 MG cell line. Furthermore, tumoursphere formation in the U-87 MG glioma xenograft model was blocked by eIF3c knockdown. The involvement of eIF3c in the tumorigenesis of glioma was confirmed, suggesting eIF3c may be a promising therapy target in human glioma.

  11. Challenges and lessons learned from the translation of evidence-based childhood asthma interventions: a commentary on the MCAN initiative.

    Science.gov (United States)

    Ohadike, Yvonne U; Malveaux, Floyd J; Lesch, Julie Kennedy

    2011-11-01

    The Merck Childhood Asthma Network (MCAN) used evidence-based interventions (EBIs) for children with asthma to design community-based programs in a wide variety of settings--with varying resource constraints and priorities--that were often determined by the program context. Although challenges were faced, lessons learned strongly suggest that adapting and implementing EBIs is feasible in a variety of settings using a multisite approach. Lessons learned during the MCAN initiative presented unique opportunities to refine best practices that proved to be important to translation of EBIs in community-based settings. The adopted best practices were based on experiential learning during different phases of the project cycle, including monitoring and evaluation, translational research, and implementing policies in local program environments. Throughout this discussion it is important to note the importance of program context in determining the effectiveness of the interventions, opportunities to scale them, their affordability, and the ability to sustain them. Lessons learned from this effort will be important not only to advance science-based approaches to manage childhood asthma but also to assist in closing the gap between intervention development (discovery) and program dissemination and implementation (delivery).

  12. Eukaryotic initiation factor 3 (eIF3) and 5’ mRNA leader sequences as agents of translational regulation in Arabidopsis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    von Arnim, Albrecht G. [Univ. of Tennessee, Knoxville, TN (United States)

    2015-02-04

    Protein synthesis, or translation, consumes a sizable fraction of the cell’s energy budget, estimated at 5% and up to 50% in differentiated and growing cells, respectively. Plants also invest significant energy and biomass to construct and maintain the translation apparatus. Translation is regulated by a variety of external stimuli. Compared to transcriptional control, attributes of translational control include reduced sensitivity to stochastic fluctuation, a finer gauge of control, and more rapid responsiveness to environmental stimuli. Yet, our murky understanding of translational control allows few generalizations. Consequently, translational regulation is underutilized in the context of transgene regulation, although synthetic biologists are now beginning to appropriate RNA-level gene regulation into their regulatory circuits. We also know little about how translational control contributes to the diversity of plant form and function. This project explored how an emerging regulatory mRNA sequence element, upstream open reading frames (uORFs), is integrated with the general translation initiation machinery to permit translational regulation on specific mRNAs.

  13. The local translation of a top-down football-based initiative for health

    DEFF Research Database (Denmark)

    Bennike, Søren; Ottesen, Laila

    The voluntary based sports system is challenged by societal changes. Firstly we observe a transformation in the sport activity pattern, whereas still more are involved with sport in a self-organized or commercial form and secondly the state’s overall financial ability is reduced. As the voluntary...... based sport is heavily state funded, the non-governmental sports organizations representing the voluntary sports clubs, feel they have to position the role of sport to legitimize their existence. In this quest the connection of sport and health plays a huge role. In Denmark the Football Association has...... structure of the state subsidized voluntary sport sector, no club can be forced to organise Football Fitness neither be dictated how they organise it. Partly due to this fact, the initiative has a flexible design, with the possibility to incorporate local inputs. That means the realization comes down...

  14. The same allele of translation initiation factor 4E mediates resistance against two Potyvirus spp. in Pisum sativum

    DEFF Research Database (Denmark)

    Bruun-Rasmussen, M.; Møller, I.S.; Tulinius, G.

    2007-01-01

    was overcome, and virus from these plants had a codon change causing an Arg to His change at position 116 of the predicted viral genome-linked protein (VPg). Accordingly, plants carrying the wlv resistance gene were infected upon inoculation with BYMV-W derived from cDNA with a His codon at position 116......Pathogenicity of two sequenced isolates of Bean yellow mosaic virus (BYMV) was established on genotypes of Pisum sativum L. reported to carry resistance genes to BYMV and other potyviruses. Resistance to the white lupin strain of BYMV (BYMV-W) is inherited as a recessive gene named wlv that maps...... to linkage group VI together with other Potyvirus resistances. One of these, sbm1, confers resistance to strains of Pea seedborne mosaic virus and previously has been identified as a mutant allele of the eukaryotic translation initiation factor 4E gene (eIF4E). Sequence comparison of eIF4E from BYMV...

  15. Predictive combinatorial design of mRNA translation initiation regions for systematic optimization of gene expression levels.

    Science.gov (United States)

    Seo, Sang Woo; Yang, Jae-Seong; Cho, Han-Saem; Yang, Jina; Kim, Seong Cheol; Park, Jong Moon; Kim, Sanguk; Jung, Gyoo Yeol

    2014-03-31

    Balancing the amounts of enzymes is one of the important factors to achieve optimum performance of a designed metabolic pathway. However, the random mutagenesis approach is impractical since it requires searching an unnecessarily large number of variants and often results in searching a narrow range of expression levels which are out of optimal level. Here, we developed a predictive combinatorial design method, called UTR Library Designer, which systematically searches a large combinatorial space of expression levels. It accomplishes this by designing synthetic translation initiation region of mRNAs in a predictive way based on a thermodynamic model and genetic algorithm. Using this approach, we successfully enhanced lysine and hydrogen production in Escherichia coli. Our method significantly reduced the number of variants to be explored for covering large combinatorial space and efficiently enhanced pathway efficiency, thereby facilitating future efforts in metabolic engineering and synthetic biology.

  16. Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice R; Gomes-Marcondes, Maria Cristina C

    2007-01-01

    Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C – pregnant control, W – tumour-bearing, and P – pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L – pregnant leucine, WL – tumour-bearing, and PL – pair-fed, which received the same amount of food as ingested by the WL group. The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2α and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway

  17. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

    DEFF Research Database (Denmark)

    NN, NN; Mugavero, Michael J; May, Margaret

    2008-01-01

    OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between.......04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). CONCLUSION: Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because...

  18. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

    NARCIS (Netherlands)

    Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C; Niesters, Bert

    2008-01-01

    OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between

  19. The 5' untranslated mRNA region base content can greatly affect translation initiation in the absence of secondary structures in Prevotella bryantii TC1-1.

    Science.gov (United States)

    Seničar, Lenart; Accetto, Tomaž

    2015-01-01

    It has become clear lately that many bacteria and even whole bacterial phyla do not use the classical Shine-Dalgarno sequence mediated pathway of protein translation initiation. The prominent phylum Bacteroidetes is one of them, and this was shown not only using bioinformatic but also functional reporter gene studies in its representative Prevotella bryantii. The latter studies revealed much higher sensitivity toward secondary structures in 5(') untranslated mRNA regions (5(') UTRs) during translation initiation compared to Escherichia coli. It was proposed that in the absence of Shine-Dalgarno sequence interaction the key elements enabling translation initiation are local absence of secondary structures in 5(') UTRs, and the ribosomal protein S1 which binds to mRNA. Here, we evaluate the 5(') UTRs devoid of secondary structures but containing divergent nucleotide compositions in P. bryantii reporter assay. We show that base composition profoundly affects the amount of the reporter synthesized, and further that these amounts were in agreement with S1 protein binding affinity for adenine/uracil bases in mRNA. This is the first, though indirect, clue that S1 is actually involved in translation initiation in Bacteroidetes and adds the second layer of control beside mRNA secondary structure affecting translation initiation in this phylum. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G.

    Science.gov (United States)

    Tarun, S Z; Sachs, A B

    1996-12-16

    Although the cap structure and the poly(A) tail are on opposite ends of the mRNA molecule, previous work has suggested that they interact to enhance translation and inhibit mRNA degradation. Here we present biochemical data that show that the proteins bound to the mRNA cap (eIF-4F) and poly(A) tail (Pab1p) are physically associated in extracts from the yeast Saccharomyces cerevisiae. Specifically, we find that Pab1p co-purifies and co-immunoprecipitates with the eIF-4G subunit of eIF-4F. The Pab1p binding site on the recombinant yeast eIF-4G protein Tif4632p was mapped to a 114-amino-acid region just proximal to its eIF-4E binding site. Pab1p only bound to this region when complexed to poly(A). These data support the model that the Pablp-poly(A) tail complex on mRNA can interact with the cap structure via eIF-4G.

  1. Rethinking Unconventional Translation in Neurodegeneration.

    Science.gov (United States)

    Gao, Fen-Biao; Richter, Joel D; Cleveland, Don W

    2017-11-16

    Eukaryotic translation is tightly regulated to ensure that protein production occurs at the right time and place. Recent studies on abnormal repeat proteins, especially in age-dependent neurodegenerative diseases caused by nucleotide repeat expansion, have highlighted or identified two forms of unconventional translation initiation: usage of AUG-like sites (near cognates) or repeat-associated non-AUG (RAN) translation. We discuss how repeat proteins may differ due to not just unconventional initiation, but also ribosomal frameshifting and/or imperfect repeat DNA replication, expansion, and repair, and we highlight how research on translation of repeats may uncover insights into the biology of translation and its contribution to disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Assigning Quantitative Function to Post-Translational Modifications Reveals Multiple Sites of Phosphorylation That Tune Yeast Pheromone Signaling Output

    Energy Technology Data Exchange (ETDEWEB)

    Pincus, David; Ryan, Christopher J.; Smith, Richard D.; Brent, Roger; Resnekov, Orna; Hakimi, Mohamed Ali

    2013-03-12

    Cell signaling systems transmit information by post-­translationally modifying signaling proteins, often via phosphorylation. While thousands of sites of phosphorylation have been identified in proteomic studies, the vast majority of sites have no known function. Assigning functional roles to the catalog of uncharacterized phosphorylation sites is a key research challenge. Here we present a general approach to address this challenge and apply it to a prototypical signaling pathway, the pheromone response pathway in Saccharomyces cerevisiae. The pheromone pathway includes a mitogen activated protein kinase (MAPK) cascade activated by a G-­protein coupled receptor (GPCR). We used mass spectrometry-based proteomics to identify sites whose phosphorylation changed when the system was active, and evolutionary conservation to assign priority to a list of candidate MAPK regulatory sites. We made targeted alterations in those sites, and measured the effects of the mutations on pheromone pathway output in single cells. Our work identified six new sites that quantitatively tuned system output. We developed simple computational models to find system architectures that recapitulated the quantitative phenotypes of the mutants. Our results identify a number of regulated phosphorylation events that contribute to adjust the input-­output relationship of this model eukaryotic signaling system. We believe this combined approach constitutes a general means not only to reveal modification sites required to turn a pathway on and off, but also those required for more subtle quantitative effects that tune pathway output. Our results further suggest that relatively small quantitative influences from individual regulatory phosphorylation events endow signaling systems with plasticity that evolution may exploit to quantitatively tailor signaling outcomes.

  3. RatA (YfjG), an Escherichia coli toxin, inhibits 70S ribosome association to block translation initiation.

    Science.gov (United States)

    Zhang, Yonglong; Inouye, Masayori

    2011-03-01

    RatA (YfjG) is a toxin encoded by the ratA-ratB (yfjG-yfjF) operon on the Escherichia coli genome. Induction of RatA led to the inhibition of protein synthesis, while DNA and RNA synthesis was not affected. The stability of mRNAs was also unchanged as judged by in vivo primer extension experiments and by Northern blotting analysis. The ribosome profile of the cells overexpressing RatA showed that 70S ribosomes as well as polysomes significantly decreased with concomitant increase of 50S and 30S subunits. The addition of purified RatA to a cell-free system inhibited the formation of 70S ribosomes even in the presence of 6 mM Mg(2+) . RatA was specifically associated with 50S subunits, indicating that it binds to 50S subunits to block its association with 30S subunits leading to the inhibition of formation of 70S ribosomes. However, RatA did not cause dissociation of 70S ribosomes and its anti-association activity was blocked by paromomycin, an inhibitor for IF3, an essential initiation factor, having 21% sequence homology with RatA. Here we demonstrate that RatA is a new E. coli toxin, which effectively blocks the translation initiation step. We propose that this toxin of previously unknown function be renamed as RatA (Ribosome association toxin A). © 2011 Blackwell Publishing Ltd.

  4. Selection of random RNA fragments as method for searching for a site of regulation of translation of E. coli streptomycin mRNA by ribosomal protein S7.

    Science.gov (United States)

    Surdina, A V; Rassokhin, T I; Golovin, A V; Spiridonova, V A; Kraal, B; Kopylov, A M

    2008-06-01

    In E. coli cells ribosomal small subunit biogenesis is regulated by RNA-protein interactions involving protein S7. S7 initiates the subunit assembly interacting with 16S rRNA. During shift-down of rRNA synthesis level, free S7 inhibits self-translation by interacting with 96 nucleotides long specific region of streptomycin (str) mRNA between cistrons S12 and S7 (intercistron). Many bacteria do not have the extended intercistron challenging development of specific approaches for searching putative mRNA regulatory regions, which are able to interact with proteins. The paper describes application of SERF approach (Selection of Random RNA Fragments) to reveal regulatory regions of str mRNA. Set of random DNA fragments has been generated from str operon by random hydrolysis and then transcribed into RNA; the fragments being able to bind protein S7 (serfamers) have been selected by iterative rounds. S7 binds to single serfamer, 109 nucleotide long (RNA109), derived from the intercistron. After multiple copying and selection, the intercistronic mutant (RNA109) has been isolated; it has enhanced affinity to S7. RNA109 binds to the protein better than authentic intercistronic str mRNA; apparent dissociation constants are 26 +/- 5 and 60 +/- 8 nM, respectively. Location of S7 binding site on the mRNA, as well as putative mode of regulation of coupled translation of S12 and S7 cistrons have been hypothesized.

  5. Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, Mohammad [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Ito, Akihiro, E-mail: akihiro-i@riken.jp [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan); Ishfaq, Muhammad; Bradshaw, Elliot [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Yoshida, Minoru [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan)

    2016-02-05

    The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

  6. Locating the site of diagonal tension crack initiation and path in reinforced concrete beams

    Directory of Open Access Journals (Sweden)

    H.S.S. Abou El-Mal

    2015-03-01

    Full Text Available The most favorable site of diagonal tension crack initiation has been attempted to be located. Due to the numerous interacted parameters affecting both site and angle of diagonal tension crack initiation, twelve possible sites were investigated, at midheight of the shear span and at the bottom surface near the support of the beam with vertical and diagonal orientations. The first diagonal tension crack initiated from the bottom tip of the diagonal pre-crack at midheight of the beam as a result of constraint release. To verify the previous finding, a single diagonal pre-crack has been created at midheight of only one side of the shear spans in both normal and fiber reinforced concrete (FRC beams. FRC beam showed different behavior, where couple of diagonal tension cracks initiated at both sides from the tip of flexural cracks regardless of the existence of pre-crack at one side of the beam.

  7. Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation

    Science.gov (United States)

    Marintchev, Assen; Edmonds, Katherine A.; Marintcheva, Boriana; Hendrickson, Elthea; Oberer, Monika; Suzuki, Chikako; Herdy, Barbara; Sonenberg, Nahum; Wagner, Gerhard

    2009-01-01

    Summary The RNA helicase eIF4A plays a key role in unwinding of mRNA and scanning during translation initiation. Free eIF4A is a poor helicase and requires the accessory proteins eIF4G and eIF4H. However, the structure of the helicase complex and the mechanisms of stimulation of eIF4A activity have remained elusive. Here we report the topology of the eIF4A/4G/4H helicase complex, which is built from multiple experimentally observed domain-domain contacts. Remarkably, some of the interactions are continuously rearranged during the ATP binding/hydrolysis cycle of the helicase. We show that the accessory proteins modulate the affinity of eIF4A for ATP by interacting simultaneously with both helicase domains and promoting either the closed, ATP-bound conformation or the open, nucleotide-free conformation. The topology of the complex and the spatial arrangement of the RNA-binding surfaces offer insights into their roles in stimulation of helicase activity and the mechanisms of mRNA unwinding and scanning. PMID:19203580

  8. Eukaryotic Translation Initiation Factor 3a (eIF3a) Promotes Cell Proliferation and Motility in Pancreatic Cancer.

    Science.gov (United States)

    Wang, Shu Qian; Liu, Yu; Yao, Min Ya; Jin, Jing

    2016-10-01

    Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma.

  9. Eukaryotic Translation Initiation Factor eIFiso4G Is Required to Regulate Violaxanthin De-epoxidase Expression in Arabidopsis*

    Science.gov (United States)

    Chen, Zhong; Jolley, Blair; Caldwell, Christian; Gallie, Daniel R.

    2014-01-01

    The eukaryotic translation initiation factor (eIF) 4G is a scaffold protein that organizes the assembly of those initiation factors needed to recruit the 40 S ribosomal subunit to an mRNA. Plants, like many eukaryotes, express two eIF4G isoforms. eIFiso4G, one of the isoforms specific to plants, is unique among eukaryotic eIF4G proteins in that it is highly divergent and unusually small in size, raising the possibility of functional specialization. In this study, the role of eIFiso4G in plant growth was investigated using null mutants for the eIF4G isoforms in Arabidopsis. eIFiso4G loss of function mutants exhibited smaller cell, leaf, plant size, and biomass accumulation that correlated with its reduced photosynthetic activity, phenotypes not observed with the eIF4G loss of function mutant. Although no change in photorespiration or dark respiration was observed in the eIFiso4G loss of function mutant, a reduction in chlorophyll levels and an increase in the level of nonphotochemical quenching were observed. An increase in xanthophyll cycle activity and the generation of reactive oxygen species contributed to the qE and qI components of nonphotochemical quenching, respectively. An increase in the transcript and protein levels of violaxanthin de-epoxidase in the eIFiso4G loss of function mutant and an increase in its xanthophyll de-epoxidation state correlated with the higher qE associated with loss of eIFiso4G expression. These observations indicate that eIFiso4G expression is required to regulate violaxanthin de-epoxidase expression and to support photosynthetic activity. PMID:24706761

  10. Eukaryotic translation initiation factor eIFiso4G is required to regulate violaxanthin De-epoxidase expression in Arabidopsis.

    Science.gov (United States)

    Chen, Zhong; Jolley, Blair; Caldwell, Christian; Gallie, Daniel R

    2014-05-16

    The eukaryotic translation initiation factor (eIF) 4G is a scaffold protein that organizes the assembly of those initiation factors needed to recruit the 40 S ribosomal subunit to an mRNA. Plants, like many eukaryotes, express two eIF4G isoforms. eIFiso4G, one of the isoforms specific to plants, is unique among eukaryotic eIF4G proteins in that it is highly divergent and unusually small in size, raising the possibility of functional specialization. In this study, the role of eIFiso4G in plant growth was investigated using null mutants for the eIF4G isoforms in Arabidopsis. eIFiso4G loss of function mutants exhibited smaller cell, leaf, plant size, and biomass accumulation that correlated with its reduced photosynthetic activity, phenotypes not observed with the eIF4G loss of function mutant. Although no change in photorespiration or dark respiration was observed in the eIFiso4G loss of function mutant, a reduction in chlorophyll levels and an increase in the level of nonphotochemical quenching were observed. An increase in xanthophyll cycle activity and the generation of reactive oxygen species contributed to the qE and qI components of nonphotochemical quenching, respectively. An increase in the transcript and protein levels of violaxanthin de-epoxidase in the eIFiso4G loss of function mutant and an increase in its xanthophyll de-epoxidation state correlated with the higher qE associated with loss of eIFiso4G expression. These observations indicate that eIFiso4G expression is required to regulate violaxanthin de-epoxidase expression and to support photosynthetic activity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Quality improvement initiative: Preventative Surgical Site Infection Protocol in Vascular Surgery.

    Science.gov (United States)

    Parizh, David; Ascher, Enrico; Raza Rizvi, Syed Ali; Hingorani, Anil; Amaturo, Michael; Johnson, Eric

    2018-02-01

    Objective A quality improvement initiative was employed to decrease single institution surgical site infection rate in open lower extremity revascularization procedures. In an attempt to lower patient morbidity, we developed and implemented the Preventative Surgical Site Infection Protocol in Vascular Surgery. Surgical site infections lead to prolonged hospital stays, adjunctive procedure, and additive costs. We employed targeted interventions to address the common risk factors that predispose patients to post-operative complications. Methods Retrospective review was performed between 2012 and 2016 for all surgical site infections after revascularization procedures of the lower extremity. A quality improvement protocol was initiated in January 2015. Primary outcome was the assessment of surgical site infection rate reduction in the pre-protocol vs. post-protocol era. Secondary outcomes evaluated patient demographics, closure method, perioperative antibiotic coverage, and management outcomes. Results Implementation of the protocol decreased the surgical site infection rate from 6.4% to 1.6% p = 0.0137). Patient demographics and comorbidities were assessed and failed to demonstrate a statistically significant difference among the infection and no-infection groups. Wound closure with monocryl suture vs. staple proved to be associated with decreased surgical site infection rate ( p site infections in the vascular surgery population are effective and necessary. Our data suggest that there may be benefit in the incorporation of MRSA and Gram-negative coverage as part of the Surgical Care Improvement Project perioperative guidelines.

  12. A Clinical Trial of Translation of Evidence Based Interventions to Mobile Tablets and Illness Specific Internet Sites.

    Science.gov (United States)

    Smith, Carol E; Piamjariyakul, Ubolrat; Werkowitch, Marilyn; Yadrich, Donna Macan; Thompson, Noreen; Hooper, Dedrick; Nelson, Eve-Lynn

    2016-03-01

    This article describes a method to translate an evidence based health care intervention to the mobile environment. This translation assisted patient participants to: avoid life threatening infections; monitor emotions and fatigue; keep involved in healthy activities. The mobile technology also decreased costs by reducing for example travel to visit health care providers. Testing of this translation method and its use by comparison groups of patients adds to the knowledge base for assessing technology for its impact on health outcome measures. The challenges and workflow of designing materials for the mobile format are described. Transitioning clinical trial verified interventions, previously provided in person to patients, onto tablet and internet platforms is an important process that must be evaluated. In this study, our evidence based guide's intravenous (IV) homeCare interventions (IVhomeCare) were delivered via Apple iPad mini™ tablet audiovisual instruction / discussion sessions and on a website. Each iPad audiovisual session (n = 41), included three to five families, a mental health specialist, and healthcare professionals. Patients and their family caregivers readily learned to use the wireless mobile tablets, and the IVhomeCare interventions, as described here, were successfully translated onto these mobile technology platforms. Using Likert scale responses on a questionnaire (1 = not helpful and 5 = very helpful) participants indicated that they gained problem solving skills for home care through iPad group discussion ( M = 4.60, SD = 0.60). The firewall protected videoconferencing in real time with multiple healthcare professionals effectively allowed health history taking and visual inspection of the patient's IV insertion site for signs of infection. Supportive interactions with peer families on videoconferencing were documented during discussions. Discussion topics included low moods, fatigue, infection worry, how to maintain independence, and need

  13. Identification of Plasmodium falciparum translation initiation eIF2β subunit: direct interaction with Protein Phosphatase type 1

    Directory of Open Access Journals (Sweden)

    Géraldine eTellier

    2016-05-01

    Full Text Available Protein phosphatase 1 (PP1c is one of the main phosphatases whose function is shaped by many regulators to confer a specific location and a selective function for this enzyme. Here, we report that eukaryotic initiation factor 2 of P. falciparum (PfeIF2β is an interactor of PfPP1c. Sequence analysis of PfeIF2 revealed a deletion of 111 amino acids when compared to its human counterpart and the presence of two potential binding motifs to PfPP1 (29FGEKKK34, 103KVAW106. As expected, we showed that PfeIF2 binds PfeIF2 and PfeIF5, confirming its canonical interaction with partners of the translation complex. Studies of the PfeIF2-PfPP1 interaction using wild-type, single and double mutated versions of PfeIF2β revealed that both binding motifs are critical. We next showed that PfeIF2 is able to induce Germinal Vesicle BreakDown (GVBD when expressed in Xenopus oocytes, an indicator of its capacity to regulate PP1. Only combined mutations of both binding motifs abolished the interaction with PP1 and the induction of GVBD. In P. falciparum, although the locus is accessible for genetic manipulation, PfeIF2 seems to play an essential role in intraerythrocytic cycle as no viable knockout parasites were detectable. Interestingly, as for PfPP1, the subcellular fractionation of P. falciparum localized PfeIF2β in cytoplasm and nuclear extracts, suggesting a potential effect on PfPP1 in both compartments and raising the question of a non-canonical function of PfeIf2 in the nucleus. Hence, the role played by PfeIF2 in blood stage parasites could occur at multiple levels involving the binding to proteins of the translational complex and to PfPP1.

  14. Structure and functions of the translation initiation factor eIF4E and its role in cancer development and treatment.

    Science.gov (United States)

    Piserà, Arianna; Campo, Adele; Campo, Salvatore

    2018-01-20

    In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukaryotic gene expression occurs principally at the initiation step. In this context, it is critical that the eukaryotic translation initiation factor eIF4E bind to the 7-methylguanosine (m7G) cap present at the 5'-UTRs of most eukaryotic mRNAs. Combined with other initiation factors, eIF4E mediates the mRNA recruitment on ribosomes to start the translation. Moreover, the eIF4E nuclear bodies are involved in the export of specific mRNAs from the nucleus to the cytoplasm. In this review, we focus on the eIF4E structure and its physiological functions, and describe the role of eIF4E in cancer development and progression and the current therapeutic strategies to target eIF4E. Copyright © 2018 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  15. Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein

    International Nuclear Information System (INIS)

    Zhao, Hui; Wang, Hong; Liu, Huihui; Teng, Maikun; Li, Xu

    2012-01-01

    The crystallization and preliminary crystallographic studies of the carboxy-terminal domain of D. melanogaster eukaryotic translation initiation factor 5C domain-containing protein are reported. The Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2B∊, eIF4γ, eIF5 etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space group I4, with unit-cell parameters a = b = 81.05, c = 57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal

  16. Investigation of the translation-initiation factor IF2 gene, infB, as a tool to study the population structure of Streptococcus agalactiae

    DEFF Research Database (Denmark)

    Hedegaard, J; Hauge, M; Fage-Larsen, J

    2000-01-01

    The sequence of infB, encoding the prokaryotic translation-initiation factor 2 (IF2), was determined in eight strains of Streptococcus agalactiae (group B streptococcus) and an alignment revealed limited intraspecies diversity within S. agalactiae. The amino acid sequence of IF2 from S. agalactiae...

  17. The Site of Spontaneous Ectopic Spike Initiation Facilitates Signal Integration in a Sensory Neuron.

    Science.gov (United States)

    Städele, Carola; Stein, Wolfgang

    2016-06-22

    Essential to understanding the process of neuronal signal integration is the knowledge of where within a neuron action potentials (APs) are generated. Recent studies support the idea that the precise location where APs are initiated and the properties of spike initiation zones define the cell's information processing capabilities. Notably, the location of spike initiation can be modified homeostatically within neurons to adjust neuronal activity. Here we show that this potential mechanism for neuronal plasticity can also be exploited in a rapid and dynamic fashion. We tested whether dislocation of the spike initiation zone affects signal integration by studying ectopic spike initiation in the anterior gastric receptor neuron (AGR) of the stomatogastric nervous system of Cancer borealis Like many other vertebrate and invertebrate neurons, AGR can generate ectopic APs in regions distinct from the axon initial segment. Using voltage-sensitive dyes and electrophysiology, we determined that AGR's ectopic spike activity was consistently initiated in the neuropil region of the stomatogastric ganglion motor circuits. At least one neurite branched off the AGR axon in this area; and indeed, we found that AGR's ectopic spike activity was influenced by local motor neurons. This sensorimotor interaction was state-dependent in that focal axon modulation with the biogenic amine octopamine, abolished signal integration at the primary spike initiation zone by dislocating spike initiation to a distant region of the axon. We demonstrate that the site of ectopic spike initiation is important for signal integration and that axonal neuromodulation allows for a dynamic adjustment of signal integration. Although it is known that action potentials are initiated at specific sites in the axon, it remains to be determined how the precise location of action potential initiation affects neuronal activity and signal integration. We addressed this issue by studying ectopic spiking in the axon of

  18. Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site

    International Nuclear Information System (INIS)

    Collins, C.J.; Underdahl, J.P.; Levene, R.B.; Ravera, C.P.; Morin, M.J.; Dombalagian, M.J.; Ricca, G.; Livingston, D.M.; Lynch, D.C.

    1987-01-01

    A series of overlapping cosmid genomic clones have been isolated that contain the entire coding unit of the human gene for van Willebrand factor (vWf), a major component of the hemostatic system. The cloned segments span ≅ 175 kilobases of human DNA sequence, and hybridization analysis suggest that the vWf coding unit is ≅150 kilobases in length. Within one of these clones, the vWF transcription initiation site has been mapped and a portion of the vWf promoter region has been sequenced, revealing a typical TATA box, a downstream CCAAT box, and a perfect downstream repeat of the 8 base pairs containing the transcription start site. Sequencing of a segment of another genomic clone has revealed the vWF translation termination codon. Where tested, comparative restriction analysis of cloned and chromosomal DNA segments strongly suggests that no major alterations occurred during cloning and that there is only one complete copy of the vWf gene in the human haploid genome. Similar analyses of DNA from vWf-producing endothelial cells and nonexpressing leukocytes suggest that vWf gene expression is not accompanied by gross genomic rearrangements. In addition, there is significant homology of C-terminal coding sequences among the vWf genes of several vertebrate species

  19. Characterization of a eukaryotic translation initiation factor 5A homolog from Tamarix androssowii involved in plant abiotic stress tolerance.

    Science.gov (United States)

    Wang, Liuqiang; Xu, Chenxi; Wang, Chao; Wang, Yucheng

    2012-07-26

    The eukaryotic translation initiation factor 5A (eIF5A) promotes formation of the first peptide bond at the onset of protein synthesis. However, the function of eIF5A in plants is not well understood. In this study, we characterized the function of eIF5A (TaeIF5A1) from Tamarix androssowii. The promoter of TaeIF5A1 with 1,486 bp in length was isolated, and the cis-elements in the promoter were identified. A WRKY (TaWRKY) and RAV (TaRAV) protein can specifically bind to a W-box motif in the promoter of TaeIF5A1 and activate the expression of TaeIF5A1. Furthermore, TaeIF5A1, TaWRKY and TaRAV share very similar expression pattern and are all stress-responsive gene that functions in the abscisic acid (ABA) signaling pathway, indicating that they are components of a single regulatory pathway. Transgenic yeast and poplar expressing TaeIF5A1 showed elevated protein levels combined with improved abiotic stresses tolerance. Furthermore, TaeIF5A1-transformed plants exhibited enhanced superoxide dismutase (SOD) and peroxidase (POD) activities, lower electrolyte leakage and higher chlorophyll content under salt stress. These results suggested that TaeIF5A1 is involved in abiotic stress tolerance, and is likely regulated by transcription factors TaWRKY and TaRAV both of which can bind to the W-box motif. In addition, TaeIF5A1 may mediate stress tolerance by increasing protein synthesis, enhancing ROS scavenging by improving SOD and POD activities, and preventing chlorophyll loss and membrane damage. Therefore, eIF5A may play an important role in plant adaptation to changing environmental conditions.

  20. An AUG codon conserved for protein function rather than translational initiation: the story of the protein sElk1.

    Directory of Open Access Journals (Sweden)

    Noemie Legrand

    Full Text Available Elk1 belongs to the ternary complex (TCF subfamily of the ETS-domain transcription factors. Several studies have implicated an important function for Elk1 in the CNS including synaptic plasticity and cell differentiation. Whilst studying ELK1 gene expression in rat brain a 54 aa N-terminally truncated isoform lacking the DBD was observed on immunoblots. A similar protein was also detected in NGF differentiated PC12 cells. It was proposed that this protein, referred to as sElk1, arose due to a de-novo initiation event at the second AUG codon on the Elk1 ORF. Transient over-expression of sElk1 potentiated neurite growth in the PC12 model and induced differentiation in the absence of NGF, leading to the proposition that it may have a specific function in the CNS. Here we report on the translational expression from the mouse and rat transcript and compare it with our earlier published work on human. Results demonstrate that the previously observed sElk1 protein is a non-specific band arising from the antibody employed. The tight conservation of the internal AUG reported to drive sElk1 expression is in fact coupled to Elk1 protein function, a result consistent with the Elk1-SRE crystal structure. It is also supported by the observed conservation of this methionine in the DBD of all ETS transcription factors independent of the N- or C-terminal positioning of this domain. Reporter assays demonstrate that elements both within the 5'UTR and downstream of the AUGElk1 serve to limit 40S access to the AUGsElk1 codon.

  1. Characterization of a eukaryotic translation initiation factor 5A homolog from Tamarix androssowii involved in plant abiotic stress tolerance

    Directory of Open Access Journals (Sweden)

    Wang Liuqiang

    2012-07-01

    Full Text Available Abstract Background The eukaryotic translation initiation factor 5A (eIF5A promotes formation of the first peptide bond at the onset of protein synthesis. However, the function of eIF5A in plants is not well understood. Results In this study, we characterized the function of eIF5A (TaeIF5A1 from Tamarix androssowii. The promoter of TaeIF5A1 with 1,486 bp in length was isolated, and the cis-elements in the promoter were identified. A WRKY (TaWRKY and RAV (TaRAV protein can specifically bind to a W-box motif in the promoter of TaeIF5A1 and activate the expression of TaeIF5A1. Furthermore, TaeIF5A1, TaWRKY and TaRAV share very similar expression pattern and are all stress-responsive gene that functions in the abscisic acid (ABA signaling pathway, indicating that they are components of a single regulatory pathway. Transgenic yeast and poplar expressing TaeIF5A1 showed elevated protein levels combined with improved abiotic stresses tolerance. Furthermore, TaeIF5A1-transformed plants exhibited enhanced superoxide dismutase (SOD and peroxidase (POD activities, lower electrolyte leakage and higher chlorophyll content under salt stress. Conclusions These results suggested that TaeIF5A1 is involved in abiotic stress tolerance, and is likely regulated by transcription factors TaWRKY and TaRAV both of which can bind to the W-box motif. In addition, TaeIF5A1 may mediate stress tolerance by increasing protein synthesis, enhancing ROS scavenging by improving SOD and POD activities, and preventing chlorophyll loss and membrane damage. Therefore, eIF5A may play an important role in plant adaptation to changing environmental conditions.

  2. Post-translational modifications near the quinone binding site of mammalian complex I.

    Science.gov (United States)

    Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2013-08-23

    Complex I (NADH:ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 44 protein subunits with one arm buried in the inner membrane of the mitochondrion and the orthogonal arm protruding about 100 Å into the matrix. The protruding arm contains the binding sites for NADH, the primary acceptor of electrons flavin mononucleotide (FMN), and a chain of seven iron-sulfur clusters that carries the electrons one at a time from FMN to a coenzyme Q molecule bound in the vicinity of the junction between the two arms. In the structure of the closely related bacterial enzyme from Thermus thermophilus, the quinone is thought to bind in a tunnel that spans the interface between the two arms, with the quinone head group close to the terminal iron-sulfur cluster, N2. The tail of the bound quinone is thought to extend from the tunnel into the lipid bilayer. In the mammalian enzyme, it is likely that this tunnel involves three of the subunits of the complex, ND1, PSST, and the 49-kDa subunit. An arginine residue in the 49-kDa subunit is symmetrically dimethylated on the ω-N(G) and ω-N(G') nitrogen atoms of the guanidino group and is likely to be close to cluster N2 and to influence its properties. Another arginine residue in the PSST subunit is hydroxylated and probably lies near to the quinone. Both modifications are conserved in mammalian enzymes, and the former is additionally conserved in Pichia pastoris and Paracoccus denitrificans, suggesting that they are functionally significant.

  3. Translator awareness Translator awareness

    Directory of Open Access Journals (Sweden)

    Wolfram Wilss

    2008-04-01

    Full Text Available If we want to encompass adequately the wide-ranging field of human translation, it is necessary to include in translation studies (TS the concept of translator awareness (or translator consciousness, for that matter. However, this is more easily said than done, because this concept does not easily lend itself to definition, let alone to measurement, e. g., by investigating translator behaviour. To put it bluntly: Translator awareness is a fuzzy concept. Like many obviously difficult-to-define concepts, with which dialogue in TS is burdened, translator awareness lacks an articulated theory within which different forms of translator behaviour can be convincingly related to, or distinguished from, one another. Hence, TS has so far not tackled, at least not systematically, the issue of translator awareness. If we want to encompass adequately the wide-ranging field of human translation, it is necessary to include in translation studies (TS the concept of translator awareness (or translator consciousness, for that matter. However, this is more easily said than done, because this concept does not easily lend itself to definition, let alone to measurement, e. g., by investigating translator behaviour. To put it bluntly: Translator awareness is a fuzzy concept. Like many obviously difficult-to-define concepts, with which dialogue in TS is burdened, translator awareness lacks an articulated theory within which different forms of translator behaviour can be convincingly related to, or distinguished from, one another. Hence, TS has so far not tackled, at least not systematically, the issue of translator awareness.

  4. [Translation and cross-cultural adaptation of the Brazilian version of the Hospital Survey on Patient Safety Culture: initial stage].

    Science.gov (United States)

    Reis, Claudia Tartaglia; Laguardia, Josué; Martins, Mônica

    2012-11-01

    Patient safety culture assessment allows hospitals to identify and prospectively manage safety issues in work routines. This article aimed to describe the cross-cultural adaptation of the Hospital Survey on Patient Safety Culture (HSOPSC) into Brazilian Portuguese. A universalist approach was adopted to assess conceptual, item, and semantic equivalence. The methodology involved the following stages: (1) translation of the questionnaire into Portuguese; (2) back-translation into English; (3) an expert panel to prepare a draft version; and (4) assessment of verbal understanding of the draft by a sample of the target population. The questionnaire was translated into Portuguese, and the scale's final version included 42 items. The target population sample assessed all the items as easy to understand. The questionnaire has been translated into Portuguese and adapted to the Brazilian hospital context, but it is necessary to assess its measurement equivalence, external validity, and reproducibility.

  5. Initial Results on the F-logic to OWL Bi-directional Translation on a Tabled Prolog Engine

    OpenAIRE

    Fodor, Paul

    2008-01-01

    In this paper, we show our results on the bi-directional data exchange between the F-logic language supported by the Flora2 system and the OWL language. Most of the TBox and ABox axioms are translated preserving the semantics between the two representations, such as: proper inclusion, individual definition, functional properties, while some axioms and restrictions require a change in the semantics, such as: numbered and qualified cardinality restrictions. For the second case, we translate the...

  6. The rice eukaryotic translation initiation factor 3 subunit f (OseIF3f is involved in microgametogenesis

    Directory of Open Access Journals (Sweden)

    Qi eLi

    2016-04-01

    Full Text Available Microgametogenesis is the postmeiotic pollen developmental phase when unicellular microspores develop into mature tricellular pollen. In rice, microgametogenesis can influence grain yields to a great degree because pollen abortion occurs more easily during microgametogenesis than during other stages of pollen development. However, our knowledge of the genes involved in microgametogenesis in rice remains limited. Due to the dependence of pollen development on the regulatory mechanisms of protein expression, we identified the encoding gene of the eukaryotic translation initiation factor 3, subunit f in Oryza sativa (OseIF3f. Immunoprecipitation combined with mass spectrometry confirmed that OseIF3f was a subunit of rice eIF3, which consisted of at least 12 subunits including eIF3a, eIF3b, eIF3c, eIF3d, eIF3e, eIF3f, eIF3g, eIF3h, eIF3i, eIF3k, eIF3l and eIF3m. OseIF3f showed high mRNA levels in immature florets and is highly abundant in developing anthers. Subcellular localization analysis showed that OseIF3f was localized to the cytosol and the endoplasmic reticulum in rice root cells. We further analyzed the biological function of OseIF3f using the double-stranded RNA-mediated interference (RNAi approach. The OseIF3f-RNAi lines grew normally at the vegetative stage but displayed a large reduction in seed production and pollen viability, which is associated with the down-regulation of OseIF3f. Further cytological observations of pollen development revealed that the OseIF3f-RNAi lines showed no obvious abnormalities at the male meiotic stage and the unicellular microspore stage. However, compared to the wild type, OseIF3f-RNAi lines contained a higher percentage of arrested unicellular pollen at the bicellular stage and a higher percentage of arrested unicellular and bicellular pollen, and aborted pollen at the tricellular stage. These results indicate that OseIF3f plays a role in microgametogenesis.

  7. The site of embolization related to infarct size, oedema and clinical outcome in a rat stroke model - further translational stroke research

    DEFF Research Database (Denmark)

    Overgaard, Karsten; Rasmussen, Rune S; Johansen, Flemming F

    2010-01-01

    Reliable models are essential for translational stroke research to study the pathophysiology of ischaemic stroke in an effort to find therapies that may ultimately reduce oedema, infarction and mortality in the clinic. The purpose of this study was to investigate the relation between the site...... of arterial embolization and the subsequent oedema, infarction and clinical outcome in a rat embolic stroke model....

  8. Initial site characterisation of a dissolved hydrocarbon groundwater plume discharging to a surface water environment

    International Nuclear Information System (INIS)

    Westbrook, S.J.; Commonwealth Scientific and Industrial Research Organisation Land and Water, Wembley, WA; Davis, G.B.; Rayner, J.L.; Fisher, S.J.; Clement, T.P.

    2000-01-01

    Preliminary characterisation of a dissolved hydrocarbon groundwater plume flowing towards a tidally- and seasonally-forced estuarine system has been completed at a site in Perth, Western Australia. Installation and sampling of multiport boreholes enabled fine scale (0.5-m) vertical definition of hydrocarbon concentrations. Vertical electrical conductivity profiles from multiport and spear probe sampling into the river sediments indicated that two groundwater/river water interfaces or dispersion zones are present: (a) an upper dispersion zone between brackish river water and groundwater, and (b) a lower interface between groundwater and deeper saline water. On-line water level loggers show that near-shore groundwater levels are also strongly influence by tidal oscillation. Results from the initial site characterisation will be used to plan further investigations of contaminated groundwater/surface water interactions and the biodegradation processes occurring at the site

  9. Translational initiation in Leishmania tarentolae and Phytomonas serpens (Kinetoplastida) is strongly influenced by pre-ATG triplet and its 5´ sequence context

    Czech Academy of Sciences Publication Activity Database

    Lukeš, Julius; Paris, Zdeněk; Regmi, Sandesh; Breitling, R.; Mureev, S.; Kushnir, S.; Pyatkov, K.; Jirků, Milan; Alexandrov, K. A.

