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Sample records for optimal translation initiation

  1. 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.

  2. Universally conserved translation initiation factors.

    Science.gov (United States)

    Kyrpides, N C; Woese, C R

    1998-01-06

    The process by which translation is initiated has long been considered similar in Bacteria and Eukarya but accomplished by a different unrelated set of factors in the two cases. This not only implies separate evolutionary histories for the two but also implies that at the universal ancestor stage, a translation initiation mechanism either did not exist or was of a different nature than the extant processes. We demonstrate herein that (i) the "analogous" translation initiation factors IF-1 and eIF-1A are actually related in sequence, (ii) the "eukaryotic" translation factor SUI1 is universal in distribution, and (iii) the eukaryotic/archaeal translation factor eIF-5A is homologous to the bacterial translation factor EF-P. Thus, the rudiments of translation initiation would seem to have been present in the universal ancestor stage. However, significant development and refinement subsequently occurred independently on both the bacterial lineage and on the archaeal/eukaryotic line.

  3. TRII: A Probabilistic Scoring of Drosophila melanogaster Translation Initiation Sites

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    Rice Michael D

    2010-01-01

    Full Text Available Relative individual information is a measurement that scores the quality of DNA- and RNA-binding sites for biological machines. The development of analytical approaches to increase the power of this scoring method will improve its utility in evaluating the functions of motifs. In this study, the scoring method was applied to potential translation initiation sites in Drosophila to compute Translation Relative Individual Information (TRII scores. The weight matrix at the core of the scoring method was optimized based on high-confidence translation initiation sites identified by using a progressive partitioning approach. Comparing the distributions of TRII scores for sites of interest with those for high-confidence translation initiation sites and random sequences provides a new methodology for assessing the quality of translation initiation sites. The optimized weight matrices can also be used to describe the consensus at translation initiation sites, providing a quantitative measure of preferred and avoided nucleotides at each position.

  4. New universal rules of eukaryotic translation initiation fidelity.

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    Hadas Zur

    Full Text Available The accepted model of eukaryotic translation initiation begins with the scanning of the transcript by the pre-initiation complex from the 5'end until an ATG codon with a specific nucleotide (nt context surrounding it is recognized (Kozak rule. According to this model, ATG codons upstream to the beginning of the ORF should affect translation. We perform for the first time, a genome-wide statistical analysis, uncovering a new, more comprehensive and quantitative, set of initiation rules for improving the cost of translation and its efficiency. Analyzing dozens of eukaryotic genomes, we find that in all frames there is a universal trend of selection for low numbers of ATG codons; specifically, 16-27 codons upstream, but also 5-11 codons downstream of the START ATG, include less ATG codons than expected. We further suggest that there is selection for anti optimal ATG contexts in the vicinity of the START ATG. Thus, the efficiency and fidelity of translation initiation is encoded in the 5'UTR as required by the scanning model, but also at the beginning of the ORF. The observed nt patterns suggest that in all the analyzed organisms the pre-initiation complex often misses the START ATG of the ORF, and may start translation from an alternative initiation start-site. Thus, to prevent the translation of undesired proteins, there is selection for nucleotide sequences with low affinity to the pre-initiation complex near the beginning of the ORF. With the new suggested rules we were able to obtain a twice higher correlation with ribosomal density and protein levels in comparison to the Kozak rule alone (e.g. for protein levels r=0.7 vs. r=0.31; p<10(-12.

  5. Architecture of human translation initiation factor 3.

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

    2013-06-04

    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.

  6. Influence of Translation Initiation on Organellar Protein Targeting in Arabidopsis

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    Sally A. Mackenzie

    2011-04-18

    A primary focus of the Mackenzie laboratory is the elucidation of processes and machinery for mitochondrial genome maintenance and transmission in higher plants. We have found that numerous organellar DNA maintenance components in plants appear to be dual targeted to mitochondria and plastids. Of particular interest was the observation that some twin (tandemly arrayed) dual targeting presequences appeared to utilize non-AUG alternative translation initiation, allowing for multiple translation starts at a single gene. Two aspects of this phenomenon were of particular interest: (1) Alternative translation initiation might provide a mechanism to regulate protein targeting temporally and spatially, a possibility that had not been demonstrated previously, and (2) alternative translation initiation might occur in genes involved in nuclear-controlled mitochondrial genome recombination, thought to be exclusively mitochondrial in their function. During the course of this research, we pursued three aims, with an emphasis on two specific genes of interest: POLgamma2, an organellar DNA polymerase, and MSH1, a MutS homolog thought to participate in mitochondrial, but not plastid, genome recombination surveillance. Our aims were to (1) Identify additional genes within Arabidopsis and other genomes that employ non-AUG alternative translation initiation, (2) Locate sequences upstream to the annotated AUG that confer alternative non-AUG translation initiation activity, and (3) Identify cis and trans factors that influence start site selection in genes with non-AUG starts. Toward these ends, we have shown that non-AUG initiation occurs in a number of genes, likely influencing targeting behavior of the protein. We have also shown that start site selection is strongly influenced by Kozak consensus sequence environment, indicating that alternative translation initiation in plants occurs by relaxation of ribosome scanning.

  7. 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

  8. Regulation of Translation Initiation under Biotic and Abiotic Stresses

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    Ana B. Castro-Sanz

    2013-02-01

    Full Text Available Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response. In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery. Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation. In others, the mechanisms leading to the control of translation are viral- or stress-specific. In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants. In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations.

  9. 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

    2014-04-01

    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.

  10. [Role of eukaryotic translation initiation factor 4G in tumor].

    Science.gov (United States)

    Zhang, Si; Huang, Nan; Pan, Xia; Zang, Jing-Lei; Guan, Xin-Xin; Zhang, Jian-Hua; Liu, Liu-Cheng; Lei, Xiao-Yong

    2016-04-25

    Eukaryotic translation initiation factor 4G (eIF4G) is a scaffold component of eukaryotic translation initiation factor 4F (eIF4F) complex, which takes principal part in the initiating of protein synthesis. Both two subtypes (eIF4G1 and eIF4G2) of eIF4G were found to be closely related with various tumors. The eIF4G1 expression is significantly up-regulated in breast cancer, cervical cancer, nasopharyngeal carcinoma, lung squamous cell carcinoma, prostatic carcinoma and other malignant tumors, compared with those in adjacent tissues; and the eIF4G2 is obviously over-expressed in diffuse large B cell lymphoma and acute myeloid leukemia, but low-expressed in bladder transitional cell carcinoma. This paper reviews the progress in the study of the role of eIF4G in tumor genesis, development, diagnosis and prognosis.

  11. Empirical Investigation of Optimization Algorithms in Neural Machine Translation

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    Bahar Parnia

    2017-06-01

    Full Text Available Training neural networks is a non-convex and a high-dimensional optimization problem. In this paper, we provide a comparative study of the most popular stochastic optimization techniques used to train neural networks. We evaluate the methods in terms of convergence speed, translation quality, and training stability. In addition, we investigate combinations that seek to improve optimization in terms of these aspects. We train state-of-the-art attention-based models and apply them to perform neural machine translation. We demonstrate our results on two tasks: WMT 2016 En→Ro and WMT 2015 De→En.

  12. Knowledge Translation Interventions to Improve the Timing of Dialysis Initiation

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    Chau, Elaine M. T.; Manns, Braden J.; Garg, Amit X.; Sood, Manish M.; Kim, S. Joseph; Naimark, David; Nesrallah, Gihad E.; Soroka, Steven D.; Beaulieu, Monica; Dixon, Stephanie; Alam, Ahsan; Tangri, Navdeep

    2016-01-01

    Background: Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney function) has risen rapidly in the past 2 decades in Canada and internationally, despite absence of established health benefits and higher costs. In 2014, a Canadian guideline on the timing of dialysis initiation, recommending an intent-to-defer approach, was published. Objective: The objective of this study is to evaluate the efficacy and safety of a knowledge translation intervention to promote the intent-to-defer approach in clinical practice. Design: This study is a multicenter, 2-arm parallel, cluster randomized trial. Setting: The study involves 55 advanced chronic kidney disease clinics across Canada. Patients: Patients older than 18 years who are managed by nephrologists for more than 3 months, and initiate dialysis in the follow-up period are included in the study. Measurements: Outcomes will be measured at the patient-level and enumerated within a cluster. Data on characteristics of each dialysis start will be determined by linkages with the Canadian Organ Replacement Register. Primary outcomes include the proportion of patients who start dialysis early with an estimated glomerular filtration rate greater than 10.5 mL/min/1.73 m2 and start dialysis in hospital as inpatients or in an emergency room setting. Secondary outcomes include the rate of change in early dialysis starts; rates of hospitalizations, deaths, and cost of predialysis care (wherever available); quarterly proportion of new starts; and acceptability of the knowledge translation materials. Methods: We randomized 55 multidisciplinary chronic disease clinics (clusters) in Canada to receive either an active knowledge translation intervention or no intervention for the uptake of the guideline on the timing of dialysis initiation. The active knowledge translation intervention consists of audit and feedback as well as patient- and provider-directed educational tools delivered at a comprehensive in

  13. Conflict between translation initiation and elongation in vertebrate mitochondrial genomes.

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    Xuhua Xia

    Full Text Available The strand-biased mutation spectrum in vertebrate mitochondrial genomes results in an AC-rich L-strand and a GT-rich H-strand. Because the L-strand is the sense strand of 12 protein-coding genes out of the 13, the third codon position is overall strongly AC-biased. The wobble site of the anticodon of the 22 mitochondrial tRNAs is either U or G to pair with the most abundant synonymous codon, with only one exception. The wobble site of Met-tRNA is C instead of U, forming the Watson-Crick match with AUG instead of AUA, the latter being much more frequent than the former. This has been attributed to a compromise between translation initiation and elongation; i.e., AUG is not only a methionine codon, but also an initiation codon, and an anticodon matching AUG will increase the initiation rate. However, such an anticodon would impose selection against the use of AUA codons because AUA needs to be wobble-translated. According to this translation conflict hypothesis, AUA should be used relatively less frequently compared to UUA in the UUR codon family. A comprehensive analysis of mitochondrial genomes from a variety of vertebrate species revealed a general deficiency of AUA codons relative to UUA codons. In contrast, urochordate mitochondrial genomes with two tRNA(Met genes with CAU and UAU anticodons exhibit increased AUA codon usage. Furthermore, six bivalve mitochondrial genomes with both of their tRNA-Met genes with a CAU anticodon have reduced AUA usage relative to three other bivalve mitochondrial genomes with one of their two tRNA-Met genes having a CAU anticodon and the other having a UAU anticodon. We conclude that the translation conflict hypothesis is empirically supported, and our results highlight the fine details of selection in shaping molecular evolution.

  14. A genome-wide survey of alternative translational initiation events in Homo sapiens

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Alternative translational initiation is an important mechanism to increase the diversity of gene products. Although some of alternative translational initiation events have been reported, such information remains anecdotal and does not allow for any generalizations. The number of the known alternative translational initiation genes is so few that we know little about its mechanism. There is a great demand to discover more alternative translational initiation genes. However, it is arduously time-consuming to discover novel alternative translational initiation genes by the experimental method. Therefore we systematically analyzed protein sequences available in public database and predicted 1237 protein clusters as potential alternative translational initiation events. We concluded that about 8%—10% of human genes have alternative translational initiation sites. The results significantly increased the number of alternative translation initiation events and indicated that alternative translation initiation is an important and general regulation mechanism in the cellular process.