    2006-01-01

    Roč. 148, č. 2 (2006), s. 125-132 ISSN 0166-6851 R&D Projects: GA AV ČR 1QS600220554 Grant - others:Deutsche Forschungsgemeinschaft(DE) AL484/5-3 Institutional research plan: CEZ:AV0Z60220518 Keywords : Kinetoplastida * translation * initiation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.641, year: 2006

  10. ERK 1/2 kinase metabolic pathway is responsible for phosphorylation of translation initiation factor eIF4E during in vitro maturation of pig oocytes

    Czech Academy of Sciences Publication Activity Database

    Ellederová, Zdeňka; Cais, Ondřej; Šušor, Andrej; Uhlířová, Kateřina; Kovářová, Hana; Jelínková, Lucie; Tomek, W.; Kubelka, Michal

    2008-01-01

    Roč. 75, č. 2 (2008), s. 309-317 ISSN 1040-452X R&D Projects: GA ČR GA524/04/0104 Grant - others:Deutsche Forschungsgemeinschaft(DE) 463 TSE 113/28 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50110509 Keywords : meiosis * translation initiation * eIF4E Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.287, year: 2008

  11. Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein.

    Science.gov (United States)

    Zhao, Hui; Wang, Hong; Liu, Huihui; Teng, Maikun; Li, Xu

    2012-11-01

    The Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2Bℇ, eIF4γ, eIF5 etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space group I4, with unit-cell parameters a=b=81.05, c=57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal.

  12. Epstein Barr virus-encoded EBNA1 interference with MHC class I antigen presentation reveals a close correlation between mRNA translation initiation and antigen presentation.

    Directory of Open Access Journals (Sweden)

    Sebastien Apcher

    Full Text Available Viruses are known to employ different strategies to manipulate the major histocompatibility (MHC class I antigen presentation pathway to avoid recognition of the infected host cell by the immune system. However, viral control of antigen presentation via the processes that supply and select antigenic peptide precursors is yet relatively unknown. The Epstein-Barr virus (EBV-encoded EBNA1 is expressed in all EBV-infected cells, but the immune system fails to detect and destroy EBV-carrying host cells. This immune evasion has been attributed to the capacity of a Gly-Ala repeat (GAr within EBNA1 to inhibit MHC class I restricted antigen presentation. Here we demonstrate that suppression of mRNA translation initiation by the GAr in cis is sufficient and necessary to prevent presentation of antigenic peptides from mRNAs to which it is fused. Furthermore, we demonstrate a direct correlation between the rate of translation initiation and MHC class I antigen presentation from a certain mRNA. These results support the idea that mRNAs, and not the encoded full length proteins, are used for MHC class I restricted immune surveillance. This offers an additional view on the role of virus-mediated control of mRNA translation initiation and of the mechanisms that control MHC class I restricted antigen presentation in general.

  13. Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1

    Czech Academy of Sciences Publication Activity Database

    Tellier, G.; Lenne, A.; Cailliau-Maggio, K.; Cabezas-Cruz, A.; Valdés, James J.; Martoriati, A.; Aliouat, El M.; Gosset, P.; Delaire, B.; Fréville, A.; Pierrot, C.; Khalife, J.

    2016-01-01

    Roč. 7, MAY 26 (2016), č. článku 777. ISSN 1664-302X Institutional support: RVO:60077344 Keywords : Plasmodium falciparum * Protein Phosphatase type1 * eIF2b * protein-protein interaction * translation complex Subject RIV: EE - Microbiology, Virology Impact factor: 4.076, year: 2016

  14. Keats’s sonnet on Chapman’s translation of Homer: manuscript of early draft and initial publication

    Directory of Open Access Journals (Sweden)

    Brian Franklin Head

    2016-08-01

    Full Text Available This study presents the earliest known manuscript of Keats's sonnet to Chapman’s translation of the Iliad (1611, in comparison with the first publication of the poem by Keats (1816. A comparative reading is provided, along with related philological and literary comments.

  15. Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation.

    Science.gov (United States)

    Kozel, Caitlin; Thompson, Brytteny; Hustak, Samantha; Moore, Chelsea; Nakashima, Akio; Singh, Chingakham Ranjit; Reid, Megan; Cox, Christian; Papadopoulos, Evangelos; Luna, Rafael E; Anderson, Abbey; Tagami, Hideaki; Hiraishi, Hiroyuki; Slone, Emily Archer; Yoshino, Ken-Ichi; Asano, Masayo; Gillaspie, Sarah; Nietfeld, Jerome; Perchellet, Jean-Pierre; Rothenburg, Stefan; Masai, Hisao; Wagner, Gerhard; Beeser, Alexander; Kikkawa, Ushio; Fleming, Sherry D; Asano, Katsura

    2016-10-14

    ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. A New GLORIA (Global Research Initiative in Alpine Environments Site in Southwestern Montana

    Science.gov (United States)

    Apple, M. E.; Warden, J. E.; Apple, C. J.; Pullman, T. Y.; Gallagher, J. H.

    2008-12-01

    Global climate change is predicted to have a major impact on the alpine environments and plants of western North America. Alpine plant species and treelines may migrate upwards due to warmer temperatures. Species composition, vegetation cover, and the phenology of photosynthesis, flowering, pollination, and seed dispersal may change. The Global Research Initiative in Alpine Environments (GLORIA) is a network of alpine sites established with the goal of understanding the interactions between climate change and alpine plants. The Continental Divide traverses Southwestern Montana, where the flora contains representative species from both sides of the divide. In the summer of 2008, we established a GLORIA site in southwestern Montana east of the Continental Divide with the objective of determining whether the temperature changes at the site, and if so, how temperature changes influence alpine plants. We are monitoring soil temperature along with species composition and percent cover of alpine plants at four sub-summits along an ascending altitudinal gradient. We placed the treeline, lower alpine, and upper alpine sites on Mt. Fleecer (45°49'36.06"N, 112°48'08.18"W, 2886.2 m (9469 ft)) and the highest sub-summit on Keokirk Mountain, (45°35'37.94"N, 112°57'03.89"W, 2987.3 m (9801 ft)) in the Pioneer Range. Interesting species on these mountains include Lewisia pygmaea, the Pygmy Bitterroot, Silene acaulis, the Moss Campion, Eritrichium nanum, the Alpine Forget-Me-Not, Lloydia serotina, the Alpine Lily, and Pinus albicaulis, the Whitebark Pine. This new site will remain in place indefinitely. Baseline and subsequent data from this site will be linked with the global network of GLORIA sites with which we will assess changes in alpine flora.

  17. NIa-Pro of Papaya ringspot virus interacts with Carica papaya eukaryotic translation initiation factor 3 subunit G (CpeIF3G).

    Science.gov (United States)

    Gao, Le; Tuo, Decai; Shen, Wentao; Yan, Pu; Li, Xiaoying; Zhou, Peng

    2015-02-01

    The interaction of papaya eukaryotic translation initiation factor 3 subunit G (CpeIF3G) with Papaya ringspot virus (PRSV) NIa-Pro was validated using a bimolecular fluorescence complementation assay in papaya protoplasts based on the previous yeast two-hybrid assay results. The C-terminal (residues 133-239) fragment of PRSV NIa-Pro and the central domain (residues 59-167) of CpeIF3G were required for effective interaction between NIa-Pro and CpeIF3G as shown by a Sos recruitment yeast two-hybrid system with several deletion mutants of NIa-Pro and CpeIF3G. The central domain of CpeIF3G, which contains a C2HC-type zinc finger motif, is required to bind to other eIFs of the translational machinery. In addition, quantitative real-time reverse transcription PCR assay confirmed that PRSV infection leads to a 2- to 4.5-fold up-regulation of CpeIF3G mRNA in papaya. Plant eIF3G is involved in various stress response by enhancing the translation of resistance-related proteins. It is proposed that the NIa-Pro-CpeIF3G interaction may impair translation preinitiation complex assembly of defense proteins and interfere with host defense.

  18. Preliminary safety evaluation, based on initial site investigation data. Planning document

    International Nuclear Information System (INIS)

    Hedin, Allan

    2002-12-01

    This report is a planning document for the preliminary safety evaluations (PSE) to be carried out at the end of the initial stage of SKBs ongoing site investigations for a deep repository for spent nuclear fuel. The main purposes of the evaluations are to determine whether earlier judgements of the suitability of the candidate area for a deep repository with respect to long-term safety holds up in the light of borehole data and to provide feed-back to continued site investigations and site specific repository design. The preliminary safety evaluations will be carried out by a safety assessment group, based on a site model, being part of a site description, provided by a site modelling group and a repository layout within that model suggested by a repository engineering group. The site model contains the geometric features of the site as well as properties of the host rock. Several alternative interpretations of the site data will likely be suggested. Also the biosphere is included in the site model. A first task for the PSE will be to compare the rock properties described in the site model to previously established criteria for a suitable host rock. This report gives an example of such a comparison. In order to provide more detailed feedback, a number of thermal, hydrological, mechanical and chemical analyses of the site will also be included in the evaluation. The selection of analyses is derived from the set of geosphere and biosphere analyses preliminarily planned for the comprehensive safety assessment named SR-SITE, which will be based on a complete site investigation. The selection is dictated primarily by the expected feedback to continued site investigations and by the availability of data after the PSE. The repository engineering group will consider several safety related factors in suggesting a repository layout: Thermal calculations will be made to determine a minimum distance between canisters avoiding canister surface temperatures above 100 deg C

  19. An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome.

    Directory of Open Access Journals (Sweden)

    Yi-Hsuan Wu

    Full Text Available The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5' end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5' UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5' UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5' UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome.

  20. Global Research Initiative in Alpine Environments: A New GLORIA Site in Southwestern Montana

    Science.gov (United States)

    Apple, M. E.; Pullman, T. Y.; Mitman, G. G.

    2007-12-01

    Global climate change is expected to have pronounced effects on the alpine environments and thus the alpine plants of western North America. Predicted responses include an upward migration of treelines, altered species compositions, changes in the percentage of land covered by vegetation, and a change in the phenology of alpine plants. To determine the effects of climate change on the alpine flora of southwestern Montana, we are installing a GLORIA (Global Research Initiative in Alpine Environments) site in order to monitor temperature, species composition, and percent cover of vascular plants, lichens, and mosses along an ascending altitudinal gradient. We are including lichens and mosses because of their importance as ecological indicator species. The abundance and spatial distribution of lichens and mosses provides essential baseline data for long-term monitoring of local and global impacts on the environment. Mt. Fleecer (9250 ft.), which is west of the continental divide and semi-isolated from other peaks in the Anaconda-Pintlar Range, is currently the most likely location for the southwestern Montana GLORIA site. Mt. Fleecer is accessible because it does not have the steep and hazardous glaciated talus cirques that characterize many of the neighboring, higher peaks. However, if an accessible and suitable higher summit is found, then it will be included as the highest summit in the GLORIA site. Interesting species at Mt. Fleecer include the whitebark pine, Pinus albicaulis, which is a keystone species in high mountain ecosystems of the western United States and Canada, the green gentian, Frasera speciosa, and the shooting star, Dodecatheon pulchellum. Data from this site will become part of a global network of GLORIA sites with which we will assess changes in alpine flora. Information gained from this GLORIA site can also be used as a link between studies of alpine climate change and related investigations on the timing of snowmelt and its influence on

  1. Initial source and site characterization studies for the U.C. Santa Barbara campus

    Energy Technology Data Exchange (ETDEWEB)

    Archuleta, R.; Nicholson, C.; Steidl, J.; Gurrola, L.; Alex, C.; Cochran, E.; Ely, G.; Tyler, T. [University of California, Santa Barbara (United States)

    1997-12-01

    The University of California Campus-Laboratory Collaboration (CLC) project is an integrated 3 year effort involving Lawrence Livermore National Laboratory (LLNL) and four UC campuses - Los Angeles (UCLA), Riverside (UCR), Santa Barbara (UCSB), and San Diego (UCSD) - plus additional collaborators at San Diego State University (SDSU), at Los Alamos National Laboratory and in industry. The primary purpose of the project is to estimate potential ground motions from large earthquakes and to predict site-specific ground motions for one critical structure on each campus. This project thus combines the disciplines of geology, seismology, geodesy, soil dynamics, and earthquake engineering into a fully integrated approach. Once completed, the CLC project will provide a template to evaluate other buildings at each of the four UC campuses, as well as provide a methodology for evaluating seismic hazards at other critical sites in California, including other UC locations at risk from large earthquakes. Another important objective of the CLC project is the education of students and other professional in the application of this integrated, multidisciplinary, state-of-the-art approach to the assessment of earthquake hazard. For each campus targeted by the CLC project, the seismic hazard study will consist of four phases: Phase I - Initial source and site characterization, Phase II - Drilling, logging, seismic monitoring, and laboratory dynamic soil testing, Phase III - Modeling of predicted site-specific earthquake ground motions, and Phase IV - Calculations of 3D building response. This report cover Phase I for the UCSB campus and incudes results up through March 1997.

  2. Initial evaluation of the radioecological situation at the Semipalatinsk Test Site in the Republic of Kazakhstan

    International Nuclear Information System (INIS)

    Voigt, G.; Semiochkina, N.

    1998-01-01

    The Semipalatinsk Test Site (STS) located in the Republic of Kazakhstan (Figure 1.1) was one of the major nuclear weapon test sites of the former Soviet Union. At the site, four hundred fifty six nuclear explosions took place between 1949 and 1989 within the STS (Mikhailov et al. 1996; Dubasov et al. 1994a), resulting in radioactive contamination both within and around the STS. Incidences of radiation related illnesses in such areas may be higher than normal levels (Burkhart 1996). Published estimates of the resulting dose to the public vary according to the source, but an independent study (Grosche 1996) indicated that as many as 30,000-40,000 people could have been exposed to an average dose of 1.6 Sv (160 rem) or more (mainly due to short-lived radionuclides such as 131 I). A detailed international assessment of the impact of these tests on the local population has not yet been undertaken. A current investigation under the acronym, RADTEST, includes an evaluation of Semipalatinsk as part of a broad review of internal and external doses to people arising from nuclear tests at many different sites in the world. In the context of the European Commission funded project RESTORE (Restoration Strategy for Radioactive Contaminated Ecosystems) an attempt is being made to assess the present radiolecological situation in the STS. This initial report collates currently available data published in Russian-language literature and internal CIS reports, reports from Europe and the USA, and other international literature. In this initial evaluation, only an overview of published data made available to the RESTORE project is provided and briefly discussed. In addition, further assessments including experimental work are suggested. Additional sources of data will be pursued and will be integrated with experimental results in the final evaluation report. (orig.)

  3. Initial evaluation of the radioecological situation at the Semipalatinsk Test Site in the Republic of Kazakhstan

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, G.; Semiochkina, N. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Strahlenschutz

    1998-12-31

    The Semipalatinsk Test Site (STS) located in the Republic of Kazakhstan (Figure 1.1) was one of the major nuclear weapon test sites of the former Soviet Union. At the site, four hundred fifty six nuclear explosions took place between 1949 and 1989 within the STS (Mikhailov et al. 1996; Dubasov et al. 1994a), resulting in radioactive contamination both within and around the STS. Incidences of radiation related illnesses in such areas may be higher than normal levels (Burkhart 1996). Published estimates of the resulting dose to the public vary according to the source, but an independent study (Grosche 1996) indicated that as many as 30,000-40,000 people could have been exposed to an average dose of 1.6 Sv (160 rem) or more (mainly due to short-lived radionuclides such as {sup 131}I). A detailed international assessment of the impact of these tests on the local population has not yet been undertaken. A current investigation under the acronym, RADTEST, includes an evaluation of Semipalatinsk as part of a broad review of internal and external doses to people arising from nuclear tests at many different sites in the world. In the context of the European Commission funded project RESTORE (Restoration Strategy for Radioactive Contaminated Ecosystems) an attempt is being made to assess the present radiolecological situation in the STS. This initial report collates currently available data published in Russian-language literature and internal CIS reports, reports from Europe and the USA, and other international literature. In this initial evaluation, only an overview of published data made available to the RESTORE project is provided and briefly discussed. In addition, further assessments including experimental work are suggested. Additional sources of data will be pursued and will be integrated with experimental results in the final evaluation report. (orig.)

  4. Localization of human RNase Z isoforms: dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation.

    Directory of Open Access Journals (Sweden)

    Walter Rossmanith

    Full Text Available RNase Z is an endonuclease responsible for the removal of 3' extensions from tRNA precursors, an essential step in tRNA biogenesis. Human cells contain a long form (RNase Z(L encoded by ELAC2, and a short form (RNase Z(S; ELAC1. We studied their subcellular localization by expression of proteins fused to green fluorescent protein. RNase Z(S was found in the cytosol, whereas RNase Z(L localized to the nucleus and mitochondria. We show that alternative translation initiation is responsible for the dual targeting of RNase Z(L. Due to the unfavorable context of the first AUG of ELAC2, translation apparently also starts from the second AUG, whereby the mitochondrial targeting sequence is lost and the protein is instead routed to the nucleus. Our data suggest that RNase Z(L is the enzyme involved in both, nuclear and mitochondrial tRNA 3' end maturation.

  5. Translational autocontrol of the Escherichia coli hfq RNA chaperone gene.

    Science.gov (United States)

    Vecerek, Branislav; Moll, Isabella; Bläsi, Udo

    2005-06-01

    The conserved bacterial RNA chaperone Hfq has been shown to play an important role in post-transcriptional regulation. Here, we demonstrate that Hfq synthesis is autoregulated at the translational level. We have mapped two Hfq binding sites in the 5'-untranslated region of hfq mRNA and show that Hfq binding inhibits formation of the translation initiation complex. In vitro translation and in vivo studies further revealed that Hfq binding to both sites is required for efficient translational repression of hfq mRNA.

  6. Small RNAs targeting transcription start site induce heparanase silencing through interference with transcription initiation in human cancer cells.

    Directory of Open Access Journals (Sweden)

    Guosong Jiang

    Full Text Available Heparanase (HPA, an endo-h-D-glucuronidase that cleaves the heparan sulfate chain of heparan sulfate proteoglycans, is overexpressed in majority of human cancers. Recent evidence suggests that small interfering RNA (siRNA induces transcriptional gene silencing (TGS in human cells. In this study, transfection of siRNA against -9/+10 bp (siH3, but not -174/-155 bp (siH1 or -134/-115 bp (siH2 region relative to transcription start site (TSS locating at 101 bp upstream of the translation start site, resulted in TGS of heparanase in human prostate cancer, bladder cancer, and gastric cancer cells in a sequence-specific manner. Methylation-specific PCR and bisulfite sequencing revealed no DNA methylation of CpG islands within heparanase promoter in siH3-transfected cells. The TGS of heparanase did not involve changes of epigenetic markers histone H3 lysine 9 dimethylation (H3K9me2, histone H3 lysine 27 trimethylation (H3K27me3 or active chromatin marker acetylated histone H3 (AcH3. The regulation of alternative splicing was not involved in siH3-mediated TGS. Instead, siH3 interfered with transcription initiation via decreasing the binding of both RNA polymerase II and transcription factor II B (TFIIB, but not the binding of transcription factors Sp1 or early growth response 1, on the heparanase promoter. Moreover, Argonaute 1 and Argonaute 2 facilitated the decreased binding of RNA polymerase II and TFIIB on heparanase promoter, and were necessary in siH3-induced TGS of heparanase. Stable transfection of the short hairpin RNA construct targeting heparanase TSS (-9/+10 bp into cancer cells, resulted in decreased proliferation, invasion, metastasis and angiogenesis of cancer cells in vitro and in athymic mice models. These results suggest that small RNAs targeting TSS can induce TGS of heparanase via interference with transcription initiation, and significantly suppress the tumor growth, invasion, metastasis and angiogenesis of cancer cells.

  7. Somitogenesis clock-wave initiation requires differential decay and multiple binding sites for clock protein.

    Directory of Open Access Journals (Sweden)

    Mark Campanelli

    2010-04-01

    Full Text Available Somitogenesis is a process common to all vertebrate embryos in which repeated blocks of cells arise from the presomitic mesoderm (PSM to lay a foundational pattern for trunk and tail development. Somites form in the wake of passing waves of periodic gene expression that originate in the tailbud and sweep posteriorly across the PSM. Previous work has suggested that the waves result from a spatiotemporally graded control protein that affects the oscillation rate of clock-gene expression. With a minimally constructed mathematical model, we study the contribution of two control mechanisms to the initial formation of this gene-expression wave. We test four biologically motivated model scenarios with either one or two clock protein transcription binding sites, and with or without differential decay rates for clock protein monomers and dimers. We examine the sensitivity of wave formation with respect to multiple model parameters and robustness to heterogeneity in cell population. We find that only a model with both multiple binding sites and differential decay rates is able to reproduce experimentally observed waveforms. Our results show that the experimentally observed characteristics of somitogenesis wave initiation constrain the underlying genetic control mechanisms.

  8. Development of movie caption translation lecture site using MobileMotion{sub TM}; MobileMotion{sub TM} wo mochiita jimaku hon'yaku koza site no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    The site of Internet that performs the correspondence education for bringing up a movie caption translator was developed. Correspondence education that fully deepens understanding was obtained by distributing a motion picture using MPEG-4 distribution software (MobileMotion{sub TM}) and performing the learning based on bi-directional communication. HTML distribution and E-mail transmission and reception are done from Gaga Communications, and a MobileMotion{sub TM} file is distributed from the OnDemand Server of Toshiba. This reduces the communication traffic of heavy motion picture data. (translated by NEDO)

  9. RNA interference-mediated silencing of eukaryotic translation initiation factor 3, subunit B (EIF3B) gene expression inhibits proliferation of colon cancer cells.

    Science.gov (United States)

    Wang, Zheng; Chen, Jinxian; Sun, Jianhua; Cui, Zhe; Wu, Hui

    2012-06-26

    A key factor underlying the control of the cellular growth, size and proliferation involves the regulation of the total protein synthesis. Most often, the initial stages of mRNA translation are rate limiting, which involves a group of eukaryotic translation initiation factors (EIFs). Research advances focused on the inhibition of their expression and activity hold the key to the initiation and progression of tumor and tumor prognosis. We performed RNA interference (RNAi) with the lentivirus vector system to silence the EIF3B gene using the colon cancer cell strain SW1116. The negative control included the normal target cells infected with the negative control virus whereas the knockdown cells included the normal target cells transfected with the RNAi target virus. We tested the inhibition resulting from the decreased expression of EIF3B gene on the proliferation rate of SW1116 cells, including the cell cycle, apoptosis and clonability. Compared with the negative control, the impact of EIF3B gene expression in SW1116 cells on the levels of mRNA and protein in the knockdown group, was significantly inhibited (P cell proliferation rate and clonability were also significantly inhibited (P cells in the G1 phase (P cells.

  10. Initial site characterization and evaluation of radionuclide contaminated soil waste burial grounds

    International Nuclear Information System (INIS)

    Phillips, S.J.; Reisenauer, A.E.; Rickard, W.H.; Sandness, G.A.

    1977-02-01

    A survey of historical records and literature containing information on the contents of 300 Area and North Burial Grounds was completed. Existing records of radioactive waste location, type, and quantity within each burial ground facility were obtained and distributed to cooperating investigators. A study was then initiated to evaluate geophysical exploration techniques for mapping buried waste materials, waste containers, and trench boundaries. Results indicate that a combination of ground penetrating radar, magnetometer, metal detector, and acoustic measurements will be effective but will require further study, hardware development, and field testing. Drilling techniques for recovering radionuclide-contaminated materials and sediment cores were developed and tested. Laboratory sediment characterization and fluid transport and monitoring analyses were begun by installation of in situ transducers at the 300 North Burial Ground site. Biological transport mechanisms that control radionuclide movement at contaminated sites were also studied. Flora and fauna presently inhabiting specific burial ground areas were identified and analyzed. Future monitoring of specific mammal populations will permit determination of dose rate and pathways of contaminated materials contained in and adjacent to burial ground sites

  11. A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo

    DEFF Research Database (Denmark)

    Damgaard, Christian Kroun; Kahns, Søren; Lykke-Andersen, Søren

    2008-01-01

    Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin mRNAs, harb...... a promoter-proximal 5′ splice site via its U1 snRNA interaction can feed back to stimulate transcription initiation by enhancing preinitiation complex assembly.......Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin mRNAs......, harboring wild-type or various 5′ splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5′ splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced...

  12. Assessment of Effectiveness of Geologic Isolation Systems: REFERENCE SITE INITIAL ASSESSMENT FOR A SALT DOME REPOSITORY

    Energy Technology Data Exchange (ETDEWEB)

    Harwell, M. A.; Brandstetter, A.; Benson, G. L.; Raymond, J. R.; Brandley, D. J.; Serne, R. J.; Soldat, J. K.; Cole, C. R.; Deutsch, W. J.; Gupta, S. K.; Harwell, C. C.; Napier, B. A.; Reisenauer, A. E.; Prater, L. S.; Simmons, C. S.; Strenge, D. L.; Washburn, J. F.; Zellmer, J. T.

    1982-06-01

    As a methodology demonstration for the Office of Nuclear Waste Isolation (ONWI), the Assessment of Effectiveness of Geologic Isolation Systems (AEGIS) Program conducted an initial reference site analysis of the long-term effectiveness of a salt dome repository. The Hainesville Salt Dome in Texas was chosen to be representative of the Gulf Coast interior salt domes; however, the Hainesville Site has been eliminated as a possible nuclear waste repository site. The data used for this exercise are not adequate for an actual assessment, nor have all the parametric analyses been made that would adequately characterize the response of the geosystem surrounding the repository. Additionally, because this was the first exercise of the complete AEGIS and WASTE Rock Interaction Technology (WRIT) methodology, this report provides the initial opportunity for the methodology, specifically applied to a site, to be reviewed by the community outside the AEGIS. The scenario evaluation, as a part of the methodology demonstration, involved consideration of a large variety of potentially disruptive phenomena, which alone or in concert could lead to a breach in a salt dome repository and to a subsequent transport of the radionuclides to the environment. Without waste- and repository-induced effects, no plausible natural geologic events or processes which would compromise the repository integrity could be envisioned over the one-million-year time frame after closure. Near-field (waste- and repository-induced) effects were excluded from consideration in this analysis, but they can be added in future analyses when that methodology development is more complete. The potential for consequential human intrusion into salt domes within a million-year time frame led to the consideration of a solution mining intrusion scenario. The AEGIS staff developed a specific human intrusion scenario at 100 years and 1000 years post-closure, which is one of a whole suite of possible scenarios. This scenario

  13. Assessment of Effectiveness of Geologic Isolation Systems: REFERENCE SITE INITIAL ASSESSMENT FOR A SALT DOME REPOSITORY

    Energy Technology Data Exchange (ETDEWEB)

    Harwell, M. A.; Brandstetter, A.; Benson, G. L.; Bradley, D. J.; Serne, R. J.; Soldat, J. K; Cole, C. R.; Deutsch, W. J.; Gupta, S. K.; Harwell, C. C.; Napier, B. A.; Reisenauer, A. E.; Prater, L. S.; Simmons, C. S.; Strenge, D. L.; Washburn, J. F.; Zellmer, J. T.

    1982-06-01

    As a methodology demonstration for the Office of Nuclear Waste Isolation (ONWI), the Assessment of Effectiveness of Geologic Isolation Systems (AEGIS) Program conducted an initial reference site analysis of the long-term effectiveness of a salt dome repository. The Hainesville Salt Dome in Texas was chosen to be representative of the Gulf Coast interior salt domes; however, the Hainesville Site has been eliminated as a possible nuclear waste repository site. The data used for this exercise are not adequate for an actual assessment, nor have all the parametric analyses been made that would adequately characterize the response of the geosystem surrounding the repository. Additionally, because this was the first exercise of the complete AEGIS and WASTE Rock Interaction Technology (WRIT) methodology, this report provides the initial opportunity for the methodology, specifically applied to a site, to be reviewed by the community outside the AEGIS. The scenario evaluation, as a part of the methodology demonstration, involved consideration of a large variety of potentially disruptive phenomena, which alone or in concert could lead to a breach in a salt dome repository and to a subsequent transport of the radionuclides to the environment. Without waste- and repository-induced effects, no plausible natural geologic events or processes which would compromise the repository integrity could be envisioned over the one-million-year time frame after closure. Near-field (waste- and repository-induced) effects were excluded from consideration in this analysis, but they can be added in future analyses when that methodology development is more complete. The potential for consequential human intrusion into salt domes within a million-year time frame led to the consideration of a solution mining intrusion scenario. The AEGIS staff developed a specific human intrusion scenario at 100 years and 1000 years post-closure, which is one of a whole suite of possible scenarios. This scenario

  14. Russian translations for Cochrane.

    Science.gov (United States)

    Yudina, E V; Ziganshina, L E

    2015-01-01

    Cochrane collaboration has made a huge contribution to the development of evidence-based medicine; Cochrane work is the international gold standard of independent, credible and reliable high-quality information in medicine. Over the past 20 years the Cochrane Collaboration helped transforming decision-making in health and reforming it significantly, saving lives and contributing to longevity [1]. Until recently, Cochrane evidence were available only in English, which represents a significant barrier to their wider use in non-English speaking countries. To provide access to evidence, obtained from Cochrane Reviews, for health professionals and general public (from non-English-speaking countries), bypassing language barriers, Cochrane collaboration in 2014 initiated an international project of translating Plain language summaries of Cochrane Reviews into other languages [2, 3]. Russian translations of Plain language summaries were started in May 2014 by the team from Kazan Federal University (Department of Basic and Clinical Pharmacology; 2014-2015 as an Affiliated Centre in Tatarstan of the Nordic Cochrane Centre, since August 2015 as Cochrane Russia, a Russian branch of Cochrane Nordic, Head - Liliya Eugenevna Ziganshina) on a voluntary basis. To assess the quality of Russian translations of Cochrane Plain Language Summaries (PLS) and their potential impact on the Russian speaking community through user feedback with the overarching aim of furthering the translations project. We conducted the continuous online survey via Google Docs. We invited respondents through the electronic Russian language discussion forum on Essential Medicines (E-lek), links to survey on the Russian Cochrane.org website, invitations to Cochrane contributors registered in Archie from potential Russian-speaking countries. We set up the survey in Russian and English. The respondents were asked to respond to the questionnaire regarding the relevance and potential impact of the Cochrane Russian

  15. Eukaryotic translation initiation factor 5A inhibition alters physiopathology and immune responses in a “humanized” transgenic mouse model of type 1 diabetes

    OpenAIRE

    Imam, Shahnawaz; Mirmira, Raghavendra G.; Jaume, Juan C.

    2014-01-01

    Therapeutic options for treatment of type 1 diabetes (T1D) are still missing. New avenues for immune modulation need to be developed. Here we attempted at altering the diabetes outcome of our humanized model of T1D by inhibiting translation-initiation factor eIF5A hypusination in vivo. Double-transgenic (DQ8-GAD65) mice were immunized with adenoviral vectors carrying GAD65 for diabetes induction. Animals were subsequently treated with deoxyhypusine synthase (DHS) inhibitor GC7 and monitored f...

  16. ReportSites - A Computational Method to Extract Positional and Physico- Chemical Information from Large-Scale Proteomic Post-Translational Modification Datasets

    DEFF Research Database (Denmark)

    Edwards, Alistair; Edwards, Gregory; Larsen, Martin Røssel

    2012-01-01

    environment of a particular amino acid residue, or group of residues, within large-scale proteomic data sets, using peptide sequences characterized by mass spectrometry combined with protein sequence databases. The program is ideally suited to distilling regional and spatial information from post......-translational modification data sets, wherein patterns of sequence surrounding processed sites may reveal more about the functional and structural requirements of the modification and the biochemical processes that regulate them. Results: We developed Report Sites using a test set of phosphoproteomic data from rat...

  17. Translation and Initial Validation of the Japanese Version of the Self-Beliefs Related to Social Anxiety Scale.

    Science.gov (United States)

    Maeda, Shunta; Shimada, Hironori; Sato, Tomoya; Tashiro, Kyoko; Tanaka, Yuki

    2017-04-01

    Cognitive models of social anxiety posit that there are several types of maladaptive beliefs responsible for persistent social anxiety. Although these beliefs are theoretically important, currently there is no validated measure of these beliefs in Japan. In the present study, we translated into Japanese a well-validated measure of these beliefs, the Self-Beliefs Related to Social Anxiety (SBSA) Scale. The psychometric properties of the scale were also examined in two nonclinical samples ( ns = 401 and 30). Using confirmatory factor analysis, the Japanese version of the SBSA was found to have a correlated three-factor structure that consisted of "conditional beliefs," "unconditional beliefs," and "high standard beliefs." In addition, the Japanese version of the SBSA and its subscales demonstrated good internal consistency reliability and test-retest reliability. The Japanese version of the SBSA also demonstrated good convergent and divergent validity. Future applications of the Japanese version of the SBSA are discussed.

  18. Machine Translation Project

    Science.gov (United States)

    Bajis, Katie

    1993-01-01

    The characteristics and capabilities of existing machine translation systems were examined and procurement recommendations were developed. Four systems, SYSTRAN, GLOBALINK, PC TRANSLATOR, and STYLUS, were determined to meet the NASA requirements for a machine translation system. Initially, four language pairs were selected for implementation. These are Russian-English, French-English, German-English, and Japanese-English.

  19. How MCM loading and spreading specify eukaryotic DNA replication initiation sites [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Olivier Hyrien

    2016-08-01

    Full Text Available DNA replication origins strikingly differ between eukaryotic species and cell types. Origins are localized and can be highly efficient in budding yeast, are randomly located in early fly and frog embryos, which do not transcribe their genomes, and are clustered in broad (10-100 kb non-transcribed zones, frequently abutting transcribed genes, in mammalian cells. Nonetheless, in all cases, origins are established during the G1-phase of the cell cycle by the loading of double hexamers of the Mcm 2-7 proteins (MCM DHs, the core of the replicative helicase. MCM DH activation in S-phase leads to origin unwinding, polymerase recruitment, and initiation of bidirectional DNA synthesis. Although MCM DHs are initially loaded at sites defined by the binding of the origin recognition complex (ORC, they ultimately bind chromatin in much greater numbers than ORC and only a fraction are activated in any one S-phase. Data suggest that the multiplicity and functional redundancy of MCM DHs provide robustness to the replication process and affect replication time and that MCM DHs can slide along the DNA and spread over large distances around the ORC. Recent studies further show that MCM DHs are displaced along the DNA by collision with transcription complexes but remain functional for initiation after displacement. Therefore, eukaryotic DNA replication relies on intrinsically mobile and flexible origins, a strategy fundamentally different from bacteria but conserved from yeast to human. These properties of MCM DHs likely contribute to the establishment of broad, intergenic replication initiation zones in higher eukaryotes.

  20. DbPTM 3.0: an informative resource for investigating substrate site specificity and functional association of protein post-translational modifications.

    Science.gov (United States)

    Lu, Cheng-Tsung; Huang, Kai-Yao; Su, Min-Gang; Lee, Tzong-Yi; Bretaña, Neil Arvin; Chang, Wen-Chi; Chen, Yi-Ju; Chen, Yu-Ju; Huang, Hsien-Da

    2013-01-01

    Protein modification is an extremely important post-translational regulation that adjusts the physical and chemical properties, conformation, stability and activity of a protein; thus altering protein function. Due to the high throughput of mass spectrometry (MS)-based methods in identifying site-specific post-translational modifications (PTMs), dbPTM (http://dbPTM.mbc.nctu.edu.tw/) is updated to integrate experimental PTMs obtained from public resources as well as manually curated MS/MS peptides associated with PTMs from research articles. Version 3.0 of dbPTM aims to be an informative resource for investigating the substrate specificity of PTM sites and functional association of PTMs between substrates and their interacting proteins. In order to investigate the substrate specificity for modification sites, a newly developed statistical method has been applied to identify the significant substrate motifs for each type of PTMs containing sufficient experimental data. According to the data statistics in dbPTM, >60% of PTM sites are located in the functional domains of proteins. It is known that most PTMs can create binding sites for specific protein-interaction domains that work together for cellular function. Thus, this update integrates protein-protein interaction and domain-domain interaction to determine the functional association of PTM sites located in protein-interacting domains. Additionally, the information of structural topologies on transmembrane (TM) proteins is integrated in dbPTM in order to delineate the structural correlation between the reported PTM sites and TM topologies. To facilitate the investigation of PTMs on TM proteins, the PTM substrate sites and the structural topology are graphically represented. Also, literature information related to PTMs, orthologous conservations and substrate motifs of PTMs are also provided in the resource. Finally, this version features an improved web interface to facilitate convenient access to the resource.

  1. Left Transperitoneal Adrenalectomy with a Laparoendoscopic Single-Site Surgery Combined Technique: Initial Case Reports

    Directory of Open Access Journals (Sweden)

    Yasuhiro Sumino

    2011-01-01

    Full Text Available Laparoendoscopic single-site surgery (LESS is a step toward the development of minimally invasive surgery. It is initially difficult for surgeons with limited experience to perform the surgery. We describe two cases of left adrenalectomy with a LESS combined with the addition of an accessory port. After a 2.5-cm skin incision was made at the level of the paraumbilicus to insert the primary 12-mm trocar for the laparoscope, a 5-mm nonbladed trocar was placed through the skin incision side-by-side with the primary trocar. A second 3-mm nonbladed trocar was then placed along the anterior axillary line; a multichannel trocar was not used as a single port. Both adrenalectomies were completed successfully. In patients with a minor adrenal tumor, a combined technique using LESS and an additional port is easier than LESS alone and may, therefore, be a bridge between the conventional laparoscopic approach and LESS.

  2. Internal ribosome entry site-mediated translation of a mammalian mRNA is regulated by amino acid availability

    NARCIS (Netherlands)

    Fernandez, J.; Yaman, I.; Mishra, R.; Merrick, W. C.; Snider, M. D.; Lamers, W. H.; Hatzoglou, M.

    2001-01-01

    The cationic amino acid transporter, Cat-1, facilitates the uptake of the essential amino acids arginine and lysine. Amino acid starvation causes accumulation and increased translation of cat-1 mRNA, resulting in a 58-fold increase in protein levels and increased arginine uptake. A bicistronic mRNA

  3. U.S. Department of Energy's site screening, site selection, and initial characterization for storage of CO2 in deep geological formations

    Science.gov (United States)

    Rodosta, T.D.; Litynski, J.T.; Plasynski, S.I.; Hickman, S.; Frailey, S.; Myer, L.

    2011-01-01

    The U.S. Department of Energy (DOE) is the lead Federal agency for the development and deployment of carbon sequestration technologies. As part of its mission to facilitate technology transfer and develop guidelines from lessons learned, DOE is developing a series of best practice manuals (BPMs) for carbon capture and storage (CCS). The "Site Screening, Site Selection, and Initial Characterization for Storage of CO2 in Deep Geological Formations" BPM is a compilation of best practices and includes flowchart diagrams illustrating the general decision making process for Site Screening, Site Selection, and Initial Characterization. The BPM integrates the knowledge gained from various programmatic efforts, with particular emphasis on the Characterization Phase through pilot-scale CO2 injection testing of the Validation Phase of the Regional Carbon Sequestration Partnership (RCSP) Initiative. Key geologic and surface elements that suitable candidate storage sites should possess are identified, along with example Site Screening, Site Selection, and Initial Characterization protocols for large-scale geologic storage projects located across diverse geologic and regional settings. This manual has been written as a working document, establishing a framework and methodology for proper site selection for CO2 geologic storage. This will be useful for future CO2 emitters, transporters, and storage providers. It will also be of use in informing local, regional, state, and national governmental agencies of best practices in proper sequestration site selection. Furthermore, it will educate the inquisitive general public on options and processes for geologic CO2 storage. In addition to providing best practices, the manual presents a geologic storage resource and capacity classification system. The system provides a "standard" to communicate storage and capacity estimates, uncertainty and project development risk, data guidelines and analyses for adequate site characterization, and

  4. Translation Theory 'Translated'

    DEFF Research Database (Denmark)

    Wæraas, Arild; Nielsen, Jeppe

    2016-01-01

    common theoretical approaches to translation within the organization and management discipline: actor-network theory, knowledge-based theory, and Scandinavian institutionalism. Although each of these approaches already has borne much fruit in research, the literature is diverse and somewhat fragmented......Translation theory has proved to be a versatile analytical lens used by scholars working from different traditions. On the basis of a systematic literature review, this study adds to our understanding of the ‘translations’ of translation theory by identifying the distinguishing features of the most......, but also overlapping. We discuss the ways in which the three versions of translation theory may be combined and enrich each other so as to inform future research, thereby offering a more complete understanding of translation in and across organizational settings....

  5. Knockdown of eukaryotic translation initiation factor 3 subunit D (eIF3D) inhibits proliferation of acute myeloid leukemia cells.

    Science.gov (United States)

    Liu, Guo-Zhen; Liu, Ji-Zhu; Li, Xiao-Qing; Zhang, Li; Li, Shuang-Jing; Xiao, Tai-Wu; Wang, Jing-Xia; Li, Guang-Yao; Liu, Yusen

    2018-01-01

    Various eukaryotic translation initiation factors (eIFs) have been implicated in carcinoma development. Eukaryotic translation initiation factor 3 subunit D (eIF3D) has recently been shown to regulate the growth of several types of human cancer cells. However, the function of eIF3D in acute myeloid leukemia (AML) remains unclear. In this study, we investigated the expression of eIF3D in three AML cell lines and a lymphoblast cell line, and found that eIF3D was expressed in all four leukemia cell lines. To explore the role of eIF3D in AML cell proliferation, lentivirus-mediated RNA interference was applied to knock down the expression of eIF3D in U937 cells. The expression of eIF3D was significantly downregulated in U937 cells after eIF3D knockdown, as confirmed by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Knockdown of eIF3D significantly inhibited proliferation of U937 cells. Furthermore, flow cytometry analysis revealed that eIF3D silencing induced cell cycle arrest at the G2/M phase, ultimately leading to apoptosis. Our results indicate that eIF3D plays a key role in the proliferation of AML cells, and suggest that eIF3D silencing might be a potential therapeutic strategy for leukemia.

  6. TRADUCCIÓN DE ACRÓNIMOS Y SIGLAS EN TEXTOS MÉDICOS DE CARDIOLOGÍA / Translation of acronyms and initialisms in medical texts on cardiology

    Directory of Open Access Journals (Sweden)

    Ana V. Fernández Peraza

    2013-01-01

    cumplimiento de su función comunicativa fundamental, brindar información útil al personal de la salud. / Abstract Introduction and Objectives: Acronyms and initialisms are frequently used in medical texts. Their translation is not only language-dependent, but also culture-bound. The objective of this research was to analyze the problems associated to the translation from English into Spanish of acronyms and initialisms used in medical texts on Cardiology. Method: This is a qualitative, interpretive, descriptive, synchronic study based on the lexical analysis of acronyms and initialisms in the English source text (ST and the Spanish target text (TT, within the framework of descriptive translation studies. An empirical textual sample of 8 medical articles on Cardiology was analyzed, as well as their corresponding translations into Spanish. Results: In the corpus 83 acronyms and initialisms were identified. Only 15 were identified as acronyms. When analyzing the acronyms and initialisms, it was found that, in most of the cases, suitable solutions were given to the translation problems posed by their use in the TT, and such solutions coincided with the ones proposed in the reviewed literature on the topic. Some difficulties were found, however; they were related to the use of acronyms and initialisms appearing in the ST without their full form or without an explanation, especially those referring to institutions and regional or national organizations. Conclusions: Acronyms and initialisms are not only linguistic forms, but they are also objective phenomena within scientific culture and they are cultural referents. That is why their use and translation imply linguistic as well as extra-linguistic considerations which demand from the translator the use of auxiliary sources and reference materials, including interviews to specialists, to achieve quality and precision in the translated text. This will guarantee the fulfillment of its main communicative function, that is, to provide

  7. TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites.

    Science.gov (United States)

    Ammerman, Michelle L; Presnyak, Vladimir; Fisk, John C; Foda, Bardees M; Read, Laurie K

    2010-11-01

    TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5' ends of pan-edited RNAs than at their 3' ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3' to 5' progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3' ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA-RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3' to 5' progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs.

  8. Hepatitis C virus internal ribosome entry site (IRES) stem loop IIId contains a phylogenetically conserved GGG triplet essential for translation and IRES folding.

    Science.gov (United States)

    Jubin, R; Vantuno, N E; Kieft, J S; Murray, M G; Doudna, J A; Lau, J Y; Baroudy, B M

    2000-11-01

    The hepatitis C virus (HCV) internal ribosome entry site (IRES) is a highly structured RNA element that directs cap-independent translation of the viral polyprotein. Morpholino antisense oligonucleotides directed towards stem loop IIId drastically reduced HCV IRES activity. Mutagenesis studies of this region showed that the GGG triplet (nucleotides 266 through 268) of the hexanucleotide apical loop of stem loop IIId is essential for IRES activity both in vitro and in vivo. Sequence comparison showed that apical loop nucleotides (UUGGGU) were absolutely conserved across HCV genotypes and the GGG triplet was strongly conserved among related Flavivirus and Pestivirus nontranslated regions. Chimeric IRES elements with IIId derived from GB virus B (GBV-B) in the context of the HCV IRES possess translational activity. Mutations within the IIId stem loop that abolish IRES activity also affect the RNA structure in RNase T(1)-probing studies, demonstrating the importance of correct RNA folding to IRES function.

  9. Preliminary safety evaluation for the Laxemar subarea. Based on data and site descriptions after the initial site investigation stage

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Johan [JA Streamflow AB, Aelvsjoe (Sweden)

    2006-03-15

    The main objectives of this Preliminary Safety Evaluation (PSE) of the Laxemar subarea have been to determine, with limited efforts, whether the feasibility study's judgement of the suitability of the candidate area with respect to long-term safety holds up in the light of the actual site investigation data; to provide feedback to continued site investigations and site-specific repository design and to identify site-specific scenarios and geoscientific issues for further analyses. The PSE focuses on comparing the attained knowledge of the sites with the suitability criteria as set out by SKB in 2000. These criteria both concern properties of the site judged to be necessary for safety and engineering (requirements) and properties judged to be beneficial (preferences). The findings are then evaluated in order to provide feedback to continued investigations and design work. The PSE does not aim at comparing sites and does not assess compliance with safety and radiation protection criteria. The latter is eventually done in coming Safety Assessments. This preliminary safety evaluation shows that, according to existing data, the Laxemar subarea meets all safety requirements. The evaluation also shows that the Laxemar subarea meets most of the safety preferences, but for some aspects of the site description further reduction of the uncertainties would enhance the safety case. Despite the stated concerns, there is no reason, from a safety point of view, not to continue the Site Investigations at the Laxemar subarea. There are uncertainties to resolve and the safety would eventually need to be verified through a proper safety assessment. Only some of the uncertainties noted in the Site Descriptive Model have safety implications and need further resolution for this reason. Furthermore, uncertainties may need resolving for other reasons, such as giving an adequate assurance of site understanding or assisting in optimising design. Notably, there are questions about the

  10. Preliminary safety evaluation for the Laxemar subarea. Based on data and site descriptions after the initial site investigation stage

    International Nuclear Information System (INIS)

    Andersson, Johan

    2006-03-01

    The main objectives of this Preliminary Safety Evaluation (PSE) of the Laxemar subarea have been to determine, with limited efforts, whether the feasibility study's judgement of the suitability of the candidate area with respect to long-term safety holds up in the light of the actual site investigation data; to provide feedback to continued site investigations and site-specific repository design and to identify site-specific scenarios and geoscientific issues for further analyses. The PSE focuses on comparing the attained knowledge of the sites with the suitability criteria as set out by SKB in 2000. These criteria both concern properties of the site judged to be necessary for safety and engineering (requirements) and properties judged to be beneficial (preferences). The findings are then evaluated in order to provide feedback to continued investigations and design work. The PSE does not aim at comparing sites and does not assess compliance with safety and radiation protection criteria. The latter is eventually done in coming Safety Assessments. This preliminary safety evaluation shows that, according to existing data, the Laxemar subarea meets all safety requirements. The evaluation also shows that the Laxemar subarea meets most of the safety preferences, but for some aspects of the site description further reduction of the uncertainties would enhance the safety case. Despite the stated concerns, there is no reason, from a safety point of view, not to continue the Site Investigations at the Laxemar subarea. There are uncertainties to resolve and the safety would eventually need to be verified through a proper safety assessment. Only some of the uncertainties noted in the Site Descriptive Model have safety implications and need further resolution for this reason. Furthermore, uncertainties may need resolving for other reasons, such as giving an adequate assurance of site understanding or assisting in optimising design. Notably, there are questions about the

  11. The katG mRNA of Mycobacterium tuberculosis and Mycobacterium smegmatis is processed at its 5' end and is stabilized by both a polypurine sequence and translation initiation

    Directory of Open Access Journals (Sweden)

    Magnoni Francesca

    2008-04-01

    Full Text Available Abstract Background In Mycobacterium tuberculosis and in Mycobacterium smegmatis the furA-katG loci, encoding the FurA regulatory protein and the KatG catalase-peroxidase, are highly conserved. In M. tuberculosis furA-katG constitute a single operon, whereas in M. smegmatis a single mRNA covering both genes could not be found. In both species, specific 5' ends have been identified: the first one, located upstream of the furA gene, corresponds to transcription initiation from the furA promoter; the second one is the katG mRNA 5' end, located in the terminal part of furA. Results In this work we demonstrate by in vitro transcription and by RNA polymerase Chromatin immunoprecipitation that no promoter is present in the M. smegmatis region covering the latter 5' end, suggesting that it is produced by specific processing of longer transcripts. Several DNA fragments of M. tuberculosis and M. smegmatis were inserted in a plasmid between the sigA promoter and the lacZ reporter gene, and expression of the reporter gene was measured. A polypurine sequence, located four bp upstream of the katG translation start codon, increased beta-galactosidase activity and stabilized the lacZ transcript. Mutagenesis of this sequence led to destabilization of the mRNA. Analysis of constructs, in which the polypurine sequence of M. smegmatis was followed by an increasing number of katG codons, demonstrated that mRNA stability requires translation of at least 20 amino acids. In order to define the requirements for the 5' processing of the katG transcript, we created several mutations in this region and analyzed the 5' ends of the transcripts: the distance from the polypurine sequence does not seem to influence the processing, neither the sequence around the cutting point. Only mutations which create a double stranded region around the processing site prevented RNA processing. Conclusion This is the first reported case in mycobacteria, in which both a polypurine sequence

  12. Translation into Greek and initial validity and reliability testing of a modified version of the SCIM III, in both English and Greek, for self-use.

    Science.gov (United States)

    Michailidou, Christina; Marston, Louise; De Souza, Lorraine H

    2016-01-01

    To translate and culturally adapt the Spinal Cord Injury Measure version III (SCIM III) into Greek (GR-SCIM III). To conduct initial testing of psychometric properties of both measures by self-report. Forward-backward translation was conducted to produce the GR-SCIM III. Participants completed the English or Greek versions in 2008-2009. Both versions were examined for multidimensionality, internal consistency and concurrent/criterion validity with the EQ-5D. Forty-five Greek adults with spinal cord injury (SCI) (23 males), mean age 61 (SD17) years; mean time since injury 11 (SD9) years, completed the GR-SCIM III. One hundred and seventy four English-speaking adults with SCI (111 males), mean age 47 (SD12) years; mean time since injury 12 (SD11) years, completed the SCIM III. Unidimensionality was confirmed for both versions. Internal consistency was acceptable (α = 0.78 for both). Validity was strong for the "self-care" subscale (GR-SCIM III ρ = -0.78, SCIM III ρ = -0.75) and moderate for the "mobility" subscale (GR-SCIM III ρ = -0.58, SCIM III ρ = -0.45). This has been the first function scale translated and validated in Greek for people with SCI. Both the GR-SCIM III and SCIM III are reliable for use by self-report. More studies are needed to further examine their psychometric properties and compare with observation or interview. The Greek version of the Spinal Cord Independence Measure version III (SCIM) is valid and reliable for self-report. Further testing is needed to assess psychometric qualities not assessed in the present study. Researchers and therapists in Greece can use a specific measure to assess functional independence in people with Spinal Cord Injury (SCI). Consideration needs to be given to the participants' type of injury, which may affect the results of SCIM III.

  13. 5'-Terminal AUGs in Escherichia coli mRNAs with Shine-Dalgarno Sequences: Identification and Analysis of Their Roles in Non-Canonical Translation Initiation.

    Directory of Open Access Journals (Sweden)

    Heather J Beck

    Full Text Available Analysis of the Escherichia coli transcriptome identified a unique subset of messenger RNAs (mRNAs that contain a conventional untranslated leader and Shine-Dalgarno (SD sequence upstream of the gene's start codon while also containing an AUG triplet at the mRNA's 5'- terminus (5'-uAUG. Fusion of the coding sequence specified by the 5'-terminal putative AUG start codon to a lacZ reporter gene, as well as primer extension inhibition assays, reveal that the majority of the 5'-terminal upstream open reading frames (5'-uORFs tested support some level of lacZ translation, indicating that these mRNAs can function both as leaderless and canonical SD-leadered mRNAs. Although some of the uORFs were expressed at low levels, others were expressed at levels close to that of the respective downstream genes and as high as the naturally leaderless cI mRNA of bacteriophage λ. These 5'-terminal uORFs potentially encode peptides of varying lengths, but their functions, if any, are unknown. In an effort to determine whether expression from the 5'-terminal uORFs impact expression of the immediately downstream cistron, we examined expression from the downstream coding sequence after mutations were introduced that inhibit efficient 5'-uORF translation. These mutations were found to affect expression from the downstream cistrons to varying degrees, suggesting that some 5'-uORFs may play roles in downstream regulation. Since the 5'-uAUGs found on these conventionally leadered mRNAs can function to bind ribosomes and initiate translation, this indicates that canonical mRNAs containing 5'-uAUGs should be examined for their potential to function also as leaderless mRNAs.

  14. The translation initiation factor eIF4E regulates the sex-specific expression of the master switch gene Sxl in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Patricia L Graham

    2011-07-01

    Full Text Available In female fruit flies, Sex-lethal (Sxl turns off the X chromosome dosage compensation system by a mechanism involving a combination of alternative splicing and translational repression of the male specific lethal-2 (msl-2 mRNA. A genetic screen identified the translation initiation factor eif4e as a gene that acts together with Sxl to repress expression of the Msl-2 protein. However, eif4e is not required for Sxl mediated repression of msl-2 mRNA translation. Instead, eif4e functions as a co-factor in Sxl-dependent female-specific alternative splicing of msl-2 and also Sxl pre-mRNAs. Like other factors required for Sxl regulation of splicing, eif4e shows maternal-effect female-lethal interactions with Sxl. This female lethality can be enhanced by mutations in other co-factors that promote female-specific splicing and is caused by a failure to properly activate the Sxl-positive autoregulatory feedback loop in early embryos. In this feedback loop Sxl proteins promote their own synthesis by directing the female-specific alternative splicing of Sxl-Pm pre-mRNAs. Analysis of pre-mRNA splicing when eif4e activity is compromised demonstrates that Sxl-dependent female-specific splicing of both Sxl-Pm and msl-2 pre-mRNAs requires eif4e activity. Consistent with a direct involvement in Sxl-dependent alternative splicing, eIF4E is associated with unspliced Sxl-Pm pre-mRNAs and is found in complexes that contain early acting splicing factors--the U1/U2 snRNP protein Sans-fils (Snf, the U1 snRNP protein U1-70k, U2AF38, U2AF50, and the Wilms' Tumor 1 Associated Protein Fl(2d--that have been directly implicated in Sxl splicing regulation.

  15. Antisense oligonucleotide targeting eukaryotic translation initiation factor 4E reduces growth and enhances chemosensitivity of non-small-cell lung cancer cells.

    Science.gov (United States)

    Thumma, S C; Jacobson, B A; Patel, M R; Konicek, B W; Franklin, M J; Jay-Dixon, J; Sadiq, A; De, A; Graff, J R; Kratzke, R A

    2015-08-01

    Elevated levels of eukaryotic translation initiation factor 4E (eIF4E) enhance translation of many malignancy-related proteins, such as vascular endothelial growth factor (VEGF), c-Myc and osteopontin. In non-small-cell lung cancer (NSCLC), levels of eIF4E are significantly increased compared with normal lung tissue. Here, we used an antisense oligonucleotide (ASO) to inhibit the expression of eIF4E in NSCLC cell lines. eIF4E levels were significantly reduced in a dose-dependent manner in NSCLC cells treated with eIF4E-specific ASO (4EASO) compared with control ASO. Treatment of NSCLC cells with the 4EASO resulted in decreased cap-dependent complex formation, decreased cell proliferation and increased sensitivity to gemcitabine. At the molecular level, repression of eIF4E with ASO resulted in decreased expression of the oncogenic proteins VEGF, c-Myc and osteopontin, whereas expression of β-actin was unaffected. Based on these findings, we conclude that eIF4E-silencing therapy alone or in conjunction with chemotherapy represents a promising approach deserving of further investigation in future NSCLC clinical trials.

  16. Initiating a participatory action research process in the Agincourt health and socio-demographic surveillance site.

    Science.gov (United States)

    Wariri, Oghenebrume; D'Ambruoso, Lucia; Twine, Rhian; Ngobeni, Sizzy; van der Merwe, Maria; Spies, Barry; Kahn, Kathleen; Tollman, Stephen; Wagner, Ryan G; Byass, Peter

    2017-06-01

    Despite progressive health policy, disease burdens in South Africa remain patterned by deeply entrenched social inequalities. Accounting for the relationships between context, health and risk can provide important information for equitable service delivery. The aims of the research were to initiate a participatory research process with communities in a low income setting and produce evidence of practical relevance. We initiated a participatory action research (PAR) process in the Agincourt health and socio-demographic surveillance site (HDSS) in rural north-east South Africa. Three village-based discussion groups were convened and consulted about conditions to examine, one of which was under-5 mortality. A series of discussions followed in which routine HDSS data were presented and participants' subjective perspectives were elicited and systematized into collective forms of knowledge using ranking, diagramming and participatory photography. The process concluded with a priority setting exercise. Visual and narrative data were thematically analyzed to complement the participants' analysis. A range of social and structural root causes of under-5 mortality were identified: poverty, unemployment, inadequate housing, unsafe environments and shortages of clean water. Despite these constraints, single mothers were often viewed as negligent. A series of mid-level contributory factors in clinics were also identified: overcrowding, poor staffing, delays in treatment and shortages of medications. In a similar sense, pronounced blame and negativity were directed toward clinic nurses in spite of the systems constraints identified. Actions to address these issues were prioritized as: expanding clinics, improving accountability and responsiveness of health workers, improving employment, providing clean water, and expanding community engagement for health promotion. We initiated a PAR process to gain local knowledge and prioritize actions. The process was acceptable to those

  17. Pdx1 is post-translationally modified in vivo and serine 61 is the principal site of phosphorylation

    DEFF Research Database (Denmark)

    Frogne, Thomas; Sylvestersen, Kathrine Beck; Kubicek, Stefan

    2012-01-01

    signaling. Several studies have shown that post-translational modifications are regulating Pdx1 activity through intracellular localization and binding to co-factors. Understanding the signaling cues converging on Pdx1 and modulating its activity is therefore an attractive approach in diabetes treatment. We......Maintaining sufficient levels of Pdx1 activity is a prerequisite for proper regulation of blood glucose homeostasis and beta cell function. Mice that are haploinsufficient for Pdx1 display impaired glucose tolerance and lack the ability to increase beta cell mass in response to decreased insulin...

  18. Uterine cervical cancer with brain metastasis as the initial site of presentation.

    Science.gov (United States)

    Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

    2015-07-01

    Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

  19. A proteogenomics approach integrating proteomics and ribosome profiling increases the efficiency of protein identification and enables the discovery of alternative translation start sites

    Science.gov (United States)

    Koch, Alexander; Gawron, Daria; Steyaert, Sandra; Ndah, Elvis; Crappé, Jeroen; De Keulenaer, Sarah; De Meester, Ellen; Ma, Ming; Shen, Ben; Gevaert, Kris; Van Criekinge, Wim; Van Damme, Petra; Menschaert, Gerben

    2015-01-01

    Next-generation transcriptome sequencing is increasingly integrated with mass spectrometry to enhance MS-based protein and peptide identification. Recently, a breakthrough in transcriptome analysis was achieved with the development of ribosome profiling (ribo-seq). This technology is based on the deep sequencing of ribosome-protected mRNA fragments, thereby enabling the direct observation of in vivo protein synthesis at the transcript level. In order to explore the impact of a ribo-seq-derived protein sequence search space on MS/MS spectrum identification, we performed a comprehensive proteome study on a human cancer cell line, using both shotgun and N-terminal proteomics, next to ribosome profiling, which was used to delineate (alternative) translational reading-frames. By including protein-level evidence of sample-specific genetic variation and alternative translation, this strategy improved the identification score of 69 proteins and identified 22 new proteins in the shotgun experiment. Furthermore, we discovered 18 new alternative translation start sites in the N-terminal proteomics data and observed a correlation between the quantitative measures of ribo-seq and shotgun proteomics with a Pearson correlation coefficient ranging from 0.483 to 0.664. Overall, this study demonstrated the benefits of ribosome profiling for MS-based protein and peptide identification and we believe this approach could develop into a common practice for next-generation proteomics. PMID:25156699

  20. Tandem affinity purification of histones, coupled to mass spectrometry, identifies associated proteins and new sites of post-translational modification in Saccharomyces cerevisiae.

    Science.gov (United States)

    Valero, M Luz; Sendra, Ramon; Pamblanco, Mercè

    2016-03-16

    Histones and their post-translational modifications contribute to regulating fundamental biological processes in all eukaryotic cells. We have applied a conventional tandem affinity purification strategy to histones H3 and H4 of the yeast Saccharomyces cerevisiae. Mass spectrometry analysis of the co-purified proteins revealed multiple associated proteins, including core histones, which indicates that tagged histones may be incorporated to the nucleosome particle. Among the many other co-isolated proteins there are histone chaperones, elements of chromatin remodeling, of nucleosome assembly/disassembly, and of histone modification complexes. The histone chaperone Rtt106p, two members of chromatin assembly FACT complex and Psh1p, an ubiquitin ligase, were the most abundant proteins obtained with both H3-TAP and H4-TAP, regardless of the cell extraction medium stringency. Our mass spectrometry analyses have also revealed numerous novel post-translational modifications, including 30 new chemical modifications in histones, mainly by ubiquitination. We have discovered not only new sites of ubiquitination but that, besides lysine, also serine and threonine residues are targets of ubiquitination on yeast histones. Our results show the standard tandem affinity purification procedure is suitable for application to yeast histones, in order to isolate and characterize histone-binding proteins and post-translational modifications, avoiding the bias caused by histone purification from a chromatin-enriched fraction. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Preliminary safety evaluation for the Simpevarp subarea. Based on data and site descriptions after the initial site investigation stage

    International Nuclear Information System (INIS)

    2005-04-01

    The main objectives of this Preliminary safety evaluation (PSE) of the Simpevarp subarea are: to determine, whether the feasibility study's judgement of the suitability of the candidate area with respect to long-term safety holds up in the light of the site investigation data; to provide feedback to continued site investigations and site-specific repository design and to identify site specific scenarios and geoscientific issues for further analyses. The PSE focuses on comparing the attained knowledge of the sites with the suitability criteria as set out by SKB in the report SKB-TR--00-12. These criteria both concern properties of the site judged to be necessary for safety and engineering (requirements) and properties judged to be beneficial (preferences). The findings are then evaluated in order to provide feedback to continued investigations and design work. The PSE does not aim at comparing sites and does not assess compliance with safety and radiation protection criteria. The evaluation shows that even considering remaining uncertainties, the Simpevarp subarea meets all safety requirements and most of the safety preferences. Consequently, from a safety point of view, there is no reason not to continue the Site Investigations of the Simpevarp subarea. There are still uncertainties to resolve and the safety would eventually need to be verified through a full safety assessment. Still, this Preliminary Safety Evaluation demonstrates that it is likely that a safe repository for spent nuclear fuel of the KBS-3 type could be constructed at the site. The following feedback is provided to the site investigations and the associated site modelling: Reducing the uncertainty on the deformation zone geometry within the Simpevarp subarea would allow for a more specified layout, although the sensitivity analysis shows that the space needed is rather robust with respect to uncertainties in the zones. There is substantial uncertainty in the discrete fracture network (DFN) model

  2. Structural Studies of RNA Helicases Involved in Eukaryotic Pre-mRNA Splicing, Ribosome Biogenesis, and Translation Initiation

    DEFF Research Database (Denmark)

    He, Yangzi

    and ligates the neighbouring exons to generate mature mRNAs. Prp43 is an RNA helicase of the DEAH/RHA family. In yeast, once mRNAs are released, Prp43 catalyzes the disassembly of spliceosomes. The 18S, 5.8S and 25S rRNAs are transcribed as a single polycistronic transcript—the 35S pre......-rRNA. It is nucleolytically cleaved and chemically modified to generate mature rRNAs, which assemble with ribosomal proteins to form the ribosome. Prp43 is required for the processing of the 18S rRNA. Using X-ray crystallography, I determined a high resolution structure of Prp43 bound to ADP, the first structure of a DEAH....../RHA helicase. It defined the conserved structural features of all DEAH/RHA helicases, and unveiled a novel nucleotide binding site. Additionally a preliminary low resolution structure of a ternary complex comprising Prp43, a non-hydrolyzable ATP analogue, and a single-stranded RNA, was obtained. The ribosome...

  3. Preliminary safety evaluation for the Forsmark area. Based on data and site descriptions after the initial site investigation stage

    International Nuclear Information System (INIS)

    Andersson, Johan

    2005-08-01

    The main objectives of this Preliminary Safety Evaluation (PSE) of the Forsmark area have been to determine, with limited efforts, whether the feasibility study's judgement of the suitability of the candidate area with respect to long-term safety holds up in the light of the actual site investigation data; to provide feedback to continued site investigations and site-specific repository design and to identify site-specific scenarios and geoscientific issues for further analyses. The PSE focuses on comparing the attained knowledge of the sites with the suitability criteria as set out by SKB. The PSE does not aim at comparing sites and does not assess compliance with safety and radiation protection criteria. The evaluation shows that, even considering remaining uncertainties, the Forsmark area meets all stated safety requirements and preferences. Consequently, from a safety point of view, there is no reason not to continue the Site Investigations of the Forsmark area. There are still uncertainties to resolve and the safety would eventually need to be verified through a full safety assessment. Nevertheless, this Preliminary Safety Evaluation demonstrates that it is likely that a safe repository for spent nuclear fuel of the KBS-3 type could be constructed at the site. The following feedback is provided to the site investigations and the associated site modelling: Reducing the uncertainty on the deformation zone geometry inside the target area would be needed to more firmly define locations of the suitable deposition volumes. There is substantial uncertainty in the Discrete Fracture Network model. Further reduction of the uncertainties, if needed, would probably only be possible from the underground, detailed investigation phase. Efforts need also be spent on improving the DFN-modelling. There are assumptions made in current models that could be challenged and there seems to be room for better use of the borehole information. It is particularly important to provide

  4. Establishing a health demographic surveillance site in Bhaktapur district, Nepal: initial experiences and findings

    Directory of Open Access Journals (Sweden)

    Aryal Umesh

    2012-09-01

    Full Text Available Abstract Background A health demographic surveillance system (HDSS provides longitudinal data regarding health and demography in countries with coverage error and poor quality data on vital registration systems due to lack of public awareness, inadequate legal basis and limited use of data in health planning. The health system in Nepal, a low-income country, does not focus primarily on health registration, and does not conduct regular health data collection. This study aimed to initiate and establish the first HDSS in Nepal. Results We conducted a baseline survey in Jhaukhel and Duwakot, two villages in Bhaktapur district. The study surveyed 2,712 households comprising a total population of 13,669. The sex ratio in the study area was 101 males per 100 females and the average household size was 5. The crude birth and death rates were 9.7 and 3.9/1,000 population/year, respectively. About 11% of births occurred at home, and we found no mortality in infants and children less than 5 years of age. Various health problems were found commonly and some of them include respiratory problems (41.9%; headache, vertigo and dizziness (16.7%; bone and joint pain (14.4%; gastrointestinal problems (13.9%; heart disease, including hypertension (8.8%; accidents and injuries (2.9%; and diabetes mellitus (2.6%. The prevalence of non-communicable disease (NCD was 4.3% (95% CI: 3.83; 4.86 among individuals older than 30 years. Age-adjusted odds ratios showed that risk factors, such as sex, ethnic group, occupation and education, associated with NCD. Conclusion Our baseline survey demonstrated that it is possible to collect accurate and reliable data in a village setting in Nepal, and this study successfully established an HDSS site. We determined that both maternal and child health are better in the surveillance site compared to the entire country. Risk factors associated with NCDs dominated morbidity and mortality patterns.

  5. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

    Science.gov (United States)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  6. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential

    Science.gov (United States)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    Objective. The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Approach. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Main results. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. Significance. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  7. Identification of minimal sequences of the Rhopalosiphum padi virus 5' untranslated region required for internal initiation of protein synthesis in mammalian, plant and insect translation systems

    DEFF Research Database (Denmark)

    Groppelli, Elisabetta; Belsham, Graham; Roberts, Lisa O.

    2007-01-01

    (rabbit reticulocyte lysate), plant (wheatgerm extract) and insect (Sf21 cells) translation systems have now been defined. A fragment (nt 426–579) from the 3' portion of the 5' UTR can direct translation in each of these translation systems. In addition, a distinct region (nt 300–429) is also active. Thus...

  8. The enactment of knowledge translation: a study of the Collaborations for Leadership in Applied Health Research and Care initiative within the English National Health Service

    Science.gov (United States)

    D’Andreta, Daniela; Scarbrough, Harry; Evans, Sarah

    2014-01-01

    Objectives We contribute to existing knowledge translation (KT) literature by developing the notion of ‘enactment’ and illustrate this through an interpretative, comparative case-study analysis of three Collaborations for Leadership in Applied Health Research and Care (CLAHRC) initiatives. We argue for a focus on the way in which the CLAHRC model has been ‘enacted’ as central to the different KT challenges and capabilities encountered. Methods A comparative, mixed method study created a typology of enactments (Classical, Home-grown and Imported) using qualitative analysis and social network analysis. Results We identify systematic differences in the enactment of the CLAHRC model. The sources of these different enactments are subsequently related to variation in formative interpretations and leadership styles, the implementation of different governance structures, and the relative epistemic differences between the professional groups involved. Conclusions Enactment concerns the creative agency of individuals and groups in constituting a particular context for their work through their local interpretation of a particular KT model. Our theory of enactment goes beyond highlighting variation between CLAHRCs, to explore the mechanisms that influence the way a particular model is interpreted and acted upon. We thus encourage less focus on conceptual models and more on the formative role played by leaders of KT initiatives. PMID:24048695

  9. The enactment of knowledge translation: a study of the Collaborations for Leadership in Applied Health Research and Care initiative within the English National Health Service.

    Science.gov (United States)

    D'Andreta, Daniela; Scarbrough, Harry; Evans, Sarah

    2013-10-01

    We contribute to existing knowledge translation (KT) literature by developing the notion of 'enactment' and illustrate this through an interpretative, comparative case-study analysis of three Collaborations for Leadership in Applied Health Research and Care (CLAHRC) initiatives. We argue for a focus on the way in which the CLAHRC model has been 'enacted' as central to the different KT challenges and capabilities encountered. A comparative, mixed method study created a typology of enactments (Classical, Home-grown and Imported) using qualitative analysis and social network analysis. We identify systematic differences in the enactment of the CLAHRC model. The sources of these different enactments are subsequently related to variation in formative interpretations and leadership styles, the implementation of different governance structures, and the relative epistemic differences between the professional groups involved. Enactment concerns the creative agency of individuals and groups in constituting a particular context for their work through their local interpretation of a particular KT model. Our theory of enactment goes beyond highlighting variation between CLAHRCs, to explore the mechanisms that influence the way a particular model is interpreted and acted upon. We thus encourage less focus on conceptual models and more on the formative role played by leaders of KT initiatives.

  10. Understanding translation

    DEFF Research Database (Denmark)

    Schjoldager, Anne Gram; Gottlieb, Henrik; Klitgård, Ida

    Understanding Translation is designed as a textbook for courses on the theory and practice of translation in general and of particular types of translation - such as interpreting, screen translation and literary translation. The aim of the book is to help you gain an in-depth understanding...... of the phenomenon of translation and to provide you with a conceptual framework for the analysis of various aspects of professional translation. Intended readers are students of translation and languages, but the book will also be relevant for others who are interested in the theory and practice of translation...... - translators, language teachers, translation users and literary, TV and film critics, for instance. Discussions focus on translation between Danish and English....

  11. Multiple copies of eukaryotic translation initiation factors in Brassica rapa facilitate redundancy, enabling diversification through variation in splicing and broad-spectrum virus resistance.

    Science.gov (United States)

    Nellist, Charlotte F; Qian, Wei; Jenner, Carol E; Moore, Jonathan D; Zhang, Shujiang; Wang, Xiaowu; Briggs, William H; Barker, Guy C; Sun, Rifei; Walsh, John A

    2014-01-01

    Recessive strain-specific resistance to a number of plant viruses in the Potyvirus genus has been found to be based on mutations in the eukaryotic translation initiation factor 4E (eIF4E) and its isoform, eIF(iso)4E. We identified three copies of eIF(iso)4E in a number of Brassica rapa lines. Here we report broad-spectrum resistance to the potyvirus Turnip mosaic virus (TuMV) due to a natural mechanism based on the mis-splicing of the eIF(iso)4E allele in some TuMV-resistant B. rapa var. pekinensis lines. Of the splice variants, the most common results in a stop codon in intron 1 and a much truncated, non-functional protein. The existence of multiple copies has enabled redundancy in the host plant's translational machinery, resulting in diversification and emergence of the resistance. Deployment of the resistance is complicated by the presence of multiple copies of the gene. Our data suggest that in the B. rapa subspecies trilocularis, TuMV appears to be able to use copies of eIF(iso)4E at two loci. Transformation of different copies of eIF(iso)4E from a resistant B. rapa line into an eIF(iso)4E knockout line of Arabidopsis thaliana proved misleading because it showed that, when expressed ectopically, TuMV could use multiple copies which was not the case in the resistant B. rapa line. The inability of TuMV to access multiple copies of eIF(iso)4E in B. rapa and the broad spectrum of the resistance suggest it may be durable. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  12. The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites

    International Nuclear Information System (INIS)

    Rivas-Aravena, Andrea; Ramdohr, Pablo; Vallejos, Maricarmen; Valiente-Echeverria, Fernando; Dormoy-Raclet, Virginie; Rodriguez, Felipe; Pino, Karla; Holzmann, Cristian; Huidobro-Toro, J. Pablo; Gallouzi, Imed-Eddine; Lopez-Lastra, Marcelo

    2009-01-01

    The human embryonic-lethal abnormal vision (ELAV)-like protein, HuR, has been recently found to be involved in the regulation of protein synthesis. In this study we show that HuR participates in the translational control of the HIV-1 and HCV IRES elements. HuR functions as a repressor of HIV-1 IRES activity and acts as an activator of the HCV IRES. The effect of HuR was evaluated in three independent experimental systems, rabbit reticulocyte lysate, HeLa cells, and Xenopus laevis oocytes, using both overexpression and knockdown approaches. Furthermore, results suggest that HuR mediated regulation of HIV-1 and HCV IRESes does not require direct binding of the protein to the RNA nor does it need the nuclear translocation of the IRES-containing RNAs. Finally, we show that HuR has a negative impact on post-integration steps of the HIV-1 replication cycle. Thus, our observations yield novel insights into the role of HuR in the post-transcriptional regulation of HCV and HIV-1 gene expression.

  13. Frequent dual initiation of reverse transcription in murine leukemia virus-based vectors containing two primer-binding sites

    International Nuclear Information System (INIS)

    Voronin, Yegor A.; Pathak, Vinay K.

    2003-01-01

    Retroviruses package two copies of viral RNA into each virion. Although each RNA contains a primer-binding site for initiation of DNA synthesis, it is unknown whether reverse transcription is initiated on both RNAs. To determine whether a single virion is capable of initiating reverse transcription more than once, we constructed a murine leukemia virus-based vector containing a second primer-binding site (PBS) derived from spleen necrosis virus and inserted the green fluorescent protein gene (GFP) between the two PBSs. Initiation of reverse transcription at either PBS results in a provirus that expresses GFP. However, initiation at both PBSs can result in the deletion of GFP, which can be detected by flow cytometry and Southern blotting analysis. Approximately 22-29% of the proviruses formed deleted the GFP in a single replication cycle, indicating the minimum proportion of virions that initiated reverse transcription on both PBSs. These results show that a significant proportion of MLV-based vectors containing two PBSs have the capacity to initiate reverse transcription more than once

  14. Translation as (Global) Writing

    Science.gov (United States)

    Horner, Bruce; Tetreault, Laura

    2016-01-01

    This article explores translation as a useful point of departure and framework for taking a translingual approach to writing engaging globalization. Globalization and the knowledge economy are putting renewed emphasis on translation as a key site of contest between a dominant language ideology of monolingualism aligned with fast capitalist…

  15. An internal ribosome entry site directs translation of the 3'-gene from Pelargonium flower break virus genomic RNA: implications for infectivity.

    Science.gov (United States)

    Fernández-Miragall, Olga; Hernández, Carmen

    2011-01-01

    Pelargonium flower break virus (PFBV, genus Carmovirus) has a single-stranded positive-sense genomic RNA (gRNA) which contains five ORFs. The two 5'-proximal ORFs encode the replicases, two internal ORFs encode movement proteins, and the 3'-proximal ORF encodes a polypeptide (p37) which plays a dual role as capsid protein and as suppressor of RNA silencing. Like other members of family Tombusviridae, carmoviruses express ORFs that are not 5'-proximal from subgenomic RNAs. However, in one case, corresponding to Hisbiscus chlorotic ringspot virus, it has been reported that the 3'-proximal gene can be translated from the gRNA through an internal ribosome entry site (IRES). Here we show that PFBV also holds an IRES that mediates production of p37 from the gRNA, raising the question of whether this translation strategy may be conserved in the genus. The PFBV IRES was functional both in vitro and in vivo and either in the viral context or when inserted into synthetic bicistronic constructs. Through deletion and mutagenesis studies we have found that the IRES is contained within a 80 nt segment and have identified some structural traits that influence IRES function. Interestingly, mutations that diminish IRES activity strongly reduced the infectivity of the virus while the progress of the infection was favoured by mutations potentiating such activity. These results support the biological significance of the IRES-driven p37 translation and suggest that production of the silencing suppressor from the gRNA might allow the virus to early counteract the defence response of the host, thus facilitating pathogen multiplication and spread.

  16. An internal ribosome entry site directs translation of the 3'-gene from Pelargonium flower break virus genomic RNA: implications for infectivity.

    Directory of Open Access Journals (Sweden)

    Olga Fernández-Miragall

    Full Text Available Pelargonium flower break virus (PFBV, genus Carmovirus has a single-stranded positive-sense genomic RNA (gRNA which contains five ORFs. The two 5'-proximal ORFs encode the replicases, two internal ORFs encode movement proteins, and the 3'-proximal ORF encodes a polypeptide (p37 which plays a dual role as capsid protein and as suppressor of RNA silencing. Like other members of family Tombusviridae, carmoviruses express ORFs that are not 5'-proximal from subgenomic RNAs. However, in one case, corresponding to Hisbiscus chlorotic ringspot virus, it has been reported that the 3'-proximal gene can be translated from the gRNA through an internal ribosome entry site (IRES. Here we show that PFBV also holds an IRES that mediates production of p37 from the gRNA, raising the question of whether this translation strategy may be conserved in the genus. The PFBV IRES was functional both in vitro and in vivo and either in the viral context or when inserted into synthetic bicistronic constructs. Through deletion and mutagenesis studies we have found that the IRES is contained within a 80 nt segment and have identified some structural traits that influence IRES function. Interestingly, mutations that diminish IRES activity strongly reduced the infectivity of the virus while the progress of the infection was favoured by mutations potentiating such activity. These results support the biological significance of the IRES-driven p37 translation and suggest that production of the silencing suppressor from the gRNA might allow the virus to early counteract the defence response of the host, thus facilitating pathogen multiplication and spread.

  17. An Internal Ribosome Entry Site Directs Translation of the 3′-Gene from Pelargonium Flower Break Virus Genomic RNA: Implications for Infectivity

    Science.gov (United States)

    Fernández-Miragall, Olga; Hernández, Carmen

    2011-01-01

    Pelargonium flower break virus (PFBV, genus Carmovirus) has a single-stranded positive-sense genomic RNA (gRNA) which contains five ORFs. The two 5′-proximal ORFs encode the replicases, two internal ORFs encode movement proteins, and the 3′-proximal ORF encodes a polypeptide (p37) which plays a dual role as capsid protein and as suppressor of RNA silencing. Like other members of family Tombusviridae, carmoviruses express ORFs that are not 5′-proximal from subgenomic RNAs. However, in one case, corresponding to Hisbiscus chlorotic ringspot virus, it has been reported that the 3′-proximal gene can be translated from the gRNA through an internal ribosome entry site (IRES). Here we show that PFBV also holds an IRES that mediates production of p37 from the gRNA, raising the question of whether this translation strategy may be conserved in the genus. The PFBV IRES was functional both in vitro and in vivo and either in the viral context or when inserted into synthetic bicistronic constructs. Through deletion and mutagenesis studies we have found that the IRES is contained within a 80 nt segment and have identified some structural traits that influence IRES function. Interestingly, mutations that diminish IRES activity strongly reduced the infectivity of the virus while the progress of the infection was favoured by mutations potentiating such activity. These results support the biological significance of the IRES-driven p37 translation and suggest that production of the silencing suppressor from the gRNA might allow the virus to early counteract the defence response of the host, thus facilitating pathogen multiplication and spread. PMID:21818349

  18. Novel forms of Paired-like homeodomain transcription factor 2 (PITX2: Generation by alternative translation initiation and mRNA splicing

    Directory of Open Access Journals (Sweden)

    Bernard Daniel J

    2008-03-01

    Full Text Available Abstract Background Members of the Paired-like homeodomain transcription factor (PITX gene family, particularly PITX1 and PITX2, play important roles in normal development and in differentiated cell functions. Three major isoforms of PITX2 were previously reported to be produced through both alternative mRNA splicing (PITX2A and PITX2B and alternative promoter usage (PITX2C. The proteins derived from these mRNAs contain identical homeodomain and carboxyl termini. Differences in the amino-termini of the proteins may confer functional differences in some contexts. Results Here, we report the identification of two novel PITX2 isoforms. First, we demonstrate that the Pitx2c mRNA generates two protein products, PITX2Cα and PITX2Cβ, via alternative translation initiation. Second, we identified a novel mRNA splice variant, Pitx2b2, which uses the same 5' splice donor in intron 2 as Pitx2b (hereafter referred to as Pitx2b1, but employs an alternative 3' splice acceptor, leading to an in-frame deletion of 39 base pairs relative to Pitx2b1. Pitx2b2 mRNA is expressed in both murine and human pituitary. The data show that in a murine gonadotrope cell line and adult murine pituitary what was previously thought to be PITX2B1 is actually PITX2Cβ, or perhaps PITX2B2. PITX2B1 is expressed at lower levels than previously thought. PITX2Cβ and PITX2B2 activate gonadotrope-specific gene promoter-reporters similarly to known PITX2 isoforms. Conclusion We have identified and characterized two novel isoforms of PITX2, generated by alternative translation initiation (PITX2Cβ and alternative mRNA splicing (PITX2B2. These proteins show similar DNA binding and trans-activation functions as other PITX2 isoforms in vitro, though their conservation across species suggests that they may play distinct, as yet unidentified, roles in vivo.