  15. A genome-wide survey of alternative translational initiation events in Homo sapiens

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jing; CAI Jun; LI YanDa

    2007-01-01

    Alternative translational initiation is an important mechanism to increase the diversity of gene products.Although some of alternative translational initiation events have been reported, such information remains anecdotal and does not allow for any generalizations. The number of the known alternative translational initiation genes is so few that we know little about its mechanism. There is a great demand to discover more alternative translational initiation genes. However, it is arduously time-consuming to discover novel alternative translational initiation genes by the experimental method. Therefore we systematically analyzed protein sequences available in public database and predicted 1237 protein clusters as potential alternative translational initiation events. We concluded that about 8%-10% of human genes have alternative translational initiation sites. The results significantly increased the number of alternative translation initiation events and indicated that alternative translation initiation is an important and general regulation mechanism in the cellular process.

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

    DEFF Research Database (Denmark)

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

    recombination into Bacterial Artificial Chromosomes (BAC) clones, containing the full-length Paderborn sequence under the transcriptional control of a T7 promoter and a selection marker in place of the IRES. RNA transcripts were produced in vitro and electroporated into porcine PK15 cells. Rescued mutant...... viruses were obtained after one cell culture passage from constructs with more than 75 % translation efficiency compared to the wildtype IRES. cDNA was generated from these clones and sequenced to verify the maintenance of the changes in the IRES. These results show that full-length viable mutant viruses......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...

  17. 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

    in vitro and electroporated into porcine PK15 cells. Rescued mutant viruses were obtained from RNAs that contained mutations within domain IIIf which retained more than 75% of wt translation efficiency. Sequencing of cDNA generated from these rescued viruses verified the maintenance of the introduced......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...... amplified and inserted into dicistronic reporter plasmids encoding Fluc and Rluc under the control of a T7 promoter. The mutations were within domains II, IIId1 and IIIf of the IRES. The plasmids were transfected into BHK cells infected with the recombinant vaccinia virus, vTF7-3, which expresses the T7 RNA...

  18. Data Center Optimization Initiative Strategic Plans

    Data.gov (United States)

    Social Security Administration — On August 1, 2016, the Office of Management and Budget issued memorandum M-16-19, establishing the Data Center Optimization Initiative (DCOI). The DCOI, as described...

  19. Maximizing protein translation rate in the non-homogeneous ribosome flow model: a convex optimization approach.

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    Poker, Gilad; Zarai, Yoram; Margaliot, Michael; Tuller, Tamir

    2014-11-06

    Translation is an important stage in gene expression. During this stage, macro-molecules called ribosomes travel along the mRNA strand linking amino acids together in a specific order to create a functioning protein. An important question, related to many biomedical disciplines, is how to maximize protein production. Indeed, translation is known to be one of the most energy-consuming processes in the cell, and it is natural to assume that evolution shaped this process so that it maximizes the protein production rate. If this is indeed so then one can estimate various parameters of the translation machinery by solving an appropriate mathematical optimization problem. The same problem also arises in the context of synthetic biology, namely, re-engineer heterologous genes in order to maximize their translation rate in a host organism. We consider the problem of maximizing the protein production rate using a computational model for translation-elongation called the ribosome flow model (RFM). This model describes the flow of the ribosomes along an mRNA chain of length n using a set of n first-order nonlinear ordinary differential equations. It also includes n + 1 positive parameters: the ribosomal initiation rate into the mRNA chain, and n elongation rates along the chain sites. We show that the steady-state translation rate in the RFM is a strictly concave function of its parameters. This means that the problem of maximizing the translation rate under a suitable constraint always admits a unique solution, and that this solution can be determined using highly efficient algorithms for solving convex optimization problems even for large values of n. Furthermore, our analysis shows that the optimal translation rate can be computed based only on the optimal initiation rate and the elongation rate of the codons near the beginning of the ORF. We discuss some applications of the theoretical results to synthetic biology, molecular evolution, and functional genomics.

  20. The Innovative Medicines Initiative moves translational immunology forward.

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    Goldman, Michel; Wittelsberger, Angela; De Magistris, Maria-Teresa

    2013-02-01

    The Innovative Medicines Initiative (IMI) was established in 2008 as a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations with the mission to promote the development of novel therapies through collaborative efforts based on the concept of pre-competitive research. Several consortia supported by IMI are dedicated to immuno-inflammatory disorders, immune-based biopharmaceuticals and vaccines. Herein, we present the key principles underlying IMI, briefly review the status of projects related to translational immunology, and present future topics of interest to immunologists.

  1. Efficient translation initiation dictates codon usage at gene start

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    Bentele, Kajetan; Saffert, Paul; Rauscher, Robert; Ignatova, Zoya; Blüthgen, Nils

    2013-01-01

    The genetic code is degenerate; thus, protein evolution does not uniquely determine the coding sequence. One of the puzzles in evolutionary genetics is therefore to uncover evolutionary driving forces that result in specific codon choice. In many bacteria, the first 5–10 codons of protein-coding genes are often codons that are less frequently used in the rest of the genome, an effect that has been argued to arise from selection for slowed early elongation to reduce ribosome traffic jams. However, genome analysis across many species has demonstrated that the region shows reduced mRNA folding consistent with pressure for efficient translation initiation. This raises the possibility that unusual codon usage is a side effect of selection for reduced mRNA structure. Here we discriminate between these two competing hypotheses, and show that in bacteria selection favours codons that reduce mRNA folding around the translation start, regardless of whether these codons are frequent or rare. Experiments confirm that primarily mRNA structure, and not codon usage, at the beginning of genes determines the translation rate. PMID:23774758

  2. Geometry optimization made simple with translation and rotation coordinates

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    Wang, Lee-Ping; Song, Chenchen

    2016-06-01

    The effective description of molecular geometry is important for theoretical studies of intermolecular interactions. Here we introduce a new translation-rotation-internal coordinate (TRIC) system which explicitly includes the collective translations and rotations of molecules, or parts of molecules such as monomers or ligands, as degrees of freedom. The translations are described as the centroid position and the orientations are represented with the exponential map parameterization of quaternions. When TRIC is incorporated into geometry optimization calculations, the performance is consistently superior to existing coordinate systems for a diverse set of systems including water clusters, organic semiconductor donor-acceptor complexes, and small proteins, all of which are characterized by nontrivial intermolecular interactions. The method also introduces a new way to scan the molecular orientations while allowing orthogonal degrees of freedom to relax. Our findings indicate that an explicit description of molecular translation and rotation is a natural way to traverse the many-dimensional potential energy surface.

  3. Prodigal: prokaryotic gene recognition and translation initiation site identification

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    Land Miriam L

    2010-03-01

    Full Text Available Abstract Background The quality of automated gene prediction in microbial organisms has improved steadily over the past decade, but there is still room for improvement. Increasing the number of correct identifications, both of genes and of the translation initiation sites for each gene, and reducing the overall number of false positives, are all desirable goals. Results With our years of experience in manually curating genomes for the Joint Genome Institute, we developed a new gene prediction algorithm called Prodigal (PROkaryotic DYnamic programming Gene-finding ALgorithm. With Prodigal, we focused specifically on the three goals of improved gene structure prediction, improved translation initiation site recognition, and reduced false positives. We compared the results of Prodigal to existing gene-finding methods to demonstrate that it met each of these objectives. Conclusion We built a fast, lightweight, open source gene prediction program called Prodigal http://compbio.ornl.gov/prodigal/. Prodigal achieved good results compared to existing methods, and we believe it will be a valuable asset to automated microbial annotation pipelines.

  4. Optimization of translation profiles enhances protein expression and solubility.

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    Hess, Anne-Katrin; Saffert, Paul; Liebeton, Klaus; Ignatova, Zoya

    2015-01-01

    mRNA is translated with a non-uniform speed that actively coordinates co-translational folding of protein domains. Using structure-based homology we identified the structural domains in epoxide hydrolases (EHs) and introduced slow-translating codons to delineate the translation of single domains. These changes in translation speed dramatically improved the solubility of two EHs of metagenomic origin in Escherichia coli. Conversely, the importance of transient attenuation for the folding, and consequently solubility, of EH was evidenced with a member of the EH family from Agrobacterium radiobacter, which partitions in the soluble fraction when expressed in E. coli. Synonymous substitutions of codons shaping the slow-transiting regions to fast-translating codons render this protein insoluble. Furthermore, we show that low protein yield can be enhanced by decreasing the free folding energy of the initial 5'-coding region, which can disrupt mRNA secondary structure and enhance ribosomal loading. This study provides direct experimental evidence that mRNA is not a mere messenger for translation of codons into amino acids but bears an additional layer of information for folding, solubility and expression level of the encoded protein. Furthermore, it provides a general frame on how to modulate and fine-tune gene expression of a target protein.

  5. Optimization of translation profiles enhances protein expression and solubility.

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    Anne-Katrin Hess

    Full Text Available mRNA is translated with a non-uniform speed that actively coordinates co-translational folding of protein domains. Using structure-based homology we identified the structural domains in epoxide hydrolases (EHs and introduced slow-translating codons to delineate the translation of single domains. These changes in translation speed dramatically improved the solubility of two EHs of metagenomic origin in Escherichia coli. Conversely, the importance of transient attenuation for the folding, and consequently solubility, of EH was evidenced with a member of the EH family from Agrobacterium radiobacter, which partitions in the soluble fraction when expressed in E. coli. Synonymous substitutions of codons shaping the slow-transiting regions to fast-translating codons render this protein insoluble. Furthermore, we show that low protein yield can be enhanced by decreasing the free folding energy of the initial 5'-coding region, which can disrupt mRNA secondary structure and enhance ribosomal loading. This study provides direct experimental evidence that mRNA is not a mere messenger for translation of codons into amino acids but bears an additional layer of information for folding, solubility and expression level of the encoded protein. Furthermore, it provides a general frame on how to modulate and fine-tune gene expression of a target protein.

  6. Archaeal translation initiation revisited: the initiation factor 2 and eukaryotic initiation factor 2B alpha-beta-delta subunit families

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    Kyrpides, N. C.; Woese, C. R.

    1998-01-01

    As the amount of available sequence data increases, it becomes apparent that our understanding of translation initiation is far from comprehensive and that prior conclusions concerning the origin of the process are wrong. Contrary to earlier conclusions, key elements of translation initiation originated at the Universal Ancestor stage, for homologous counterparts exist in all three primary taxa. Herein, we explore the evolutionary relationships among the components of bacterial initiation factor 2 (IF-2) and eukaryotic IF-2 (eIF-2)/eIF-2B, i.e., the initiation factors involved in introducing the initiator tRNA into the translation mechanism and performing the first step in the peptide chain elongation cycle. All Archaea appear to posses a fully functional eIF-2 molecule, but they lack the associated GTP recycling function, eIF-2B (a five-subunit molecule). Yet, the Archaea do posses members of the gene family defined by the (related) eIF-2B subunits alpha, beta, and delta, although these are not specifically related to any of the three eukaryotic subunits. Additional members of this family also occur in some (but by no means all) Bacteria and even in some eukaryotes. The functional significance of the other members of this family is unclear and requires experimental resolution. Similarly, the occurrence of bacterial IF-2-like molecules in all Archaea and in some eukaryotes further complicates the picture of translation initiation. Overall, these data lend further support to the suggestion that the rudiments of translation initiation were present at the Universal Ancestor stage.