  19. An Initial Evaluation of Siting Considerations on Current and Future Wind Deployment

    Energy Technology Data Exchange (ETDEWEB)

    Tegen, Suzanne [National Renewable Energy Lab. (NREL), Golden, CO (United States); Lantz, Eric [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mai, Trieu [National Renewable Energy Lab. (NREL), Golden, CO (United States); Heimiller, Donna [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hand, Maureen [National Renewable Energy Lab. (NREL), Golden, CO (United States); Ibanez, Eduardo [GE Energy Consulting, Denver, CO (United States)

    2016-07-01

    This report provides a deeper understanding of the wind project development process, from desktop studies to a successful project in the ground. It examines three siting consideration categories that wind project sponsors must include in the development process: wildlife (species that live in, near, or migrate through the area where wind development is possible), radar (wind turbines can cause interference with radar signals), and public engagement (representing communities and stakeholders who live near wind power projects). The research shows that although this country's abundant wind resource provides numerous options for addressing siting considerations, actually siting individual projects is becoming more difficult because of regulatory and other uncertainties. Model results are based on the premise that developers will be able to site, permit, and build successful projects, which is not always the case in reality.

  20. Initial Operation of the Savannah River Site Advanced Storage Monitoring Facility

    International Nuclear Information System (INIS)

    McCurry, D.R.

    2001-01-01

    An advanced storage monitoring facility has been constructed at the Savannah River Site capable of storing sensitive nuclear materials (SNM) with access to monitoring information available over the Internet. This system will also have monitoring information available over the Internet to appropriate users. The programs will ultimately supply authenticated and encrypted data from the storage sites to certified users to demonstrate the capability of using the Internet as a safe and secure communications medium for remote monitoring of sensitive items

  1. N1-guanyl-1,7-diaminoheptane enhances the chemosensitivity of NSCLC cells to cetuximab through inhibition of eukaryotic translation initiation factor 5A2 activation.

    Science.gov (United States)

    Wang, X; Jiang, R; Cui, E-H; Feng, W-M; Guo, H-H; Gu, D-H; Tang, C-W; Xue, T; Bao, Y

    2016-04-01

    N1-guanyl-1, 7-diaminoheptane (GC7), an inhibitor of deoxyhypusine synthase has been shown to exhibit significant anti-cancer activity. However, the biological role of eukaryotic translation initiation factor 5A2 activation (EIF5A2) and GC7 on drug resistance in non-small cell lung cancer (NSCLC) has not been investigated. In this study, we aimed to investigate the therapeutic effect of GC7 combined with cetuximab in NSCLC therapy. The current study used cell viability assays, EdU incorporation assays, and western blot to detect that the GC7 exhibited synergistic cytotoxicity with cetuximab in NSCLC. CCK-8 assays showed that combined treatment with GC7 and cetuximab significantly inhibited the viabilities in three NSCLC cell lines. In addition, EdU incorporation assays also indicated that GC7 co-treatment remarkably enhanced the cetuximab sensitivity in NSCLC cells. Nevertheless, down-regulation of EIF5A2 diminished the regulatory role of GC7 in cetuximab cytotoxicity. Western blot showed that transfection of EIF5A2 siRNA significantly suppressed the protein expression of EIF5A2 in NSCLC cells. These findings demonstrate that combined treatment with GC7 could enhance cetuximab sensitivity by inhibiting EIF5A2 in NSCLC cells, implying the potential clinical application of GC7 in cetuximab-based chemotherapy for NSCLC patients.

  2. MicroRNA-216a inhibits the growth and metastasis of oral squamous cell carcinoma by targeting eukaryotic translation initiation factor 4B.

    Science.gov (United States)

    Li, Lei; Ma, Hui-Qiang

    2015-08-01

    There is increasing evidence to suggest that microRNAs (miRNAs; miRs) are involved in the development of oral squamous cell carcinoma (OSCC). miR-216a has been identified as being involved in tumorigenesis, however, the mechanisms of miR-216a in various types of cancer, either as a tumor suppressor or as an oncogenic miRNA, and the specific regulatory role of miR-216a in OSCC remain to be elucidated. The present study demonstrated that the expression of miR-216a was significantly reduced in OSCC tissues and cell lines. Overexpression of miR-216a significantly suppressed the proliferation, colony formation, migration and invasion of the OSCC cells. In addition, eukaryotic translation initiation factor 4B (EIF4B) was identified as a direct target of miR-216a, which was observed to be upregulated in the OSCC tissues. Furthermore, overexpression of EIF4B significantly attenuated the antitumor effect of miR-216a, and a negative correlation was observed between miR-216a and EIF4B in the OSCC tissues. Taken together, these findings indicated that miR-216a has a suppressive role in OSCC cells by directly targeting EIF4B, and may function as a potential prognostic biomarker and novel therapeutic target.

  3. Myxoma Virus Immunomodulatory Protein M156R is a Structural Mimic of Eukaryotic Translation Initiation Factor eIF2 alpha

    Energy Technology Data Exchange (ETDEWEB)

    Ramelot, Theresa A.; Cort, John R.; Yee, Adelinda; Liu, Furong; Goshe, Michael B.; Edwards, Aled M.; Smith, Richard D.; Arrowsmith, Cheryl H.; Dever, Thomas E.; Kennedy, Michael A.

    2002-10-04

    M156R, the product of the myxoma virus M156R open reading frame, is a protein of unknown function. However, several homologs of M156R from other viruses are immunomodulatory proteins that bind to interferon-induced protein kinase PKR and inhibit phosphorylation of the eukaryotic translation initiation factor eIF2a. In this study, we have determined the nuclear magnetic resonance (NMR) structure of M156R, the first structure of a myxoma virus protein. The fold consists of a five-stranded antiparallel b-barrel with two of the strands connected by a long loop and a short a-helix. The similarity between M156R and the predicted S1 motif structure of eIF2a suggests that the viral homologs are pseudosubstrate inhibitors of PKR that mimic eIF2a in order to compete for binding to PKR. A homology modeled structure of the well studied vaccinia virus K3L was generated based on alignment with M156R. Residues important for binding to PKR are conserved residues on the surface of the b-barrel and in the mobile loop, identifying the putative PKR recognition motif.

  4. Translational control of ribosomal protein S15.

    Science.gov (United States)

    Portier, C; Philippe, C; Dondon, L; Grunberg-Manago, M; Ebel, J P; Ehresmann, B; Ehresmann, C

    1990-08-27

    The expression of ribosomal protein S15 is shown to be translationally and negatively autocontrolled using a fusion within a reporter gene. Isolation and characterization of several deregulated mutants indicate that the regulatory site (the translational operator site) overlaps the ribosome loading site of the S15 messenger. In this region, three domains, each exhibiting a stem-loop structure, were determined using chemical and enzymatic probes. The most downstream hairpin carries the Shine-Dalgarno sequence and the initiation codon. Genetic and structural data derived from mutants constructed by site-directed mutagenesis show that the operator is a dynamic structure, two domains of which can form a pseudoknot. Binding of S15 to these two domains suggests that the pseudoknot could be stabilized by S15. A model is presented in which two alternative structures would explain the molecular basis of the S15 autocontrol.

  5. [Phosphate sites of RNA-ligands interacting with ribosome at different stages of translation. Thiophosphate method of analysis].

    Science.gov (United States)

    Dabrowski, M; Junemann, R; Schafer, M A; Spahn, C M; Nierhaus, K H; Alekseeva, E V; Dontsova, O A; Shpanchenko, O V; Bogdanov, A A

    1996-11-01

    A novel footprinting method was recently developed which identifies phosphate groups of RNA involved in strong RNA-RNA and RNA-protein interactions. The method is based on iodine-dependent RNA cleavage at phosphothioate groups as long as these groups are not protected from iodine. Our recent studies of mRNA and tRNA regions protected in active ribosomes are summarized; initiation state of ribosomes as well as two elongation states in pre- and post-translocational states were analyzed. Only one phosphate group of mRNA, which was two positions upstream of the decoding codons, was weakly protected in longation complexes, whereas this group and the phosphate groups in the Shine-Dalgarno sequence were protected in the initiation complex. No protection was observed downstream of the decoding codons. On the contrary, numerous phosphate residues of tRNA were protected by the ribosome. The tRNA protection patterns significantly varied between two tRNAs simultaneously bound to the ribosome. The protection pattern of an individual tRNA was not significantly affected by translocation. The data indicate that both tRNA molecules are tightly bound to the ribosome, whereas mRNA is fixed predominantly by two tRNAs via codon-anticodon interaction. A possible translocation mechanism is suggested.

  6. Factors Related to Initiating Interpersonal Contacts on Internet Dating Sites: A View From the Social Exchange Theory

    Directory of Open Access Journals (Sweden)

    Rivka Shtatfeld

    2009-12-01

    Full Text Available The purpose of this study was to identify factors that influence dating-site users to initiate contact with potential romantic partners. The study was carried out by observing online behaviors and analyzing the profiles and authentic messages of these users (N = 106 over seven months. Contacts made by and with the research participants were analyzed in terms of the relationships between initiators‘ and receivers‘ demographic variables (marital status, age, level of education, income, writing skills, and stated physical appearance. In addition, the relationship between contacting partners and site accessibility was examined. The findings revealed that dating-site users initiated contact primarily with those having a similar marital status or slightly better characteristics (income, education, writing skills. In regard to writing skills, it was found that skilled writers attracted more contacts than did less skilled writers. However, the factor that was found to be most significantly related to initiating contact was the length of time that elapsed from last connection to the site, which implies the perceived accessibility of potential romantic partners. The findings were explained in terms of the Social Exchange Theory: people are attracted to those who grant them rewards.

  7. Translational Creativity

    DEFF Research Database (Denmark)

    Nielsen, Sandro

    2010-01-01

    is given to genre conventions in source texts and the ways in which they can best be translated. I propose that translators of statutes with an informative function in expert-to-expert communication may be allowed limited translational creativity when translating specific types of genre convention....... This creativity is a result of translators adopting either a source-language or a target-language oriented strategy and is limited by the pragmatic principle of co-operation. Examples of translation options are provided illustrating the different results in target texts. The use of a target-language oriented......A long-established approach to legal translation focuses on terminological equivalence making translators strictly follow the words of source texts. Recent research suggests that there is room for some creativity allowing translators to deviate from the source texts. However, little attention...

  8. Translation as iniciation

    Directory of Open Access Journals (Sweden)

    Evelyn Martina Schuler Zea

    2016-09-01

    Full Text Available http://dx.doi.org/10.5007/2175-7968.2016v36n3p192        In an increasingly noteworthy manner translation appears as a process, device or configuration that is not limited do textual dimension, but inserted in the wider context of ritual, social and technical exchanges. This is a moment of overflowing or expansion of translation, which requires a specific attention. This extratextual proceeding of translation is taken here as a motif to rethink the practice and conceptualization of translation under the figure of shamanic initiation. Specifically, the purpose here is to elaborate articulations in the event of shamanic initiation as narrated in The falling sky (Kopenawa & Albert, 2010, 2013, 2015, emphasizing questions of access to otherness, interlocution with it and the ways of transformation that traverse the double field of anthropology and translation.

  9. Renewable Energy Initiatives at Canadian Sport Stadiums: A Content Analysis of Web-Site Communications

    Directory of Open Access Journals (Sweden)

    Chris Chard

    2013-11-01

    Full Text Available Researchers have positioned renewable energy as sustainable and able to mitigate environmental issues associated with fossil fuels. Further, sustainable initiatives have been offered as a point of differentiation for brands. In order to reap the benefits of such differentiation, managers must communicate the initiatives to relevant stakeholders. The research question guiding the current investigation thus was: What is the communication by Canadian sport stadium operators to calls for sustainable initiatives, specifically in the area of renewable energy? The examination included the 15 sport stadiums that hosted a professional team in Canada and their web-based stadium communications on renewable energy (SCORE. Understandings and competencies in renewable energy are proposed as a new function of sport stadium management; communication of these competencies is seen as a key point of differentiation and best practice.

  10. Parental Involvement in Active Transport to School Initiatives: A Multi-Site Case Study

    Science.gov (United States)

    Eyler, Amy; Baldwin, Julie; Carnoske, Cheryl; Nickelson, Jan; Troped, Philip; Steinman, Lesley; Pluto, Delores; Litt, Jill; Evenson, Kelly; Terpstra, Jennifer; Brownson, Ross; Schmid, Thomas

    2008-01-01

    Background: Increasing physical activity in youth is a recommended approach to curbing the childhood obesity epidemic. One way to help increase children's daily activity is to promote active transportation to and from school (ATS). Purpose: The purpose of this case study was to explore parental perception of, and participation in, ATS initiatives.…

  11. Determination of entry site for acute type A aortic dissection by initial enhanced CT-scan

    Energy Technology Data Exchange (ETDEWEB)

    Mase, Takenori; Narumiya, Chihiro; Aoyama, Takahiko; Nagata, Yoshihisa [Aichi Medical Univ., Nagakute (Japan). School of Medicine

    2002-01-01

    Acute type A aortic dissection presents a surgical emergency because conservative therapy is not effective in the majority of instances. Enhanced CT-scan of the chest is commonly available and is considered to be an optimal diagnostic method for this disease. The operative strategy is to resect the primary tear to close the entry site of the aortic dissection and replace it with a tubular Dacron graft. Therefore, the existence of the entry site is important in determining the operative procedure. Based on the numerical value of the enhanced CT-scan inspection, the present study seeks to preoperatively identify the location of the presumed entry site in aortic dissection. From May 1996 to June 1999, 21 consecutive patients (Marfan's syndrome excluded) with acute type A aortic dissection underwent surgical treatment. Nineteen patients were preoperatively examined by enhanced CT-scan: 11 men and 8 women, with a mean age of 61 years. CT-scan slices used for early diagnosis were of the ascending aorta, aortic arch, descending aorta, and thoracoabdominal aorta. The largest diameters of the whole and true lumen were measured from cross-sectional aortic images with a personal computer, and the areas of the whole and true lumen were obtained by the manual tracing method. The true ratio was calculated for the largest diameter and area of the whole lumen. The nineteen patients were divided into two groups according to the location of the entry site based on the operating views. Seven patients with the entry site in the ascending aorta were classified as group A, and twelve patients with the entry site further in the aortic arch and descending aorta were classified as group B. Comparisons were performed by non-parametric analysis. Moreover, a discriminant analysis was applied to evaluate the classification between the two groups. The ratio of the largest diameter of the true lumen in group A at the level of the ascending and descending aorta was significantly greater than

  12. Determination of entry site for acute type A aortic dissection by initial enhanced CT-scan

    International Nuclear Information System (INIS)

    Mase, Takenori; Narumiya, Chihiro; Aoyama, Takahiko; Nagata, Yoshihisa

    2002-01-01

    Acute type A aortic dissection presents a surgical emergency because conservative therapy is not effective in the majority of instances. Enhanced CT-scan of the chest is commonly available and is considered to be an optimal diagnostic method for this disease. The operative strategy is to resect the primary tear to close the entry site of the aortic dissection and replace it with a tubular Dacron graft. Therefore, the existence of the entry site is important in determining the operative procedure. Based on the numerical value of the enhanced CT-scan inspection, the present study seeks to preoperatively identify the location of the presumed entry site in aortic dissection. From May 1996 to June 1999, 21 consecutive patients (Marfan's syndrome excluded) with acute type A aortic dissection underwent surgical treatment. Nineteen patients were preoperatively examined by enhanced CT-scan: 11 men and 8 women, with a mean age of 61 years. CT-scan slices used for early diagnosis were of the ascending aorta, aortic arch, descending aorta, and thoracoabdominal aorta. The largest diameters of the whole and true lumen were measured from cross-sectional aortic images with a personal computer, and the areas of the whole and true lumen were obtained by the manual tracing method. The true ratio was calculated for the largest diameter and area of the whole lumen. The nineteen patients were divided into two groups according to the location of the entry site based on the operating views. Seven patients with the entry site in the ascending aorta were classified as group A, and twelve patients with the entry site further in the aortic arch and descending aorta were classified as group B. Comparisons were performed by non-parametric analysis. Moreover, a discriminant analysis was applied to evaluate the classification between the two groups. The ratio of the largest diameter of the true lumen in group A at the level of the ascending and descending aorta was significantly greater than that

  13. 'Inhabiting' the Translator's Habitus – Antjie Krog as Translator ...

    African Journals Online (AJOL)

    Drawing on the Bourdieusian concept of habitus and its applicability in the field of translation, this article discusses Antjie Krog's profile in the practice of translation in. South Africa. Bourdieu's conceptualisation of the relationship between the initiating activities of translators and the structures which constrain and enable ...

  14. Noninvasive identification of initial site of abnormal ventricular activation by least-square phase analysis of radionuclide cineangiograms.

    Science.gov (United States)

    Turner, D A; Von Behren, P L; Ruggie, N T; Hauser, R G; Denes, P; Ali, A; Messer, J V; Fordham, E W; Groch, M W

    1982-06-01

    Least-square phase analysis (LSPA) of radionuclide cineangiograms demonstrates the sequence of onset of inward ventricular movement noninvasively. To validate the method and explore its ability to identify abnormal initial sites of ventricular activation, LSPA was applied to 14 patients with pacemakers (one with electrodes in two locations) (group 1) and three patients with recurrent ventricular tachycardia (VT) (group 2) who had undergone electrophysiologic endocardial mapping. The segment in which the site of initial ventricular activation was located was correctly identified in 13 of 15 paced studies and in two of three group 2 patients during VT. Pacing increased the duration of spread of onset of inward ventricular movement, and the duration of spread of onset correlated well with the duration of the QRS (r = 0.80). The sequence of onset of inward ventricular movement during VT was similar to the sequence of depolarization in all three group 2 patients. These preliminary results suggest that the sequence of onset of ventricular contraction as depicted by LSPA is a valid representation of the actual contraction sequence and that LSPA or radionuclide cineangiography correctly identifies abnormal sites of initial ventricular activation.

  15. Nariva Swamp Ramsar Site, Trinidad and Tobago (West Indies) Wetland Habitat Restoration Initiative

    Science.gov (United States)

    Montserrat Carbonell; Nadra Nathai-Gyan

    2005-01-01

    Trinidad and Tobago, a twin island nation, is the most southerly of the Caribbean islands and lies just 11 km off the coast of Venezuela, near the Orinoco delta. Trinidad, the larger of the two islands, is approximately 5,000 km² and the Nariva Swamp is located on its eastern coast (fig. 1). In 1993, this site was designated as a wetland of international...

  16. Polycistronic transcription of fused cassettes and identification of translation initiation signals in an unusual gene cassette array from Pseudomonas aeruginosa [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Érica L. Fonseca

    2015-11-01

    Full Text Available The gene cassettes found in class 1 integrons are generally promoterless units composed by an open reading frame (ORF, a short 5’ untranslated region (UTR and a 3’ recombination site (attC. Fused gene cassettes are generated by partial or total loss of the attC from the first cassette in an array, creating, in some cases, a fusion with the ORF from the next cassette. These structures are rare and little is known about their mechanisms of mobilization and expression. The aim of this study was to evaluate the dynamic of mobilization and transcription of the gcu14-blaGES-1/aacA4 gene cassette array, which harbours a fused gene cassette represented by blaGES-1/aacA4. The cassette array was analyzed by Northern blot and real-time reverse transcription-polymerase chain reaction (RT-PCR in order to assess the transcription mechanism of blaGES-1/aacA4 fused cassette. Also, inverse polymerase chain reactions (PCR were performed to detect the free circular forms of gcu14, blaGES-1 and aacA4. The Northern blot and real time RT-PCR revealed a polycistronic transcription, in which the fused cassette blaGES-1/aacA4 is transcribed as a unique gene, while gcu14 (with a canonical attC recombination site has a monocistronic transcription. The gcu14 cassette, closer to the weak configuration of cassette promoter (PcW, had a higher transcription level than blaGES-1/aacA4, indicating that the cassette position affects the transcript amounts. The presence of ORF-11 at attI1, immediately preceding gcu14, and of a Shine-Dalgarno sequence upstream blaGES-1/aacA4 composes a scenario for the occurrence of array translation. Inverse PCR generated amplicons corresponding to gcu14, gcu14-aacA4 and gcu14-blaGES-1/aacA4 free circular forms, but not to blaGES-1 and aacA4 alone, indicating that the GES-1 truncated attC is not substrate of integrase activity and that these genes are mobilized together as a unique cassette. This study was original in showing the transcription

  17. Fluorofenidone attenuates bleomycin-induced pulmonary fibrosis by inhibiting eukaryotic translation initiation factor 3a (eIF3a) in rats.

    Science.gov (United States)

    Wu, Yue-Han; Li, Xian-Wei; Li, Wen-Qun; Li, Xiao-Hui; Li, Yuan-Jian; Hu, Gao-Yun; Liu, Zhao-Qian; Li, Dai

    2016-02-15

    Fluorofenidone is a novel derivative of l-mimosine. It has remarkable anti-fibrotic properties. In this study, we established that fluorofenidone ameliorates pulmonary fibrosis (PF) both in vivo and in vitro by specifically inhibiting the expression of eukaryotic translation initiation factor 3a (eIF3a). eIF3a plays an important role in the development and progression of PF. An animal model of PF was induced by intratracheal instillation of bleomycin (5mg/kg) in rats. Rats were orally administered with fluorofenidone (250, 500 mg/kg/d·[i.g.]) and pirfenidone (500 mg/kg/d·[i.g.]) for 28 days. Primary pulmonary fibroblasts were cultured to determine the effect of fluorofenidone on TGF-β1-induced (5 ng/ml) proliferation and differentiation of fibroblasts. The expression/level of eIF3a, TGF-β1, α-SMA, collagen I, and collagen III were analyzed by ELISA, real-time PCR, and western blot. The cell proliferation rate was determined by MTS assay. The results indicate that fluorofenidone significantly improves the pathological changes in lung tissues and reduces the deposition of collagen by inhibiting eIF3a in rats with bleomycin-induced PF. Moreover, in a culture of pulmonary fibroblasts, fluorofenidone decreased the up-regulation of TGF-β1-induced eIF3a by inhibiting the proliferation of cells and reducing the expression of α-SMA, collagen I, and collagen III. These findings suggest that eIF3a is a new and special target of fluorofenidone, which could be potentially used in the development of a drug that treats PF. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Eukaryotic translation initiation factor 5A2 regulates the migration and invasion of hepatocellular carcinoma cells via pathways involving reactive oxygen species.

    Science.gov (United States)

    Liu, Rong-Rong; Lv, Ya-Su; Tang, Yue-Xiao; Wang, Yan-Fang; Chen, Xiao-Ling; Zheng, Xiao-Xiao; Xie, Shang-Zhi; Cai, Ying; Yu, Jun; Zhang, Xian-Ning

    2016-04-26

    Eukaryotic translation initiation factor 5A2 (eIF5A2) has been identified as a critical gene in tumor metastasis. Research has suggested that reactive oxygen species (ROS) serve as signaling molecules in cancer cell proliferation and migration. However, the mechanisms linking eIF5A2 and ROS are not fully understood. Here, we investigated the effects of ROS on the eIF5A2-induced epithelial-mesenchymal transition (EMT) and migration in six hepatocellular carcinoma (HCC) cell lines. Western hybridization, siRNA transfection, transwell migration assays, wound-healing assays, and immunofluorescence analysis were used. The protein levels of eIF5A2 in tumor and adjacent tissue samples from 90 HCC patients with detailed clinical, pathological, and clinical follow-up data were evaluated. Overexpression of eIF5A2 was found in cancerous tissues compared with adjacent tissues. We found that eIF5A2 overexpression in HCC was associated with reduced overall survival. Knockdown of eIF5A2 and intracellular reduction of ROS significantly suppressed the invasion and metastasis of HCC cells. Interestingly, N1-guanyl-1, 7-diaminoheptane (GC7) suppressed the intracellular ROS levels. After blocking the EMT, administration of GC7 or N-acetyl-L-cysteine did not reduce cell migration further. Based on the experimental data, we concluded that inhibition of eIF5A2 alters progression of the EMT to decrease the invasion and metastasis of HCC cells via ROS-related pathways.

  19. Eukaryotic translation initiation factor 3B accelerates the progression of esophageal squamous cell carcinoma by activating β-catenin signaling pathway.

    Science.gov (United States)

    Xu, Fengkai; Xu, Cheng-Zhi; Gu, Jie; Liu, Xiaoming; Liu, Ronghua; Huang, Enyu; Yuan, Yunfeng; Zhao, Guangyin; Jiang, Jiahao; Xu, Chen; Chu, Yiwei; Lu, Chunlai; Ge, Di

    2016-07-12

    Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors. Eukaryotic translation initiation factors 3B (EIF3B) is considered to influence tumor proliferation, invasion, apoptosis and cell cycle, which act together to promote the progression of tumors. However, the role of EIF3B in ESCC is unknown. This study aims to explore the clinical and biological role of EIF3B in ESCC. EIF3B expressions were up-regulated in both ESCC tissues and cell lines. Overexpression of EIF3B was associated with tumor depth, lymph node metastasis and advanced TNM stage. Importantly, patients with high EIF3B expression suffered shorter overall and disease-free survival. Knockdown of EIF3B could inhibit cell proliferation and invasion, promote cell apoptosis, and interfere the cell cycle in vitro. EIF3B-knockdown cells could form smaller subcutaneous tumors in vivo. Finally, we demonstrated EIF3B could activate β-catenin signaling pathway. Immunohistochemical staining and Western blot were performed to detect the EIF3B expression in ESCC patient tissues and cell lines. The association between EIF3B expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. Then, CCK-8, colony-formation, Transwell and wound-healing assay were performed to compare the bio-functional change after knockdown of EIF3B. Flow cytometry was applied to analyze the change of cell apoptosis and cycle induced by EIF3B knockdown. Tumor xenograft assay was done to verify the in-vitro results. EIF3B might serve as a novel marker for predicting prognosis of ESCC patients and as a potential therapeutic target, individually or together with other subunits of EIF3 complex.

  20. Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Li Xin

    2010-04-01

    Full Text Available Abstract Background The aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1 in nasopharyngeal carcinoma (NPC and its correlation with clinicopathologic features, including patients' survival time. Methods Using real-time PCR, we detected the expression of EIF4G1 in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. EIF4G1 protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of EIF4G1 on cell invasion and tumorigenesis were investigated. Results The expression levels of EIF4G1 mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells (P EIF4G1 protein was higher in NPC tissues than that in the nasopharyngeal tissues (P EIF4G1 protein in tumors were positively correlated with tumor T classification (P = 0.039, lymph node involvement (N classification, P = 0.008, and the clinical stages (P = 0.003 of NPC patients. Patients with higher EIF4G1 expression had shorter overall survival time (P = 0.019. Multivariate analysis showed that EIF4G1 expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of EIF4G1 not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed in vivo xenograft tumor growth. Conclusion Our data suggest that EIF4G1 can serve as a biomarker for the prognosis of NPC patients.

  1. Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq).

    Science.gov (United States)

    Langley, Alexander R; Gräf, Stefan; Smith, James C; Krude, Torsten

    2016-12-01

    Next-generation sequencing has enabled the genome-wide identification of human DNA replication origins. However, different approaches to mapping replication origins, namely (i) sequencing isolated small nascent DNA strands (SNS-seq); (ii) sequencing replication bubbles (bubble-seq) and (iii) sequencing Okazaki fragments (OK-seq), show only limited concordance. To address this controversy, we describe here an independent high-resolution origin mapping technique that we call initiation site sequencing (ini-seq). In this approach, newly replicated DNA is directly labelled with digoxigenin-dUTP near the sites of its initiation in a cell-free system. The labelled DNA is then immunoprecipitated and genomic locations are determined by DNA sequencing. Using this technique we identify >25,000 discrete origin sites at sub-kilobase resolution on the human genome, with high concordance between biological replicates. Most activated origins identified by ini-seq are found at transcriptional start sites and contain G-quadruplex (G4) motifs. They tend to cluster in early-replicating domains, providing a correlation between early replication timing and local density of activated origins. Origins identified by ini-seq show highest concordance with sites identified by SNS-seq, followed by OK-seq and bubble-seq. Furthermore, germline origins identified by positive nucleotide distribution skew jumps overlap with origins identified by ini-seq and OK-seq more frequently and more specifically than do sites identified by either SNS-seq or bubble-seq. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. TRANSLATING FEMINISM

    OpenAIRE

    Gajewska, Agnieszka

    2012-01-01

    Translating feminism Pointing to manifold and long-lasting connections between feminism and translation, the article first presents a selection of multilingual writers (Narcyza Żmichowska and Deborah Vogel), translators (Zofia Żeleńska and Kazimiera Iłłakowiczówna) and translation commentators (Joanna Lisek and Karolina Szymaniak) to ponder why the work of early Polish feminists is neglected. It seems that one of the reasons might be the current colonization of Polish femini...

  3. The Translation Initiation Factor 1A (TheIF1A) fromTamarix hispidaIs Regulated by a Dof Transcription Factor and Increased Abiotic Stress Tolerance.

    Science.gov (United States)

    Yang, Guiyan; Yu, Lili; Wang, Yucheng; Wang, Chao; Gao, Caiqiu

    2017-01-01

    Eukaryotic translation initiation factor 1A ( eIF1A ) functions as an mRNA scanner and AUG initiation codon locator. However, few studies have clarified the role of eIF1A in abiotic stress. In this study, we cloned eIF1A ( TheIF1A ) from Tamarix hispida and found its expression to be induced by NaCl and polyethylene glycol (PEG) in roots, stems, and leaves. Compared to control, TheIF1A root expression was increased 187.63-fold when exposed to NaCl for 6 h, suggesting a potential abiotic stress response for this gene. Furthermore, transgenic tobacco plants overexpressing TheIF1A exhibited enhanced seed germination and a higher total chlorophyll content under salt and mannitol stresses. Increased superoxide dismutase, peroxidase, glutathione transferase and glutathione peroxidase activities, as well as decreased electrolyte leakage rates and malondialdehyde contents, were observed in TheIF1A -transgenic tobacco and T. hispida seedlings under salt and mannitol stresses. Histochemical staining suggested that TheIF1A improves reactive oxygen species (ROS) scavenging in plants. Moreover, TheIF1A may regulate expression of stress-related genes, including TOBLTP , GST , MnSOD , NtMPK9 , poxN1 , and CDPK15 . Moreover, a 1352-bp promoter fragment of TheIF1A was isolated, and cis -elements were identified. Yeast one-hybrid assays showed that ThDof can specifically bind to the Dof motif present in the promoter. In addition, ThDof showed expression patterns similar to those of TheIF1A under NaCl and PEG stresses. These findings suggest the potential mechanism and physiological roles of TheIF1A . ThDof may be an upstream regulator of TheIF1A , and TheIF1A may function as a stress response regulator to improve plant salt and osmotic stress tolerance via regulation of associated enzymes and ROS scavenging, thereby reducing cell damage under stress conditions.

  4. Initial Results on the Mineralogy and Geochemistry of the Mar Exploration Rover Gusev Landing Site

    Science.gov (United States)

    Christensen, P. R.

    2004-05-01

    The Spirit rover has investigated the geochemistry and mineralogy of the Gusev crater site using in situ Alpha Proton X-Ray, Mossbauer, visible, and infrared spectroscopy. The Gusev site is covered with angular to sub-rounded rocks that are typically less than 1 m in maximum dimension. More than 90 percent of these rocks are dark-toned, with the remainder being lighter-toned rocks that may predominantly be dark rocks with a thin (10's of microns) coating of easily removed fines. APXS analysis has been obtained of a rock (Adirondack) following the removal by grinding of the surface dust and the upper few mm of the rock surface. These data give a modal mineralogy corresponding to olivine basalt. High quality Mini-TES data have not been obtained of a completely dust-free rock surface. The Mini-TES data of Adirondack do show long wavelength (15-25 microns) absorptions due to olivine of composition ~Fo60. All of the rocks observed are very compositionally homogeneous in the Mini-TES spectra. These findings are consistent with the detection of olivine-bearing basalt at this site from orbital TES infrared spectroscopy. Mossbauer spectra of Adirondack show the presence of forsteritic olivine and magnetite, with possible pyroxene. The soils at Gusev are a mixture of reddish fine-grained to sandy materials, granular-sized particles that occur in ripple forms, and minor pebbles. Mini-TES spectra of the soil show an excellent match to the TES spectra of high-albedo, fine-grained material found in regional bright regions that is interpreted to be windblown dust. This agreement suggests at least the uppermost layer of the soil at Gusev has been accumulated from airfall dust. By analogy with prior analysis of TES data these materials contain several percent carbonate, minor bound water, and a framework silicate interpreted to be either feldspar or zeolite. APXS spectra show similar oxide abundances to those determined for the Pathfinder site, except for higher MgO, and lower

  5. Site characterization of the Romanian Seismic Network stations: a national initiative and its first preliminary results

    Science.gov (United States)

    Grecu, Bogdan; Zahria, Bogdan; Manea, Elena; Neagoe, Cristian; Borleanu, Felix; Diaconescu, Mihai; Constantinescu, Eduard; Bala, Andrei

    2017-04-01

    The seismic activity in Romania is dominated by the intermediate-depth earthquakes occurring in Vrancea region, although weak to moderate crustal earthquakes are produced regularly in different areas of the country. The National Institute for Earth Physics (NIEP) built in the last years an impressive infrastructure for monitoring this activity, known as the Romanian Seismic Network (RSN). At present, RSN consists of 122 seismic stations, of which 70 have broadband velocity sensors and 42 short period sensors. One hundred and eleven stations out of 122 have accelerometer sensors collocated with velocity sensors and only 10 stations have only accelerometers. All the stations record continuously the ground motion and the data are transmitted in real-time to the Romanian National Data Center (RoNDC), in Magurele. Last year, NIEP has started a national project that addresses the characterization of all real-time seismic stations that constitute the RSN. We present here the steps that were undertaken and the preliminary results obtained since the beginning the project. The first two activities consisted of collecting all the existent technical and geological data, with emphasize on the latter. Then, we performed station noise investigations and analyses in order to characterize the noise level and estimate the resonances of the sites. The computed H/V ratios showed clear resonant peaks at different frequencies which correlate relatively well with the thickness of the sedimentary package beneath the stations. The polarization analysis of the H/V ratios indicates for some stations a strong directivity of the resonance peak which suggests possible topographic effects at the stations. At the same time, special attention was given to the estimation of the site amplification from earthquake data. The spectral ratios obtained from the analysis of more than 50 earthquakes with magnitudes (Mw) larger than 4.1 are characterized by similar resonance peaks as those obtained from

  6. The Field Lysimeter Test Facility (FLTF) at the Hanford Site: Installation and initial tests

    International Nuclear Information System (INIS)

    Gee, G.W.; Kirkham, R.R.; Downs, J.L.; Campbell, M.D.

    1989-02-01

    The objectives of this program are to test barrier design concepts and to demonstrate a barrier design that meets established performance criteria for use in isolating wastes disposed of near-surface at the Hanford Site. Specifically, the program is designed to assess how well the barriers perform in controlling biointrusion, water infiltration, and erosion, as well as evaluating interactions between environmental variables and design factors of the barriers. To assess barrier performance and design with respect to infiltration control, field lysimeters and small- and large-scale field plots are planned to test the performance of specific barrier designs under actual and modified (enhanced precipitation) climatic conditions. The Field Lysimeter Test Facility (FLTF) is located in the 600 Area of the Hanford Site just east of the 200 West Area and adjacent to the Hanford Meteorological Station. The FLTF data will be used to assess the effectiveness of selected protective barrier configurations in controlling water infiltration. The facility consists of 14 drainage lysimeters (2 m dia x 3 m deep) and four precision weighing lysimeters (1.5 m x 1.5 m x 1.7 m deep). The lysimeters are buried at grade and aligned in a parallel configuration, with nine lysimeters on each side of an underground instrument chamber. The lysimeters were filled with materials to simulate a multilayer protective barrier system. Data gathered from the FLTF will be used to compare key barrier components and to calibrate and test models for predicting long-term barrier performance

  7. Modeling time to recovery and initiating event frequency for loss of off-site power incidents at nuclear power plants

    International Nuclear Information System (INIS)

    Iman, R.L.; Hora, S.C.

    1988-01-01

    Industry data representing the time to recovery of loss of off-site power at nuclear power plants for 63 incidents caused by plant-centered losses, grid losses, or severe weather losses are fit with exponential, lognormal, gamma and Weibull probability models. A Bayesian analysis is used to compare the adequacy of each of these models and to provide uncertainty bounds on each of the fitted models. A composite model that combines the probability models fitted to each of the three sources of data is presented as a method for predicting the time to recovery of loss of off-site power. The composite model is very general and can be made site specific by making adjustments on the models used, such as might occur due to the type of switchyard configuration or type of grid, and by adjusting the weights on the individual models, such as might occur with weather conditions existing at a particular plant. Adjustments in the composite model are shown for different models used for switchyard configuration and for different weights due to weather. Bayesian approaches are also presented for modeling the frequency of initiating events leading to loss of off-site power. One Bayesian model assumes that all plants share a common incidence rate for loss of off-site power, while the other Bayesian approach models the incidence rate for each plant relative to the incidence rates of all other plants. Combining the Bayesian models for the frequency of the initiating events with the composite Bayesian model for recovery provides the necessary vehicle for a complete model that incorporates uncertainty into a probabilistic risk assessment

  8. Terrace Geochemistry at the Shiprock, New Mexico, Disposal Site - WM2017-17232 Initial Phase

    Energy Technology Data Exchange (ETDEWEB)

    Kautsky, Mark [USDOE Office of Legacy Management, Washington, DC (United States); Ranalli, Tony [Navarro Research and Engineering, Oak Ridge, TN (United States); Dander, David [Navarro Research and Engineering, Oak Ridge, TN (United States); Miller, David [Navarro Research and Engineering, Oak Ridge, TN (United States)

    2017-03-08

    The objective of this investigation was to identify and differentiate potential non- mill-related water inputs to a shallow terrace groundwater system through the use of aqueous chemical and isotopic tracers at a former uranium- and vanadium-ore processing facility. Terrace groundwater in the vicinity of the Shiprock, New Mexico, site is hypothesized to be largely anthropogenic because natural rates of recharge in the terrace are likely insufficient to sustain a continuous water table in the terrace alluvial system, as observed in several analogue terrace locations east of the site and in response to post-mill dewatering efforts across the site. The terrace is composed of alluvial sand and gravel and weathered and unweathered Mancos Shale. Terrace groundwater exists and flows in the alluvium and to a much less extent in the Mancos Shale. Historical data established that in both the terrace and floodplain below the terrace, mill-derived uranium and sulfate is found primarily in the alluvium and the upper portion of the weathered Mancos Shale. Groundwater extraction is being conducted in the vicinity of former mill operations and in washes and seeps to dewater the formation and remove contamination, thus eliminating these exposure pathways and minimizing movement to the floodplain. However, past and present contribution of non-mill anthropogenic water sources may be hindering the dewatering effort, resulting in reduced remedy effectiveness. Groundwater source signatures can be determined based on chemical and isotopic ratios and are used to help identify and delineate both mill and non-mill water contributions. Aqueous chemical and isotopic tracers, such as 234U/238U activity ratios and uranium concentrations, δ34S sulfate and sulfate concentrations, tritium concentrations, and δ2Hwater and δ18O water are being used in this Phase I study. The aqueous chemical and isotopic analysis has identified areas on the terrace where groundwater is derived from mill

  9. Depressing effect of caffeine at crayfish neuromuscular synapses II. Initial search for possible sites of action.

    Science.gov (United States)

    Celenza, Kathryn M; Shugert, Elizabeth; Vélez, Samuel J

    2007-05-01

    Caffeine's unexpected depression of synaptic transmission in the superficial flexor muscle system (SFM) of Procambarus clarkii was studied by looking at three known sites of action of this drug: via adenosine and ryanodine receptors and inhibition of phosphodiesterase.1. JPs did not change in size when exposed to physiological concentrations of adenosine, suggesting that the SFM system lacks presynaptic adenosine receptors.2. JPs slightly increased in size in the presence of a phosphodiesterase inhibitor, the opposite response to that obtained with caffeine, suggesting that caffeine is not acting via this pathway.3. A calcium ionophore immediately enhanced synaptic transmission in the SFM system but when given in combination with caffeine the enhancement is reduced and declines over time.4. Serotonin enhanced synaptic transmission in the SFM system, but when given in combination with caffeine this enhancement was not observed.5. These caffeine effects are interpreted in terms of alterations to the calcium homeostatic mechanisms of the terminals.

  10. Typologically robust statistical machine translation : Understanding and exploiting differences and similarities between languages in machine translation

    NARCIS (Netherlands)

    Daiber, J.

    2018-01-01

    Machine translation systems often incorporate modeling assumptions motivated by properties of the language pairs they initially target. When such systems are applied to language families with considerably different properties, translation quality can deteriorate. Phrase-based machine translation

  11. Implementation of a referral to discharge glycemic control initiative for reduction of surgical site infections in gynecologic oncology patients.