  7. Gene and translation initiation site prediction in metagenomic sequences

    Energy Technology Data Exchange (ETDEWEB)

    Hyatt, Philip Douglas [ORNL; LoCascio, Philip F [ORNL; Hauser, Loren John [ORNL; Uberbacher, Edward C [ORNL

    2012-01-01

    Gene prediction in metagenomic sequences remains a difficult problem. Current sequencing technologies do not achieve sufficient coverage to assemble the individual genomes in a typical sample; consequently, sequencing runs produce a large number of short sequences whose exact origin is unknown. Since these sequences are usually smaller than the average length of a gene, algorithms must make predictions based on very little data. We present MetaProdigal, a metagenomic version of the gene prediction program Prodigal, that can identify genes in short, anonymous coding sequences with a high degree of accuracy. The novel value of the method consists of enhanced translation initiation site identification, ability to identify sequences that use alternate genetic codes and confidence values for each gene call. We compare the results of MetaProdigal with other methods and conclude with a discussion of future improvements.

  8. 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.

  9. Optimization of speed and accuracy of decoding in translation.

    Science.gov (United States)

    Wohlgemuth, Ingo; Pohl, Corinna; Rodnina, Marina V

    2010-11-03

    The speed and accuracy of protein synthesis are fundamental parameters for understanding the fitness of living cells, the quality control of translation, and the evolution of ribosomes. In this study, we analyse the speed and accuracy of the decoding step under conditions reproducing the high speed of translation in vivo. We show that error frequency is close to 10⁻³, consistent with the values measured in vivo. Selectivity is predominantly due to the differences in k(cat) values for cognate and near-cognate reactions, whereas the intrinsic affinity differences are not used for tRNA discrimination. Thus, the ribosome seems to be optimized towards high speed of translation at the cost of fidelity. Competition with near- and non-cognate ternary complexes reduces the rate of GTP hydrolysis in the cognate ternary complex, but does not appreciably affect the rate-limiting tRNA accommodation step. The GTP hydrolysis step is crucial for the optimization of both the speed and accuracy, which explains the necessity for the trade-off between the two fundamental parameters of translation.

  10. The nucleotide-binding site of bacterial translation initiation factor 2 (IF2) as a metabolic sensor

    NARCIS (Netherlands)

    Milon, P.; Tischenko, E.V.; Tomsic, J.; Caserta, E.; Folkers, G.E.; La Teana, A.; Rodnina, M.V.; Pon, C.L.; Boelens, R.; Gualerzi, C.O.

    2006-01-01

    Translational initiation factor 2 (IF2) is a guanine nucleotide-binding protein that can bind guanosine 3′,5′-(bis) diphosphate (ppGpp), an alarmone involved in stringent response in bacteria. In cells growing under optimal conditions, the GTP concentration is very high, and that of ppGpp very low.

  11. Targeted codon optimization improves translational fidelity for an Fc fusion protein.

    Science.gov (United States)

    Hutterer, Katariina M; Zhang, Zhongqi; Michaels, Mark Leo; Belouski, Ed; Hong, Robert W; Shah, Bhavana; Berge, Mark; Barkhordarian, Hedieh; Le, Eleanor; Smith, Steve; Winters, Dwight; Abroson, Frank; Hecht, Randy; Liu, Jennifer

    2012-11-01

    High levels of translational errors, both truncation and misincorporation in an Fc-fusion protein were observed. Here, we demonstrate the impact of several commercially available codon optimization services, and compare to a targeted strategy. Using the targeted strategy, only codons known to have translational errors are modified. For an Fc-fusion protein expressed in Escherichia coli, the targeted strategy, in combination with appropriate fermentation conditions, virtually eliminated misincorporation (proteins produced with a wrong amino acid sequence), and reduced the level of truncation. The use of full optimization using commercially available strategies reduced the initial errors, but introduced different misincorporations. However, truncation was higher using the targeted strategy than for most of the full optimization strategies. This targeted approach, along with monitoring of translation fidelity and careful attention to fermentation conditions is key to minimizing translational error and ensuring high-quality expression. These findings should be useful for other biopharmaceutical products, as well as any other transgenic constructs where protein quality is important.

  12. Mapping codon usage of the translation initiation region in porcine reproductive and respiratory syndrome virus genome

    Directory of Open Access Journals (Sweden)

    Dou Yong-xi

    2011-10-01

    Full Text Available Abstract Background Porcine reproductive and respitatory syndrome virus (PRRSV is a recently emerged pathogen and severely affects swine populations worldwide. The replication of PRRSV is tightly controlled by viral gene expression and the codon usage of translation initiation region within each gene could potentially regulate the translation rate. Therefore, a better understanding of the codon usage pattern of the initiation translation region would shed light on the regulation of PRRSV gene expression. Results In this study, the codon usage in the translation initiation region and in the whole coding sequence was compared in PRRSV ORF1a and ORFs2-7. To investigate the potential role of codon usage in affecting the translation initiation rate, we established a codon usage model for PRRSV translation initiation region. We observed that some non-preferential codons are preferentially used in the translation initiation region in particular ORFs. Although some positions vary with codons, they intend to use codons with negative CUB. Furthermore, our model of codon usage showed that the conserved pattern of CUB is not directly consensus with the conserved sequence, but shaped under the translation selection. Conclusions The non-variation pattern with negative CUB in the PRRSV translation initiation region scanned by ribosomes is considered the rate-limiting step in the translation process.

  13. Optimal Down Regulation of mRNA Translation

    Science.gov (United States)

    Zarai, Yoram; Margaliot, Michael; Tuller, Tamir

    2017-01-01

    Down regulation of mRNA translation is an important problem in various bio-medical domains ranging from developing effective medicines for tumors and for viral diseases to developing attenuated virus strains that can be used for vaccination. Here, we study the problem of down regulation of mRNA translation using a mathematical model called the ribosome flow model (RFM). In the RFM, the mRNA molecule is modeled as a chain of n sites. The flow of ribosomes between consecutive sites is regulated by n + 1 transition rates. Given a set of feasible transition rates, that models the outcome of all possible mutations, we consider the problem of maximally down regulating protein production by altering the rates within this set of feasible rates. Under certain conditions on the feasible set, we show that an optimal solution can be determined efficiently. We also rigorously analyze two special cases of the down regulation optimization problem. Our results suggest that one must focus on the position along the mRNA molecule where the transition rate has the strongest effect on the protein production rate. However, this rate is not necessarily the slowest transition rate along the mRNA molecule. We discuss some of the biological implications of these results.

  14. Optimizing clinical environments for knowledge translation: strategies for nursing leaders.

    Science.gov (United States)

    Scott, Shannon D; VandenBeld, Brenda; Cummings, Greta G

    2011-10-01

    Using findings from our recent study that found that a context of uncertainty in the work environment hindered nurses' research utilization, we suggest strategies for nurse managers and leaders to optimize clinical environments and support efforts to put research into clinical practice (knowledge translation). Two important sources of uncertainty were the complexity of teamwork and inconsistency in management and leadership styles. To reduce the uncertainty arising from teamwork, we propose (a) clarifying nurses' scopes of practice, (b) increasing knowledge sharing through supporting journal clubs and enhanced computer access and (c) creating safe venues for multidisciplinary dialogue. To reduce uncertainty arising from variations in management and leadership, we propose (a) developing policies that enhance the consistency of leadership and clarify the strategic direction of the management team, (b) clearly communicating those policies to nurses and (c) providing explicit rationales for treatment changes. Small, incremental steps can be taken to realize substantive changes in clinical environments in order to optimize nursing work environments for knowledge translation.

  15. Optimal Down Regulation of mRNA Translation

    Science.gov (United States)

    Zarai, Yoram; Margaliot, Michael; Tuller, Tamir

    2017-01-01

    Down regulation of mRNA translation is an important problem in various bio-medical domains ranging from developing effective medicines for tumors and for viral diseases to developing attenuated virus strains that can be used for vaccination. Here, we study the problem of down regulation of mRNA translation using a mathematical model called the ribosome flow model (RFM). In the RFM, the mRNA molecule is modeled as a chain of n sites. The flow of ribosomes between consecutive sites is regulated by n + 1 transition rates. Given a set of feasible transition rates, that models the outcome of all possible mutations, we consider the problem of maximally down regulating protein production by altering the rates within this set of feasible rates. Under certain conditions on the feasible set, we show that an optimal solution can be determined efficiently. We also rigorously analyze two special cases of the down regulation optimization problem. Our results suggest that one must focus on the position along the mRNA molecule where the transition rate has the strongest effect on the protein production rate. However, this rate is not necessarily the slowest transition rate along the mRNA molecule. We discuss some of the biological implications of these results. PMID:28120903

  16. Dengue Virus Utilizes a Novel Strategy for Translation Initiation When Cap-Dependent Translation Is Inhibited

    OpenAIRE

    Edgil, Dianna; Polacek, Charlotta; Harris, Eva

    2006-01-01

    Viruses have developed numerous mechanisms to usurp the host cell translation apparatus. Dengue virus (DEN) and other flaviviruses, such as West Nile and yellow fever viruses, contain a 5′ m7GpppN-capped positive-sense RNA genome with a nonpolyadenylated 3′ untranslated region (UTR) that has been presumed to undergo translation in a cap-dependent manner. However, the means by which the DEN genome is translated effectively in the presence of capped, polyadenylated cellular mRNAs is unknown. Th...

  17. Ctk1 function is necessary for full translation initiation activity in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Coordes, Britta; Brünger, Katharina M; Burger, Kaspar

    2015-01-01

    Translation is a fundamental and highly regulated cellular process. Previously, we reported that the kinase and transcription elongation factor Ctk1 increases fidelity during translation elongation in Saccharomyces cerevisiae. Here, we show that loss of Ctk1 function also affects the initiation...... step of translation. Translation active extracts from Ctk1 depleted cells show impaired translation activity of capped, but not CrPV IRES containing mRNA reporters. Furthermore, the formation of 80S initiation complexes is decreased, which is probably due to reduced subunit joining. In addition, we...... determined the changes in the phosphorylation pattern of a ribosome enriched fraction after depletion of Ctk1. Thus, we provide a catalogue of phosphoproteomic changes dependent on Ctk1. Taken together, our data suggest a stimulatory function of Ctk1 in 80S formation during translation initiation....

  18. Ctk1 Function Is Necessary for Full Translation Initiation Activity in Saccharomyces cerevisiae

    Science.gov (United States)

    Coordes, Britta; Brünger, Katharina M.; Burger, Kaspar; Soufi, Boumediene; Horenk, Juliane; Eick, Dirk; Olsen, Jesper V.

    2014-01-01

    Translation is a fundamental and highly regulated cellular process. Previously, we reported that the kinase and transcription elongation factor Ctk1 increases fidelity during translation elongation in Saccharomyces cerevisiae. Here, we show that loss of Ctk1 function also affects the initiation step of translation. Translation active extracts from Ctk1-depleted cells show impaired translation activity of capped mRNA, but not mRNA reporters containing the cricket paralysis virus (CrPV) internal ribosome entry site (IRES). Furthermore, the formation of 80S initiation complexes is decreased, which is probably due to reduced subunit joining. In addition, we determined the changes in the phosphorylation pattern of a ribosome enriched fraction after depletion of Ctk1. Thus, we provide a catalogue of phosphoproteomic changes dependent on Ctk1. Taken together, our data suggest a stimulatory function of Ctk1 in 80S formation during translation initiation. PMID:25416238

  19. The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs.

    OpenAIRE

    Kaufman, R J; Davies, M V; Pathak, V K; Hershey, J W

    1989-01-01

    Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha) by the double-stranded RNA-activated inhibitor (DAI) kinase correlates with inhibition of translation initiation. The importance of eIF-2 alpha phosphorylation in regulating translation was studied by expression of specific mutants of eIF-2 alpha in COS-1 cells. DNA transfection of certain plasmids could activate DAI kinase and result in poor translation of plasmid-derived mRNAs. In these cases,...

  20. Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia

    Science.gov (United States)

    Licursi, Maria; Carmona-Martinez, Ricardo A.; Razavi, Seyd; Hirasawa, Kensuke

    2015-01-01

    Internal ribosome entry site (IRES)-mediated translation is an essential replication step for certain viruses. As IRES-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral IRES-mediated translation initiation by using bicistronic reporter constructs containing an IRES element of encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV), hepatitis C virus (HCV), human rhinovirus (HRV) or poliovirus (PV). Under mild hypothermic conditions (30 and 35°C), we observed increases in the efficiency of translation initiation by HCV and HRV IRES elements compared to translation initiation at 37°C. The promotion of HRV IRES activity was observed as early as 2 hours after exposure to mild hypothermia. We also confirmed the promotion of translation initiation by HRV IRES under mild hypothermia in multiple cell lines. The expression levels and locations of polypyrimidine tract-binding protein (PTB) and upstream of N-Ras (unr), the IRES trans-acting factors (ITAFs) of HCV and HRV IRES elements, were not modulated by the temperature shift from 37°C to 30°C. Taken together, this study demonstrates that efficiency of translation initiation by some viral IRES elements is temperature dependent. PMID:25951166

  1. Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia.

    Directory of Open Access Journals (Sweden)

    Maria Licursi

    Full Text Available Internal ribosome entry site (IRES-mediated translation is an essential replication step for certain viruses. As IRES-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral IRES-mediated translation initiation by using bicistronic reporter constructs containing an IRES element of encephalomyocarditis virus (EMCV, foot-and-mouth disease virus (FMDV, hepatitis C virus (HCV, human rhinovirus (HRV or poliovirus (PV. Under mild hypothermic conditions (30 and 35°C, we observed increases in the efficiency of translation initiation by HCV and HRV IRES elements compared to translation initiation at 37°C. The promotion of HRV IRES activity was observed as early as 2 hours after exposure to mild hypothermia. We also confirmed the promotion of translation initiation by HRV IRES under mild hypothermia in multiple cell lines. The expression levels and locations of polypyrimidine tract-binding protein (PTB and upstream of N-Ras (unr, the IRES trans-acting factors (ITAFs of HCV and HRV IRES elements, were not modulated by the temperature shift from 37°C to 30°C. Taken together, this study demonstrates that efficiency of translation initiation by some viral IRES elements is temperature dependent.

  2. 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.

  3. Deciphering the Translational Determinants of Prostate Cancer Initiation and Progression

    Science.gov (United States)

    2012-07-01

    reverse 59-GAGGTTTGTGCTTGTCTGGC-39; rpS19 forward 59-GCTGGCCAAACATAAAGAGC-39, reverse 59-CTGGGTCTGAC ACCGTTTCT-39; 5S rRNA forward 59...agarose gel to visualize 18S and 28S rRNA . Fractions 7–13 were found to correspond to the polysome fractions and were used for further qPCR analysis. [35S...of select mRNAs 40S 60S Global changes in translation (eg. Control of rRNA synthesis by TIF-1A and UBF) ATG AAA ATG AAA 4EBP S6K1/2 Complex Figure

  4. Optimizing cell sourcing for clinical translation of tissue engineered ears.

    Science.gov (United States)

    Morrison, Kerry A; Cohen, Benjamin P; Asanbe, Ope; Dong, Xue; Harper, Alice; Bonassar, Lawrence J; Spector, Jason A

    2016-12-05

    Background . Currently, the major impediment to clinical translation of our previously described platform for the fabrication of high fidelity, patient-specific tissue engineered ears is the development of a clinically optimal cell sourcing strategy. A limited autologous auricular chondrocyte (AuC) supply in conjunction with rapid chondrocyte de-differentiation during in vitro expansion currently makes clinical translation more challenging. Mesenchymal stem cells (MSCs) offer significant promise due to their inherent chondrogenic potential, and large availability through minimally invasive procedures. Herein, we demonstrate the promise of AuC/MSC co-culture to fabricate elastic cartilage using 50% fewer AuC than standard approaches. Bovine auricular chondrocytes (bAuC) and bovine MSC (bMSC) were encapsulated within 10 mg ml(-1) type I collagen hydrogels in ratios of bAuC:bMSC 100:0, 50:50, and 0:100 at a density of 25 million cells ml(-1) hydrogel. One mm thick collagen sheet gels were fabricated, and thereafter, 8 mm diameter discs were extracted using a biopsy punch. Discs were implanted subcutaneously in the dorsa of nude mice (NU/NU) and harvested after 1 and 3 months. Gross analysis of explanted discs revealed bAuC:bMSC co-culture discs maintained their size and shape, and exhibited native auricular cartilage-like elasticity after 1 and 3 months of implantation. Co-culture discs developed into auricular cartilage, with viable chondrocytes within lacunae, copious proteoglycan and elastic fiber deposition, and a distinct perichondrial layer. Biochemical analysis confirmed that co-culture discs deposited critical cartilage molecular components more readily than did both bAuC and bMSC discs after 1 and 3 months, and proteoglycan content significantly increased between 1 and 3 months. We have successfully demonstrated an innovative cell sourcing strategy that facilitates our efforts to achieve clinical translation of our high fidelity, patient-specific ears for

  5. 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

  6. 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.

  7. NMR studies of the GTP/GDP binding domain of translation initiation factor IF2

    NARCIS (Netherlands)

    Tishchenko, Evgeny Vladimirovich

    2005-01-01

    Translation Initiation Factor 2 (IF2) plays an important role in the initiation stage of bacterial protein biosynthesis. This protein binds both fMet-tRNA and 30S ribosomal subunit in the presence of GTP, and it stimulates the formation of the 70S initiation complex. The NMR samples of the 15N-, 15N

  8. THE MECHANISM OF EUKARYOTIC TRANSLATION INITIATION AND PRINCIPLES OF ITS REGULATION

    OpenAIRE

    2010-01-01

    Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control over gene expression. Progress over recent years in determining the structures and activities of initiation factors, and in mapping their interactions within ribosomal initiation complexes, has significantly advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation f...

  9. Internal Initiation of Translation of mRNA in the Methylotrophic Yeast Hansenula polymorpha.

    Science.gov (United States)

    Mardanova, E S; Beletsky, A V; Ravin, N V

    2016-05-01

    Besides regular cap-dependent translation of mRNA, eukaryotes exploit internal initiation of translation driven by internal ribosome entry sites (IRESs). It is supposed that internal initiation provides translation of cellular mRNAs under stress conditions where the cap-dependent initiation is reduced. A number of IRESs have been characterized in mammalian mRNAs, but only a few examples are known in lower eukaryotes, particularly in yeasts. Here we identified two IRESs in the thermotolerant methylotrophic yeast Hansenula polymorpha DL-1. These sites are located in 5'-untranslated regions of genes HPODL_02249 and HPODL_04025 encoding a hypothetical membrane protein and actin-binding protein, respectively. In Saccharomyces cerevisiae cells, both IRESs drive expression of a second gene of a bicistronic mRNA, as well as translation of hairpin-containing monocistronic mRNA. The possibility of spurious splicing or presence of a cryptic promoter in the IRES sequences was ruled out, indicating that expression of a second gene of a bicistronic mRNA was IRES-dependent. We evaluated IRES activity of both elements and found that under normal physiological conditions its contribution to the overall translation of the respective mRNAs in yeast cells is about 0.3-0.4%. Therefore, these results suggest that the IRES-dependent translation initiation mechanism exists in Hansenula polymorpha.

  10. Ribosome collisions and Translation efficiency: Optimization by codon usage and mRNA destabilization

    DEFF Research Database (Denmark)

    Mitarai, Namiko; Sneppen, Kim; Pedersen, Steen

    2008-01-01

    Individual mRNAs are translated by multiple ribosomes that initiate translation with an interval of a few seconds. The ribosome speed is codon dependent, and ribosome queuing has been suggested to explain specific data for translation of some mRNAs in vivo. By modeling the stochastic translation...... process as a traffic problem, we here analyze conditions and consequences of collisions and queuing. The model allowed us to determine the on-rate (0.8 to 1.1 initiations/s) and the time (1 s) the preceding ribosome occludes initiation for Escherichia coli lacZ mRNA in vivo. We find that ribosome...... collisions and queues are inevitable consequences of a stochastic translation mechanism that reduce the translation efficiency substantially on natural mRNAs. The cells minimize collisions by having its mRNAs being unstable and by a highly selected codon usage in the start of the mRNA. The cost of m...

  11. The distribution of synonymous codon choice in the translation initiation region of dengue virus.

    Directory of Open Access Journals (Sweden)

    Jian-hua Zhou

    Full Text Available Dengue is the most common arthropod-borne viral (Arboviral illness in humans. The genetic features concerning the codon usage of dengue virus (DENV were analyzed by the relative synonymous codon usage, the effective number of codons and the codon adaptation index. The evolutionary distance between DENV and the natural hosts (Homo sapiens, Pan troglodytes, Aedes albopictus and Aedes aegypti was estimated by a novel formula. Finally, the synonymous codon usage preference for the translation initiation region of this virus was also analyzed. The result indicates that the general trend of the 59 synonymous codon usage of the four genotypes of DENV are similar to each other, and this pattern has no link with the geographic distribution of the virus. The effect of codon usage pattern of Aedes albopictus and Aedes aegypti on the formation of codon usage of DENV is stronger than that of the two primates. Turning to the codon usage preference of the translation initiation region of this virus, some codons pairing to low tRNA copy numbers in the two primates have a stronger tendency to exist in the translation initiation region than those in the open reading frame of DENV. Although DENV, like other RNA viruses, has a high mutation to adapt its hosts, the regulatory features about the synonymous codon usage have been 'branded' on the translation initiation region of this virus in order to hijack the translational mechanisms of the hosts.

  12. Dual-acting riboswitch control of translation initiation and mRNA decay.

    Science.gov (United States)

    Caron, Marie-Pier; Bastet, Laurène; Lussier, Antony; Simoneau-Roy, Maxime; Massé, Eric; Lafontaine, Daniel A

    2012-12-11

    Riboswitches are mRNA regulatory elements that control gene expression by altering their structure in response to specific metabolite binding. In bacteria, riboswitches consist of an aptamer that performs ligand recognition and an expression platform that regulates either transcription termination or translation initiation. Here, we describe a dual-acting riboswitch from Escherichia coli that, in addition to modulating translation initiation, also is directly involved in the control of initial mRNA decay. Upon lysine binding, the lysC riboswitch adopts a conformation that not only inhibits translation initiation but also exposes RNase E cleavage sites located in the riboswitch expression platform. However, in the absence of lysine, the riboswitch folds into an alternative conformation that simultaneously allows translation initiation and sequesters RNase E cleavage sites. Both regulatory activities can be individually inhibited, indicating that translation initiation and mRNA decay can be modulated independently using the same conformational switch. Because RNase E cleavage sites are located in the riboswitch sequence, this riboswitch provides a unique means for the riboswitch to modulate RNase E cleavage activity directly as a function of lysine. This dual inhibition is in contrast to other riboswitches, such as the thiamin pyrophosphate-sensing thiM riboswitch, which triggers mRNA decay only as a consequence of translation inhibition. The riboswitch control of RNase E cleavage activity is an example of a mechanism by which metabolite sensing is used to regulate gene expression of single genes or even large polycistronic mRNAs as a function of environmental changes.