    Science.gov (United States)

    Hopkins, Laura; Brown-Broderick, Jennifer; Hearn, James; Malcolm, Janine; Chan, James; Hicks-Boucher, Wendy; De Sousa, Filomena; Walker, Mark C; Gagné, Sylvain

    2017-08-01

    To evaluate the frequency of surgical site infections before and after implementation of a comprehensive, multidisciplinary perioperative glycemic control initiative. As part of a CUSP (Comprehensive Unit-based Safety Program) initiative, between January 5 and December 18, 2015, we implemented comprehensive, multidisciplinary glycemic control initiative to reduce SSI rates in patients undergoing major pelvic surgery for a gynecologic malignancy ('Group II'). Key components of this quality of care initiative included pre-operative HbA1c measurement with special triage for patients meeting criteria for diabetes or pre-diabetes, standardization of available intraoperative insulin choices, rigorous pre-op/intra-op/post-op glucose monitoring with control targets set to maintain BG ≤10mmol/L (180mg/dL) and communication/notification with primary care providers. Effectiveness was evaluated against a similar control group of patients ('Group I') undergoing surgery in 2014 prior to implementation of this initiative. We studied a total of 462 patients. Subjects in the screened (Group II) and comparison (Group I) groups were of similar age (avg. 61.0, 60.0years; p=0.422) and BMI (avg. 31.1, 32.3kg/m 2 ; p=0.257). Descriptive statistics served to compare surgical site infection (SSI) rates and other characteristics across groups. Women undergoing surgery prior to implementation of this algorithm (n=165) had an infection rate of 14.6%. Group II (n=297) showed an over 2-fold reduction in SSI compared to Group I [5.7%; p=0.001, adjRR: 0.45, 95% CI: (0.25, 0.81)]. Additionally, approximately 19% of Group II patients were newly diagnosed with either prediabetes (HbA1C 6.0-6.4) or diabetes (HbA1C≥6.5) and were referred to family or internal medicine for appropriate management. Implementation of a comprehensive multidisciplinary glycemic control initiative can lead to a significant reduction in surgical site infections in addition to early identification of an important health

  12. Staphylococcal phage 2638A endolysin is lytic for Staphylococcus aureus and harbors an inter-lytic-domain secondary translational start site.

    Science.gov (United States)

    Abaev, Igor; Foster-Frey, Juli; Korobova, Olga; Shishkova, Nina; Kiseleva, Natalia; Kopylov, Pavel; Pryamchuk, Sergey; Schmelcher, Mathias; Becker, Stephen C; Donovan, David M

    2013-04-01

    Staphylococcus aureus is a notorious pathogen highly successful at developing resistance to virtually all antibiotics to which it is exposed. Staphylococcal phage 2638A endolysin is a peptidoglycan hydrolase that is lytic for S. aureus when exposed externally, making it a new candidate antimicrobial. It shares a common protein organization with more than 40 other reported staphylococcal peptidoglycan hydrolases. There is an N-terminal M23 peptidase domain, a mid-protein amidase 2 domain (N-acetylmuramoyl-L-alanine amidase), and a C-terminal SH3b cell wall-binding domain. It is the first phage endolysin reported with a secondary translational start site in the inter-lytic-domain region between the peptidase and amidase domains. Deletion analysis indicates that the amidase domain confers most of the lytic activity and requires the full SH3b domain for maximal activity. Although it is common for one domain to demonstrate a dominant activity over the other, the 2638A endolysin is the first in this class of proteins to have a high-activity amidase domain (dominant over the N-terminal peptidase domain). The high activity amidase domain is an important finding in the quest for high-activity staphylolytic domains targeting novel peptidoglycan bonds.

  13. MicroRNA-9 enhances sensitivity to cetuximab in epithelial phenotype hepatocellular carcinoma cells through regulation of the eukaryotic translation initiation factor 5A-2.

    Science.gov (United States)

    Xue, Fei; Liang, Yuntian; Li, Zhenrong; Liu, Yanhui; Zhang, Hongwei; Wen, Yu; Yan, Lei; Tang, Qiang; Xiao, Erhui; Zhang, Dongyi

    2018-01-01

    Hepatocellular carcinoma (HCC) is one of the most widespread malignant human tumors worldwide. Treatment options include radiotherapy, surgical intervention and chemotherapy; however, drug resistance is an ongoing treatment concern. In the present study, the effects of a microRNA (miR/miRNA), miR-9, on the sensitivity of HCC cell lines to the epidermal growth factor receptor inhibitor, cetuximab, were examined. miR-9 has been proposed to serve a role in tumorigenesis and tumor progression. In the present study, bioinformatics analyses identified the eukaryotic translation initiation factor 5A2 (eIF-5A-2) as a target of miR-9. The expression levels of miR-9 and eIF-5A-2 were examined by reverse transcription-quantitative polymerase chain reaction and HCC cell lines were transfected with miR-9 mimics and inhibitors to determine the effects of the miRNA on cell proliferation and viability. The miR-9 mimic was revealed to significantly increase the sensitivity of epithelial phenotype HCC cells (Hep3B and Huh7) to cetuximab, while the miR-9 inhibitor triggered the opposite effect. There were no significant differences in sensitivity to cetuximab observed in mesenchymal phenotype HCC cells (SNU387 and SNU449). Cells lines displaying high expression levels of eIF-5A-2 were more resistant to cetuximab. Transfection of cells with a miR-9 mimic resulted in downregulation of the expression of eIF-5A-2 mRNA, while an miR-9 inhibitor increased expression. When expression of eIF-5A-2 was knocked down with siRNA, the effects of miR-9 on cetuximab sensitivity were no longer observed. Taken together, these data support a role for miR-9 in enhancing the sensitivity of epithelial phenotype HCC cells to cetuximab through regulation of eIF-5A-2.

  14. NASA's Beachside Corrosion Test Site and Current Environmentally Friendly Corrosion Control Initiatives

    Science.gov (United States)

    Russell, Richard W.; Calle, Luz Marina; Johnston, Frederick; Montgomery, Eliza L.; Curran, Jerome P.; Kolody, Mark R.

    2013-01-01

    NASA began corrosion studies at the Kennedy Space Center (KSC) in 1966 during the Gemini/Apollo Programs with the evaluation of long-term corrosion protective coatings for carbon steel. KSC's Beachside Corrosion Test Site (BCTS), which has been documented by the American Society of Materials (ASM) as one of the most corrosive, naturally occurring, environments in the world, was established at that time. With the introduction of the Space Shuttle in 1981, the already highly corrosive conditions at the launch pad were rendered even more severe by the acid ic exhaust from the solid rocket boosters. In the years that followed, numerous studies have identified materials, coatings, and maintenance procedures for launch hardware and equipment exposed to the highly corrosive environment at the launch pad. This paper presents a historical overview of over 45 years of corrosion and coating evaluation studies and a description of the BCTS's current capabilities. Additionally, current research and testing programs involving chromium free coatings, environmentally friendly corrosion preventative compounds, and alternates to nitric acid passivation will be discussed.

  15. Savannah River Site waste vitrification projects initiated throughout the United States: Disposal and recycle options

    International Nuclear Information System (INIS)

    Jantzen, C.M.

    2000-01-01

    A vitrification process was developed and successfully implemented by the US Department of Energy's (DOE) Savannah River Site (SRS) and at the West Valley Nuclear Services (WVNS) to convert high-level liquid nuclear wastes (HLLW) to a solid borosilicate glass for safe long term geologic disposal. Over the last decade, SRS has successfully completed two additional vitrification projects to safely dispose of mixed low level wastes (MLLW) (radioactive and hazardous) at the SRS and at the Oak Ridge Reservation (ORR). The SRS, in conjunction with other laboratories, has also demonstrated that vitrification can be used to dispose of a wide variety of MLLW and low-level wastes (LLW) at the SRS, at ORR, at the Los Alamos National Laboratory (LANL), at Rocky Flats (RF), at the Fernald Environmental Management Project (FEMP), and at the Hanford Waste Vitrification Project (HWVP). The SRS, in conjunction with the Electric Power Research Institute and the National Atomic Energy Commission of Argentina (CNEA), have demonstrated that vitrification can also be used to safely dispose of ion-exchange (IEX) resins and sludges from commercial nuclear reactors. In addition, the SRS has successfully demonstrated that numerous wastes declared hazardous by the US Environmental Protection Agency (EPA) can be vitrified, e.g. mining industry wastes, contaminated harbor sludges, asbestos containing material (ACM), Pb-paint on army tanks and bridges. Once these EPA hazardous wastes are vitrified, the waste glass is rendered non-hazardous allowing these materials to be recycled as glassphalt (glass impregnated asphalt for roads and runways), roofing shingles, glasscrete (glass used as aggregate in concrete), or other uses. Glass is also being used as a medium to transport SRS americium (Am) and curium (Cm) to the Oak Ridge Reservation (ORR) for recycle in the ORR medical source program and use in smoke detectors at an estimated value of $1.5 billion to the general public

  16. Instrument translation and initial psychometric evaluation of the Chinese version of the Self-Management of Type 1 Diabetes for Adolescents scale.

    Science.gov (United States)

    Guo, Jia; Dixon, Jane K; Whittemore, Robin; He, Guo-Ping

    2013-04-01

    To translate the validated measure, Self-Management of Type 1 Diabetes in Adolescents, into the Mandarin Chinese language and to test the psychometric properties of the Chinese version. Although research on self-management of Type 1 diabetes has been increasing over the past 20 years, few health-related instruments have been available in the Chinese language for youth with Type 1 diabetes. A two-phase design was used in this study, including instrument translation and psychometric testing. The instrument translation, from October 2008-April 2009, included three steps: forward translation, back translation, and comparison of versions via Translation Validity Index - with multiple rounds, group discussion, and achievement of consensus at each step. Psychometric properties of the Chinese version Schilling's Self-Management of Type 1 Diabetes for Adolescents scale was assessed in a convenience sample of 136 Chinese youth (ages 8-19) with Type 1 diabetes between June 2009-August 2009. The internal consistency and test-retest reliabilities indicated generally good consistency and temporal stability of the Chinese version. Evidence of construct validity and criterion-related validity was obtained via correlations of subscales with established measures of diabetes adherence and quality of life and also with haemoglobin A1c. Results from hypothesis testing also supported construct validity. The Chinese version of Self-Management of Type 1 Diabetes for Adolescents scale is sound and will facilitate cross-cultural studies, while also enabling nurses to monitor and enhance the diabetes self-management of Chinese youth with Type 1 diabetes. © 2012 Blackwell Publishing Ltd.

  17. [Translational dental medicine].

    Science.gov (United States)

    Zheng, Li-Wei; Wang, Qi; Zhou, Xue-Dong

    2011-06-01

    Over the last decade, as tremendous innovations have been achieved in scientific technology, translational medicine has come into the focus of academic medicine, and significant intellectual and financial efforts have been made to initiate a multitude of bench-to-bedside projects. The concept of translational medicine is described as the transfer of new understandings of disease mechanisms gained in the laboratory into the development of new methods for diagnosis, therapy, and prevention and their first testing in humans, meanwhile, translational medicine also is described as a patient-oriented population research and the translation of results from clinical studies into everyday clinical practice and health decision making. Translational medicine is a hot spot in recent academic field, and it is crucial for improving the living standard of population and renewing the research idea and technology. It has, however, significant obstacles during the approach of translational medicine. We here review the background, concept, current situation of translational dental medicine, key components and obstacles of translational medicine.

  18. Initial Observations and Activities of Curiosity's Mars Hand Lens Imager (MAHLI) at the Gale Field Site

    Science.gov (United States)

    Aileen Yingst, R.; Edgett, Kenneth; MSL Science Team

    2013-04-01

    The Mars Hand Lens Imager (MAHLI) is a 2-megapixel focusable macro lens color camera on the turret on the Mars Science Laboratory rover, Curiosity's, robotic arm. The investigation centers on stratigraphy, grain-scale texture, structure, mineralogy, and morphology. MAHLI acquires focused images at working distances of 2.1 cm to infinity; at 2.1 cm the scale is 14 µm/pixel; at 6.9 cm it is 31 µm/pixel, like the Spirit and Opportunity Microscopic Imagers (MI). Most MAHLI use during the first 100 Martian days (sols) was focused on instrument, rover, and robotic arm engineering check-outs and risk reduction, including (1) interrogation of an eolian sand shadow for suitability for scooping, decontamination of the sample collection and processing system (CHIMRA, Collection and Handling for In-Situ Martian Rock Analysis), and first solid sample delivery to the Chemistry and Mineralogy (CheMin) and Sample Analysis at Mars (SAM) instruments; (2) documentation of the nature of this sand; (3) verification that samples were delivered to SAM and passed through a 150 µm mesh and a 2 mm funnel throat in the CheMin inlet; (4) development of methods for future precision robotic arm positioning of MAHLI and the Alpha Particle X-Ray Spectrometer (APXS); and (5) use of MAHLI autofocus for range-finding to determine locations to position the scoop before each scooping event. Most Sol 0-100 MAHLI images were obtained at scales of 31-110 µm/pixel; some geologic targets were imaged at 21-31 µm/pixel. No opportunities to position the camera close enough to obtain 14-20 µm/pixel images were available during this initial period. Only two rocks, named Jake Matijevic and Bathurst Inlet, were imaged at a resolution higher than MI. Both were dark gray and mantled with dust and fine/very fine sand. In both cases, the highest resolution images of these rocks show no obvious, indisputable grains, suggesting that grain sizes (as expressed at the rock surfaces) are sieved (≤ 150 µm) and

  19. Host and viral translational mechanisms during cricket paralysis virus infection.

    Science.gov (United States)

    Garrey, Julianne L; Lee, Yun-Young; Au, Hilda H T; Bushell, Martin; Jan, Eric

    2010-01-01

    The dicistrovirus is a positive-strand single-stranded RNA virus that possesses two internal ribosome entry sites (IRES) that direct translation of distinct open reading frames encoding the viral structural and nonstructural proteins. Through an unusual mechanism, the intergenic region (IGR) IRES responsible for viral structural protein expression mimics a tRNA to directly recruit the ribosome and set the ribosome into translational elongation. In this study, we explored the mechanism of host translational shutoff in Drosophila S2 cells infected by the dicistrovirus, cricket paralysis virus (CrPV). CrPV infection of S2 cells results in host translational shutoff concomitant with an increase in viral protein synthesis. CrPV infection resulted in the dissociation of eukaryotic translation initiation factor 4G (eIF4G) and eIF4E early in infection and the induction of deIF2alpha phosphorylation at 3 h postinfection, which lags after the initial inhibition of host translation. Forced dephosphorylation of deIF2alpha by overexpression of dGADD34, which activates protein phosphatase I, did not prevent translational shutoff nor alter virus production, demonstrating that deIF2alpha phosphorylation is dispensable for host translational shutoff. However, premature induction of deIF2alpha phosphorylation by thapsigargin treatment early in infection reduced viral protein synthesis and replication. Finally, translation mediated by the 5' untranslated region (5'UTR) and the IGR IRES were resistant to impairment of eIF4F or eIF2 in translation extracts. These results support a model by which the alteration of the deIF4F complex contribute to the shutoff of host translation during CrPV infection, thereby promoting viral protein synthesis via the CrPV 5'UTR and IGR IRES.

  20. Found in translation

    DEFF Research Database (Denmark)

    Tietjen, Anne

    2018-01-01

    on a teaching experiment in landscape architecture education, this paper proposes teaching creative site analysis as a translation process of observed site conditions into desirable future site conditions. Guided by actor-network theory, the paper outlines, first, a conceptual framework for creative site...... analysis. Second, it presents the applied educational procedure, with a focus on the decisive step from inventory to intervention which is the formulation of a design problem. The teaching experiment shows that onsite studies of spatial controversies in the form of recent physical changes, emerging new...... for the students. Overall, the produced design work and the student evaluations show that translation offers an operational framework for teaching a creative approach to site analysis....

  1. The contribution to site core damage frequency from independent occurrences of initiators in two or more units: How low is it?

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong-San; Park, Jin Hee; Lim, Ho Gon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    Stutzke estimated the site risk by summing the contribution from common cause initiators and the contribution from single-unit initiators. He considered some kinds of multi-unit accident sequences caused by single-unit initiators. However, the contribution from independent occurrences of initiators in two or more units at a site was not taken into account. The purpose of this study is to estimate the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site. Some assumptions and methods used in this analysis are firstly described, and the results and conclusions of the analysis are described. In this study, the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site was estimated. A Korean six-unit site was selected as the reference site and the at-power internal events Level 1 PSA model for an OPR1000 unit at the reference site was used as the base model, and was modified to deal with some major dependencies between units at the site. Specifically, the availability of the AAC D/G, dependencies between offsite power recovery actions in different unis, and inter-unit CCF modeling for risk-significant components such as diesel generators were taken into account. As a result, the sum of dual-unit CDF due to independent occurrences of initiators in two units at the reference site was estimated to be sufficiently low to be neglected.

  2. Revising Translations

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten Wølch; Schjoldager, Anne

    2011-01-01

    out by specialised revisers, but by staff translators, who revise the work of colleagues and freelancers on an ad hoc basis. Corrections are mostly given in a peer-to-peer fashion, though the work of freelancers and inexperienced in-house translators is often revised in an authoritative (nonnegotiable...

  3. Translating democracy

    DEFF Research Database (Denmark)

    Doerr, Nicole

    2012-01-01

    grassroots activists in social movements use translation as a novel practice to debate political alternatives in the European Union's (EU) multilingual public sphere. In recent years, new cross-European protest movements have created the multilingual discursive democracy arena known as the European Social...... to the national context. In the ESF, grassroots deliberators work using a novel practice of translation that has the potential to include marginalized groups. It is, however, a distinct kind of translation that activists use. Translation, compared to EU-official practices of multilingualism, affects a change...... in institutionalized habits and norms of deliberation. Addressing democratic theorists, my findings suggest that translation could be a way to think about difference not as a hindrance but as a resource for democracy in linguistically heterogeneous societies and public spaces, without presupposing a shared language...

  4. Engineering of ribosomal shunt-modulating eukaryotic ON riboswitches by using a cell-free translation system.

    Science.gov (United States)

    Ogawa, Atsushi

    2015-01-01

    A number of natural and artificial bacterial riboswitches have been reported thus far. However, they generally function only in bacteria, not in eukaryotes. This is because of the differences of expression mechanisms (transcription, translation, and so on) between these two main types of organisms. For example, the mechanism of translation initiation is quite different between bacteria and eukaryotes, especially in ribosome loading on mRNA. While the bacterial ribosome binds to a well-conserved, internal sequence some bases before the start codon to initiate translation, the eukaryotic one is loaded on the 5' terminus with the help of certain eukaryotic initiation factors. This means not only that bacterial riboswitches regulating translation initiation are not available in eukaryotic translation systems, but also that it is physically difficult to construct eukaryotic ON riboswitches that regulate the eukaryotic canonical translation initiation, because an aptamer cannot be inserted upstream of the ribosome loading site. However, the mechanism of noncanonical translation initiation via "ribosomal shunt" enables us to design translation initiation-modulating (specifically, ribosomal shunt-modulating) eukaryotic ON riboswitches. This chapter describes a facile method for engineering these ribosomal shunt-modulating eukaryotic ON riboswitches by using a cell-free translation system. Because these riboswitches do not require hybridization switching thanks to a unique shunting mechanism, they have the major advantages of a low energy requirement for upregulation and relatively straightforward design over common hybridization switch-based ON riboswitches. © 2015 Elsevier Inc. All rights reserved.

  5. Leucine-induced activation of translational initiation is partly regulated by the branched-chain α-keto acid dehydrogenase complex in C2C12 cells

    International Nuclear Information System (INIS)

    Nakai, Naoya; Shimomura, Yoshiharu; Tamura, Tomohiro; Tamura, Noriko; Hamada, Koichiro; Kawano, Fuminori; Ohira, Yoshinobu

    2006-01-01

    Branched-chain amino acid leucine has been shown to activate the translational regulators through the mammalian target of rapamycin. However, the leucine's effects are self-limiting because leucine promotes its own disposal by an oxidative pathway. The irreversible and rate-limiting step in the leucine oxidation pathway is catalyzed by the branched-chain α-keto acid dehydrogenase (BCKDH) complex. The complex contains E1 (α2β2), E2, and E3 subunits, and its activity is abolished by phosphorylation of the E1α subunit by BCKDH kinase. The relationship between the activity of BCKDH complex and leucine-mediated activation of the protein translation was investigated using the technique of RNA interference. The activity of BCKDH complex in C2C12 cell was modulated by transfection of small interfering RNA (siRNA) for BCKDH E2 subunit or BCKDH kinase. Transfection of siRNAs decreased the mRNA expression and protein amount of corresponding gene. Suppression of either E2 subunit or kinase produced opposite effects on the cell proliferation and the activation of translational regulators by leucine. Suppression of BCKDH kinase for 48 h resulted in decreasing cell proliferation. In contrast, E2 suppression led to increased amount of total cellular protein. The phosphorylation of p70 S6 kinase by leucine was increased in E2-siRNA transfected C2C12 cells, whereas the leucine's effect was diminished in kinase-siRNA transfected cells. These results suggest that the activation of the translational regulators by leucine was partly regulated by the activity of BCKDH complex

  6. Completion Report for Multi-Site Incentive MRT 2779 Implement ASC Tripod Initiative by 30SEP08

    Energy Technology Data Exchange (ETDEWEB)

    East, D; Cerutti, J; Noe, J; Cupps, K; Loncaric, J; Sturtevant, J

    2008-09-22

    This report provides documentation and evidence for the completion of the deployment of the Tripod common operating system (TripodOS, also known as and generally referred to below as TOSS). Background documents for TOSS are provided in Appendices A and B, including the initial TOSS proposal accepted by ASC HQ and Executives in July 2007 and a Governance Model defined by a Tri-Lab working group in September 2007. Appendix C contains a document that clarifies the intent and requirements for the completion criteria associated with MRT 2779. The deployment of TOSS is a Multi-Site Incentive from the ASC FY08-09 Implementation Plan due at the end of Quarter 4 in FY08.

  7. The initial investigation of Fatu-ma-Futi : an ancient coastal village site, Tutuila Island, Territory of American Samoa

    International Nuclear Information System (INIS)

    Addison, D.J.; Walter, G.; Morrison, A.

    2007-01-01

    Results of inital excavations at Fatu-ma-Futi Village are reported. Stratigraphy in two test pits was similar, with compacted surface layers of a car-parking lot underlain by a layer of clayey sand, fire-affected rock and ancient pebble-gravel paving, which slowly graded into the original beach surface. Post-moulds, shell midden, and basalt flakes were found in both units and human remains in one. Near-basal radiocarbon dates on charcoal suggest initial occupation of a newly formed littoral environment in the period of about 1600 to 1300 cal BP. Permanent habitation came later, with evidence of large-scale basalt tool manufacture towards the end of the sequence. This site is important for understanding current topics in Samoan prehistory, including settlement pattern and coastal geomorphology, marine exploitation and reef health, human lifestyle, health and burial practices, domestic architectural morphology; and the Tutuila basal export industry. (author). 37 refs., 8 figs., 7 tabs

  8. Binary translation using peephole translation rules

    Science.gov (United States)

    Bansal, Sorav; Aiken, Alex

    2010-05-04

    An efficient binary translator uses peephole translation rules to directly translate executable code from one instruction set to another. In a preferred embodiment, the translation rules are generated using superoptimization techniques that enable the translator to automatically learn translation rules for translating code from the source to target instruction set architecture.

  9. Hepatitis C virus translation preferentially depends on active RNA replication.

    Directory of Open Access Journals (Sweden)

    Helene Minyi Liu

    Full Text Available Hepatitis C virus (HCV RNA initiates its replication on a detergent-resistant membrane structure derived from the endoplasmic reticulum (ER in the HCV replicon cells. By performing a pulse-chase study of BrU-labeled HCV RNA, we found that the newly-synthesized HCV RNA traveled along the anterograde-membrane traffic and moved away from the ER. Presumably, the RNA moved to the site of translation or virion assembly in the later steps of viral life cycle. In this study, we further addressed how HCV RNA translation was regulated by HCV RNA trafficking. When the movement of HCV RNA from the site of RNA synthesis to the Golgi complex was blocked by nocodazole, an inhibitor of ER-Golgi transport, HCV protein translation was surprisingly enhanced, suggesting that the translation of viral proteins occurred near the site of RNA synthesis. We also found that the translation of HCV proteins was dependent on active RNA synthesis: inhibition of viral RNA synthesis by an NS5B inhibitor resulted in decreased HCV viral protein synthesis even when the total amount of intracellular HCV RNA remained unchanged. Furthermore, the translation activity of the replication-defective HCV replicons or viral RNA with an NS5B mutation was greatly reduced as compared to that of the corresponding wildtype RNA. By performing live cell labeling of newly synthesized HCV RNA and proteins, we further showed that the newly synthesized HCV proteins colocalized with the newly synthesized viral RNA, suggesting that HCV RNA replication and protein translation take place at or near the same site. Our findings together indicate that the translation of HCV RNA is coupled to RNA replication and that the both processes may occur at the same subcellular membrane compartments, which we term the replicasome.

  10. Loss-of-function analysis reveals distinct requirements of the translation initiation factors eIF4E, eIF4E-3, eIF4G and eIF4G2 in Drosophila spermatogenesis.

    Directory of Open Access Journals (Sweden)

    Sanjay Ghosh

    Full Text Available In eukaryotes, post-transcriptional regulation of gene expression has a key role in many cellular and developmental processes. Spermatogenesis involves a complex developmental program that includes changes in cell cycle dynamics and dramatic cellular remodeling. Translational control is critical for spermatogenesis in Drosophila as many mRNAs synthesized in the spermatocytes are translated only much later during spermatid differentiation. Testes-specific translation initiation factors eIF4E-3 and eIF4G2 are essential specifically for male fertility. However, details of their roles during different stages of spermatogenesis are unknown, and the role of canonical translation initiation factors in spermatogenesis remains unexplored. In this study, we addressed the functional role of eIF4E-1, eIF4E-3, eIF4G and eIF4G2 in testes development and formation of mature sperm. Using the UAS-Gal4 system and RNA interference, we systematically knocked down these four genes in different stages of germ cell development, and in the somatic cells. Our results show that eIF4E-1 function in early germ cells and the surrounding somatic cells is critical for spermatogenesis. Both eIF4E-1 and eIF4E-3 are required in spermatocytes for chromosome condensation and cytokinesis during the meiotic stages. Interestingly, we find that eIF4G knockdown did not affect male fertility while eIF4G2 has distinct functions during spermatogenesis; it is required in early germ cells for proper meiotic divisions and spermatid elongation while its abrogation in spermatocytes caused meiotic arrest. Double knockdown of eIF4G and eIF4G2 shows that these proteins act redundantly during the early stages of spermatogenesis. Taken together, our analysis reveals spatio-temporal roles of the canonical and testes-specific translation initiation factors in coordinating developmental programs during spermatogenesis.

  11. Can neural machine translation do simultaneous translation?

    OpenAIRE

    Cho, Kyunghyun; Esipova, Masha

    2016-01-01

    We investigate the potential of attention-based neural machine translation in simultaneous translation. We introduce a novel decoding algorithm, called simultaneous greedy decoding, that allows an existing neural machine translation model to begin translating before a full source sentence is received. This approach is unique from previous works on simultaneous translation in that segmentation and translation are done jointly to maximize the translation quality and that translating each segmen...

  12. Application of a topical vapocoolant spray decreases pain at the site of initial intradermal anaesthetic injection during ultrasound-guided breast needle biopsy

    International Nuclear Information System (INIS)

    Collado-Mesa, F.; Net, J.M.; Arheart, K.; Klevos, G.A.; Yepes, M.M.

    2015-01-01

    Aim: To assess whether the application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy decreases pain at the site of the initial injection. Materials and methods: In this institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study, 50 women aged 49.1 ± 1.6 years (mean ± standard error) were recruited and provided written informed consent. Participants served as their own controls and were blinded as to whether a topical vapocoolant spray or a placebo was used immediately prior to the initial local anaesthetic injection at two separate biopsy sites. With the exception of the application of vapocoolant or placebo, the entire ultrasound-guided procedure was performed according to a routine protocol. Participants recorded pain at initial injection site on a visual analogue scale. General linear mixed models for repeated measures analysis of variance and a 0.05 significance level were used. Results: Application of topical vapocoolant spray was shown to significantly decrease pain at the site of initial intradermal anaesthetic injection as compared to placebo (p<0.001). Treatment effect was independent of age of the subject, race/ethnicity, operator, type of biopsy device, and histopathology result. No complications from vapocoolant spray use were reported. Conclusion: Application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy significantly decreases pain at the site of the initial injection and could contribute to improve the patient's overall procedural experience. -- Highlights: •Topical vapocoolant spray decreased pain at site of initial anesthetic injection (

  13. Machine Translation and Other Translation Technologies.

    Science.gov (United States)

    Melby, Alan

    1996-01-01

    Examines the application of linguistic theory to machine translation and translator tools, discusses the use of machine translation and translator tools in the real world of translation, and addresses the impact of translation technology on conceptions of language and other issues. Findings indicate that the human mind is flexible and linguistic…

  14. A new look at the promoter of the human monoamine oxidase A gene: mapping transcription initiation sites and capacity to drive luciferase expression.

    Science.gov (United States)

    Denney, R M; Sharma, A; Dave, S K; Waguespack, A

    1994-09-01

    Monoamine oxidase (MAO) A (EC 1.4.3.4) oxidizes norepinephrine and serotonin and is expressed in a cell type-specific manner. Recent evidence that MAO A-deficient males in a large Dutch kindred suffer from mild mental retardation and occasional episodes of impulsive aggressive behavior makes it important to understand how the human MAO A promoter is regulated. Conventional primer extension analyses of MAO A mRNA in earlier studies predicted incorrect transcription initiation sites for the human MAO A promoter. Reverse transcription and polymerase chain reaction (PCR) readily detected MAO A mRNA initiated 5' to -135 bp but not 5' to -226 bp (5' to the ATG initiation codon). PCR-assisted primer extension and RNase protection assays reveal that most MAO A mRNA is initiated between -30 and -40, which resembles a eukaryotic initiator element. Depending on the tissue source, a minor, variable proportion of MAO A mRNAs is initiated more distally at approximately -95 and -136, within the more proximal of two 90-bp GC-rich tandem repeats. Genomic DNA segments spanning -4 to -200 and -465 or -935, but not -4 to -82, drive robust luciferase expression in mammalian cells. We conclude that (a) the primary transcription initiation site occurs at a putative initiator (lnr) element located between -30 and -40, with a minor, tissue-specific proportion of additional initiation near -95 and -136; and (b) MAO A-luciferase reporter constructs that contained all the known transcription initiation sites exhibited no evidence for inhibitory cis elements between -200 and at least -935. The apparent inhibitory activity previously reported for sequences 5' to the most proximal PvuII site may have resulted from the use of partial promoter constructs that omitted the putative lnr element.

  15. Correlation between particle multiplicity and location on virion RNA of the assembly initiation site for viruses of the tobacco mosaic virus group.

    Science.gov (United States)

    Fukuda, M; Meshi, T; Okada, Y; Otsuki, Y; Takebe, I

    1981-07-01

    The initiation site for reconstitution on genome RNA was determined by electron microscopic serology for a watermelon strain of cucumber green mottle mosaic virus (CGMMV-W), which is chemically and serologically related to tobacco mosaic virus (TMV). The initiation site was located at the same position as that of the cowpea strain, a virus that produces short rods of encapsidated subgenomic messenger RNA for the coat protein (a two-component TMV), being about 320 nucleotides away from the 3' terminus, and hence within the coat protein cistron. Although CGMMV-W was until now believed to be a single-component TMV, the location of the initiation site indicated the presence of short rods containing coat protein messenger RNA in CGMMV-W-infected tissue, as in the case for the cowpea strain. We found such short rods in CGMMV-W-infected tissue. The results confirmed our previous hypothesis that the site of the initiation region for reconstitution determines the rod multiplicity of TMV. The finding of the second two-component TMV, CGMMV, indicates that the cowpea strain of TMV is not unique in being a two-component virus and that the location of the assembly initiation site on the genome RNA can be a criterion for grouping of viruses.

  16. Machine Translation

    Indian Academy of Sciences (India)

    LANT has a suite of related Language Technology products: LANT-Master, a language checker, integrates into existing word processors like MS-Word and allows the vocabulary and style oftexts to be in a controlled language which can then be automatically translated; Pangaea is an electronic dictionary that allows the.

  17. Translation Competence

    DEFF Research Database (Denmark)

    Vandepitte, Sonia; Mousten, Birthe; Maylath, Bruce

    2014-01-01

    After Kiraly (2000) introduced the collaborative form of translation in classrooms, Pavlovic (2007), Kenny (2008), and Huertas Barros (2011) provided empirical evidence that testifies to the impact of collaborative learning. This chapter sets out to describe the collaborative forms of learning...

  18. Asymmetries of Translation

    Directory of Open Access Journals (Sweden)

    Maja Gorčeva

    2015-01-01

    Full Text Available Given the incompatibility between aesthetic and economic approaches to literary translation, the A. perceives a lack of creative initiative in the international socialisation of Bulgarian literature within its literary field (and especially in the subfield of criticism. Together with a probable inability to (reintegrate ethnically Bulgarian emigré writers, this gives Bulgarian literature a “repellent capacity”. Pointing at non-mainstream developments in both literature and translation may offer a way out: Gorčeva recommends abundant analytical and not self-exoticising self-representation. She also stresses that not only interliterary ‘export’ but also ‘import’ forges a literature’s status, and suggests that “small” literatures can take part in interliterary communication as equals in so far as they have the opportunity to keep on translating not in an assimilative but in a foreignising manner.

  19. Translating Signs, Producing Subjects

    Directory of Open Access Journals (Sweden)

    Brett Neilson

    2009-08-01

    Full Text Available This paper moves between two streets: Liverpool Road in the Sydney suburb of Ashfield and Via Sarpi in the Italian city of Milan. What connects these streets is that both have become important sites for businesses in the Chinese diaspora. Moreover, both are streets on which locals have expressed desires for Chinese signs to be translated into the national lingua franca. The paper argues that the cultural politics inherent in this demand for translation cannot be fully understood in the context of national debates about diversity and integration. It is also necessary to consider the emergence of the official Chinese Putonghua as global language, which competes with English but also colonizes dialects and minority languages. In the case of these dual language signs, the space between languages can neither be reduced to a contact zone of minority and majority cultures nor celebrated as a ‘third space’ where the power relations implied by such differences are subverted. At stake is rather a space characterised by what Naoki Sakai calls the schema of co-figuration, which allows the representation of translation as the passage between two equivalents that resemble each other and thus makes possible their determination as conceptually different and comparable. Drawing on arguments about translation and citizenship, the paper critically interrogates the ethos of interchangeability implied by this regime of translation. A closing argument is made for a vision of the common that implies neither civilisational harmony nor the translation of all values into a general equivalent. Primary sources include government reports, internet texts and media stories. These are analyzed using techniques of discourse analysis and interpreted with the help of secondary literature concerning globalisation, language and migration. The disciplinary matrix cuts and mixes between cultural studies, translation studies, citizenship studies, globalization studies and

  20. Hemostatic Wound Dressing for Postinterventional Hemostasis in Large Femoral Artery Access Sites: An Initial Efficacy and Safety Study.

    Science.gov (United States)

    Sauer, Alexander; Dierks, Alexander; Wolfschmidt, Franziska; Hassold, Nicole; Bley, Thorsten A; Kickuth, Ralph

    2016-10-01

    To present the results of a prospective single-center study that evaluated the safety and efficacy of a hemostatic dressing following femoral artery access. Within a 9-month period, 80 patients (mean age 68±14 years; 55 men) were treated with a hemostatic dressing patch (Hematrix Active Patch) containing aminocaproic acid, calcium chloride, and thrombin after endovascular procedures via a 6- to 8-F femoral artery access. After removing the sheath, the wound dressing was placed on the puncture site followed by constant manual compression adapted to the sheath size (specified pressure times: 8 minutes for 6-F, 9 minutes for 7-F, and 10 minutes for 8-F). Patients were treated with an additional pressure bandage for 24 hours. Hemostasis was checked clinically and with duplex ultrasound after patch removal and at 24 hours. Patient characteristics [platelets, systolic blood pressure, international normalized ratio (INR), and partial thromboplastin time (PTT)], sheath sizes, and approach direction were compared among patients with successful hemostasis (within specified pressure times) vs those with prolonged compression. A total of 39 6-F, 19 7-F, and 22 8-F sheaths were employed. In 73 (91.2%) of 80 patients, hemostasis was reached within the prespecified pressure times (mean 8.8±0.8 minutes). In 7 patients (4 6-F, 1 7-F, 2 8-F) a longer compression time was necessary (mean 34±30 minutes). No serious major complication occurred. Twelve (15.0%) minor and 5 (6.3%) moderate subcutaneous hematomas were observed. Two (2.5%) false aneurysms were treated successfully. Ambulation and discharge was possible within 24 hours in 79 (98.7%) cases. Patients with initial hemostasis and those with prolonged compression did not differ substantially (p>0.05) according to sheath size, approach direction, INR (1.09±0.3 vs 1.11±0.3), platelets (234±47×10(3)/µL vs 249±93×10(3)/µL), systolic blood pressure (150±26 vs 152±17 mm Hg), or PTT (31±7.9 vs 34.8±10.0 seconds). The

  1. The development and implementation of the national evaluation strategy of Access to Care, a multi-site linkage to care initiative in the United States.

    Science.gov (United States)

    Kim, Jeeyon Janet; Maulsby, Cathy; Kinsky, Suzanne; Riordan, Maura; Charles, Vignetta; Jain, Kriti; Holtgrave, David R

    2014-10-01

    The Access to Care (A2C) is a multi-site initiative that seeks to increase the access to and retention in effective HIV healthcare and support services by people living with HIV across the United States. As the initiative implemented evidence-based programs in new settings with diverse populations, it was important to document these innovative efforts to contribute to the evidence base for best practices. In a partnership between Johns Hopkins University, AIDS United, and the A2C sites, a national evaluation strategy was developed and implemented to build knowledge about how linkage to care interventions could be most effectively implemented within the context of local, real-world settings. This article provides an overview of the efforts to develop and implement a national monitoring and evaluation strategy for a multi-site initiative. The findings may be of utility for other HIV interventions that are seeking to incorporate a monitoring and evaluation component into their efforts.

  2. Word translation entropy in translation

    DEFF Research Database (Denmark)

    Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard

    2016-01-01

    This study reports on an investigation into the relationship between the number of translation alternatives for a single word and eye movements on the source text. In addition, the effect of word order differences between source and target text on eye movements on the source text is studied. In p...

  3. Beyond Translation

    DEFF Research Database (Denmark)

    Olwig, Mette Fog

    2013-01-01

    This article contributes to the growing scholarship on local development practitioners by re-examining conceptualizations of practitioners as ‘brokers’ strategically translating between ‘travelling’ (development institution) rationalities and ‘placed’ (recipient area) rationalities in relation...... and practice spurred by new challenges deriving from climate change anxiety, the study shows how local practitioners often make local activities fit into travelling development rationalities as a matter of habit, rather than as a conscious strategy. They may therefore cease to ‘translate’ between different...... rationalities. This is shown to have important implications for theory, research and practice concerning disaster risk reduction and climate change adaptation in which such translation is often expected....

  4. Translational genomics

    Directory of Open Access Journals (Sweden)

    Martin Kussmann

    2014-09-01

    Full Text Available The term “Translational Genomics” reflects both title and mission of this new journal. “Translational” has traditionally been understood as “applied research” or “development”, different from or even opposed to “basic research”. Recent scientific and societal developments have triggered a re-assessment of the connotation that “translational” and “basic” are either/or activities: translational research nowadays aims at feeding the best science into applications and solutions for human society. We therefore argue here basic science to be challenged and leveraged for its relevance to human health and societal benefits. This more recent approach and attitude are catalyzed by four trends or developments: evidence-based solutions; large-scale, high dimensional data; consumer/patient empowerment; and systems-level understanding.

  5. Feasibility Study of Biopower in East Helena, Montana. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Moriarty, K.

    2013-02-01

    The U.S. Environmental Protection Agency (EPA) developed the RE-Powering America's Land initiative to reuse contaminated sites for renewable energy generation when aligned with the community's vision for the site. The former American Smelting and Refining Company (Asarco) smelter in East Helena, Montana, was selected for a feasibility study under the initiative. Biomass was chosen as the renewable energy resource based on the wood products industry in the area. Biopower was selected as the technology based on Montana's renewable portfolio standard (RPS) requiring utilities to purchase renewable power.

  6. Translation Factors Specify Cellular Metabolic State

    Directory of Open Access Journals (Sweden)

    Juan Mata

    2016-08-01

    Full Text Available In this issue of Cell Reports, Shah et al. present evidence that a subcomplex of the eIF3 translation initiation factor regulates translation of mRNAs encoding components of the mitochondrial electron transport chain and glycolytic enzymes, thus linking translational control with energy metabolism.

  7. Translating Harbourscapes

    DEFF Research Database (Denmark)

    Diedrich, Lisa Babette

    This thesis investigates site-specific design approaches in contemporary harbour transformation. The integration into the urban fabric of disused harbour areas, those spatial leftovers of late 19th- and 20th-century heavy industry, is a major task of contemporary urban planning. Common solutions...... certain design approaches integrate the site into the urban fabric by making use of that which already exists on a harbour site. The current understanding of site, design and site specificity is discussed and updated to define the analytical framework for the thesis’s case study. Six European design...... projects are scrutinized for their site specificity, namely the Euromediterranée 2 project in Marseille, the Ile de Nantes project in Nantes, the Tagus Cycle Track through Lisbon’s harbour, the Port’s Visual Quality Programme in Rotterdam, the Right Bank redevelopment in Bordeaux, and the open space plan...

  8. Evidence of Parallel Processing During Translation

    DEFF Research Database (Denmark)

    Balling, Laura Winther; Hvelplund, Kristian Tangsgaard; Sjørup, Annette Camilla

    2014-01-01

    Three eye tracking experiments test the hypothesis that translation involves parallel rather than sequential processing of the source and target texts. In Experiment 1, a group of professional translators translated texts from their native language Danish into English. The texts included both...... conclude that translation is a parallel process and that literal translation is likely to be a universal initial default strategy in translation. This conclusion is strengthened by the fact that all three experiments were relatively naturalistic, due to the combination of remote eye tracking and mixed......-effects regression modeling....

  9. Polyhomologation based on in situ generated Boron-thexyl-silaboracyclic initiating sites: a novel strategy towards the synthesis of polyethylene-based complex architectures

    KAUST Repository

    Zhang, Zhen

    2015-04-10

    A novel strategy, based on the in situ generated Boron-thexyl-silaboracyclic initiating sites for the polyhomologation of dimethylsulfoxonium methylide, has been developed for the synthesis of complex polyethylene-based architectures. As examples, the synthesis of a 4-arm polyethylene star, three (polystyrene)(polyethylene)2 3-miktoarm stars and a PE-branched double graft copolymers are given.