  13. Stability of optimal-wave-front-sample coupling under sample translation and rotation

    CERN Document Server

    Anderson, Benjamin R; Eilers, Hergen

    2015-01-01

    The method of wavefront shaping to control optical properties of opaque media is a promising technique for authentication applications. One of the main challenges of this technique is the sensitivity of the wavefront-sample coupling to translation and/or rotation. To better understand how translation and rotation affect the wavefront- sample coupling we perform experiments in which we first optimize reflection from an opaque surface--to obtain an optimal wavefront--and then translate or rotate the surface and measure the new reflected intensity pattern. By using the correlation between the optimized and translated or rotated patterns we determine how sensitive the wavefront-sample coupling is. These experiments are performed for different spatial-light-modulator (SLM) bin sizes, beam-spot sizes, and nanoparticle concentrations. We find that all three parameters affect the different positional changes, implying that an optimization scheme can be used to maximize the stability of the wavefront-sample coupling. ...

  14. Initialization and Optimation of Deformable Models

    DEFF Research Database (Denmark)

    Jensen, Rune Fisker; Carstensen, Jens Michael; Madsen, Kaj

    1999-01-01

    The deformable model literature has in general been very focused on the formulation and development of new models or the solution of a specific application. Teh final and crucial steps of initialization and optimazation of the deformable model, needed for making inference, have received very little...

  15. Initiation Style Optimization of Aimed Warhead by Numerical Simulation

    Institute of Scientific and Technical Information of China (English)

    WEI Ji-feng; LI Na; WEN Yu-quan; WANG Wen-jie

    2008-01-01

    The kill characteristics of aimed warhead were studied.Emphasis on the improvement of initiation system,experiments and three dimensional numerical investigations were carried out.Simulation results of side three initiation points fit experiments well.Optimal initiation style is obtained through further simulation.It shows that the effective fragments and the effective kill energy of the optimal scheme increase 12.8%and 10.1%respectively.

  16. Leaderless genes in bacteria: clue to the evolution of translation initiation mechanisms in prokaryotes

    Directory of Open Access Journals (Sweden)

    Hu Gang-Qing

    2011-07-01

    Full Text Available Abstract Background Shine-Dalgarno (SD signal has long been viewed as the dominant translation initiation signal in prokaryotes. Recently, leaderless genes, which lack 5'-untranslated regions (5'-UTR on their mRNAs, have been shown abundant in archaea. However, current large-scale in silico analyses on initiation mechanisms in bacteria are mainly based on the SD-led initiation way, other than the leaderless one. The study of leaderless genes in bacteria remains open, which causes uncertain understanding of translation initiation mechanisms for prokaryotes. Results Here, we study signals in translation initiation regions of all genes over 953 bacterial and 72 archaeal genomes, then make an effort to construct an evolutionary scenario in view of leaderless genes in bacteria. With an algorithm designed to identify multi-signal in upstream regions of genes for a genome, we classify all genes into SD-led, TA-led and atypical genes according to the category of the most probable signal in their upstream sequences. Particularly, occurrence of TA-like signals about 10 bp upstream to translation initiation site (TIS in bacteria most probably means leaderless genes. Conclusions Our analysis reveals that leaderless genes are totally widespread, although not dominant, in a variety of bacteria. Especially for Actinobacteria and Deinococcus-Thermus, more than twenty percent of genes are leaderless. Analyzed in closely related bacterial genomes, our results imply that the change of translation initiation mechanisms, which happens between the genes deriving from a common ancestor, is linearly dependent on the phylogenetic relationship. Analysis on the macroevolution of leaderless genes further shows that the proportion of leaderless genes in bacteria has a decreasing trend in evolution.

  17. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    Science.gov (United States)

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  18. 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.

  19. Moco biosynthesis and the ATAC acetyltransferase engage translation initiation by inhibiting latent PKR activity.

    Science.gov (United States)

    Suganuma, Tamaki; Swanson, Selene K; Florens, Laurence; Washburn, Michael P; Workman, Jerry L

    2016-02-01

    Molybdenum cofactor (Moco) biosynthesis is linked to c-Jun N-terminal kinase (JNK) signaling in Drosophila through MoaE, a molybdopterin (MPT) synthase subunit that is also a component of the Ada Two A containing (ATAC) acetyltransferase complex. Here, we show that human MPT synthase and ATAC inhibited PKR, a double-stranded RNA-dependent protein kinase, to facilitate translation initiation of iron-responsive mRNA. MPT synthase and ATAC directly interacted with PKR and suppressed latent autophosphorylation of PKR and its downstream phosphorylation of JNK and eukaryotic initiation factor 2α (eIF2α). The suppression of eIF2α phosphorylation via MPT synthase and ATAC prevented sequestration of the guanine nucleotide exchange factor eIF2B, which recycles eIF2-GDP to eIF2-GTP, resulting in the promotion of translation initiation. Indeed, translation of the iron storage protein, ferritin, was reduced in the absence of MPT synthase or ATAC subunits. Thus, MPT synthase and ATAC regulate latent PKR signaling and link transcription and translation initiation.

  20. Rewarding Excellent Teaching: The Translation of a Policy Initiative in the United Kingdom

    Science.gov (United States)

    Turner, Rebecca; Gosling, David

    2012-01-01

    The need to provide more significant rewards for "teaching excellence" in order to provide parity of status with research in higher education has often been asserted. This paper examines ways in which the idea of rewarding excellent teaching has been understood and translated within a large teaching and learning initiative that was…

  1. Comparative analysis of contextual bias around the translation initiation sites in plant genomes.

    Science.gov (United States)

    Gupta, Paras; Rangan, Latha; Ramesh, T Venkata; Gupta, Mudit

    2016-09-07

    Nucleotide distribution around translation initiation site (TIS) is thought to play an important role in determining translation efficiency. Kozak in vertebrates and later Joshi et al. in plants identified context sequence having a key role in translation efficiency, but a great variation regarding this context sequence has been observed among different taxa. The present study aims to refine the context sequence around initiation codon in plants and addresses the sampling error problem by using complete genomes of 7 monocots and 7 dicots separately. Besides positions -3 and +4, significant conservation at -2 and +5 positions was also found and nucleotide bias at the latter two positions was shown to directly influence translation efficiency in the taxon studied. About 1.8% (monocots) and 2.4% (dicots) of the total sequences fit the context sequence from positions -3 to +5, which might be indicative of lower number of housekeeping genes in the transcriptome. A three base periodicity was observed in 5' UTR and CDS of monocots and only in CDS of dicots as confirmed against random occurrence and annotation errors. Deterministic enrichment of GCNAUGGC in monocots, AANAUGGC in dicots and GCNAUGGC in plants around TIS was also established (where AUG denotes the start codon), which can serve as an arbiter of putative TIS with efficient translation in plants.

  2. 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.

  3. Co-Optimization of Fuels & Engines (Co-Optima) Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Farrell, John T [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-10-04

    This is the keynote presentation on the Co-Optimization of Fuels and Engines (Co-Optima) Initiative delivered at SAE International's ICE 2017 - 13th International Conference on Engines & Vehicles held in Capri, Italy.

  4. The alveolate translation initiation factor 4E family reveals a custom toolkit for translational control in core dinoflagellates.

    Science.gov (United States)

    Jones, Grant D; Williams, Ernest P; Place, Allen R; Jagus, Rosemary; Bachvaroff, Tsvetan R

    2015-02-10

    Dinoflagellates are eukaryotes with unusual cell biology and appear to rely on translational rather than transcriptional control of gene expression. The eukaryotic translation initiation factor 4E (eIF4E) plays an important role in regulating gene expression because eIF4E binding to the mRNA cap is a control point for translation. eIF4E is part of an extended, eukaryote-specific family with different members having specific functions, based on studies of model organisms. Dinoflagellate eIF4E diversity could provide a mechanism for dinoflagellates to regulate gene expression in a post-transcriptional manner. Accordingly, eIF4E family members from eleven core dinoflagellate transcriptomes were surveyed to determine the diversity and phylogeny of the eIF4E family in dinoflagellates and related lineages including apicomplexans, ciliates and heterokonts. The survey uncovered eight to fifteen (on average eleven) different eIF4E family members in each core dinoflagellate species. The eIF4E family members from heterokonts and dinoflagellates segregated into three clades, suggesting at least three eIF4E cognates were present in their common ancestor. However, these three clades are distinct from the three previously described eIF4E classes, reflecting diverse approaches to a central eukaryotic function. Heterokonts contain four clades, ciliates two and apicomplexans only a single recognizable eIF4E clade. In the core dinoflagellates, the three clades were further divided into nine sub-clades based on the phylogenetic analysis and species representation. Six of the sub-clades included at least one member from all eleven core dinoflagellate species, suggesting duplication in their shared ancestor. Conservation within sub-clades varied, suggesting different selection pressures. Phylogenetic analysis of eIF4E in core dinoflagellates revealed complex layering of duplication and conservation when compared to other eukaryotes. Our results suggest that the diverse eIF4E family in

  5. 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.

  6. Calicivirus translation initiation requires an interaction between VPg and eIF4E

    Science.gov (United States)

    Goodfellow, Ian; Chaudhry, Yasmin; Gioldasi, Ioanna; Gerondopoulos, Andreas; Natoni, Alessandro; Labrie, Louisette; Laliberté, Jean-François; Roberts, Lisa

    2005-01-01

    Unlike other positive-stranded RNA viruses that use either a 5′-cap structure or an internal ribosome entry site to direct translation of their messenger RNA, calicivirus translation is dependent on the presence of a protein covalently linked to the 5′ end of the viral genome (VPg). We have shown a direct interaction of the calicivirus VPg with the cap-binding protein eIF4E. This interaction is required for calicivirus mRNA translation, as sequestration of eIF4E by 4E-BP1 inhibits translation. Functional analysis has shown that VPg does not interfere with the interaction between eIF4E and the cap structure or 4E-BP1, suggesting that VPg binds to eIF4E at a different site from both cap and 4E-BP1. This work lends support to the idea that calicivirus VPg acts as a novel ‘cap substitute' during initiation of translation on virus mRNA. PMID:16142217

  7. Single-strand DNA translation initiation step analyzed by Isothermal Titration Calorimetry

    Energy Technology Data Exchange (ETDEWEB)

    Damian, Luminita, E-mail: luminitadamian@microcal.eu.com [CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, IPBS, F-31077 Toulouse (France); IUB, School of Engineering and Science, D-28727 Bremen (Germany); Marty-Detraves, Claire, E-mail: claire.detraves@free.fr [CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, IPBS, F-31077 Toulouse (France); Winterhalter, Mathias [IUB, School of Engineering and Science, D-28727 Bremen (Germany); Fournier, Didier, E-mail: Didier.Fournier@ipbs.fr [CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, IPBS, F-31077 Toulouse (France); Paquereau, Laurent, E-mail: Laurent.Paquereau@ipbs.fr [CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, IPBS, F-31077 Toulouse (France)

    2009-07-31

    Is single-strand DNA translatable? Since the 60s, the question still remains whether or not DNA could be directly translated into protein. Some discrepancies in the results were reported about functional translation of single-strand DNA but all results converged on a similar behavior of RNA and ssDNA in the initiation step. Isothermal Titration Calorimetry method was used to determine thermodynamic constants of interaction between single-strand DNA and S30 extract of Escherichia coli. Our results showed that the binding was not affected by the nature of the template tested and the dissociation constants were in the same range when ssDNA (K{sub d} = 3.62 {+-} 2.1 x 10{sup -8} M) or the RNA corresponding sequence (K{sub d} = 2.7 {+-} 0.82 x 10{sup -8} M) bearing SD/ATG sequences were used. The binding specificity was confirmed by antibiotic interferences which block the initiation complex formation. These results suggest that the limiting step in translation of ssDNA is the elongation process.

  8. 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.