  10. Cryptic Protein Priming Sites in Two Different Domains of Duck Hepatitis B Virus Reverse Transcriptase for Initiating DNA Synthesis In Vitro▿

    Science.gov (United States)

    Boregowda, Rajeev K.; Lin, Li; Zhu, Qin; Tian, Fang; Hu, Jianming

    2011-01-01

    Initiation of reverse transcription in hepadnaviruses is accomplished by a unique protein-priming mechanism whereby a specific Y residue in the terminal protein (TP) domain of the viral reverse transcriptase (RT) acts as a primer to initiate DNA synthesis, which is carried out by the RT domain of the same protein. When separate TP and RT domains from the duck hepatitis B virus (DHBV) RT protein were tested in a trans-complementation assay in vitro, the RT domain could also serve, unexpectedly, as a protein primer for DNA synthesis, as could a TP mutant lacking the authentic primer Y (Y96) residue. Priming at these other, so-called cryptic, priming sites in both the RT and TP domains shared the same requirements as those at Y96. A mini RT protein with both the TP and RT domains linked in cis, as well as the full-length RT protein, could also initiate DNA synthesis using cryptic priming sites. The cryptic priming site(s) in TP was found to be S/T, while those in the RT domain were Y and S/T. As with the authentic TP Y96 priming site, the cryptic priming sites in the TP and RT domains could support DNA polymerization subsequent to the initial covalent linkage of the first nucleotide to the priming amino acid residue. These results provide new insights into the complex mechanisms of protein priming in hepadnaviruses, including the selection of the primer residue and the interactions between the TP and RT domains that is essential for protein priming. PMID:21593164

  11. Travelers' use of the WSDOT traffic conditions web site : customer satisfaction evaluation -- Metropolitan Model Deployment Initiative : Seattle, Washington

    Science.gov (United States)

    2000-01-28

    This report presents the results of an evaluation of public use of the Washington State Department of Transportation's (WSDOT) traffic conditions web site. This research was sponsored by the US Department of Transportation to assess customer satisfac...

  12. Translational coupling in Escherichia coli of a heterologous Bacillus subtilis-Escherichia coli gene fusion.

    OpenAIRE

    Zaghloul, T I; Doi, R H

    1986-01-01

    The efficient expression in Escherichia coli of the Tn9-derived chloramphenicol acetyltransferase (EC 2.3.1.28) gene fused distal to the promoter and N terminus of the Bacillus subtilis aprA gene was dependent on the initiation of translation from the ribosome-binding site in the aprA gene.

  13. The Beads of Translation: Using Beads to Translate mRNA into a Polypeptide Bracelet

    Science.gov (United States)

    Dunlap, Dacey; Patrick, Patricia

    2012-01-01

    During this activity, by making beaded bracelets that represent the steps of translation, students simulate the creation of an amino acid chain. They are given an mRNA sequence that they translate into a corresponding polypeptide chain (beads). This activity focuses on the events and sites of translation. The activity provides students with a…

  14. Translating a wicked problem

    DEFF Research Database (Denmark)

    Tietjen, Anne; Jørgensen, Gertrud

    2016-01-01

    In a time of increasing globalisation and urbanisation, shrinking peripheral rural areas have become a truly wicked planning problem in many European countries. Although a problem can be easily perceived and measured by various indicators, the precise definition of the problem is problematic. Based......, place-based and project-oriented process directed at concrete physical outcomes. We frame strategic planning as a translation process where the interaction between human and non-human actors translates a unique, complex and contested situation into an innovated situation. We find that local physical......-understandings, increased social capital, and follow-up projects initiated beyond the actual planning process. We conclude that local physical projects, when conceived in a collaborative and strategic manner, can contribute to sustainable adaptation to rural shrinkage....

  15. Efficient use of a translation start codon in BDNF exon I.

    Science.gov (United States)

    Koppel, Indrek; Tuvikene, Jürgen; Lekk, Ingrid; Timmusk, Tõnis

    2015-09-01

    The brain-derived neurotrophic factor (BDNF) gene contains a number of 5' exons alternatively spliced with a common 3' exon. BDNF protein is synthesized from alternative transcripts as a prepro-precursor encoded by the common 3' exon IX, which has a translation start site 21 bp downstream of the splicing site. BDNF mRNAs containing exon I are an exception to this arrangement as the last three nucleotides of this exon constitute an in-frame AUG. Here, we show that this AUG is efficiently used for translation initiation in PC12 cells and cultured cortical neurons. Use of exon I-specific AUG produces higher levels of BDNF protein than use of the common translation start site, resulting from a higher translation rate. No differences in protein degradation, constitutive or regulated secretion were detected between BDNF isoforms with alternative 5' termini. As the BDNF promoter preceding exon I is known to be highly regulated by neuronal activity, our results suggest that the function of this translation start site may be efficient stimulus-dependent synthesis of BDNF protein. The brain-derived neurotrophic factor (BDNF) gene contains multiple untranslated 5' exons alternatively spliced to one common protein-coding 3' exon. However, exon I contains an in-frame ATG in a favorable translation context. Here, we show that use of this ATG is associated with more efficient protein synthesis than the commonly used ATG in exon IX. © 2015 International Society for Neurochemistry.

  16. A national strategy for identification, prioritisation and management of pollution from abandoned non-coal mine sites in England and Wales. I. Methodology development and initial results.

    Science.gov (United States)

    Mayes, W M; Johnston, D; Potter, H A B; Jarvis, A P

    2009-10-15

    In regions affected by historic non-coal (principally metal) mining activity, government agencies are often faced with the challenge of deploying limited remedial resources at abandoned mine sites to achieve maximum improvements in the chemical and ecological quality of impacted ground and surface waters. As such, strategies for the defensible allocation of public funds require comprehensive and systematic frameworks by which to identify and prioritise polluting sites for remediation. This paper describes the development and initial findings of such a national initiative in England and Wales which allies catchment-scale environmental impact assessments using existing public archive data, with recognition of the uncertainty in impact appraisals arising from disparities in data availability between sites and regions. The methodology identifies polluting sites and takes account not only of the chemical and ecological impacts of mine water discharges on receiving watercourses, but also of socio-economic factors such as conservation and heritage concerns, which can both impede or complement efforts to remediate mine sites. Using a Geographic Information System database and a suite of spatial analyses employing Boolean operators, both the extent of the pollution problem from abandoned non-coal mines in England and Wales (6% of 7815 surface water bodies are affected nationally) and the insight that can be gleaned from systematic analyses of existing archive data are highlighted. The results of the nationwide survey can be used as a dynamic database to inform future remedial planning, in terms of prioritising impacted river basins and abandoned non-coal mine sites themselves for either remediation or future monitoring efforts. As the assessment framework is built upon existing water quality and ecological data and mine site/geological data, there is considerable scope for the approach to be applied elsewhere where the legacy of historic mining persists through the

  17. Melanoma Patients with Unknown Primary Site or Nodal Recurrence after Initial Diagnosis Have a Favourable Survival Compared to Those with Synchronous Lymph Node Metastasis and Primary Tumour

    OpenAIRE

    Weide, Benjamin; Faller, Christine; Els?sser, Margrit; B?ttner, Petra; Pflugfelder, Annette; Leiter, Ulrike; Eigentler, Thomas Kurt; Bauer, J?rgen; Meier, Friedegund; Garbe, Claus

    2013-01-01

    BACKGROUND: A direct comparison of prognosis between patients with regional lymph node metastases (LNM) detected synchronously with the primary melanoma (primary LNM), patients who developed their first LNM subsequently (secondary LNM) and those with initial LNM in melanoma with unknown primary site (MUP) is missing thus far. PATIENTS AND METHODS: Survival of 498 patients was calculated from the time point of the first macroscopic LNM using Kaplan Meier and multivariate Cox hazard regression ...

  18. Site-directed subsurface environmental initiative: Five year summary and plan for fundamental research in subsoils and in groundwater, FY 1989-FY 1993

    International Nuclear Information System (INIS)

    1987-10-01

    The overall goal of this research initiative is to develop the necessary scientific basis for resolution of key technical obstacles to defining and remediating contamination at DOE and other waste sites. To accomplish this goal, the resouces of the national laboratories, universities, and DOE sites will be fully utilized to develop and demonstrate improved, cost-effective, and environmentally acceptable techniques for predicting the behavior of contaminants and reducing their concentrations in ground water. This document is a preliminary plan to set general research directions for a program extending into the 1990s. The needs and milestones identified in this plan may change with additional guidance from DOE sites. Promising research opportunities will be identified as part of national laboratory submissions of preliminary proposals

  19. A public health Immunization Resource Web site for chiropractors: discussion of current issues and future challenges for evidence-based initiatives for the chiropractic profession.

    Science.gov (United States)

    Khorsan, Raheleh; Smith, Monica; Hawk, Cheryl; Haas, Mitchell

    2009-01-01

    The Immunization Information Resource Web site is provided as a public service by the Chiropractic Health Care Section of the American Public Health Association. The site compiles annotated bibliographies of citations from the scientific literature, as well as other authoritative peer-reviewed information sources on this topic. Our intent was to create a resource of information for health care professionals that is current, accurate, objective, evidence based, and as user-friendly as possible. This article describes the Internet-based Immunization Information Resource Web site developed and sponsored by the Chiropractic Health Care Section of the American Public Health Association and discusses current issues and future challenges for sustaining and further advancing such evidence-based initiatives for the chiropractic profession.

  20. Initial success of native grasses is contingent on multiple interactions among exotic grass competition, temporal priority, rainfall and site effects.

    Science.gov (United States)

    Young, Truman P; Zefferman, Emily P; Vaughn, Kurt J; Fick, Stephen

    2014-12-05

    Ecological communities are increasingly being recognized as the products of contemporary drivers and historical legacies that are both biotic and abiotic. In an attempt to unravel multiple layers of ecological contingency, we manipulated (i) competition with exotic annual grasses, (ii) the timing of this competition (temporal priority in arrival/seeding times) and (iii) watering (simulated rainfall) in a restoration-style planting of native perennial grasses. In addition, we replicated this experiment simultaneously at three sites in north-central California. Native perennial grasses had 73-99 % less cover when planted with exotic annuals than when planted alone, but this reduction was greatly ameliorated by planting the natives 2 weeks prior to the exotics. In a drought year, irrigation significantly reduced benefits of early planting so that these benefits resembled those observed in a non-drought year. There were significant differences across the three sites (site effects and interactions) in (i) overall native cover, (ii) the response of natives to competition, (iii) the strength of the temporal priority effect and (iv) the degree to which supplemental watering reduced priority effects. These results reveal the strong multi-layered contingency that underlies even relatively simple communities. Published by Oxford University Press on behalf of the Annals of Botany Company.

  1. Finite element analysis of the influence of elastic anisotropy on stress intensification at stress corrosion cracking initiation sites in fcc alloys

    Science.gov (United States)

    Meric de Bellefon, G.; van Duysen, J. C.

    2018-05-01

    A recent finite-element method (FEM)-based study from the present authors quantified the effect of elastic anisotropy of grains on stress intensification at potential intergranular stress corrosion cracking (IGSCC) initiation sites in austenitic stainless steels. In particular, it showed that the auxetic behavior of grains (negative Poisson's ratio) in some directions plays a very important role in IGSCC initiation, since it can induce local stress intensification factors of about 1.6. A similar effect is expected for other fcc alloys such as Ni-based alloys. The present article confirms those results and paves the way to the definition of an IGSCC susceptibility index by identifying grain configurations that are the most favorable for crack initiation. The index will rely on the probability to get those configurations on surface of specimens.

  2. HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus

    Directory of Open Access Journals (Sweden)

    Santiago Guerrero

    2015-01-01

    Full Text Available Eukaryotic translation is a complex process composed of three main steps: initiation, elongation, and termination. During infections by RNA- and DNA-viruses, the eukaryotic translation machinery is used to assure optimal viral protein synthesis. Human immunodeficiency virus type I (HIV-1 uses several non-canonical pathways to translate its own proteins, such as leaky scanning, frameshifting, shunt, and cap-independent mechanisms. Moreover, HIV-1 modulates the host translation machinery by targeting key translation factors and overcomes different cellular obstacles that affect protein translation. In this review, we describe how HIV-1 proteins target several components of the eukaryotic translation machinery, which consequently improves viral translation and replication.

  3. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Price Landfill Site in Pleasantville, New Jersey. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Salasovich, J.; Geiger, J.; Mosey, G.; Healey, V.

    2013-05-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Price Landfill site in Pleasantville, New Jersey, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site. This study did not assess environmental conditions at the site.

  4. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Tower Road Site in Aurora, Colorado. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Van Geet, O.; Mosey, G.

    2013-03-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Tower Road site in Aurora, Colorado, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site. This study did not assess environmental conditions at the site.

  5. Combining bulk sediment OSL and meteoric 10 Be fingerprinting techniques to identify gully initiation sites and erosion depths

    OpenAIRE

    Portenga, E.W.; Bishop, P.; Rood, D.H.; Bierman, P.R.

    2017-01-01

    Deep erosional gullies dissect landscapes around the world. Existing erosion models focus on predicting where gullies might begin to erode, but identifying where existing gullies were initiated and under what conditions is difficult, especially when historical records are unavailable. Here we outline a new approach for fingerprinting alluvium and tracing it back to its source by combining bulk sediment optically stimulated luminescence (bulk OSL) and meteoric 10Be (10Bem) measurements made on...

  6. Switch from cap- to factorless IRES-dependent 0 and +1 frame translation during cellular stress and dicistrovirus infection.

    Directory of Open Access Journals (Sweden)

    Qing S Wang

    Full Text Available Internal ribosome entry sites (IRES are utilized by a subset of cellular and viral mRNAs to initiate translation during cellular stress and virus infection when canonical cap-dependent translation is compromised. The intergenic region (IGR IRES of the Dicistroviridae uses a streamlined mechanism in which it can directly recruit the ribosome in the absence of initiation factors and initiates translation using a non-AUG codon. A subset of IGR IRESs including that from the honey bee viruses can also direct translation of an overlapping +1 frame gene. In this study, we systematically examined cellular conditions that lead to IGR IRES-mediated 0 and +1 frame translation in Drosophila S2 cells. Towards this, a novel bicistronic reporter that exploits the 2A "stop-go" peptide was developed to allow the detection of IRES-mediated translation in vivo. Both 0 and +1 frame translation by the IGR IRES are stimulated under a number of cellular stresses and in S2 cells infected by cricket paralysis virus, demonstrating a switch from cap-dependent to IRES-dependent translation. The regulation of the IGR IRES mechanism ensures that both 0 frame viral structural proteins and +1 frame ORFx protein are optimally expressed during virus infection.

  7. Demonstration of an initial screening phase for site selection for low level radioactive waste burial - an evaluation of relevant IAEA guidelines

    International Nuclear Information System (INIS)

    1984-04-01

    Low level radioactive wastes, arising from the use of radioisotopes in medicine and industry are accumulating throughout Australia. The rate of accumulation has not been large and storage of these wastes close to the point of use has proved practicable to date, but consideration must now be given to a central repository or repositories for these low level wastes. This report considers the question of selecting a site suitable for disposal of wastes by shallow ground burial. It attempts to asses the practicability of using factors suggested by the IAEA for the initial phase of site screening. The screening process described has essentially two stages. In the first, New South Wales was divided into broad structural units and these ranked in order of suitability. In the second stage, survey sites in which thick clay beds outcropped were delineated in the five highest ranking structural units. These survey sites were ranked on the basis of various geomorphological properties which largely described the hydrogeology of the site

  8. Translating 10 lessons from lean six sigma project in paper-based training site to electronic health record-based primary care practice: challenges and opportunities.

    Science.gov (United States)

    Aleem, Sohaib

    2013-01-01

    Lean Six Sigma is a well-proven methodology to enhance the performance of any business, including health care. The strategy focuses on cutting out waste and variation from the processes to improve the value and efficiency of work. This article walks through the journey of "green belt" training using a Lean Six Sigma approach and the implementation of a process improvement project that focused on wait time for patients to be examined in an urban academic primary care clinic without requiring added resources. Experiences of the training and the project at an urban paper-based satellite clinic have informed the planning efforts of a data and performance team, including implementing a 15-minute nurse "pre-visit" at primary care sites of an accountable care organization.

  9. Mapping Translation Technology Research in Translation Studies

    DEFF Research Database (Denmark)

    Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

    2017-01-01

    technology research as a subdiscipline of TS, and we define and discuss some basic concepts and models of the field that we use in the rest of the paper. Based on a small-scale study of papers published in TS journals between 2006 and 2016, Section 3 attempts to map relevant developments of translation......Due to the growing uptake of translation technology in the language industry and its documented impact on the translation profession, translation students and scholars need in-depth and empirically founded knowledge of the nature and influences of translation technology (e.g. Christensen....../Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...

  10. Airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: early injury or initiating site of autoimmunity?

    Science.gov (United States)

    Demoruelle, M. Kristen; Weisman, Michael H.; Simonian, Philip L.; Lynch, David A.; Sachs, Peter B.; Pedraza, Isabel F.; Harrington, Annie R.; Kolfenbach, Jason R.; Striebich, Christopher C.; Pham, Quyen N.; Strickland, Colin D.; Petersen, Brian D.; Parish, Mark C.; Derber, Lezlie A.; Norris, Jill M.; Holers, V. Michael; Deane, Kevin D.

    2011-01-01

    Objective To evaluate the presence of pulmonary abnormalities in subjects with rheumatoid arthritis (RA)-related autoantibody (Ab) positivity without inflammatory arthritis (IA). Methods 42 subjects without IA but with elevations of anti-cyclic citrullinated peptide antibodies and/or 2 or more rheumatoid factor isotypes (a profile that is 96% specific for RA), 15 Ab(−) controls and 12 patients with early established seropositive RA (<1 year duration) underwent spirometry and high-resolution computed tomographic (HRCT) lung imaging. Results The median age of Ab(+) subjects was 54 years-old, 52% were female and 38% were smokers (not significantly different than Ab(−) controls). No Ab(+) subject had IA on joint examination. On HRCT, 76% of Ab(+) subjects had airways abnormalities including bronchial wall thickening, bronchiectasis, centrilobular opacities and air trapping, compared to 33% of Ab(−) controls (p=0.005). The Ab(+) subjects had similar prevalence and type of lung abnormalities compared to patients with early RA. Two Ab(+) subjects with airways disease developed IA classifiable as articular RA ~13 months after lung evaluation. Conclusion Airways abnormalities that are consistent with inflammation are common in Ab(+) subjects without IA, and similar to airways abnormalities seen in early RA. These findings suggest that the lung may be an early site of autoimmune-related injury, and potentially a site of generation of RA-related autoimmunity. Further studies are needed to define the mechanistic role of lung inflammation in the development of RA. PMID:22183986

  11. Environmental Impacts of Petroleum Production: Initial Results from the Osage-Skiatook Petroleum Environmental Research Sites, Osage County, Oklahoma

    Science.gov (United States)

    Kharaka, Yousif K.; Otton, James K.

    2003-01-01

    Exploration for and production of petroleum have caused major detrimental impacts to soils, surface and ground waters, and the local ecosystems in the United States. These impacts arise primarily from the improper disposal of large volumes of saline water produced with oil and gas, from accidental hydrocarbon and produced water releases, and from abandoned oil wells that were not correctly sealed. It is important to understand the long-term and short-term effects of produced water and hydrocarbon releases from these sites in order to develop risk-based remediation plans. Remediation is particularly needed in aging and depleted fields where land use is changing from petroleum production to residential, agricultural or recreational uses. About 20 scientists from the USGS and other governmental agencies and academia are involved in a multidisciplinary investigation to study the transport, fate, and natural attenuation of inorganic salts, trace metals, organic compounds and radionuclides present in produced water, and their impacts at the Osage-Skiatook Petroleum Environmental Research (OSPER) 'A' and 'B' sites, located on the Osage Reservation in Osage County, Oklahoma. Stakeholders in the project include the Osage Nation, which holds the mineral rights, the Bureau of Indian Affairs with trust responsibility, and the Army Corps of Engineers, which owns the surface rights at these sites and manages adjacent Skiatook Lake. The 4250-hectare Skiatook Lake provides drinking water to local Tulsa suburban communities and a rural water district, and offers recreational fishing and boating opportunities to tens of thousands of visitors each year. Approximately 1.5 and 1.0 hectare of land at the OSPER 'A' (depleted Lester lease) and 'B' (active Branstetter lease) sites, respectively, are affected by salt scarring, tree kills, soil salinization and brine and petroleum contamination due to the leakage of produced water and associated hydrocarbons from brine pits and accidental

  12. TSPA 1991: An initial total-system performance assessment for Yucca Mountain; Yucca Mountain Site Characterization Project

    Energy Technology Data Exchange (ETDEWEB)

    Barnard, R.W.; Wilson, M.L.; Dockery, H.A.; Kaplan, P.G.; Eaton, R.R.; Bingham, F.W. [Sandia National Labs., Albuquerque, NM (United States); Gauthier, J.H.; Robey, T.H. [Spectra Research Inst., Albuquerque, NM (United States)

    1992-07-01

    This report describes an assessment of the long-term performance of a repository system that contains deeply buried highly radioactive waste; the system is assumed to be located at the potential site at Yucca Mountain, Nevada. The study includes an identification of features, events, and processes that might affect the potential repository, a construction of scenarios based on this identification, a selection of models describing these scenarios (including abstraction of appropriate models from detailed models), a selection of probability distributions for the parameters in the models, a stochastic calculation of radionuclide releases for the scenarios, and a derivation of complementary cumulative distribution functions (CCDFs) for the releases. Releases and CCDFs are calculated for four categories of scenarios: aqueous flow (modeling primarily the existing conditions at the site, with allowances for climate change), gaseous flow, basaltic igneous activity, and human intrusion. The study shows that models of complex processes can be abstracted into more simplified representations that preserve the understanding of the processes and produce results consistent with those of more complex models.

  13. Kinetics of CrPV and HCV IRES-mediated eukaryotic translation using single-molecule fluorescence microscopy.

    Science.gov (United States)

    Bugaud, Olivier; Barbier, Nathalie; Chommy, Hélène; Fiszman, Nicolas; Le Gall, Antoine; Dulin, David; Saguy, Matthieu; Westbrook, Nathalie; Perronet, Karen; Namy, Olivier

    2017-11-01

    Protein synthesis is a complex multistep process involving many factors that need to interact in a coordinated manner to properly translate the messenger RNA. As translating ribosomes cannot be synchronized over many elongation cycles, single-molecule studies have been introduced to bring a deeper understanding of prokaryotic translation dynamics. Extending this approach to eukaryotic translation is very appealing, but initiation and specific labeling of the ribosomes are much more complicated. Here, we use a noncanonical translation initiation based on internal ribosome entry sites (IRES), and we monitor the passage of individual, unmodified mammalian ribosomes at specific fluorescent milestones along mRNA. We explore initiation by two types of IRES, the intergenic IRES of cricket paralysis virus (CrPV) and the hepatitis C (HCV) IRES, and show that they both strongly limit the rate of the first elongation steps compared to the following ones, suggesting that those first elongation cycles do not correspond to a canonical elongation. This new system opens the possibility of studying both IRES-mediated initiation and elongation kinetics of eukaryotic translation and will undoubtedly be a valuable tool to investigate the role of translation machinery modifications in human diseases. © 2017 Bugaud et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  14. Sonic Hedgehog-GLI Family Zinc Finger 1 Signaling Pathway Promotes the Growth and Migration of Pancreatic Cancer Cells by Regulating the Transcription of Eukaryotic Translation Initiation Factor 5A2.

    Science.gov (United States)

    Xu, Xuanfu; Liu, Hua; Zhang, Hui; Dai, Weiqi; Guo, Chuanyong; Xie, Chuangao; Wei, Shumei; He, Shengli; Xu, Xiaorong

    2015-11-01

    The Hh (hedgehog) signaling pathway is still waiting for further studies because its downstream molecular mechanism remains elusive. Because EIF5A2 (eukaryotic translation initiation factor 5A2) gene was up-regulated upon Gli1 (GLI family zinc finger 1) in pancreatic cancer (PC) cells, we speculated that this pathway might promote tumor progression through regulating EIF5A2. We investigated regulation effect of Hh signaling pathway to EIF5A2 gene transcription by Gli1 knockdown or overexpression in PC cell lines first. Then, the regulation mechanism of Gli1 to EIF5A2 gene was studied at transcription level. Finally, we studied cancer-promoting effects of Gli1-dependent EIF5A2 in PC cells. The data showed that Gli1 up-regulated expression of EIF5A2 by promoting transcription via cis-acting elements in PC cells. Moreover, vimentin gene was up-regulated significantly by sonic hedgehog (SHh)/Gli1 expression increasing, and E-cadherin was significantly reduced. The EIF5A2 knockdown partially reversed cell proliferation and migration induced by artificial SHh overexpression and inhibited epithelial mesenchymal transition process in PC cells with SHh overexpression (P cells. Thus, EIF5A2 oncogene effect could be incorporated into cancer-promoting molecular network upon Hh signaling pathway.

  15. A novel point mutation in the translation initiation codon of the pre-pro-vasopressin-neurophysin II gene: Cosegregation with morphological abnormalities and clinical symptoms in autosomal dominant neurohypophyseal diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Rutishauser, J.; Boeni-Schnetzler, M.; Froesch, E.R.; Wichmann, W.; Huisman, T. [Univ. of Zuerich (Switzerland)] [and others

    1996-01-01

    Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare variant of idiopathic central diabetes insipidus. Several different mutations in the human vasopressin-neurophysin II (AVP-NP II) gene have been described. We studied nine family members from three generations of an ADNDI pedigree at the clinical, morphological, and molecular levels. AVP concentrations were measured during diagnostic fluid restriction tests. Coronal and sagittal high resolution T1-weighted images of the pituitary were obtained from affected and healthy family members. PCR was used to amplify the AVP-NP II precursor gene, and PCR products were directly sequenced. Under maximal osmotic stimulation, AVP serum levels were close to or below the detection limit in affected individuals. Magnetic resonance imaging studies revealed the characteristic hyperintense ({open_quotes}bright spot{close_quotes}) appearance of the posterior pituitary in two healthy family members. This signal was absent in all four ADNDI patients examined. The coding sequences of AVP and its carrier protein, neurophysin II, were normal in all family members examined. Affected individuals showed a novel single base deletion (G 227) in the translation initiation codon of the AVP-NP II signal peptide on one allele. The mutation in the AVP-NP II leader sequence appears to be responsible for the disease in this kindred, possibly by interfering with protein translocation. The absence of the hyperintense posterior pituitary signal in affected individuals could reflect deficient posterior pituitary function. 56 refs., 4 figs., 3 tabs.

  16. The m subunit of murine translation initiation factor eIF3 maintains the integrity of the eIF3 complex and is required for embryonic development, homeostasis, and organ size control.

    Science.gov (United States)

    Zeng, Liyong; Wan, Yihan; Li, Dan; Wu, Jing; Shao, Mengle; Chen, Jiong; Hui, Lijian; Ji, Hongbin; Zhu, Xueliang

    2013-10-18

    Mammalian eIF3 is composed of 13 subunits and is the largest eukaryotic initiation factor. eIF3 plays a key role in protein biosynthesis. However, it is not fully understood how different subunits contribute to the structural integrity and function of the eIF3 complex. Whether eIF3 is essential for embryonic development and homeostasis is also not known. Here, we show that eIF3m null embryos are lethal at the peri-implantation stage. Compound heterozygotes (eIF3m(flox)(/-)) or FABP4-Cre-mediated conditional knock-out mice are lethal at mid-gestation stages. Although the heterozygotes are viable, they show markedly reduced organ size and diminished body weight. Acute ablation of eIF3m in adult mouse liver leads to rapidly decreased body weight and death within 2 weeks; these effects are correlated with a severe decline of protein biogenesis in the liver. Protein analyses reveal that eIF3m deficiency significantly impairs the integrity of the eIF3 complex due to down-regulation of multiple other subunits. Two of the subunits, eIF3f and eIF3h, are stabilized by eIF3m through subcomplex formation. Therefore, eIF3m is required for the structural integrity and translation initiation function of eIF3. Furthermore, not only is eIF3m an essential gene, but its expression level is also important for mouse embryonic development and the control of organ size.

  17. Translation Theory and Translation Studies in China

    Science.gov (United States)

    Guo, Qin

    2012-01-01

    This dissertation is a comparative study of "translation theory" and "translation studies" in China and the West. Its focus is to investigate whether there is translation theory in the Chinese tradition. My study begins with an examination of the debate in China over whether there has already existed a system of translation…

  18. Initiation of protein synthesis in bacteria

    DEFF Research Database (Denmark)

    Laursen, Brian Søgaard; Sørensen, Hans Peter; Mortensen, Kim Kusk

    2005-01-01

    Valuable information on translation initiation is available from biochemical data and recently solved structures. We present a detailed description of current knowledge about the structure, function, and interactions of the individual components involved in bacterial translation initiation. The f...

  19. Dynamics of Chloroplast Translation during Chloroplast Differentiation in Maize.

    Directory of Open Access Journals (Sweden)

    Prakitchai Chotewutmontri

    2016-07-01

    Full Text Available Chloroplast genomes in land plants contain approximately 100 genes, the majority of which reside in polycistronic transcription units derived from cyanobacterial operons. The expression of chloroplast genes is integrated into developmental programs underlying the differentiation of photosynthetic cells from non-photosynthetic progenitors. In C4 plants, the partitioning of photosynthesis between two cell types, bundle sheath and mesophyll, adds an additional layer of complexity. We used ribosome profiling and RNA-seq to generate a comprehensive description of chloroplast gene expression at four stages of chloroplast differentiation, as displayed along the maize seedling leaf blade. The rate of protein output of most genes increases early in development and declines once the photosynthetic apparatus is mature. The developmental dynamics of protein output fall into several patterns. Programmed changes in mRNA abundance make a strong contribution to the developmental shifts in protein output, but output is further adjusted by changes in translational efficiency. RNAs with prioritized translation early in development are largely involved in chloroplast gene expression, whereas those with prioritized translation in photosynthetic tissues are generally involved in photosynthesis. Differential gene expression in bundle sheath and mesophyll chloroplasts results primarily from differences in mRNA abundance, but differences in translational efficiency amplify mRNA-level effects in some instances. In most cases, rates of protein output approximate steady-state protein stoichiometries, implying a limited role for proteolysis in eliminating unassembled or damaged proteins under non-stress conditions. Tuned protein output results from gene-specific trade-offs between translational efficiency and mRNA abundance, both of which span a large dynamic range. Analysis of ribosome footprints at sites of RNA editing showed that the chloroplast translation machinery

  20. Deposition of metallic clusters on a metallic surface at zero initial kinetic energy: Evidence for implantation and site exchanges

    Science.gov (United States)

    Nacer, B.; Massobrio, C.; Félix, C.

    1997-10-01

    We have investigated the deposition at zero impact kinetic energy of the Ag atom and clusters (Ag7,Ag19) on the (100) and (111) surfaces of Pd by molecular-dynamics simulations performed within the embedded-atom-method scheme. Our results elucidate the role played by the adsorption energy in determining the final morphology of the cluster/substrate system when ideal nondestructive deposition conditions are implemented. While implantation of the atom is not observed, we find a finite probability of site Ag-Pd exchanges in the case of clusters. Deposition-assisted mixing occurring at the topmost surface layer appears to be correlated to the size of the cluster and the orientation of the substrate, being higher for Ag7/Pd(100) and lower for Ag19/Pd(111). Total-energy calculations, combined with an analysis of the atomic motion, indicate that the structural transformation accompanying the deposition of the cluster provides the needed activation energy to induce the observed Ag-Pd atomic exchanges.

  1. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Standard Chlorine of Delaware Superfund Site in Delaware City, Delaware. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Salasovich, J.; Geiger, J.; Mosey, G.; Healey, V.

    2013-06-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Standard Chlorine of Delaware site in Delaware City, Delaware, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  2. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Kerr McGee Site in Columbus, Mississippi. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.; Mosey, G.

    2013-01-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Kerr McGee site in Columbus, Mississippi, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  3. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Sky Park Landfill Site in Eau Claire, Wisconsin. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.; Mosey, G.

    2013-01-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Sky Park Landfill site in Eau Claire, Wisconsin, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  4. Feasibility Study of Economics and Performance of Solar Photovoltaics at the VAG Mine Site in Eden and Lowell, Vermont. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.; Mosey, G.

    2013-04-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Vermont Asbestos Group (VAG) Mine site in Eden, Vermont, and Lowell, Vermont, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  5. Feasibility Study of Economics and Performance of Geothermal Power Generation at the Lakeview Uranium Mill Site in Lakeview, Oregon. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Hillesheim, M.; Mosey, G.

    2013-11-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Lakeview Uranium Mill site in Lakeview, Oregon, for a feasibility study of renewable energy production. The EPA contracted with the National Renewable Energy Laboratory (NREL) to provide technical assistance for the project. The purpose of this report is to describe an assessment of the site for possible development of a geothermal power generation facility and to estimate the cost, performance, and site impacts for the facility. In addition, the report recommends development pathways that could assist in the implementation of a geothermal power system at the site.

  6. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Snohomish County Cathcart Landfill Site in Snohomish County, Washington. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Olis, D.; Salasovich, J.; Mosey, G.; Healey, V.

    2013-04-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Snohomish County Cathcart Landfill Site in Snohomish County, Washington, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  7. Feasibility Study of Economics and Performance of Solar Photovoltaics at the TechCity East Campus Resource Conservation and Recovery Act Site in Kingston, New York. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Salasovich, James [National Renewable Energy Lab. (NREL), Golden, CO (United States); Geiger, Jesse W. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mosey, Gail [National Renewable Energy Lab. (NREL), Golden, CO (United States); Healey, Victoria [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-01-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the TechCity East Campus site in Kingston, New York, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this study is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  8. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Brisbane Baylands Brownfield Site in Brisbane, California. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Salasovich, J.; Geiger, J.; Healey, V.; Mosey, G.

    2013-04-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Brisbane Baylands site in Brisbane, California, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  9. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Former Bethlehem Steel Plant Brownfield Site in Lackawanna, New York. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Salasovich, J.; Geiger, J.; Mosey, G.; Healey, V.

    2013-04-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Former Bethlehem Steel Plant site in Lackawanna, New York, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  10. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Former Fort Ord Army Base Site in Marina, California. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Stoltenberg, B.; Konz, C.; Mosey, G.

    2013-05-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Former Fort Ord Army Base (FOAB) site in Marina, California, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  11. Initial direct comparison of 99mTc-TOC and 99mTc-TATE in identifying sites of disease in patients with proven GEP NETs.

    Science.gov (United States)

    Cwikla, Jaroslaw B; Mikolajczak, Renata; Pawlak, Dariusz; Buscombe, John R; Nasierowska-Guttmejer, Anna; Bator, Andrzej; Maecke, Helmut R; Walecki, Jerzy

    2008-07-01

    The imaging of neuroendocrine tumors has become one of the most significant areas in nuclear oncology. In an attempt to provide high-quality imaging and possible sensitivity at a reduced cost, time, and radiation dose, several (99m)Tc agents have been proposed. The aim of this initial study was to compare the tumor uptake and biodistribution of 2 new 6-hydrazinopyridine-3-carboxylic acid (HYNIC)-derivatized Tyr(3)-octreotide analogs, (99m)Tc-[HYNIC,Tyr(3)]octreotide ((99m)Tc-TOC) and (99m)Tc-[HYNIC,Tyr(3),Thr(8)]octreotide ((99m)Tc-TATE), in patients with somatostatin receptor-expressing tumors. Each of 12 patients with proven gastrointestinal pancreatic neuroendocrine tumors received a mean activity of 520 MBq of (99m)Tc-TOC and (99m)Tc-TATE. Scintigraphy with both tracers was performed 3-4 h after their injection using standard whole-body and SPECT imaging. The images were reviewed subjectively by 2 readers, who reported tumor uptake lesion by lesion. Both radiotracers demonstrated concordance between the results in 7 patients (58%). In total, 110 sites of disease were identified with (99m)Tc-TOC, compared with 115 with (99m)Tc-TATE. There was 1 case in which (99m)Tc-TOC identified sites of disease not seen on (99m)Tc-TATE imaging but 4 cases in which some sites of disease were seen with (99m)Tc-TATE and not (99m)Tc-TOC. In this initial study, both tracers seem to show similar sites of tumor, with (99m)Tc-TATE having a slight edge in the total number of lesions seen, especially in lymph node metastases.

  12. Method of forecasting pollutant transfer in an aquifer initial results obtained in a sandy medium (Barp site, Gironde)

    International Nuclear Information System (INIS)

    Madoz-Escande, C.; Peyrus, J.-C.

    1979-01-01

    Hydrogeological studies are undertaken in the context of the radiological safety of nuclear plants to forecast consequences of accidental releases of radioactive pollutants into an aquifer (transfer time, concentration at points of emergence). This quantitative forecast is obtained with the aid of a mathematical model with sequential emission. This requires a knowledge of the physical parameters of the aquifer and of the behavior of the pollutant in relation to the water-bearing medium. The physical parameters of a saturated porous medium are presented with the aid of radioactive tracer tests on a model and also in the field. The initial results obtained in a sandy medium are presented. In view of the difficulty of extrapolating to field conditions the conclusions of tests on models, it was necessary to set up a mobile laboratory with which in situ studies could be undertaken. The behavior of the pollutant in relation to the water-bearing medium is the subject of preliminary laboratory research on the laws of adsorption under different pH and temperature conditions. The numerical results obtained call for confirmation in the field. A description is given of a method which should enable the distribution coefficients to be evaluated in situ

  13. Initial field testing definition of subsurface sealing and backfilling tests in unsaturated tuff; Yucca Mountain Site Characterization Project

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, J.A. [Sandia National Labs., Albuquerque, NM (United States); Case, J.B.; Tyburski, J.R. [I. T. Corp., Albuquerque, NM (United States)

    1993-05-01

    This report contains an initial definition of the field tests proposed for the Yucca Mountain Project repository sealing program. The tests are intended to resolve various performance and emplacement concerns. Examples of concerns to be addressed include achieving selected hydrologic and structural requirements for seals, removing portions of the shaft liner, excavating keyways, emplacing cementitious and earthen seals, reducing the impact of fines on the hydraulic conductivity of fractures, efficient grouting of fracture zones, sealing of exploratory boreholes, and controlling the flow of water by using engineered designs. Ten discrete tests are proposed to address these and other concerns. These tests are divided into two groups: Seal component tests and performance confirmation tests. The seal component tests are thorough small-scale in situ tests, the intermediate-scale borehole seal tests, the fracture grouting tests, the surface backfill tests, and the grouted rock mass tests. The seal system tests are the seepage control tests, the backfill tests, the bulkhead test in the Calico Hills unit, the large-scale shaft seal and shaft fill tests, and the remote borehole sealing tests. The tests are proposed to be performed in six discrete areas, including welded and non-welded environments, primarily located outside the potential repository area. The final selection of sealing tests will depend on the nature of the geologic and hydrologic conditions encountered during the development of the Exploratory Studies Facility and detailed numerical analyses. Tests are likely to be performed both before and after License Application.

  14. Can surgical site infections be reduced with the adoption of a bundle of simultaneous initiatives? The use of NSQIP incidence data to follow multiple quality improvement interventions.

    Science.gov (United States)

    Rozario, Duncan

    2018-02-01

    Surgical site infections (SSI) are a common complication after surgical procedures. To reduce the incidence of SSIs, Oakville Trafalgar Memorial Hospital decided to institute a bundle of initiatives to change multiple factors simultaneously based on best available evidence and the understanding of infection pathophysiology. We used National Surgical Quality Improvement Program data on the incidence of SSIs in our targeted and essentials, general surgery and orthopedic surgery cases before and after the implementation of an SSI reduction bundle. This article discusses whether the use of intervention bundles may assist in the reduction of a variety of postoperative surgical complications.

  15. Translational Repression in Malaria Sporozoites

    Science.gov (United States)

    Turque, Oliver; Tsao, Tiffany; Li, Thomas; Zhang, Min

    2016-01-01

    Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1), is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host. PMID:28357358

  16. Translational repression in malaria sporozoites

    Directory of Open Access Journals (Sweden)

    Oliver Turque

    2016-04-01

    Full Text Available Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1, is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host.

  17. Why Translation Is Difficult

    DEFF Research Database (Denmark)

    Carl, Michael; Schaeffer, Moritz Jonas

    2017-01-01

    translations we investigate the effects of cross-lingual syntactic and semantic distance on translation production times and find that non-literality makes from-scratch translation and post-editing difficult. We show that statistical machine translation systems encounter even more difficulties with non-literality....

  18. N1-guanyl-1,7-diaminoheptane sensitizes bladder cancer cells to doxorubicin by preventing epithelial-mesenchymal transition through inhibition of eukaryotic translation initiation factor 5A2 activation.

    Science.gov (United States)

    Yang, Jinsong; Yu, Haogang; Shen, Mo; Wei, Wei; Xia, Lihong; Zhao, Peng

    2014-02-01

    Drug resistance greatly reduces the efficacy of doxorubicin-based chemotherapy in bladder cancer treatment; however, the underlying mechanisms are poorly understood. We aimed to investigate whether N1-guanyl-1,7-diaminoheptane (GC7), which inhibits eukaryotic translation initiation factor 5A2 (eIF5A2) activation, exerts synergistic cytotoxicity with doxorubicin in bladder cancer, and whether eIF5A2 is involved in chemoresistance to doxorubicin-based bladder cancer treatment. BIU-87, J82, and UM-UC-3 bladder cancer cells were transfected with eIF5A2 siRNA or negative control siRNA before incubation with doxorubicin alone or doxorubicin plus GC7 for 48 h. Doxorubicin cytotoxicity was enhanced by GC7 in BIU-87, J82, and UM-UC-3 cells. It significantly inhibited activity of eIF5A2, suppressed doxorubicin-induced epithelial-mesenchymal transition in BIU-87 cells, and promoted mesenchymal-epithelial transition in J82 and UM-UC-3 cells. Knockdown of eIF5A2 sensitized bladder cancer cells to doxorubicin, prevented doxorubicin-induced EMT in BIU-87 cells, and encouraged mesenchymal-epithelial transition in J82 and UM-UC-3 cells. Combination therapy with GC7 may enhance the therapeutic efficacy of doxorubicin in bladder cancer by inhibiting eIF5A2 activation and preventing epithelial-mesenchymal transition. © 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  19. Knockdown of eukaryotic translation initiation factor 4E suppresses cell growth and invasion, and induces apoptosis and cell cycle arrest in a human lung adenocarcinoma cell line.