  9. Optimization of Glioblastoma Mouse Orthotopic Xenograft Models for Translational Research.

    Science.gov (United States)

    Irtenkauf, Susan M; Sobiechowski, Susan; Hasselbach, Laura A; Nelson, Kevin K; Transou, Andrea D; Carlton, Enoch T; Mikkelsen, Tom; deCarvalho, Ana C

    2017-08-01

    Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panel of patient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex. Glioblastoma CSC from 4 patients and a glioblastoma nonstem-cell line were then implanted by using the same coordinates for evaluation of tumor location, growth rate, and morphologic and histologic features. Dye injections into one of the defined locations resulted in dye dissemination throughout the ventricles, whereas tumor cell implantation at the same location resulted in a much higher percentage of small multifocal ventricular tumors than did the other 3 locations tested. Ventricular tumors were associated with a lower tumor growth rate, as measured by in vivo bioluminescence imaging, and decreased survival in 4 of 5 cell lines. In addition, tissue oxygenation, vasculature, and the expression of astrocytic markers were altered in ventricular tumors compared with nonventricular tumors. Based on this information, we identified an optimal implantation location that avoided the ventricles and favored cortical tumor growth. To assess the effects of stress from oral drug administration, mice that underwent daily gavage were compared with stress-positive and -negative control groups. Oral gavage procedures did not significantly affect the survival of the implanted mice or physiologic measurements of stress. Our findings document the importance of optimization of the implantation site for

  10. Optimal translational swimming of a sphere at low Reynolds number

    CERN Document Server

    Felderhof, B U

    2015-01-01

    Swimming velocity and rate of dissipation of a sphere with surface distortions are discussed on the basis of the Stokes equations of low Reynolds number hydrodynamics. At first the surface distortions are assumed to cause an irrotational axisymmetric flow pattern. The efficiency of swimming is optimized within this class of flows. Subsequently more general axisymmetric polar flows with vorticity are considered. This leads to a considerably higher maximum efficiency. An additional measure of swimming performance is proposed based on the energy consumption for given amplitude of stroke.

  11. Attenuation of disease phenotype through alternative translation initiation in low-penetrance retinoblastoma.

    Science.gov (United States)

    Sánchez-Sánchez, Francisco; Ramírez-Castillejo, Carmen; Weekes, Daniel B; Beneyto, Magdalena; Prieto, Félix; Nájera, Carmen; Mittnacht, Sibylle

    2007-02-01

    Hereditary predisposition to retinoblastoma (RB) is caused by germline mutations in the retinoblastoma 1 (RB1) gene and transmits as an autosomal dominant trait. In the majority of cases disease develops in greater than 90% of carriers. However, reduced penetrance with a large portion of disease-free carrier is seen in some families. Unambiguous identification of the predisposing mutation in these families is important for accurate risk prediction in relatives and their genetic counseling but also provides conceptual information regarding the relationship between the RB1 genotype and the disease phenotype. In this study we report a novel mutation detected in 10 individuals of an extended family, only three of whom are affected by RB disease. The mutation comprises a 23-basepair (bp) duplication in the first exon of RB1 (c.43_65dup) producing a frameshift in exon 1 and premature chain termination in exon 2. Mutations resulting in premature chain termination classically are associated with high penetrance disease, as message translation may not generate functional product and nonsense mediated RNA decay (NMD) frequently eliminates the mutant transcript. However, appreciable NMD does not follow from the mutation described here and transcript expression in tissue culture cells and translation in vitro reveals that alternative in-frame translation start sites involving Met113 and possibly Met233 are used to generate truncated RB1 products (pRB94 and pRB80), known and suspected to exhibit tumor suppressor activity. These results strongly suggest that modulation of disease penetrance in this family is achieved by internal translation initiation. Our observations provide the first example for rescue of a chain-terminating mutation in RB1 through alternative translation initiation.

  12. Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E.

    Science.gov (United States)

    Ho, Bing-Ching; Yu, Sung-Liang; Chen, Jeremy J W; Chang, Sui-Yuan; Yan, Bo-Shiun; Hong, Qi-Sheng; Singh, Sher; Kao, Chuan-Liang; Chen, Hsuan-Yu; Su, Kang-Yi; Li, Ker-Chau; Cheng, Chiou-Ling; Cheng, Hao-Wei; Lee, Jen-Yi; Lee, Chun-Nan; Yang, Pan-Chyr

    2011-01-20

    Viruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. Ectopic expression of miR-141 promotes the switch from cap-dependent to cap-independent translation. Moreover, we identified a transcription factor, EGR1, which is partly responsible for miR-141 induction in response to enterovirus infection. Our results suggest that upregulation of miR-141 upon enterovirus infection can facilitate viral propagation by expediting the translational switch.

  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.

  14. Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation.

    Science.gov (United States)

    Tan, Shen Mynn; Altschuler, Gabriel; Zhao, Tian Yun; Ang, Haw Siang; Yang, Henry; Lim, Bing; Vardy, Leah; Hide, Winston; Thomson, Andrew M; Lareu, Ricky R

    2014-07-01

    LIN28 function is fundamental to the activity and behavior of human embryonic stem cells (hESCs) and induced pluripotent stem cells. Its main roles in these cell types are the regulation of translational efficiency and let-7 miRNA maturation. However, LIN28-associated mRNA cargo shifting and resultant regulation of translational efficiency upon the initiation of differentiation remain unknown. An RNA-immunoprecipitation and microarray analysis protocol, eRIP, that has high specificity and sensitivity was developed to test endogenous LIN28-associated mRNA cargo shifting. A combined eRIP and polysome analysis of early stage differentiation of hESCs with two distinct differentiation cues revealed close similarities between the dynamics of LIN28 association and translational modulation of genes involved in the Wnt signaling, cell cycle, RNA metabolism and proteasomal pathways. Our data demonstrate that change in translational efficiency is a major contributor to early stages of differentiation of hESCs, in which LIN28 plays a central role. This implies that eRIP analysis of LIN28-associated RNA cargoes may be used for rapid functional quality control of pluripotent stem cells under manufacture for therapeutic applications. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. [Translation and cultural adaptation of the Global Appraisal of Individual Needs - Initial].

    Science.gov (United States)

    Claro, Heloísa Garcia; de Oliveira, Márcia Aparecida Ferreira; Paglione, Heloisa Barbosa; Pinho, Paula Hayasi; Pereira, Maria Odete; de Vargas, Divane

    2012-10-01

    The objective of this study was to perform the translation and cultural adaptation of the Global Appraisal of Individual Needs - Initial instrument, and calculate its content validity index. This is a methodological study designed for the cultural adaptation of the instrument. The instrument was translated into Portuguese in two versions that originated the synthesis of the translations, which were then submitted to the evaluation of four judges, experts in the field of alcohol and other drugs. After the suggested changes were made, the instrument was back-translated and resubmitted to the judges and authors of the original instrument, resulting in the final version of the instrument, Avaliação Global das Necessidades Individuais - Inicial. The content validity index of the instrument was 0.91, considered valid according to the literature. The instrument Avaliação Global das Necessidades Individuais - Inicial was culturally adapted to the Portuguese language spoken in Brazil; however, it was not submitted to tests with the target population, which suggests further studies should be performed to test its reliability and validity.

  16. Translation

    OpenAIRE

    2005-01-01

    "Translation" is a life narrative about the ways in which cultural histories shape personal stories, and the capacity of the imagination to develop alternative narratives about oneself and the world. It can also be read a way of addressing the effects of what Ato Quayson calls the global process of postcolonializing. Quaysons critical perspective might be used as an interpretive lens for seeing some of the ways in which  this autobiographical narrative complicates the jargon of race, cl...

  17. Translation

    OpenAIRE

    2005-01-01

    "Translation" is a life narrative about the ways in which cultural histories shape personal stories, and the capacity of the imagination to develop alternative narratives about oneself and the world. It can also be read a way of addressing the effects of what Ato Quayson calls the global process of postcolonializing. Quaysons critical perspective might be used as an interpretive lens for seeing some of the ways in which  this autobiographical narrative complicates the jargon of race, class, ...

  18. TISs-ST: a web server to evaluate polymorphic translation initiation sites and their reflections on the secretory targets

    Directory of Open Access Journals (Sweden)

    Menossi Marcelo

    2007-05-01

    Full Text Available Abstract Background The nucleotide sequence flanking the translation initiation codon (start codon context affects the translational efficiency of eukaryotic mRNAs, and may indicate the presence of an alternative translation initiation site (TIS to produce proteins with different properties. Multi-targeting may reflect the translational variability of these other protein forms. In this paper we present a web server that performs computations to investigate the usage of alternative translation initiation sites for the synthesis of new protein variants that might have different functions. Results An efficient web-based tool entitled TISs-ST (Translation Initiation Sites and Secretory Targets evaluates putative translation initiation sites and indicates the prediction of a signal peptide of the protein encoded from this site. The TISs-ST web server is freely available to both academic and commercial users and can be accessed at http://ipe.cbmeg.unicamp.br/pub/TISs-ST. Conclusion The program can be used to evaluate alternative translation initiation site consensus with user-specified sequences, based on their composition or on many position weight matrix models. TISs-ST provides analytical and visualization tools for evaluating the periodic frequency, the consensus pattern and the total information content of a sequence data set. A search option allows for the identification of signal peptides from predicted proteins using the PrediSi software.

  19. Inhibition of Influenza Virus Replication by DNA Aptamers Targeting a Cellular Component of Translation Initiation

    Directory of Open Access Journals (Sweden)

    Paloma Rodriguez

    2016-01-01

    Full Text Available The genetic diversity of the influenza virus hinders the use of broad spectrum antiviral drugs and favors the appearance of resistant strains. Single-stranded DNA aptamers represent an innovative approach with potential application as antiviral compounds. The mRNAs of influenza virus possess a 5′cap structure and a 3′poly(A tail that makes them structurally indistinguishable from cellular mRNAs. However, selective translation of viral mRNAs occurs in infected cells through a discriminatory mechanism, whereby viral polymerase and NS1 interact with components of the translation initiation complex, such as the eIF4GI and PABP1 proteins. We have studied the potential of two specific aptamers that recognize PABP1 (ApPABP7 and ApPABP11 to act as anti-influenza drugs. Both aptamers reduce viral genome expression and the production of infective influenza virus particles. The interaction of viral polymerase with the eIF4GI translation initiation factor is hindered by transfection of infected cells with both PABP1 aptamers, and ApPABP11 also inhibits the association of NS1 with PABP1 and eIF4GI. These results indicate that aptamers targeting the host factors that interact with viral proteins may potentially have a broad therapeutic spectrum, reducing the appearance of escape mutants and resistant subtypes.

  20. 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...... 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...... annotations are analysed in detail, leading to identification of possible database errors....

  1. Dimerization of the yeast eukaryotic translation initiation factor 5A requires hypusine and is RNA dependent.

    Science.gov (United States)

    Gentz, Petra M; Blatch, Gregory L; Dorrington, Rosemary A

    2009-02-01

    Post-translational modification of the highly conserved K51 residue of the Saccharomyces cerevisiae eukaryotic translation initiation factor 5A (eIF5A) to form hypusine, is essential for its many functions including the binding of specific mRNAs. We characterized hypusinated yeast eIF5A by size-exclusion chromatography and native PAGE, showing that the protein exists as a homodimer. A K51R mutant, which was not functional in vivo eluted as a monomer and inhibition of hypusination abolished dimerization. Furthermore, treatment of dimeric eIF5A with RNase A resulted in disruption of the dimer, leading us to conclude that RNA binding is also required for dimerization of eIF5A. We present a model of dimerization, based on the Neurospora crassa structural analogue, HEX-1.