    Science.gov (United States)

    Chen, Baofu; Zhang, Bo; Xia, Lilong; Zhang, Jian; Chen, Yu; Hu, Quanteng; Zhu, Chengchu

    2015-12-01

    Eukaryotic translation initiation factor 4E (eIF4E) was shown to be upregulated in malignant human tumors. To assess the effect of downregulation of eIF4E on the proliferation and invasiveness of a human lung adenocarcinoma cell line, a short hairpin (sh)RNA targeting eIF4E was constructed and transfected into A549 human lung adenocarcinoma cells. The expression of eIF4E was determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. Cell viability was assessed using a Cell Counting kit‑8, and apoptosis levels and cell cycle distribution were assessed by flow cytometry. Invasiveness was assessed using Transwell chambers. Transfection of the A549 cells with eIF4E targeting shRNA reduced the mRNA and protein expression levels of eIF4E by >70% 48 and 72 h following transfection, and eIF4E targeting shRNA‑transfected cells were significantly less viable compared with the cells transfected with scrambled shRNA. The rate of apoptosis was also significantly increased, significantly more cells were in the G0/G1 phase and fewer were in the S phase, indicating cell cycle arrest. The fraction of transfected cells migrating across Transwell inserts were also reduced. In conclusion, inhibition of eIF4E suppressed cell growth and invasion, induced apoptosis and cell cycle arrest, suggesting that eIF4E may be a potential therapeutic target in lung adenocarcinoma.

  20. On Various Negative Translations

    Directory of Open Access Journals (Sweden)

    Gilda Ferreira

    2011-01-01

    Full Text Available Several proof translations of classical mathematics into intuitionistic mathematics have been proposed in the literature over the past century. These are normally referred to as negative translations or double-negation translations. Among those, the most commonly cited are translations due to Kolmogorov, Godel, Gentzen, Kuroda and Krivine (in chronological order. In this paper we propose a framework for explaining how these different translations are related to each other. More precisely, we define a notion of a (modular simplification starting from Kolmogorov translation, which leads to a partial order between different negative translations. In this derived ordering, Kuroda and Krivine are minimal elements. Two new minimal translations are introduced, with Godel and Gentzen translations sitting in between Kolmogorov and one of these new translations.

  1. Translation and Quality Management

    DEFF Research Database (Denmark)

    Petersen, Margrethe

    1996-01-01

    The aim of this article is to consider the issue of quality in translation. Specifically, the question under consideration is whether quality assurance in relation to translation is feasible and, if so, what some of the implications for translation theory, translation practice and the teaching of...... under the ISO 9001 standard, and section 4. discusses the implications which quality management seems to hold for the field of translation in a broad sense. Finally, section 5. concludes the article....

  2. An initial examination of carbonate production in the western equatorial Pacific: XRF results from the Pliocene-Pleistocene of IODP Site U1490

    Science.gov (United States)

    Chapman, J.; Kulhanek, D. K.; Rosenthal, Y.; Holbourn, A. E.

    2017-12-01

    International Ocean Discovery Program (IODP) Expedition 363 sought to determine the nature of and driving forces behind climate variability in the Western Pacific Warm Pool (WPWP) region throughout the Neogene on millennial, orbital, and geologic timescales. Our research focuses on the Pliocene to recent (4-0 Ma) sediment record from IODP Site U1490 to examine changes in carbonate production and burial in the WPWP as a record of variations in the regional/global carbon cycle. This interval is of particular interest because it spans the Middle Pliocene Warm Period, the initiation of Northern Hemisphere Glaciation, and the Mid-Pleistocene Transition. Site U1490 is located on the northern edge of Eauripik Rise at 05°58.95'N, 142°39.27'E in the northern part of the WPWP. At 2341 m water depth, today the site is bathed in Upper Circumpolar Deepwater. Pliocene to recent sediment primarily consists of foraminifer-rich nannofossil ooze, with the sedimentation rate varying between 1.5 and 3 cm/kyr. Initial shipboard measurement of calcium carbonate content shows little variation at low resolution (1 sample every few meters), varying between 90 and 95 wt%. We collected X-ray fluorescence (XRF) data at 2 cm resolution along the composite stratigraphic section to obtain a qualitative measure of the bulk chemistry of the sediment. We will use the weight percent calcium carbonate of discrete samples to calibrate the XRF data to generate a high-resolution carbonate record. We observe cyclical variations in the Ca/Ba, which may reflect variations in productivity and/or dissolution through this interval, although additional work is needed to fully interpret these data. Ultimately our research will allow for comparison between records obtained from these cores located in the western equatorial Pacific to those obtained in the eastern and central Pacific, which will better elucidate the nature of the carbon system during the Plio-Pleistocene.

  3. Surgical Critical Care Initiative

    Data.gov (United States)

    Federal Laboratory Consortium — The Surgical Critical Care Initiative (SC2i) is a USU research program established in October 2013 to develop, translate, and validate biology-driven critical care....

  4. Making Knowledge Actionable: Three Key Translation Moments

    Directory of Open Access Journals (Sweden)

    John R. Austin

    2013-12-01

    Full Text Available Leaders regularly experience pressure to move innovation and change initiatives through their organizations. They face the challenge of transforming organizational changes and innovations from ideas into sustained behavior. In this commentary, I argue that successful implementation requires leaders to engage in a translation process that contains three key translation “moments”. The challenges presented by these translation moments are magnified by the difficulty leaders often have in shifting from one moment to the next. Techniques for handling each translation moment are discussed.

  5. Network Basic Language Translation System: Security Infrastructure

    National Research Council Canada - National Science Library

    Mittrick, Mark R

    2007-01-01

    .... The Network Basic Language Translation System (NetBLTS) was proposed and accepted as part of the U.S. Army Research Laboratory's offering of initiatives within the Horizontal Fusion portfolio in 2003...

  6. Translation-coupling systems

    Science.gov (United States)

    Pfleger, Brian; Mendez-Perez, Daniel

    2013-11-05

    Disclosed are systems and methods for coupling translation of a target gene to a detectable response gene. A version of the invention includes a translation-coupling cassette. The translation-coupling cassette includes a target gene, a response gene, a response-gene translation control element, and a secondary structure-forming sequence that reversibly forms a secondary structure masking the response-gene translation control element. Masking of the response-gene translation control element inhibits translation of the response gene. Full translation of the target gene results in unfolding of the secondary structure and consequent translation of the response gene. Translation of the target gene is determined by detecting presence of the response-gene protein product. The invention further includes RNA transcripts of the translation-coupling cassettes, vectors comprising the translation-coupling cassettes, hosts comprising the translation-coupling cassettes, methods of using the translation-coupling cassettes, and gene products produced with the translation-coupling cassettes.

  7. Writing Through: Practising Translation

    Directory of Open Access Journals (Sweden)

    Joel Scott

    2010-05-01

    Full Text Available This essay exists as a segment in a line of study and writing practice that moves between a critical theory analysis of translation studies conceptions of language, and the practical questions of what those ideas might mean for contemporary translation and writing practice. Although the underlying preoccupation of this essay, and my more general line of inquiry, is translation studies and practice, in many ways translation is merely a way into a discussion on language. For this essay, translation is the threshold of language. But the two trails of the discussion never manage to elude each other, and these concatenations have informed two experimental translation methods, referred to here as Live Translations and Series Translations. Following the essay are a number of poems in translation, all of which come from Blanco Nuclear by the contemporary Spanish poet, Esteban Pujals Gesalí. The first group, the Live Translations consist of transcriptions I made from audio recordings read in a public setting, in which the texts were translated in situ, either off the page of original Spanish-language poems, or through a process very much like that carried out by simultaneous translators, for which readings of the poems were played back to me through headphones at varying speeds to be translated before the audience. The translations collected are imperfect renderings, attesting to a moment in language practice rather than language objects. The second method involves an iterative translation process, by which three versions of any one poem are rendered, with varying levels of fluency, fidelity and servility. All three translations are presented one after the other as a series, with no version asserting itself as the primary translation. These examples, as well as the translation methods themselves, are intended as preliminary experiments within an endlessly divergent continuum of potential methods and translations, and not as a complete representation of

  8. The initial development of the WebMedQual scale: domain assessment of the construct of quality of health web sites.

    Science.gov (United States)

    Provost, Mélanie; Koompalum, Dayin; Dong, Diane; Martin, Bradley C

    2006-01-01

    To develop a comprehensive instrument assessing quality of health-related web sites. Phase I consisted of a literature review to identify constructs thought to indicate web site quality and to identify items. During content analysis, duplicate items were eliminated and items that were not clear, meaningful, or measurable were reworded or removed. Some items were generated by the authors. Phase II: a panel consisting of six healthcare and MIS reviewers was convened to assess each item for its relevance and importance to the construct and to assess item clarity and measurement feasibility. Three hundred and eighty-four items were generated from 26 sources. The initial content analysis reduced the scale to 104 items. Four of the six expert reviewers responded; high concordance on the relevance, importance and measurement feasibility of each item was observed: 3 out of 4, or all raters agreed on 76-85% of items. Based on the panel ratings, 9 items were removed, 3 added, and 10 revised. The WebMedQual consists of 8 categories, 8 sub-categories, 95 items and 3 supplemental items to assess web site quality. The constructs are: content (19 items), authority of source (18 items), design (19 items), accessibility and availability (6 items), links (4 items), user support (9 items), confidentiality and privacy (17 items), e-commerce (6 items). The "WebMedQual" represents a first step toward a comprehensive and standard quality assessment of health web sites. This scale will allow relatively easy assessment of quality with possible numeric scoring.

  9. Sound Effects in Translation

    DEFF Research Database (Denmark)

    Mees, Inger M.; Dragsted, Barbara; Gorm Hansen, Inge

    2013-01-01

    On the basis of a pilot study using speech recognition (SR) software, this paper attempts to illustrate the benefits of adopting an interdisciplinary approach in translator training. It shows how the collaboration between phoneticians, translators and interpreters can (1) advance research, (2) have...... implications for the curriculum, (3) be pedagogically motivating, and (4) prepare students for employing translation technology in their future practice as translators. In a two-phase study in which 14 MA students translated texts in three modalities (sight, written, and oral translation using an SR program......), Translog was employed to measure task times. The quality of the products was assessed by three experienced translators, and the number and types of misrecognitions were identified by a phonetician. Results indicate that SR translation provides a potentially useful supplement to written translation...

  10. Feasibility Study of Economics and Performance of Biomass Power Generation at the Former Farmland Industries Site in Lawrence, Kansas. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Tomberlin, G.; Mosey, G.

    2013-03-01

    Under the RE-Powering America's Land initiative, the U.S. Environmental Protection Agency (EPA) provided funding to the National Renewable Energy Laboratory (NREL) to support a feasibility study of biomass renewable energy generation at the former Farmland Industries site in Lawrence, Kansas. Feasibility assessment team members conducted a site assessment to gather information integral to this feasibility study. Information such as biomass resources, transmission availability, on-site uses for heat and power, community acceptance, and ground conditions were considered.

  11. Introduction: contemporary translation studies and Bible translation ...

    African Journals Online (AJOL)

    Introduction: contemporary translation studies and Bible translation. J.A. Naude, C.H.J. Van der Merwe. Abstract. (Acta Theologica, Supplementum 2, 2002: 1-5). Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/actat.v22i1.5450.

  12. The Triticum Mosaic Virus 5' Leader Binds to Both eIF4G and eIFiso4G for Translation.

    Directory of Open Access Journals (Sweden)

    Robyn Roberts

    Full Text Available We recently identified a remarkably strong (739 nt-long IRES-like element in the 5' untranslated region (UTR of Triticum mosaic virus (TriMV, Potyviridae. Here, we define the components of the cap-binding translation initiation complex that are required for TriMV translation. Using bio-layer interferometry and affinity capture of the native translation apparatus, we reveal that the viral translation element has a ten-fold greater affinity for the large subunit eIF4G/eIFiso4G than to the cap binding protein eIF4E/eIFiso4E. This data supports a translation mechanism that is largely dependent on eIF4G and its isoform. The binding of both scaffold isoforms requires an eight base-pair-long hairpin structure located 270 nucleotides upstream of the translation initiation site, which we have previously shown to be crucial for IRES activity. Despite a weak binding affinity to the mRNA, eIFiso4G alone or in combination with eIFiso4E supports TriMV translation in a cap-binding factor-depleted wheat germ extract. Notably, TriMV 5' UTR-mediated translation is dependent upon eIF4A helicase activity, as the addition of the eIF4A inhibitor hippuristanol inhibits 5' UTR-mediated translation. This inhibition is reversible with the addition of recombinant wheat eIF4A. These results and previous observations demonstrate a key role of eIF4G and eIF4A in this unique mechanism of cap-independent-translation. This work provides new insights into the lesser studied translation mechanisms of plant virus-mediated internal translation initiation.

  13. Translation, Quality and Growth

    DEFF Research Database (Denmark)

    Petersen, Margrethe

    The paper investigates the feasibility and some of the possible consequences of applying quality management to translation. It first gives an introduction to two different schools of translation and to (total) quality management. It then examines whether quality management may, in theory......, be applied to translation and goes on to present a case study which involves a firm in the translation industry and which illustrates quality management in practice. The paper shows that applying quality management to translation is feasible and that doing so may translate into sustained growth....

  14. Pseudoknot and translational control in the expression of the S15 ribosomal protein.

    Science.gov (United States)

    Bénard, L; Philippe, C; Ehresmann, B; Ehresmann, C; Portier, C

    1996-01-01

    Translational autocontrol of the expression of the ribosomal protein S15 proceeds through the transitory formation of a pseudoknot. A synopsis of the known data is used to propose a molecular model of the mechanism involved and for the role of the pseudoknot. This latter structure is able to recruit 30S ribosomal subunits to initiate translation, but also to bind S15 and to stop translation by trapping the ribosome on its loading site. Information on the S15 protein recognition of the messenger RNA site was deduced from mutational analyses and chemical probing. A comparison of this messenger site with the S15 ribosomal binding site was conducted by analysing hydroxyl radical footprintings of these two sites. The existence of two subsites in 16S RNA suggests that the ribosomal protein S15 might present either two different binding sites or at least one common subsite. Clues for the presence of a common site between the messenger and 16S RNA are given which cannot rule out that recognition specificity is linked to a few other determinants. Whether these determinants are different or not remains an open question.

  15. Back to basics: the untreated rabbit reticulocyte lysate as a competitive system to recapitulate cap/poly(A) synergy and the selective advantage of IRES-driven translation.

    Science.gov (United States)

    Soto Rifo, Ricardo; Ricci, Emiliano P; Décimo, Didier; Moncorgé, Olivier; Ohlmann, Théophile

    2007-01-01

    Translation of most eukaryotic mRNAs involves the synergistic action between the 5' cap structure and the 3' poly(A) tail at the initiation step. The poly(A) tail has also been shown to stimulate translation of picornavirus internal ribosome entry sites (IRES)-directed translation. These effects have been attributed principally to interactions between eIF4G and poly(A)-binding protein (PABP) but also to the participation of PABP in other steps during translation initiation. As the rabbit reticulocyte lysate (RRL) does not recapitulate this cap/poly(A) synergy, several systems based on cellular cell-free extracts have been developed to study the effects of poly(A) tail in vitro but they generally exhibit low translational efficiency. Here, we describe that the non-nuclease-treated RRL (untreated RRL) is able to recapitulate the effects of poly(A) tail on translation in vitro. In this system, translation of a capped/polyadenylated RNA was specifically inhibited by either Paip2 or poly(rA), whereas translation directed by HCV IRES remained unaffected. Moreover, cleavage of eIF4G by FMDV L protease strongly stimulated translation directed by the EMCV IRES, thus recapitulating the competitive advantage that the proteolytic processing of eIF4G confers to IRES-driven RNAs.

  16. Negotiating Languages and Cultures: Enacting Translingualism through a Translation Assignment

    Science.gov (United States)

    Kiernan, Julia; Meier, Joyce; Wang, Xiqiao

    2016-01-01

    This collaborative project explores the affordances of a translation assignment in the context of a learner-centered pedagogy that places composition students' movement among languages and cultures as both a site for inquiry and subject of analysis. The translation assignment asks students to translate scholarly articles or culture stories from…

  17. The Annual Economic Burden of Syphilis: An Estimation of Direct, Productivity, and Intangible Costs for Syphilis in Guangdong Initiative for Comprehensive Control of Syphilis Sites.

    Science.gov (United States)

    Zou, Yaming; Liao, Yu; Liu, Fengying; Chen, Lei; Shen, Hongcheng; Huang, Shujie; Zheng, Heping; Yang, Bin; Hao, Yuantao

    2017-11-01

    Syphilis has continuously posed a great challenge to China. However, very little data existed regarding the cost of syphilis. Taking Guangdong Initiative for Comprehensive Control of Syphilis area as the research site, we aimed to comprehensively measure the annual economic burden of syphilis from a societal perspective. Newly diagnosed and follow-up outpatient cases were investigated by questionnaire. Reported tertiary syphilis cases and medical institutions cost were both collected. The direct economic burden was measured by the bottom-up approach, the productivity cost by the human capital method, and the intangible burden by the contingency valuation method. Three hundred five valid early syphilis cases and 13 valid tertiary syphilis cases were collected in the investigation to estimate the personal average cost. The total economic burden of syphilis was US $729,096.85 in Guangdong Initiative for Comprehensive Control of Syphilis sites in the year of 2014, with medical institutions cost accounting for 73.23% of the total. Household average direct cost of early syphilis was US $23.74. Average hospitalization cost of tertiary syphilis was US $2,749.93. Of the cost to medical institutions, screening and testing comprised the largest proportion (26%), followed by intervention and case management (22%) and operational cost (21%). Household average productivity cost of early syphilis was US $61.19. Household intangible cost of syphilis was US $15,810.54. Syphilis caused a substantial economic burden on patients, their families, and society in Guangdong. Household productivity and intangible costs both shared positive relationships with local economic levels. Strengthening the prevention and effective treatment of early syphilis could greatly help to lower the economic burden of syphilis.

  18. Initial investigation of 18F-NaF PET/CT for identification of vertebral sites amenable to surgical revision after spinal fusion surgery

    International Nuclear Information System (INIS)

    Quon, Andrew; Iagaru, Andrei; Dodd, Robert; Abreu, Marcelo Rodrigues de; Sprinz, Clarice; Hennemann, Sergio; Alves Neto, Jose Maria

    2012-01-01

    A pilot study was performed in patients with recurrent back pain after spinal fusion surgery to evaluate the ability of 18 F-NaF PET/CT imaging to correctly identify those requiring surgical intervention and to locate a site amenable to surgical intervention. In this prospective study 22 patients with recurrent back pain after spinal surgery and with equivocal findings on physical examination and CT were enrolled for evaluation with 18 F-NaF PET/CT. All PET/CT images were prospectively reviewed with the primary objective of identifying or ruling out the presence of lesions amenable to surgical intervention. The PET/CT results were then validated during surgical exploration or clinical follow-up of at least 15 months. Abnormal 18 F-NaF foci were found in 16 of the 22 patients, and surgical intervention was recommended. These foci were located at various sites: screws, cages, rods, fixation hardware, and bone grafts. In 6 of the 22 patients no foci requiring surgical intervention were found. Validation of the results by surgery (15 patients) or on clinical follow-up (7 patients) showed that 18 F-NaF PET/CT correctly predicted the presence of an abnormality requiring surgical intervention in 15 of 16 patients and was falsely positive in 1 of 16. In this initial investigation, 18 F-NaF PET/CT imaging showed potential utility for evaluation of recurrent symptoms after spinal fusion surgery by identifying those patients requiring surgical management. (orig.)

  19. Melanoma patients with unknown primary site or nodal recurrence after initial diagnosis have a favourable survival compared to those with synchronous lymph node metastasis and primary tumour.

    Directory of Open Access Journals (Sweden)

    Benjamin Weide

    Full Text Available BACKGROUND: A direct comparison of prognosis between patients with regional lymph node metastases (LNM detected synchronously with the primary melanoma (primary LNM, patients who developed their first LNM subsequently (secondary LNM and those with initial LNM in melanoma with unknown primary site (MUP is missing thus far. PATIENTS AND METHODS: Survival of 498 patients was calculated from the time point of the first macroscopic LNM using Kaplan Meier and multivariate Cox hazard regression analysis. RESULTS: Patients with secondary LNM (HR = 0.67; p = 0.009 and those with initial LNM in MUP (HR = 0.45; p = 0.008 had a better prognosis compared to patients with primary LNM (median survival time 52 and 65 vs. 24 months, respectively. A high number of involved nodes, the presence of in-transit/satellite metastases and male gender had an additional independent unfavourable effect. CONCLUSIONS: Survival of patients with LNM in MUP and with secondary LNM is similar and considerably more favourable compared to those with primary LNM. This difference needs to be considered during patient counselling and for stratification purposes in clinical trials. The assumption of an immune privilege of patients with MUP which is responsible for rejection of the primary melanoma, and results in a favourable prognosis is not supported by our data.

  20. Living in Translation

    DEFF Research Database (Denmark)

    Lykke Jakobsen, Arnt

    Exaugural presentation. A retrospect of my personal itinerary from literature, across translation studies to translation process research and a look ahead. In the retrospect, I range over diverse topics, all of which have sprung from my concern with the phenomenon of translation. I reflect on how......, as humans, we generate meaning, interpret meaning, and reformulate or translate meaning. I also reflect on the way computing has influenced research into these phenomena as seen e.g. in my creation of the Translog program and in projects I have been involved in, such as OFT (Translation of Professional...... for global communication purposes, and for improving research into translation, the phenomenon of translation and the world of translation in which we all live....

  1. Determinants of translation ambiguity

    Science.gov (United States)

    Degani, Tamar; Prior, Anat; Eddington, Chelsea M.; Arêas da Luz Fontes, Ana B.; Tokowicz, Natasha

    2016-01-01

    Ambiguity in translation is highly prevalent, and has consequences for second-language learning and for bilingual lexical processing. To better understand this phenomenon, the current study compared the determinants of translation ambiguity across four sets of translation norms from English to Spanish, Dutch, German and Hebrew. The number of translations an English word received was correlated across these different languages, and was also correlated with the number of senses the word has in English, demonstrating that translation ambiguity is partially determined by within-language semantic ambiguity. For semantically-ambiguous English words, the probability of the different translations in Spanish and Hebrew was predicted by the meaning-dominance structure in English, beyond the influence of other lexical and semantic factors, for bilinguals translating from their L1, and translating from their L2. These findings are consistent with models postulating direct access to meaning from L2 words for moderately-proficient bilinguals. PMID:27882188

  2. Translation in ESL Classes

    Directory of Open Access Journals (Sweden)

    Nagy Imola Katalin

    2015-12-01

    Full Text Available The problem of translation in foreign language classes cannot be dealt with unless we attempt to make an overview of what translation meant for language teaching in different periods of language pedagogy. From the translation-oriented grammar-translation method through the complete ban on translation and mother tongue during the times of the audio-lingual approaches, we have come today to reconsider the role and status of translation in ESL classes. This article attempts to advocate for translation as a useful ESL class activity, which can completely fulfil the requirements of communicativeness. We also attempt to identify some activities and games, which rely on translation in some books published in the 1990s and the 2000s.

  3. Translating Others, Discovering Himself: Beckett as Translator

    Directory of Open Access Journals (Sweden)

    Darren Gribben

    2011-08-01

    Full Text Available This paper examines the work of Samuel Beckett in the light of his early work as a translator of the works of other writers.  In his translations for Negro: An Anthology (1934, the Anthology of Mexican Poetry (1958, or commissioned translations for journals such as “This Quarter”, early pre-figurings of Beckett’s own thematic and linguistic concerns abound.  Rarely viewed as more than acts of raising money for himself, Beckett’s acts of translation, examined chronologically, demonstrate a writer discovering his craft, and developing his unique voice, unencumbered by the expectations of originality.  This essay posits that Beckett’s works, with their distinctive voice and characterisation, owe much to the global perspective he gained through translating across cultural, continental divides, as well as experimenting with form, which became a staple of Beckett’s own work.  Without formal training or theoretical grounding in translation, Beckett utilises the act of translation as a means of finding himself, revisiting it as a means of shaping his own unique literary voice.

  4. Translational autocontrol of the Escherichia coli ribosomal protein S15.

    Science.gov (United States)

    Portier, C; Dondon, L; Grunberg-Manago, M

    1990-01-20

    When rpsO, the gene encoding the ribosomal protein S15 in Escherichia coli, is carried by a multicopy plasmid, the mRNA synthesis rate of S15 increases with the gene dosage but the rate of synthesis of S15 does not rise. A translational fusion between S15 and beta-galactosidase was introduced on the chromosome in a delta lac strain and the expression of beta-galactosidase studied under different conditions. The presence of S15 in trans represses the beta-galactosidase level five- to sixfold, while the synthesis rate of the S15-beta-galactosidase mRNA decreases by only 30 to 50%. These data indicate that S15 is subject to autogenous translational control. Derepressed mutants were isolated and sequenced. All the point mutations map in the second codon of S15, suggesting a location for the operator site that is very near to the translation initiation codon. However, the creation of deletion mutations shows that the operator extends into the 5' non-coding part of the message, thus overlapping the ribosome loading site.

  5. Translating HOL to Dedukti

    Directory of Open Access Journals (Sweden)

    Ali Assaf

    2015-07-01

    Full Text Available Dedukti is a logical framework based on the lambda-Pi-calculus modulo rewriting, which extends the lambda-Pi-calculus with rewrite rules. In this paper, we show how to translate the proofs of a family of HOL proof assistants to Dedukti. The translation preserves binding, typing, and reduction. We implemented this translation in an automated tool and used it to successfully translate the OpenTheory standard library.

  6. Euphemism vs explicitness: A corpus-based analysis of translated ...

    African Journals Online (AJOL)

    This article examines the governing initial norms, namely explicitness and euphemism in English source texts and Ndebele translations, focusing on how these norms influenced the strategies chosen by the Ndebele translators in the translation of taboo terms. In the article, a corpus-based approach is used to identify head ...

  7. Neural Machine Translation

    OpenAIRE

    Koehn, Philipp

    2017-01-01

    Draft of textbook chapter on neural machine translation. a comprehensive treatment of the topic, ranging from introduction to neural networks, computation graphs, description of the currently dominant attentional sequence-to-sequence model, recent refinements, alternative architectures and challenges. Written as chapter for the textbook Statistical Machine Translation. Used in the JHU Fall 2017 class on machine translation.

  8. For "Translation and Theories"

    Science.gov (United States)

    Ni, Lili

    2009-01-01

    Translation studies stem from comparative literature and contrastive analysis. It involves the transfer of messages between two different language systems and cultures, and Munday (2001, p.1) notes that translation "by its nature" "is multilingual and also interdisciplinary". Translation subjects are the texts in various…

  9. Translation of vph mRNA in Streptomyces lividans and Escherichia coli after removal of the 5' untranslated leader.

    Science.gov (United States)

    Wu, C J; Janssen, G R

    1996-10-01

    The Streptomyces vinaceus viomycin phosphotransferase (vph) mRNA contains an untranslated leader with a conventional Shine-Dalgarno homology. The vph leader was removed by ligation of the vph coding sequence to the transcriptional start site of a Streptomyces or an Escherichia coli promoter, such that transcription would initiate at the first position of the vph start codon. Analysis of mRNA demonstrated that transcription initiated primarily at the A of the vph AUG translational start codon in both Streptomyces lividans and E. coli; cells expressing the unleadered vph mRNA were resistant to viomycin indicating that the Shine-Dalgarno sequence, or other features contained within the leader, was not necessary for vph translation. Addition of four nucleotides (5'-AUGC-3') onto the 5' end of the unleadered vph mRNA resulted in translation initiation from the vph start codon and the AUG triplet contained within the added sequence. Translational fusions of vph sequence to a Tn5 neo reporter gene indicated that the first 16 codons of vph coding sequence were sufficient to specify the translational start site and reading frame for expression of neomycin resistance in both E. coli and S. lividans.

  10. Speaking your Translation

    DEFF Research Database (Denmark)

    Dragsted, Barbara; Mees, Inger M.; Gorm Hansen, Inge

    2011-01-01

    In this article we discuss the translation processes and products of 14 MA students who produced translations from Danish (L1) into English (L2) under different working conditions: (1) written translation, (2) sight translation, and (3) sight translation with a speech recognition (SR) tool. Audio......, since students were dictating in their L2, we looked into the number and types of error that occurred when using the SR software. Items that were misrecognised by the program could be divided into three categories: homophones, hesitations, and incorrectly pronounced words. Well over fifty per cent...

  11. Lost in translation

    DEFF Research Database (Denmark)

    Hedegaard, Steffen; Simonsen, Jakob Grue

    2011-01-01

    of translated texts. Our results suggest (i) that frame-based classifiers are usable for author attribution of both translated and untranslated texts; (ii) that framebased classifiers generally perform worse than the baseline classifiers for untranslated texts, but (iii) perform as well as, or superior...... to the baseline classifiers on translated texts; (iv) that—contrary to current belief—naïve classifiers based on lexical markers may perform tolerably on translated texts if the combination of author and translator is present in the training set of a classifier....

  12. What is a translator?

    Directory of Open Access Journals (Sweden)

    Martha Pulido

    2016-08-01

    Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.

  13. What is a translator?

    Directory of Open Access Journals (Sweden)

    Martha Martha Pulido

    2016-05-01

    Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.

  14. Baudelaire: Translator-Auctoritas

    Directory of Open Access Journals (Sweden)

    Juan Zapata

    2017-07-01

    Full Text Available In order to achieve visibility in the media and a position recognized by both the public and their peers, translators are compelled to take advantage of spaces of enunciation such as those provided by prefaces, criticism, or biographical notes. Thanks to these spaces, in which translators deploy discursive and institutional strategies that allow them to position themselves and their translation project, translators acquire the status of translator-auctoritas, that is, a level of symbolic authority capable of endowing them with a public image. Through the detailed analysis of the editorial strategies and institutional calculations implemented by Baudelaire in order to position his project of translating Edgar Allan Poe, we show how the poet achieves the status of translator-auctoritas and the role the latter played in the construction of his own literary identity.

  15. Lost in translation?

    DEFF Research Database (Denmark)

    Granas, Anne Gerd; Nørgaard, Lotte Stig; Sporrong, Sofia Kälvemark

    2014-01-01

    OBJECTIVE: The "Beliefs about Medicines Questionnaire" (BMQ) assess balance of necessity and concern of medicines. The BMQ has been translated from English to many languages. However, the original meaning of statements, such as "My medicine is a mystery to me", may be lost in translation. The aim...... of this study is to compare three Scandinavian translations of the BMQ. (1) How reliable are the translations? (2) Are they still valid after translation? METHODS: Translated Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three native Scandinavian researchers. Linguistic differences...... and ambiguities in the 5-point Likert scale and the BMQ statements were compared. RESULTS: In the Scandinavian translations, the Likert scale expanded beyond the original version at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements, discrepancies ranged from smaller inaccuracies toward...

  16. Introduction : Translation Peripheries. The Paratextual Elements In Translation

    OpenAIRE

    Gil-Bardají, Anna

    2012-01-01

    The notion of paratext is an unquestionably important consideration for many lines of research in translation studies: the history of translation, literary translation, audiovisual translation, and the analysis of ideological discourse in translation or self-translation. This inexplicable short-age of studies on paratexts in translations was one of the reasons why the Department of Translation and Interpreting at the Universitat Autònoma de Barcelona decided to organise the 7th International ...

  17. Assessing excellence in translational cancer research: a consensus based framework.

    Science.gov (United States)

    Rajan, Abinaya; Caldas, Carlos; van Luenen, Henri; Saghatchian, Mahasti; van Harten, Wim H

    2013-10-29

    patient stratification, substantial fraction of phase I/II trials, investigator-initiated trials). Critically, the framework supports reduced bureaucracy by building on existing European evaluation systems. The excellence framework is the product of an intense stakeholder consensus building exercise. It will be piloted during an expert peer review/site visit of at least three European Comprehensive Cancer Centres. The findings regarding content, governance and implementation can have relevance for other clinical and research fields.

  18. Cross-talk between free and bound spermatozoa to modulate initial sperm:egg ratios at the site of fertilization in the mammalian oviduct.

    Science.gov (United States)

    Hunter, R H F; Gadea, J

    2014-08-01

    This essay proposes that highly localized communication between free and bound spermatozoa in the caudal portion of the oviduct acts to regulate the numbers detaching from the epithelium and progressing to the site of fertilization close to the time of ovulation. Low initial sperm:egg ratios are essential for monospermic fertilization. Liberation of surface macromolecules and metabolic prompting from activated spermatozoa, together with altered patterns of sperm movement and dynamic differences in intracellular Ca(2+) ion status between neighboring sperm cells, would influence the progressive release of spermatozoa from the reservoir in the oviduct isthmus. Different intensities of preovulatory epithelial binding, reflecting a range of states in the sperm surface membranes and associated proteins, would provide a further explanation for a chronologically staggered periovulatory detachment of spermatozoa. Intimate sperm-sperm interactions within the confines of the oviduct isthmus offer a sensitive means of fine-tuning the vanguard of competent male gametes reaching the isthmo-ampullary junction. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Partial restoration of replication of simian immunodeficiency virus by point mutations in either the dimerization initiation site (DIS) or Gag region after deletion mutagenesis within the DIS.

    Science.gov (United States)

    Guan, Y; Diallo, K; Detorio, M; Whitney, J B; Liang, C; Wainberg, M A

    2001-12-01

    We used the simian immunodeficiency virus (SIV) molecular clone SIVmac239 to generate a deletion construct, termed SD2, in which we eliminated 22 nucleotides at positions +398 to +418 within the putative dimerization initiation site (DIS) stem. This SD2 deletion severely impaired viral replication, due to adverse effects on the packaging of viral genomic RNA, the processing of Gag proteins, and viral protein patterns. However, long-term culture of SD2 in either C8166 or CEMx174 cells resulted in restoration of replication capacity, due to two different sets of three compensatory point mutations, located within both the DIS and Gag regions. In the case of C8166 cells, both a K197R and a E49K mutation were identified within the capsid (CA) protein and the p6 protein of Gag, respectively, while the other point mutation (A423G) was found within the putative DIS loop. In the case of CEMx174 cells, two compensatory mutations were present within the viral nucleocapsid (NC) protein, E18G and Q31K, in addition to the same A423G substitution as observed with C8166 cells. A set of all three mutations was required in each case for restoration of replication capacity, and either set of mutations could be substituted for the other in both the C8166 and CEMx174 cell lines.

  20. Literary Translation, Translating Culture: The Case of Shahriyar, the Famous Iranian Azeri Poet

    Directory of Open Access Journals (Sweden)

    Sajjad Kianbakht

    2016-08-01

    Full Text Available A literary translation is a device of art used to release the text from its dependence on prior cultural knowledge (Herzfeld, 2003. The present research investigates the use of pragmatic equivalence in two translations of the Azeri Turkish long poem "Haydar Bābāye Salām" by "Shahriyar". Based on Koller’s theory of equivalence (2001 four elements were assigned for the pragmatic equivalence: 1 domestication rather than foreignization, 2 naturalness of the expressions, 3 focus on target-text reader, and 4 content-based product. Thirty six stanzas from the initial, middle and final part of the poem were selected and then their two translations were analyzed according to the aforementioned elements. Moreover, based on Newmark’s model (1988 it is also investigated that whether a translation with all the four elements of pragmatic equivalence is a good one or not. According to Newmark’s model (1988 three markers of a good translation are: 1 utilization of pragmatic equivalence, 2 naturalness, and 3 not sounding like a translation. The results suggest that a translator who has utilized all the elements of pragmatic equivalence is also successful in reproducing a better translation for the target language readers. Keywords: Equivalence theory, Literary translation, Poetry translation, Pragmatic equivalence

  1. Measuring Translation Literality

    DEFF Research Database (Denmark)

    Carl, Michael; Schaeffer, Moritz

    2017-01-01

    Tirkkonen-Condit (2005: 407–408) argues that “It looks as if literal translation is [the result of] a default rendering procedure”. As a corollary, more literal translations should be easier to process, and less literal ones should be associated with more cognitive effort. In order to assess...... this hypothesis, we operationalize translation literality as 1. the word-order similarity of the source and the target text and 2. the number of possible different translation renderings. We develop a literality metric and apply it on a set of manually word and sentence aligned alternative translations. Drawing...... on the monitor hypothesis (Tirkkonen-Condit 2005) and a model of shared syntax (Hartsuiker et al. 2004) we develop a model of translation effort based on priming strength: shared combinatorial nodes and meaning representations are activated through automatized bilingual priming processes where more strongly...

  2. Struggling with Translations

    DEFF Research Database (Denmark)

    Obed Madsen, Søren

    This paper shows empirical how actors have difficulties with translating strategy texts. The paper uses four cases as different examples of what happens, and what might be difficult, when actors translate organizational texts. In order to explore this, it draws on a translation training method from...... translation theory. The study shows that for those who have produced the text, it is difficult to translate a strategy where they have to change the words so others who don’t understand the language in the text can understand it. It also shows that for those who haven’t been a part of the production, it very...... challenge the notion that actors understand all texts and that managers per se can translate a text....

  3. Translational physiology: from molecules to public health.

    Science.gov (United States)

    Seals, Douglas R

    2013-07-15

    The term 'translational research' was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by 'reverse translation' in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise.

  4. Translational ecology for hydrogeology.

    Science.gov (United States)

    Schlesinger, William H

    2013-01-01

    Translational ecology--a special discipline aimed to improve the accessibility of science to policy makers--will help hydrogeologists contribute to the solution of pressing environmental problems. Patterned after translational medicine, translational ecology is a partnership to ensure that the right science gets done in a timely fashion, so that it can be communicated to those who need it. © 2013, National Ground Water Association.

  5. The Metalanguage of Translation.

    Directory of Open Access Journals (Sweden)

    Mercedes Amanda Case

    2013-04-01

    The Metalanguage of Translation, sections of which contain materials originally published in volume nineteen of the international translation studies journal, Target (2007, presents a compilation of eleven position articles, written by eleven contributors who draw attention to the often diametric variations between the practice and conceptualization of translation studies and the language we use to describe it. This volume provides a multiplicity of metalinguistic topics covering everything from terminology and bibliography to epistemology and localization.

  6. Variational Neural Machine Translation

    OpenAIRE

    Zhang, Biao; Xiong, Deyi; Su, Jinsong; Duan, Hong; Zhang, Min

    2016-01-01

    Models of neural machine translation are often from a discriminative family of encoderdecoders that learn a conditional distribution of a target sentence given a source sentence. In this paper, we propose a variational model to learn this conditional distribution for neural machine translation: a variational encoderdecoder model that can be trained end-to-end. Different from the vanilla encoder-decoder model that generates target translations from hidden representations of source sentences al...

  7. Vajon in Translated Hungarian

    Directory of Open Access Journals (Sweden)

    Götz Andrea

    2016-12-01

    Full Text Available This paper presents an analysis of the structures the discourse marker vajon forms in translated Hungarian fiction. Although translation data has been deployed in the study of discourse markers (Aijmer & Simon- Vandenbergen, 2004, such studies do not account for translation-specific phenomena which can influence the data of their analysis. In addition, translated discourse markers could offer insights into the idiosyncratic properties of translated texts as well as the culturally defined norms of translation that guide the creation of target texts. The analysis presented in this paper extends the cross-linguistic approach beyond contrastive analysis with a detailed investigation of two corpora of translated texts in order to identify patterns which could be a sign of translation or genre norms impacting the target texts. As a result, a distinct, diverging pattern emerges between the two corpora: patterns of explicit polarity show a marked difference. However, further research is needed to clarify whether these are due to language, genre, or translation norms.

  8. Translation as cultural mediator

    Directory of Open Access Journals (Sweden)

    Roxana Petcu

    2009-01-01

    Full Text Available The aim of this paper is to analyze the role that translation plays as cultural mediator, as it already widely accepted that translation involves not just two languages, but two cultures, two worlds that are brought into close contact with each other. Obviously, between the two cultures, the two worlds that translation compares and contrasts there are both similarities and dissimilarities. What is of interest to us is the way in which dissimilarities should be approached in the process of translation, whether they should be domesticated or foreignized as Venuti put it, whether the reader should be brought closer to the text or the text closer to the reader.

  9. Translational research on advanced therapies

    Directory of Open Access Journals (Sweden)

    Filippo Belardelli

    2011-01-01

    Full Text Available Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

  10. Translational research on advanced therapies.

    Science.gov (United States)

    Belardelli, Filippo; Rizza, Paola; Moretti, Franca; Carella, Cintia; Galli, Maria Cristina; Migliaccio, Giovanni

    2011-01-01

    Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP) are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP) facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues) is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

  11. Defect in the GTPase activating protein (GAP) function of eIF5 causes repression of GCN4 translation.

    Science.gov (United States)

    Antony A, Charles; Alone, Pankaj V

    2017-05-13

    In eukaryotes, the eIF5 protein plays an important role in translation start site selection by providing the GAP (GTPase activating protein) function. However, in yeast translation initiation fidelity defective eIF5 G31R mutant causes preferential utilization of UUG as initiation codon and is termed as Suppressor of initiation codon (Sui - ) phenotype due to its hyper GTPase activity. The eIF5 G31R mutant dominantly represses GCN4 expression and confers sensitivity to 3-Amino-1,2,4-Trizole (3AT) induced starvation. The down-regulation of the GCN4 expression (Gcn - phenotype) in the eIF5 G31R mutant was not because of leaky scanning defects; rather was due to the utilization of upUUG initiation codons at the 5' regulatory region present between uORF1 and the main GCN4 ORF. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Translational Health Economics

    NARCIS (Netherlands)

    Rogowski, Wolf; John, Jürgen; IJzerman, Maarten Joost; Scheffler, Richard M.