  2. Translational diffusion of macromolecular assemblies measured using transverse-relaxation-optimized pulsed field gradient NMR.

    Science.gov (United States)

    Horst, Reto; Horwich, Arthur L; Wüthrich, Kurt

    2011-10-19

    In structural biology, pulsed field gradient (PFG) NMR spectroscopy for the characterization of size and hydrodynamic parameters of macromolecular solutes has the advantage over other techniques that the measurements can be recorded with identical solution conditions as used for NMR structure determination or for crystallization trials. This paper describes two transverse-relaxation-optimized (TRO) (15)N-filtered PFG stimulated-echo (STE) experiments for studies of macromolecular translational diffusion in solution, (1)H-TRO-STE and (15)N-TRO-STE, which include CRINEPT and TROSY elements. Measurements with mixed micelles of the Escherichia coli outer membrane protein X (OmpX) and the detergent Fos-10 were used for a systematic comparison of (1)H-TRO-STE and (15)N-TRO-STE with conventional (15)N-filtered STE experimental schemes. The results provide an extended platform for evaluating the NMR experiments available for diffusion measurements in structural biology projects involving molecular particles with different size ranges. An initial application of the (15)N-TRO-STE experiment with very long diffusion delays showed that the tedradecamer structure of the 800 kDa Thermus thermophilus chaperonin GroEL is preserved in aqueous solution over the temperature range 25-60 °C.

  3. Translational diffusion of macromolecular assemblies measured using transverse relaxation-optimized PFG-NMR

    Science.gov (United States)

    Horst, Reto; Horwich, Arthur L.

    2012-01-01

    In structural biology, pulsed field gradient (PFG) NMR for characterization of size and hydrodynamic parameters of macromolecular solutes has the advantage over other techniques that the measurements can be recorded with identical solution conditions as used for NMR structure determination or for crystallization trials. This paper describes two transverse relaxation-optimized (TRO) 15N-filtered PFG stimulated-echo (STE) experiments for studies of macromolecular translational diffusion in solution, 1H-TRO-STE and 15N-TRO-STE, which include CRINEPT and TROSY elements. Measurements with mixed micelles of the Escherichia coli outer membrane protein X (OmpX) and the detergent Fos-10 were used for a systematic comparison of 1H-TRO-STE and 15N-TRO-STE with conventional 15N-filtered STE experimental schemes. The results provide an extended platform for evaluating the NMR experiments available for diffusion measurements in structural biology projects with molecular particles of different size ranges. An initial application of the 15N-TRO-STE experiment with very long diffusion delays showed that the tedradecamer structure of the 800 kDa Thermus thermophilus chaperonin GroEL is preserved in aqueous solution over the temperature range 25–60°C. PMID:21919531

  4. Translation initiation of the replication initiator repB gene of promiscuous plasmid pMV158 is led by an extended non-SD sequence.

    Science.gov (United States)

    López-Aguilar, Celeste; Ruiz-Masó, José A; Rubio-Lepe, Tania Samir; Sanz, Marta; del Solar, Gloria

    2013-07-01

    RepB is the pMV158-encoded protein that initiates rolling-circle replication of this promiscuous plasmid. Availability of RepB is rate-limiting for the plasmid replication process, and therefore the repB gene encoding the protein is subjected to strict control. Two trans-acting plasmid elements, CopG and the antisense RNAII, are involved in controlling the synthesis of the initiator at the transcriptional and translational level, respectively. In addition to this dual control of repB expression that senses and corrects fluctuations in plasmid copy number, proper availability of RepB also relies on the adequate functionality of the transcription and translation initiation regulatory signals. Translation of repB has been postulated to depend on an atypical ribosome binding site that precedes its start codon, although such a hypothesis has never been proved. To define sequences involved in translation of repB, several mutations in the translation initiation region of the repB mRNA have been characterized by using an Escherichia coli in vitro expression system wherein the synthesis of RepB was detected and quantified. We showed that translation of repB is not coupled to that of copG and depends only on its own initiation signals. The atypical ribosome binding site, as it was defined, is not involved in translation initiation. However, the sequence just upstream of the repB start codon, encompassing the proximal box of the atypical ribosome binding site and the four bases immediately downstream of it, is indeed important for efficient translation of repB. The high degree of conservation of this sequence among the rep genes of plasmids of the same pMV158 family supports its relevancy as a translation initiation signal in mRNAs without a recognizable Shine-Dalgarno sequence.

  5. 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.

  6. Myc regulates VEGF production in B cells by stimulating initiation of VEGF mRNA translation.

    Science.gov (United States)

    Mezquita, Pau; Parghi, Sean S; Brandvold, Kimberly A; Ruddell, Alanna

    2005-01-27

    Deregulated c-myc gene expression is associated with many human and animal cancers. Myc overexpression promotes the growth of blood and lymphatic vessels, which is due in part to induction of growth factors including vascular endothelial growth factor (VEGF). We determined that the P493-6 human B-cell line increases VEGF production 10-fold upon Myc overexpression. Myc overexpression in avian B cells similarly resulted in high level VEGF production. Real-time RT-PCR analyses showed that Myc did not alter the VEGF mRNA content of these cell lines, indicating that a post-transcriptional mechanism regulates VEGF production. VEGF mRNA translation was examined by RT-PCR analysis of monosome and polysome sucrose gradient fractions from Myc-on and Myc-off P493-6 cells. Myc increased VEGF mRNA translation initiation, as VEGF mRNA loading onto polysomes increased 14-fold in Myc-on cells, and the number of ribosomes loaded per VEGF mRNA increased threefold. This translational regulation is specific to VEGF mRNA, as total polysomes show the same sucrose gradient profile in Myc-on and Myc-off cells, with no change in the percent ribosomes in polysomes, or in the number of ribosomes per polysomal mRNA. Myc stimulates VEGF production by a rapamycin- and LY294002-sensitive pathway, which does not involve alteration of eIF4E activity.

  7. The putative RNA helicase HELZ promotes cell proliferation, translation initiation and ribosomal protein S6 phosphorylation.

    Directory of Open Access Journals (Sweden)

    Philippe A Hasgall

    Full Text Available The hypoxia-inducible transcription factor (HIF is a key component of the cellular adaptation mechanisms to hypoxic conditions. HIFα subunits are degraded by prolyl-4-hydroxylase domain (PHD enzyme-dependent prolyl-4-hydroxylation of LxxLAP motifs that confer oxygen-dependent proteolytic degradation. Interestingly, only three non-HIFα proteins contain two conserved LxxLAP motifs, including the putative RNA helicase with a zinc finger domain HELZ. However, HELZ proteolytic regulation was found to be oxygen-independent, supporting the notion that a LxxLAP sequence motif alone is not sufficient for oxygen-dependent protein destruction. Since biochemical pathways involving RNA often require RNA helicases to modulate RNA structure and activity, we used luciferase reporter gene constructs and metabolic labeling to demonstrate that HELZ overexpression activates global protein translation whereas RNA-interference mediated HELZ suppression had the opposite effect. Although HELZ interacted with the poly(A-binding protein (PABP via its PAM2 motif, PABP was dispensable for HELZ function in protein translation. Importantly, downregulation of HELZ reduced translational initiation, resulting in the disassembly of polysomes, in a reduction of cell proliferation and hypophosphorylation of ribosomal protein S6.

  8. Optimization Parameter of Transformation of Parallel Translation for Ship Pitch Simulation

    Institute of Scientific and Technical Information of China (English)

    SHEN; Ji-hong

    2002-01-01

    The transformation of parallel translation can improve the smoothness of discrete series sometimes. In this paper, for ship pitch, a method to modify the system error is proposed via the transformation of parallel translation, which can give the optimize parameters using the Method of Minimum Squares. The series in the method can fit white exponential law better, and then be applied in GM (1,1) very well. The numerical experiments imply that the method is practical, which make the ship pitch system model more accurate than GM ( 1,1 ).

  9. Phosphorylation of eukaryotic translation initiation factor 4E and eukaryotic translation initiation factor 4E-binding protein (4EBP) and their upstream signaling components undergo diurnal oscillation in the mouse hippocampus: implications for memory persistence.

    Science.gov (United States)

    Saraf, Amit; Luo, Jie; Morris, David R; Storm, Daniel R

    2014-07-18

    Translation of mRNA plays a critical role in consolidation of long-term memory. Here, we report that markers of initiation of mRNA translation are activated during training for contextual memory and that they undergo diurnal oscillation in the mouse hippocampus with maximal activity observed during the daytime (zeitgeber time 4-8 h). Phosphorylation and activation of eukaryotic translation initiation factor 4E (eIF4E), eIF4E-binding protein 1 (4EBP1), ribosomal protein S6, and eIF4F cap-complex formation, all of which are markers for translation initiation, were higher in the hippocampus during the daytime compared with night. The circadian oscillation in markers of mRNA translation was lost in memory-deficient transgenic mice lacking calmodulin-stimulated adenylyl cyclases. Moreover, disruption of the circadian rhythm blocked diurnal oscillations in eIF4E, 4EBP1, rpS6, Akt, and ERK1/2 phosphorylation and impaired memory consolidation. Furthermore, repeated inhibition of translation in the hippocampus 48 h after contextual training with the protein synthesis inhibitor anisomycin impaired memory persistence. We conclude that repeated activation of markers of translation initiation in hippocampus during the circadian cycle might be critical for memory persistence. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Regulation of cap-dependent translation initiation in the early stage porcine parthenotes.

    Science.gov (United States)

    Susor, Andrej; Jelínková, Lucie; Karabínová, Pavla; Torner, Helmut; Tomek, Wolfgang; Kovárová, Hana; Kubelka, Michal

    2008-12-01

    The binding of mRNAs to ribosomes is mediated by the protein complex eIF4F in conjunction with eIF4B (eukaryotic initiation factor 4F and 4B). EIF4F is a three subunit complex consisting of eIF4A (RNA helicase), eIF4E (mRNA cap binding protein), and eIF4G (bridging protein). The crucial role is played by eIF4E, which directly binds the 5'-cap structure of the mRNA and facilitates the recruitment to the mRNA of other translation factors and the 40S ribosomal subunit. EIF4E binding to mRNA and to other initiation factors is regulated on several levels, including its phosphorylation on Ser-209, and association with its regulatory protein 4E-binding protein (4E-BP1). In this study we document that both the translation initiation factor eIF4E and its regulator 4E-BP1 become dephosphorylated in the early stage porcine zygotes already 8 hr post-activation. Similarly, the activities of ERK1/2 MAP and Mnk1 kinases, which are both involved in eIF4E phosphorylation, gradually decrease during this period with the timing similar to that of eIF4E dephosphorylation. The formation of an active eIF4F complex is also diminished after 9-15 hr post-activation, although substantial amounts of this complex have been detected also 24 hr post-activation (2-cell stage). The overall protein synthesis in the parthenotes decreases gradually from 12 hr post-activation reaching a minimum after 48 hr (4-cell stage). Although the translation is gradually decreasing during early preimplantation development, the eIF4F complex, which is temporarily formed, might be a premise for the translation of a small subset of mRNAs at this period of development.

  11. 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.

  12. Translation complex profile sequencing to study the in vivo dynamics of mRNA-ribosome interactions during translation initiation, elongation and termination.