    2016-01-01

    Translational health economics (THE) can be defined as the use of theoretical concepts and empirical methods in health economics to bridge the gap between the decision to fund and use a new health technology in clinical practice (the backend of translational medicine) and the decision to invest into

  13. Translating VDM to Alloy

    DEFF Research Database (Denmark)

    Lausdahl, Kenneth

    2013-01-01

    specifications. However, to take advantage of the automated analysis of Alloy, the model-oriented VDM specifications must be translated into a constraint-based Alloy specifications. We describe how a sub- set of VDM can be translated into Alloy and how assertions can be expressed in VDM and checked by the Alloy...

  14. Semantics via Machine Translation

    Science.gov (United States)

    Culhane, P. T.

    1977-01-01

    Recent experiments in machine translation have given the semantic elements of collocation in Russian more objective criteria. Soviet linguists in search of semantic relationships have attempted to devise a semantic synthesis for construction of a basic language for machine translation. One such effort is summarized. (CHK)

  15. Idioms and Back Translation

    Science.gov (United States)

    Griffin, Frank

    2004-01-01

    The challenges of intercultural communication are an integral part of many undergraduate business communication courses. Marketing gaffes clearly illustrate the pitfalls of translation and underscore the importance of a knowledge of the culture with which one is attempting to communicate. A good way to approach the topic of translation pitfalls in…

  16. Students' Differentiated Translation Processes

    Science.gov (United States)

    Bossé, Michael J.; Adu-Gyamfi, Kwaku; Chandler, Kayla

    2014-01-01

    Understanding how students translate between mathematical representations is of both practical and theoretical importance. This study examined students' processes in their generation of symbolic and graphic representations of given polynomial functions. The purpose was to investigate how students perform these translations. The result of the study…

  17. Staging Ethnographic Translation

    DEFF Research Database (Denmark)

    Lundberg, Pia

    2009-01-01

    Objectifying the cultural diversity of visual fieldmethods - and the analysis of balancing the cultural known and unknown through anthropological analysis (aided by the analytical concept translation (Edwin Ardener 1989))......Objectifying the cultural diversity of visual fieldmethods - and the analysis of balancing the cultural known and unknown through anthropological analysis (aided by the analytical concept translation (Edwin Ardener 1989))...

  18. Creativity, Culture and Translation

    Science.gov (United States)

    Babaee, Siamak; Wan Yahya, Wan Roselezam; Babaee, Ruzbeh

    2014-01-01

    Some scholars (Bassnett-McGuire, Catford, Brislin) suggest that a good piece of translation should be a strict reflection of the style of the original text while some others (Gui, Newmark, Wilss) consider the original text untranslatable unless it is reproduced. Opposing views by different critics suggest that translation is still a challenging…

  19. Translating the Folk.

    Science.gov (United States)

    Fletcher, Bryan

    2000-01-01

    This article looks at issues affecting Robert Garioch's translation into Scots of a sonnet from Giuseppe Gioachino Belli's Romaneschi collection. It begins with the discussion of a problem involved in writing in dialects with no settled written standard. This 'standardizing' poetry is then looked at in terms of translation and theories of the…

  20. Translation between cultures

    Directory of Open Access Journals (Sweden)

    Henrique de Oliveira Lee

    2016-05-01

    Full Text Available This article will question the pertinence of understanding interculturality in terms of translation between cultures. I shall study this hypothesis in two ways : 1 / the cosmopolitan horizon, which the idea of translation may implicate ; 2 / the critique of the premises of unique origin and homogeneity of cultures which this hypothesis makes possible.

  1. Sound Effects in Translation

    DEFF Research Database (Denmark)

    Mees, Inger M.; Dragsted, Barbara; Gorm Hansen, Inge

    2015-01-01

    On the basis of a pilot study using speech recognition (SR) software, this paper attempts to illustrate the benefits of adopting an interdisciplinary approach in translator training. It shows how the collaboration between phoneticians, translators and interpreters can (1) advance research, (2) ha...

  2. Parametrization of translational surfaces

    OpenAIRE

    Perez-Diaz, Sonia; Shen, Liyong

    2014-01-01

    The algebraic translational surface is a typical modeling surface in computer aided design and architecture industry. In this paper, we give a necessary and sufficient condition for that algebraic surface having a standard parametric representation and our proof is constructive. If the given algebraic surface is translational, then we can compute a standard parametric representation for the surface.

  3. Stimulating translational research

    DEFF Research Database (Denmark)

    Bentires-Alj, Mohamed; Rajan, Abinaya; van Harten, Wim

    2015-01-01

    Translational research leaves no-one indifferent and everyone expects a particular benefit. We as EU-LIFE (www.eu-life.eu), an alliance of 13 research institutes in European life sciences, would like to share our experience in an attempt to identify measures to promote translational research...

  4. Translation Ambiguity but Not Word Class Predicts Translation Performance

    Science.gov (United States)

    Prior, Anat; Kroll, Judith F.; Macwhinney, Brian

    2013-01-01

    We investigated the influence of word class and translation ambiguity on cross-linguistic representation and processing. Bilingual speakers of English and Spanish performed translation production and translation recognition tasks on nouns and verbs in both languages. Words either had a single translation or more than one translation. Translation…

  5. Examining English-German Translation Ambiguity Using Primed Translation Recognition

    Science.gov (United States)

    Eddington, Chelsea M.; Tokowicz, Natasha

    2013-01-01

    Many words have more than one translation across languages. Such "translation-ambiguous" words are translated more slowly and less accurately than their unambiguous counterparts. We examine the extent to which word context and translation dominance influence the processing of translation-ambiguous words. We further examine how these factors…

  6. Translation Commentary: A Happy Medium between Translation Curriculum and EAP

    Science.gov (United States)

    Shei, Chris C.-C.

    2005-01-01

    In this article, "Translation Commentary" refers to an English composition written by a learner of both English and translation, submitted together with his or her translation output. In an academic setting combining English-to-Chinese translation and English as a second language, this article deals with both the issue of translation and that of…

  7. Application of ground-truth for classification and quantification of bird movements on migratory bird habitat initiative sites in southwest Louisiana: final report

    Science.gov (United States)

    Barrow, Wylie C.; Baldwin, Michael J.; Randall, Lori A.; Pitre, John; Dudley, Kyle J.

    2013-01-01

    This project was initiated to assess migrating and wintering bird use of lands enrolled in the Natural Resources Conservation Service’s (NRCS) Migratory Bird Habitat Initiative (MBHI). The MBHI program was developed in response to the Deepwater Horizon oil spill in 2010, with the goal of improving/creating habitat for waterbirds affected by the spill. In collaboration with the University of Delaware (UDEL), we used weather surveillance radar data (Sieges 2014), portable marine radar data, thermal infrared images, and visual observations to assess bird use of MBHI easements. Migrating and wintering birds routinely make synchronous flights near dusk (e.g., departure during migration, feeding flights during winter). Weather radars readily detect birds at the onset of these flights and have proven to be useful remote sensing tools for assessing bird-habitat relations during migration and determining the response of wintering waterfowl to wetland restoration (e.g., Wetlands Reserve Program lands). However, ground-truthing is required to identify radar echoes to species or species group. We designed a field study to ground-truth a larger-scale, weather radar assessment of bird use of MBHI sites in southwest Louisiana. We examined seasonal bird use of MBHI fields in fall, winter, and spring of 2011-2012. To assess diurnal use, we conducted total area surveys of MBHI sites in the afternoon, collecting data on bird species composition, abundance, behavior, and habitat use. In the evenings, we quantified bird activity at the MBHI easements and described flight behavior (i.e., birds landing in, departing from, circling, or flying over the MBHI tract). Our field sampling captured the onset of evening flights and spanned the period of collection of the weather radar data analyzed. Pre- and post-dusk surveys were conducted using a portable radar system and a thermal infrared camera. Landbirds, shorebirds, and wading birds were commonly found on MBHI fields during diurnal

  8. Translational physiology: from molecules to public health

    Science.gov (United States)

    Seals, Douglas R

    2013-01-01

    The term ‘translational research’ was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by ‘reverse translation’ in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise. PMID:23732641

  9. Theory of Test Translation Error

    Science.gov (United States)

    Solano-Flores, Guillermo; Backhoff, Eduardo; Contreras-Nino, Luis Angel

    2009-01-01

    In this article, we present a theory of test translation whose intent is to provide the conceptual foundation for effective, systematic work in the process of test translation and test translation review. According to the theory, translation error is multidimensional; it is not simply the consequence of defective translation but an inevitable fact…

  10. Translational regulation in nutrigenomics.

    Science.gov (United States)

    Liu, Botao; Qian, Shu-Bing

    2011-11-01

    The emergence of genome-wide analysis to interrogate cellular DNA, RNA, and protein content has revolutionized the study of the control network that mediates cellular homeostasis. Nutrigenomics addresses the effect of nutrients on gene expression, which provides a basis for understanding the biological activity of dietary components. Translation of mRNAs represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular, under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are influenced by nutrient signaling. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during pathophysiological conditions by translation of selective mRNAs. Here we describe recent advances in our understanding of translational control, nutrient signaling, and their dysregulation in aging and cancer. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health.

  11. Translational Epidemiology in Psychiatry

    Science.gov (United States)

    Weissman, Myrna M.; Brown, Alan S.; Talati, Ardesheer

    2012-01-01

    Translational research generally refers to the application of knowledge generated by advances in basic sciences research translated into new approaches for diagnosis, prevention, and treatment of disease. This direction is called bench-to-bedside. Psychiatry has similarly emphasized the basic sciences as the starting point of translational research. This article introduces the term translational epidemiology for psychiatry research as a bidirectional concept in which the knowledge generated from the bedside or the population can also be translated to the benches of laboratory science. Epidemiologic studies are primarily observational but can generate representative samples, novel designs, and hypotheses that can be translated into more tractable experimental approaches in the clinical and basic sciences. This bedside-to-bench concept has not been explicated in psychiatry, although there are an increasing number of examples in the research literature. This article describes selected epidemiologic designs, providing examples and opportunities for translational research from community surveys and prospective, birth cohort, and family-based designs. Rapid developments in informatics, emphases on large sample collection for genetic and biomarker studies, and interest in personalized medicine—which requires information on relative and absolute risk factors—make this topic timely. The approach described has implications for providing fresh metaphors to communicate complex issues in interdisciplinary collaborations and for training in epidemiology and other sciences in psychiatry. PMID:21646577

  12. Exploring Translations Theories

    Directory of Open Access Journals (Sweden)

    Autor: Anthony Pym

    2016-09-01

    Full Text Available http://dx.doi.org/10.5007/2175-7968.2016v36n3p214 This work is a translation of the chapter “Descriptions – the intellectual background” serving as a complement to the chapter 5 of the book titled Exploring Translations Studies (2010 by Anthony Pym. The chapter outlines the relationship between Russian Formalism and some of the strands of the Translation Studies which emerged during the 19th century. It brings to the fore works done in Prague (Prague Circle, Bratislava, Leipzig, Holland and Flanders focusing specially on the Tel-Aviv School of Itamar-Even and Gideon Toury, the main forerunners of the Descriptive Translation Studies (DTS. By analyzing this academic context, not only it describes the type of approaches those theorists suggested, but it also discusses the ups and downs of such paradigms problematizing concepts like “translation shifts”, “assumed translations” and “norms”. This translation aims at presenting and sharing Pym’s work as clearly and fluid as the original is, so that it serves as both a historical reference and an introductory text to Translation Studies.

  13. Exploring Translations Theories

    Directory of Open Access Journals (Sweden)

    Anthony Pym

    2016-12-01

    Full Text Available This work is a translation of the chapter “Descriptions – the intellectual background” serving as a complement to the chapter 5 of the book titled Exploring Translations Studies (2010 by Anthony Pym. The chapter outlines the relationship between Russian Formalism and some of the strands of the Translation Studies which emerged during the 19th century. It brings to the fore works done in Prague (Prague Circle, Bratislava, Leipzig, Holland and Flanders focusing specially on the Tel-Aviv School of Itamar-Even and Gideon Toury, the main forerunners of the Descriptive Translation Studies (DTS. By analyzing this academic context, not only it describes the type of approaches those theorists suggested, but it also discusses the ups and downs of such paradigms problematizing concepts like “translation shifts”, “assumed translations” and “norms”. This translation aims at presenting and sharing Pym’s work as clearly and fluid as the original is, so that it serves as both a historical reference and an introductory text to Translation Studies.

  14. Notes toward a Latin American Translation Theory

    Directory of Open Access Journals (Sweden)

    Martín Gaspar

    2017-07-01

    resulting from the emergence of nation states, and describes its specificities through a comparison with the initial debate on modern Western translation theory carried out in Germany at the beginning of the 19th century. It then traces the subsequent diverse uses of translation as a procedure in the search for identity. Finally, it discusses the debate between Arguedas and Cortázar at the end of the 1960s, which reveals the tension underlying a Latin American theory of translation. On the basis of the debate and of history itself, the article concludes that one of the main roles of translation in Latin America has been to designate markers of foreignness as a cultural self-definition mechanism.

  15. The translation factors of Drosophila melanogaster.

    Science.gov (United States)

    Marygold, Steven J; Attrill, Helen; Lasko, Paul

    2017-01-02

    Synthesis of polypeptides from mRNA (translation) is a fundamental cellular process that is coordinated and catalyzed by a set of canonical 'translation factors'. Surprisingly, the translation factors of Drosophila melanogaster have not yet been systematically identified, leading to inconsistencies in their nomenclature and shortcomings in functional (Gene Ontology, GO) annotations. Here, we describe the complete set of translation factors in D. melanogaster, applying nomenclature already in widespread use in other species, and revising their functional annotation. The collection comprises 43 initiation factors, 12 elongation factors, 3 release factors and 6 recycling factors, totaling 64 of which 55 are cytoplasmic and 9 are mitochondrial. We also provide an overview of notable findings and particular insights derived from Drosophila about these factors. This catalog, together with the incorporation of the improved nomenclature and GO annotation into FlyBase, will greatly facilitate access to information about the functional roles of these important proteins.

  16. La Main à la pâte : an Internet Site for Teaching Science to ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La Main à la pâte (www.lamap.fr), a French initiative, is a vehicle that allows teachers to develop scientific content aimed at simplifying the teaching of sciences to primary schoolchildren. This project will allow Bibliotheca Alexandrina to translate the site from French into Arabic and adapt it for the Egyptian school curriculum.

  17. Pre-Feasibility Analysis of Pellet Manufacturing on the Former Loring Air Force Base Site. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Hunsberger, R.; Mosey, G.

    2014-04-01

    The U.S. Environmental Protection Agency (EPA) Office of Solid Waste and Emergency Response, in accordance with the RE-Powering America's Lands initiative, engaged the U.S. Department of Energy's (DOE) National Renewable Energy Laboratory (NREL) to conduct feasibility studies to assess the viability of developing renewable energy generating facilities on contaminated sites. This site, in Limestone, Maine -- formerly the location of the Loring Air Force Base but now owned by the Aroostook Band of Micmac -- was selected for the potential to produce heating pellets from woody feedstock. Biomass was chosen as the renewable energy resource to evaluate based on abundant woody-biomass resources available in the area. NREL also evaluates potential savings from converting existing Micmac property from oil-fired heating to pellet heating.

  18. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Chino Mine in Silver City, New Mexico. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Kiatreungwattana, K.; Geiger, J.; Healey, V.; Mosey, G.

    2013-04-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Chino Mine site in Silver City, New Mexico, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  19. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Tronox Facility in Savannah, Georgia. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Kiatreungwattana, K.; Geiger, J.; Healey, V.; Mosey, G.

    2013-03-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Tronox Facility site in Savannah, Georgia, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  20. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Peru Mill Industrial Park in the City of Deming, New Mexico. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Kiatreungwattana, K.; Geiger, J.; Healey, V.; Mosey, G.

    2013-04-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Peru Mill Industrial Park site in the City of Deming, New Mexico, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  1. Feasibility Study of Economics and Performance of Solar Photovoltaics at the Kolthoff Landfill in Cleveland, Ohio. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Salasovich, J.; Geiger, J.; Mosey, G.; Healey, V.

    2013-06-01

    The U.S. Environmental Protection Agency (EPA), Region 5, in accordance with the RE-Powering America's Land initiative, selected the Kolthoff Landfill site in Cleveland, Ohio, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) provided technical assistance for this project. The purpose of this report is to assess the site for a possible photovoltaic (PV) system installation and estimate the cost, performance, and site impacts of different PV options. In addition, the report recommends financing options that could assist in the implementation of a PV system at the site.

  2. Word Translation Entropy

    DEFF Research Database (Denmark)

    Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard

    2016-01-01

    language activation during source text reading in translation, i.e. co-activation of the two linguistic systems, employed late eye movement measures or reaction times. The current study therefore aims to investigate if and to what extent earlier eye movement measures in reading for translation show...... evidence of co-activation. Results show that the number of translation alternatives for a single word and differences between source and target text in terms of word order have an effect on very early and late eye movement measures. Results are interpreted in terms of semantic and structural cross...

  3. Word Translation Entropy

    DEFF Research Database (Denmark)

    Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard

    language activation during source text reading in translation, i.e. co-activation of the two linguistic systems, employed late eye movement measures or reaction times. The current study therefore aims to investigate if and to what extent earlier eye movement measures in reading for translation show...... evidence of co-activation. Results show that the number of translation alternatives for a single word and differences between source and target text in terms of word order have an effect on very early and late eye movement measures. Results are interpreted in terms of semantic and structural cross...

  4. Translation, Interpreting and Lexicography

    DEFF Research Database (Denmark)

    Dam, Helle Vrønning; Tarp, Sven

    2018-01-01

    Translation, interpreting and lexicography represent three separate areas of human activity, each of them with its own theories, models and methods and, hence, with its own disciplinary underpinnings. At the same time, all three disciplines are characterized by a marked interdisciplinary dimension...... in the sense that their practice fields are typically ‘about something else’. Translators may, for example, be called upon to translate medical texts, and interpreters may be assigned to work on medical speeches. Similarly, practical lexicography may produce medical dictionaries. In this perspective, the three...

  5. Perceived radial translation during centrifugation.

    NARCIS (Netherlands)

    Bos, J.E.; Correia Gracio, B.J.

    2015-01-01

    BACKGROUND: Linear acceleration generally gives rise to translation perception. Centripetal acceleration during centrifugation, however, has never been reported giving rise to a radial, inward translation perception. OBJECTIVE: To study whether centrifugation can induce a radial translation

  6. Perceived radial translation during centrifugation

    NARCIS (Netherlands)

    Bos, J.E.; Correia Grácio, B.J.

    2015-01-01

    BACKGROUND: Linear acceleration generally gives rise to translation perception. Centripetal acceleration during centrifugation, however, has never been reported giving rise to a radial, inward translation perception. OBJECTIVE: To study whether centrifugation can induce a radial translation

  7. Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress.

    Science.gov (United States)

    Tamarkin-Ben-Harush, Ana; Vasseur, Jean-Jacques; Debart, Françoise; Ulitsky, Igor; Dikstein, Rivka

    2017-02-08

    Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5'UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress.

  8. Wearable Language Translation

    National Research Council Canada - National Science Library

    Carroll, Wendell

    1999-01-01

    VIA Team Mission Statement: To develop a near real time, two way, mobile, lightweight, robust and low cost multi-lingual language translation device that can be operated with minimal training in a hands free manner...

  9. A phased translation function

    International Nuclear Information System (INIS)

    Read, R.J.; Schierbeek, A.J.

    1988-01-01

    A phased translation function, which takes advantage of prior phase information to determine the position of an oriented mulecular replacement model, is examined. The function is the coefficient of correlation between the electron density computed with the prior phases and the electron density of the translated model, evaluated in reciprocal space as a Fourier transform. The correlation coefficient used in this work is closely related to an overlap function devised by Colman, Fehlhammer and Bartels. Tests with two protein structures, one of which was solved with the help of the phased translation function, show that little phase information is required to resolve the translation problem, and that the function is relatively insensitive to misorientation of the model. (orig.)

  10. Translation and Creation

    Directory of Open Access Journals (Sweden)

    Paulo Bezerra

    2012-12-01

    Full Text Available The article begins with the differences betweenscientific and fictional translations, and focus on the second.The fictional translation works with meanings, opens itselfto the plurissignification in the purpose to create a similarity of the dissimilarity; in this process, the translator does nottranslate a language, but what a creative individuality makeswith a language. At last there is an approach to the knowledgeand skills necessaries to a translator of literature: theknowledge of the theories of the literature and of thetranslation, the capacity to preserve the national color ofthe original text and at the same time to respect the arrivallanguage, and the sensibility to his national languagevariations present in the daily and in the literary spheres.

  11. Translation for language purposes

    DEFF Research Database (Denmark)

    Schjoldager, Anne

    2003-01-01

    The paper describes the background, subjects, assumptions, procedure, and preliminary results of a small-scale experimental study of L2 translation (Danish into English) and picture verbalization in L2 (English)....

  12. Lost in Translation

    Science.gov (United States)

    Lass, Wiebke; Reusswig, Fritz

    2014-05-01

    Lost in Translation? Introducing Planetary Boundaries into Social Systems. Fritz Reusswig, Wiebke Lass Potsdam Institute for Climate Impact Research, Potsdam, Germany Identifying and quantifying planetary boundaries by interdisciplinary science efforts is a challenging task—and a risky one, as the 1972 Limits to Growth publication has shown. Even if we may be assured that scientific understanding of underlying processes of the Earth system has significantly improved since then, the challenge of translating these findings into the social systems of the planet remains crucial for any kind of action, and in many respects far more challenging. We would like to conceptualize what could also be termed a problem of coupling social and natural systems as a nested set of social translation processes, well aware of the limited applicability of the language-related translation metaphor. Societies must, first, perceive these boundaries, and they have to understand their relevance. This includes, among many other things, the organization of transdisciplinary scientific cooperation. They will then have to translate this understood perception into possible actions, i.e. strategies for different local bodies, actors, and institutional settings. This implies a lot of 'internal' translation processes, e.g. from the scientific subsystem to the mass media, the political and the economic subsystem. And it implies to develop subsystem-specific schemes of evaluation for these alternatives, e.g. convincing narratives, cost-benefit analyses, or ethical legitimacy considerations. And, finally, societies do have to translate chosen action alternatives into monitoring and evaluation schemes, e.g. for agricultural production or renewable energies. This process includes the continuation of observing and re-analyzing the planetary boundary concept itself, as a re-adjustment of these boundaries in the light of new scientific insights cannot be excluded. Taken all together, societies may well

  13. Lost in Translation

    DEFF Research Database (Denmark)

    Askehave, Inger; Zethsen, Karen Korning

    2011-01-01

    This article deals with an aspect of patient information that differs somewhat from the traditional scope of this journal; namely the linguistic and translational aspects of Patient Information Leaflets (PILs). During the past decade much work has been dedicated to making the English PILs...... as informative and lay-friendly as possible. However, much of the good work is ruined when the PIL is translated. Why is this so and what can be done about it?...

  14. Translational control of cyclins

    Directory of Open Access Journals (Sweden)

    Lai Ming-Chih

    2011-02-01

    Full Text Available Abstract Regulation of cyclin levels is important for many cell cycle-related processes and can occur at several different steps of gene expression. Translational regulation of cyclins, which occurs by a variety of regulatory mechanisms, permits a prompt response to signal transduction pathways induced by environmental stimuli. This review will summarize translational control of cyclins and its influence on cell cycle progression.

  15. Jungmann's translation of Paradise Lost

    OpenAIRE

    Janů, Karel

    2014-01-01

    This thesis examines Josef Jungmann's translation of John Milton's Paradise Lost. Josef Jungmann was one of the leading figures of the Czech National Revival and translated Milton 's poem between the years 1800 and 1804. The thesis covers Jungmann's theoretical model of translation and presents Jungmann's motives for translation of Milton's epic poem. The paper also describes the aims Jungmann had with his translation and whether he has achieved them. The reception Jungmann's translation rece...

  16. Translating Alcohol Research

    Science.gov (United States)

    Batman, Angela M.; Miles, Michael F.

    2015-01-01

    Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of streamlining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD. PMID:26259085

  17. Splicing of goose parvovirus pre-mRNA influences cytoplasmic translation of the processed mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Li, Long; Pintel, David J., E-mail: pinteld@missouri.edu

    2012-04-25

    Translation of goose parvovirus (GPV) 72 kDa Rep 1 is initiated from unspliced P9-generated mRNAs in ORF1 from the first in-frame AUG (537 AUG); however, this AUG is bypassed in spliced P9-generated RNA: translation of the 52 kDa Rep 2 protein from spliced RNA is initiated in ORF2 at the next AUG downstream (650 AUG). Usage of the 537 AUG was restored in spliced RNA when the GPV intron was replaced with a chimeric SV40 intron, or following specific mutations of the GPV intron which did not appear in the final spliced mRNA. Additionally, 650 AUG usage was gained in unspliced RNA when the GPV intron splice sites were debilitated. Splicing-dependent regulation of translation initiation was mediated in cis by GPV RNA surrounding the target AUGs. Thus, nuclear RNA processing of GPV P9-generated pre-mRNAs has a complex, but significant, effect on alternative translation initiation of the GPV Rep proteins.

  18. Training Translators for the Market in Turkey: What Should We Teach to Future Translators?

    Directory of Open Access Journals (Sweden)

    Volga Yılmaz Gümüş

    2017-01-01

    Full Text Available This study investigates the position of the translation market in translator-training and curriculum-design practices in Turkey from the perspective of various stakeholders, mainly the graduates of translator-training programs at the undergraduate level. The role of the market in curricular design and education practices in higher education has been at the core of discussions in education, specifically for disciplines that have a vocational aspect. The discussions are mostly based on theoretical grounds. This study derives from the need for empirical research on what the market expects from translators and how training programs meet these expectations. This study first presents data from a survey and interviews with graduates of translator-training programs, as this group of stakeholders is familiar with both training and market practices (supposing that they are employed professionally on the market after graduation. The initial findings obtained from the graduates were supported with interview findings from other stakeholders. The point of departure in this study was that translator training and the translation market – as two parties to translation service provision – should be in close interaction in order to improve the quality of training in higher-education institutions and the quality of translations on the market. In the present study, almost all the stakeholders agreed that there is a need for greater interaction between training and the market, and that the elements that prepare students for the market should find a place in the translation curricula. However, the results suggest that there is a need to handle the efforts to solve the problems related to training and the profession with the involvement of various stakeholders in a more systematized way. Furthermore, it is desirable to integrate market-training elements into training practices rather than offer them only in individual courses – including translation technologies

  19. Revisiting Translation Strategies and Techniques

    Directory of Open Access Journals (Sweden)

    Ngoran Constantine Tardzenyuy

    2016-10-01

    Full Text Available Many translation researchers, scholars and students or trainees have the tendency to use the terms ‘translation strategy’,’ translation technique’  ‘translation method’ and ‘translation procedure’ invariably, and sometimes with varying shades of meaning This paper attempts to define, distinguish and clarify these terms in a bid to give the study of translation the scientific basis it deserves, given that scientific terminology is bound to be clear and unequivocal. Employing the qualitative research method and secondary or documentary sources, the paper provides elaborate explanations of the terms using sourced and invented examples. The paper concludes that the term ‘translation strategy’ should be used strictly to refer to a global or general decision a translator takes before engaging  in the translation of any text. Such a general decision could concern the issue of whether the translation would be literal, foreignized or source-text oriented; or whether it would be free, oblique, domesticated or target-text-oriented. On the other hand, the paper conclusively contends that all the other terms, that is to say, ‘translation technique, ‘translation procedure’ and ‘translation method’ should be used to refer to tools or operational measures deployed   by the translator in the course of actual translation. In other words, they should be used as mechanisms for effecting general or globalizing translation strategies. Keywords: Translation, Strategy, Translation, Technique, Foreignization, Domestication.

  20. Challenges in legal translation - revisited

    Directory of Open Access Journals (Sweden)

    Ingrid Simonnæs

    2013-12-01

    Full Text Available The aim of this paper is to discuss challenges in legal translation from the view of a teacher who evaluates the work of semi-professional translators in a special setting. Recurrent translation errors may subsequently be used as a pedagogical resource in specialised translator training. The observation of recurrent challenges confronting the candidates in legal translation and the absence of formal translator training programs are the reasons why NHH now offers an on-line course in legal translation, JurDist, focusing i.a. on useful translation strategies.

  1. Emergency Medicine Resources Within the Clinical Translational Science Institutes: A Cross-sectional Study.

    Science.gov (United States)

    Meurer, William J; Quinn, James; Lindsell, Christopher; Schneider, Sandra; Newgard, Craig D

    2016-06-01

    The Clinical and Translational Science Award (CTSA) program aims to strengthen and support translational research by accelerating the process of translating laboratory discoveries into treatments for patients, training a new generation of clinical and translational researchers, and engaging communities in clinical research efforts. Yet, little is known about how emergency care researchers have interacted with and utilized the resources of academic institutions with CTSAs. The purpose of this survey was to describe how emergency care researchers use local CTSA resources, to ascertain what proportion of CTSA consortium members have active emergency care research (ECR) programs, and to solicit participation in a national CTSA-associated emergency care translational research network. This study was a survey of all emergency departments affiliated with a CTSA. Of the 65 CTSA consortium members, three had no ECR program and we obtained responses from 46 of the remaining 62 (74% response rate). The interactions with and resources used by emergency care researchers varied widely. Methodology and biostatistics support was most frequently accessed (77%), followed closely by education and training programs (60%). Several ECR programs (76%) had submitted for funding through CTSAs, with 71% receiving awards. Most CTSA consortium members had an active ECR infrastructure: 21 (46%) had 24/7 availability to recruit and screen for research, and 21 (46%) had less than 24/7 research recruitment. A number of emergency care research programs participated in National Institutes of Health research networks with the Neurological Emergencies Treatment Trials network most highly represented with 23 (59%) sites. Most ECR programs (96%) were interested in participating in a CTSA-based emergency care translational research network. Despite little initial involvement in development of the CTSA program, there has been moderate interaction between CTSAs and emergency care. There is considerable

  2. Demonstration of the Air Force Site Characterization and Analysis Penetrometer System (AFSCAPS) at Plattsburgh AFB in Support of Bioventing and Natural Attenuation Initiatives

    National Research Council Canada - National Science Library

    Gildea, Martin

    1993-01-01

    Applied Research Associates, Inc. and Dakota Technologies, Inc. are under contract to develop an improved laser induced fluorescence cone penetrometer tool for the Air Force Site Characterization Analysis Penetrometer System (AFSCAPS...

  3. Comparative studies on sequence characteristics around translation ...

    Indian Academy of Sciences (India)

    Unknown

    To minimise sampling errors, the redundant sequences were excluded, as were sequences: (1) that had incorrect initia- tion and termination codons, and (2) in which .... In human genes, the preference for the optimal nucleo- tide of the mammalian translation initiation AUG context. (GCCGCC(A/G)CCAUGG) was generally ...

  4. Eukaryotic translation initiation factor 3 (eIF3) and eIF2 can promote mRNA binding to 40S subunits independently of eIF4G in yeast

    Czech Academy of Sciences Publication Activity Database

    Jivotovskaya, A.; Valášek, Leoš; Hinnebusch, A. G.; Nielsen, K. H.

    2006-01-01

    Roč. 26, č. 4 (2006), s. 1372-1355 ISSN 0270-7306 Institutional research plan: CEZ:AV0Z50200510 Keywords : eIF2 * yeast * initiation Subject RIV: EE - Microbiology, Virology Impact factor: 6.773, year: 2006

  5. The Effect of Translators' Emotional Intelligence on Their Translation Quality

    Science.gov (United States)

    Varzande, Mohsen; Jadidi, Esmaeil

    2015-01-01

    Translators differ from each other in many ways in terms of their knowledge, professional and psychological conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' Emotional Intelligence on their translation quality. Following a "causal-comparative study," a sample of…

  6. The Impact of Translators' Academic Experience on Their Translation Quality

    Science.gov (United States)

    Varzande, Mohsen; Jadidi, Esmaeil

    2015-01-01

    Translators differ from each other in many ways in terms of their knowledge and professional conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' academic experience on their translation quality. Following a "causal-comparative study", a sample of 100 male and…

  7. Translation and cultural adaptation of the Aguado Syntax Test (AST) into Brazilian Portuguese.

    Science.gov (United States)

    Baggio, Gustavo Inheta; Hage, Simone Rocha de Vasconcellos

    2017-12-07

    To perform the translation and cultural adaptation of the Aguado Syntax Test (AST) into Brazilian Portuguese considering the linguistic and cultural reality of the language. The AST assesses the early morphosyntactic development in children aged 3 to 7 in terms of understanding and expression of various types of structures such as sentences, pronouns, verbal voices, comparisons, prepositions and verbal desinence as to number, mode and tense. The process of translation and cultural adaptation followed four steps: 1) preparation of two translations; 2) synthesis of consensual translations; 3) backtranslation; and 4) verification of equivalence between the initial translations and backtranslations that resulted in the final translated version. The whole process of translation and cultural adaptation revealed the presence of equivalence and reconciliation of the translated items and an almost complete semantic equivalence between the two translations and the absence of consistent translation difficulties. The AST was translated and culturally adapted into Brazilian Portuguese, constituting the first step towards validation and standardization of the test.

  8. Feasibility Study of Economics and Performance of a Hydroelectric Installation at the Jeddo Mine Drainage Tunnel. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, J. O.; Mosey, G.

    2013-02-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Jeddo Tunnel discharge site for a feasibility study of renewable energy potential. The purpose of this report is to assess technical and economic viability of the site for hydroelectric and geothermal energy production. In addition, the report outlines financing options that could assist in the implementation of a system.

  9. Feasibility Study of Economics and Performance of Biopower at the Chanute Air Force Base in Rantoul, Illinois. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Scarlata, C.; Mosey, G.

    2013-05-01

    The U.S. Environmental Protection Agency (EPA), in accordance with the RE-Powering America's Land initiative, selected the Former Chanute Air Force Base site in Rantoul, Illinois, for a feasibility study of renewable energy production. The National Renewable Energy Laboratory (NREL) was contacted to provide technical assistance for this project. The purpose of this study was to assess the site for a possible biopower system installation and estimate the cost, performance, and impacts of different biopower options.

  10. Translation in cell-free systems

    International Nuclear Information System (INIS)

    Jagus, R.

    1987-01-01

    The simplest, unambiguous identification of a particular mRNA is the identification of its protein product. This can be established by translation of the mRNA of interest in a cell-free protein-synthesizing system. Messenger RNA protein product identification is important in the isolation of a particular mRNA species for cDNA cloning and in the identification of positive cDNA clones. The two high-activity translation systems in common use are those prepared from rabbit reticulocytes and from wheat germ. Both systems are easy to prepare, and both are available commercially. Each has advantages and disadvantages over the other and a choice between the two will depend on the type of mRNAs to be translated, the prejudices of experience, and availability. The main disadvantage of the reticulocyte system is that it requires removal of endogenous mRNA. However, this is a relatively simple procedure. The wheat germ system does not require removal of endogenous mRNA and may translate weakly initiating mRNAs more efficiently. However, ionic optima for translation in the wheat germ system are more sensitive to the nature and concentration of mRNA and may need to be determined for each template. The biggest problem with the use of the wheat germ system is its tendency to produce incomplete translation products due to premature termination

  11. Effective knowledge management in translational medicine

    Directory of Open Access Journals (Sweden)

    Khasanova Tatiana

    2010-07-01

    Full Text Available Abstract Background The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA in the US and the Seventh Framework Programme (FP7 of EU with emphasis on translating research for human health. Methods The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern. Results The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface. Conclusions The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.

  12. Effective knowledge management in translational medicine.

    Science.gov (United States)

    Szalma, Sándor; Koka, Venkata; Khasanova, Tatiana; Perakslis, Eric D

    2010-07-19

    The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA) in the US and the Seventh Framework Programme (FP7) of EU with emphasis on translating research for human health. The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern. The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface. The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.

  13. Translation as Genesis

    Directory of Open Access Journals (Sweden)

    Joel Gilberthorpe

    2015-05-01

    Full Text Available Translation of literature is generally understood as a copy of an original. As such, it finds itself compared negatively to the original; judged and found lacking either the style or meaning of the original text it was seeking to translate. However, this paper will explore the relationship between the text and its translation through the work of Jacques Derrida and his neologisms such as the supplement and différance in addition to the work of Walter Benjamin. Through understanding the translation as a supplement, this paper will explore whether the original text was complete in and of itself. Through this and Derrida’s understanding of the play of language, I argue that translation can be understood as the palingenesis of literature, as it is only through translation that literature is reborn and lives on. Moreover, this paper will conclude with an examination of Blanchot’s distinction between the Book and the book in order to argue that literature is in itself a form of translation. Thus, the relationship between translation and literature is one of a cycle of genesis and palingenesis, as translation finds itself at both the beginning and continual rebirth of literature. La traduzione letteraria viene generalmente intesa come la copia di un originale. In quanto tale essa viene considerata negativamente in rapporto a quest’ultimo, giudicata manchevole quanto a stile o contenuto rispetto al testo originale che cerca di tradurre. Questo articolo intende esaminare la relazione tra il testo e la sua traduzione attraverso l’opera di Jacques Derrida e i suoi neologismi, come supplemento e différance, e sulla scorta degli studi di Walter Benjamin. Considerando la traduzione come un supplemento, l’articolo indaga se l’originale sia completo in e di per se stesso. Attraverso questo concetto e la prospettiva di Derrida sul gioco del linguaggio, la tesi sostenuta è che la traduzione possa essere considerata come palingenesi della

  14. Machine Translation-Assisted Language Learning: Writing for Beginners

    Science.gov (United States)

    Garcia, Ignacio; Pena, Maria Isabel

    2011-01-01

    The few studies that deal with machine translation (MT) as a language learning tool focus on its use by advanced learners, never by beginners. Yet, freely available MT engines (i.e. Google Translate) and MT-related web initiatives (i.e. Gabble-on.com) position themselves to cater precisely to the needs of learners with a limited command of a…

  15. The translator and the nature of his work | Ekpenyong | Global ...

    African Journals Online (AJOL)

    Translation – the art and science of converting the source language (SL) message into the target language (TL) – has the translator in charge of its operations, taking cognisance of the various ways adopted in the process. From the initial reading of a given text, to its interpretation, one begins to appreciate the task before ...

  16. On Interactive Teaching Model of Translation Course Based on Wechat

    Science.gov (United States)

    Lin, Wang

    2017-01-01

    Constructivism is a theory related to knowledge and learning, focusing on learners' subjective initiative, based on which the interactive approach has been proved to play a crucial role in language learning. Accordingly, the interactive approach can also be applied to translation teaching since translation itself is a bilingual transformational…

  17. Annual variation in polychlorinated biphenyl (PCB) exposure in tree swallow (Tachycineta bicolor) eggs and nestlings at Great Lakes Restoration Initiative (GLRI) study sites

    Science.gov (United States)

    Custer, Christine M.; Custer, Thomas W.; Dummer, Paul; Goldberg, Diana R.; Franson, J. Christian

    2018-01-01

    Tree swallow (Tachycineta bicolor) eggs and nestlings were collected from 16 sites across the Great Lakes to quantify normal annual variation in total polychlorinated biphenyl (PCB) exposure and to validate the sample size choice in earlier work. A sample size of five eggs or five nestlings per site was adequate to quantify exposure to PCBs in tree swallows given the current exposure levels and variation. There was no difference in PCB exposure in two randomly selected sets of five eggs collected in the same year, but analyzed in different years. Additionally, there was only modest annual variation in exposure, with between 69% (nestlings) and 73% (eggs) of sites having no differences between years. There was a tendency, both statistically and qualitatively, for there to be less exposure in the second year compared to the first year.

  18. Lessons (not) learned from mistakes about translation.

    Science.gov (United States)

    Kozak, Marilyn

    2007-11-15

    Some popular ideas about translational regulation in eukaryotes have been recognized recently as mistakes. One example is the rejection of a long-standing idea about involvement of S6 kinase in translation of ribosomal proteins. Unfortunately, new proposals about how S6 kinase might regulate translation are based on evidence that is no better than the old. Recent findings have also forced rejection of some popular ideas about the function of sequences at the 3' end of viral mRNAs and rejection of some ideas about internal ribosome entry sequences (IRESs). One long-held belief was that tissue-specific translation via an IRES underlies the neurotropism of poliovirus and the attenuation of Sabin vaccine strains. Older experiments that appeared to support this belief and recent experiments that refute it are discussed. The hypothesis that dyskeratosis congenita is caused by a defect in IRES-mediated translation is probably another mistaken idea. The supporting evidence, such as it is, comes from a mouse model of the disease and is contradicted by studies carried out with cells from affected patients. The growing use of IRESs as tools to study other questions about translation is discussed and lamented. The inefficient function of IRESs (if they are IRESs) promotes misunderstandings. I explain again why it is not valid to invoke a special mechanism of initiation based on the finding that edeine (at very low concentrations) does not inhibit the translation of a putative IRES from cricket paralysis virus. I explain why new assays, devised to rule out splicing in tests with dicistronic vectors, are not valid and why experiments with IRESs are not a good way to investigate the mechanism whereby microRNAs inhibit translation.

  19. Translation: Elements of a Craft.

    Science.gov (United States)

    Heiderson, Mazin A.

    An overview of the skills, techniques, tools, and compensation of language translators and interpreters is offered. It begins with a definition of translation and a brief history of translation in the western world. Basic principles of translation dating back to Roman writers are also outlined. A five-step process in producing a good translation…

  20. [A new change in studies of ophthalmology: translational medicine-from basic to clinic].

    Science.gov (United States)

    Liu, Xiao; Tang, Luo-sheng

    2009-03-01

    Translational medicine is a new concept in the field of international medicine that aims to reduce barriers and build relationships between clinical and basic research, and to translate scientific knowledge and research production into practical applications. Recently, the developments in the study of translational medicine in many fields have been reported abroad. However, the development of translational medicine is in the initial stage in China. A turning point will be brought to ophthalmic research by improving the development of translational research. This review introduces the concept and development of translational medicine as well as the recent advances in the studies of translational medicine in ophthalmology.