    Science.gov (United States)

    Shirokikh, Nikolay E; Archer, Stuart K; Beilharz, Traude H; Powell, David; Preiss, Thomas

    2017-04-01

    Messenger RNA (mRNA) translation is a tightly controlled process that is integral to gene expression. It features intricate and dynamic interactions of the small and large subunits of the ribosome with mRNAs, aided by multiple auxiliary factors during distinct initiation, elongation and termination phases. The recently developed ribosome profiling method can generate transcriptome-wide surveys of translation and its regulation. Ribosome profiling records the footprints of fully assembled ribosomes along mRNAs and thus primarily interrogates the elongation phase of translation. Importantly, it does not monitor multiple substeps of initiation and termination that involve complexes between the small ribosomal subunit (SSU) and mRNA. Here we describe a related method, termed 'translation complex profile sequencing' (TCP-seq), that is uniquely capable of recording positions of any type of ribosome-mRNA complex transcriptome-wide. It uses fast covalent fixation of translation complexes in live cells, followed by RNase footprinting of translation intermediates and their separation into complexes involving either the full ribosome or the SSU. The footprints derived from each type of complex are then deep-sequenced separately, generating native distribution profiles during the elongation, as well as the initiation and termination stages of translation. We provide the full TCP-seq protocol for Saccharomyces cerevisiae liquid suspension culture, including a data analysis pipeline. The protocol takes ∼3 weeks to complete by a researcher who is well acquainted with standard molecular biology techniques and who has some experience in ultracentrifugation and the preparation of RNA sequencing (RNA-seq) libraries. Basic Bash and UNIX/Linux command skills are required to use the bioinformatics tools provided.

  13. 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.

  14. Optimal Design of a Cam Mechanism with Translating Flat-Face Follower using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    I. Tsiafis

    2013-12-01

    Full Text Available The optimum design of a cam mechanism is a time consuming task, due to the numerous alternatives considerations. In the present work, the problem of design parameters optimization of a cam mechanism with translating flat - face follower is investigated from a multi - objective point of view. The design parameters, just like the cam base circle radius, the follower face width and the follower offset can be determined considering as the optimization criteria minimization of the cam size, of the input torque and of the contact stress. During the optimization procedure, a number of constraints regarding the pressure angle, the contact stress, etcare taken into account. The optimization approach, based on genetic algorithm, is applied to find the optimal solutions with respect to the a fore - mentioned objective function and to Ensure the kinematic requirements. Finally, the dynamic behavior of the designed cam mechanism is investigated considering the frictional forces.

  15. 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

    2017-03-09

    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.

  16. Codon Optimization to Enhance Expression Yields Insights into Chloroplast Translation1[OPEN

    Science.gov (United States)

    Chan, Hui-Ting; Williams-Carrier, Rosalind; Barkan, Alice

    2016-01-01

    Codon optimization based on psbA genes from 133 plant species eliminated 105 (human clotting factor VIII heavy chain [FVIII HC]) and 59 (polio VIRAL CAPSID PROTEIN1 [VP1]) rare codons; replacement with only the most highly preferred codons decreased transgene expression (77- to 111-fold) when compared with the codon usage hierarchy of the psbA genes. Targeted proteomic quantification by parallel reaction monitoring analysis showed 4.9- to 7.1-fold or 22.5- to 28.1-fold increase in FVIII or VP1 codon-optimized genes when normalized with stable isotope-labeled standard peptides (or housekeeping protein peptides), but quantitation using western blots showed 6.3- to 8-fold or 91- to 125-fold increase of transgene expression from the same batch of materials, due to limitations in quantitative protein transfer, denaturation, solubility, or stability. Parallel reaction monitoring, to our knowledge validated here for the first time for in planta quantitation of biopharmaceuticals, is especially useful for insoluble or multimeric proteins required for oral drug delivery. Northern blots confirmed that the increase of codon-optimized protein synthesis is at the translational level rather than any impact on transcript abundance. Ribosome footprints did not increase proportionately with VP1 translation or even decreased after FVIII codon optimization but is useful in diagnosing additional rate-limiting steps. A major ribosome pause at CTC leucine codons in the native gene of FVIII HC was eliminated upon codon optimization. Ribosome stalls observed at clusters of serine codons in the codon-optimized VP1 gene provide an opportunity for further optimization. In addition to increasing our understanding of chloroplast translation, these new tools should help to advance this concept toward human clinical studies. PMID:27465114

  17. FUZZY MODEL OPTIMIZATION FOR TIME SERIES DATA USING A TRANSLATION IN THE EXTENT OF MEAN ERROR

    Directory of Open Access Journals (Sweden)

    Nurhayadi

    2014-01-01

    Full Text Available Recently, many researchers in the field of writing about the prediction of stock price forecasting, electricity load demand and academic enrollment using fuzzy methods. However, in general, modeling does not consider the model position to actual data yet where it means that error is not been handled optimally. The error that is not managed well can reduce the accuracy of the forecasting. Therefore, the paper will discuss reducing error using model translation. The error that will be reduced is Mean Square Error (MSE. Here, the analysis is done mathematically and the empirical study is done by applying translation to fuzzy model for enrollment forecasting at the Alabama University. The results of this analysis show that the translation in the extent of mean error can reduce the MSE.

  18. Optimal stability polynomials for numerical integration of initial value problems

    KAUST Repository

    Ketcheson, David I.

    2013-01-08

    We consider the problem of finding optimally stable polynomial approximations to the exponential for application to one-step integration of initial value ordinary and partial differential equations. The objective is to find the largest stable step size and corresponding method for a given problem when the spectrum of the initial value problem is known. The problem is expressed in terms of a general least deviation feasibility problem. Its solution is obtained by a new fast, accurate, and robust algorithm based on convex optimization techniques. Global convergence of the algorithm is proven in the case that the order of approximation is one and in the case that the spectrum encloses a starlike region. Examples demonstrate the effectiveness of the proposed algorithm even when these conditions are not satisfied.

  19. Analysis of optimal initial glide conditions for hypersonic glide vehicles

    Directory of Open Access Journals (Sweden)

    Yan Xiaodong

    2014-04-01

    Full Text Available Hypersonic glide vehicles (HGVs are launched by a solid booster and glide through the atmosphere at high speeds. HGVs will be important means for rapid long-range delivery in the future. Given that the glide is unpowered, the initial glide conditions (IGCs are crucial for flight. This paper aims to find the optimal IGCs to improve the maneuverability and decrease the constraints of HGVs. By considering the IGCs as experiment factors, we design an orthogonal table with three factors that have five levels each by using the orthogonal experimental design method. Thereafter, we apply the Gauss pseudospectral method to perform glide trajectory optimization by using each test of the orthogonal table as the initial condition. Based on the analytic hierarchy process, an integrated indicator is established to evaluate the IGCs, which synthesizes the indexes of the maneuverability and constraints. The integrated indicator is calculated from the trajectory optimization results. Finally, optimal IGCs and valuable conclusions are obtained by using range analysis, variance analysis, and regression analysis on the integrated indicator.

  20. Optimization and translation of MSC-based hyaluronic acid hydrogels for cartilage repair

    Science.gov (United States)

    Erickson, Isaac E.

    2011-12-01

    Traumatic injury and disease disrupt the ability of cartilage to carry joint stresses and, without an innate regenerative response, often lead to degenerative changes towards the premature development of osteoarthritis. Surgical interventions have yet to restore long-term mechanical function. Towards this end, tissue engineering has been explored for the de novo formation of engineered cartilage as a biologic approach to cartilage repair. Research utilizing autologous chondrocytes has been promising, but clinical limitations in their yield have motivated research into the potential of mesenchymal stem cells (MSCs) as an alternative cell source. MSCs are multipotent cells that can differentiate towards a chondrocyte phenotype in a number of biomaterials, but no combination has successfully recapitulated the native mechanical function of healthy articular cartilage. The broad objective of this thesis was to establish an MSC-based tissue engineering approach worthy of clinical translation. Hydrogels are a common class of biomaterial used for cartilage tissue engineering and our initial work demonstrated the potential of a photo-polymerizable hyaluronic acid (HA) hydrogel to promote MSC chondrogenesis and improved construct maturation by optimizing macromer and MSC seeding density. The beneficial effects of dynamic compressive loading, high MSC density, and continuous mixing (orbital shaker) resulted in equilibrium modulus values over 1 MPa, well in range of native tissue. While compressive properties are crucial, clinical translation also demands that constructs stably integrate within a defect. We utilized a push-out testing modality to assess the in vitro integration of HA constructs within artificial cartilage defects. We established the necessity for in vitro pre-maturation of constructs before repair to achieve greater integration strength and compressive properties in situ. Combining high MSC density and gentle mixing resulted in integration strength over 500 k

  1. Virtual couch shift (VCS): accounting for patient translation and rotation by online IMRT re-optimization.

    Science.gov (United States)

    Bol, G H; Lagendijk, J J W; Raaymakers, B W

    2013-05-07

    When delivering conventional intensity modulated radiotherapy (IMRT), discrepancies between the pre-treatment CT/MRI/PET based patient geometry and the daily patient geometry are minimized by performing couch translations and/or small rotations. However, full compensation of, in particular, rotations is usually not possible. In this paper, we introduce an online 'virtual couch shift (VCS)': we translate and/or rotate the pre-treatment dose distribution to compensate for the changes in patient anatomy and generate a new plan which delivers the transformed dose distribution automatically. We show for a phantom and a cervical cancer patient case that VCS accounts for both translations and large rotations equally well in terms of DVH results and 2%/2 mm γ analyses and when the various aspects of the clinical workflow can be implemented successfully, VCS can potentially outperform physical couch translations and/or rotations. This work is performed in the context of our hybrid 1.5 T MRI linear accelerator, which can provide translations and rotations but also deformations of the anatomy. The VCS is the first step toward compensating all of these anatomical changes by online re-optimization of the IMRT dose distribution.

  2. 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.

  3. FUZZY MODEL OPTIMIZATION FOR TIME SERIES DATA USING A TRANSLATION IN THE EXTENT OF MEAN ERROR

    OpenAIRE

    Nurhayadi; ., Subanar; Abdurakhman; Agus Maman Abadi

    2014-01-01

    Recently, many researchers in the field of writing about the prediction of stock price forecasting, electricity load demand and academic enrollment using fuzzy methods. However, in general, modeling does not consider the model position to actual data yet where it means that error is not been handled optimally. The error that is not managed well can reduce the accuracy of the forecasting. Therefore, the paper will discuss reducing error using model translation. The error that will be reduced i...

  4. 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.

  5. Mathematical modeling of translation initiation for the estimation of its efficiency to computationally design mRNA sequences with desired expression levels in prokaryotes

    Directory of Open Access Journals (Sweden)

    Lee Sunjae

    2010-05-01

    Full Text Available Abstract Background Within the emerging field of synthetic biology, engineering paradigms have recently been used to design biological systems with novel functionalities. One of the essential challenges hampering the construction of such systems is the need to precisely optimize protein expression levels for robust operation. However, it is difficult to design mRNA sequences for expression at targeted protein levels, since even a few nucleotide modifications around the start codon may alter translational efficiency and dramatically (up to 250-fold change protein expression. Previous studies have used ad hoc approaches (e.g., random mutagenesis to obtain the desired translational efficiencies for mRNA sequences. Hence, the development of a mathematical methodology capable of estimating translational efficiency would greatly facilitate the future design of mRNA sequences aimed at yielding desired protein expression levels. Results We herein propose a mathematical model that focuses on translation initiation, which is the rate-limiting step in translation. The model uses mRNA-folding dynamics and ribosome-binding dynamics to estimate translational efficiencies solely from mRNA sequence information. We confirmed the feasibility of our model using previously reported expression data on the MS2 coat protein. For further confirmation, we used our model to design 22 luxR mRNA sequences predicted to have diverse translation efficiencies ranging from 10-5 to 1. The expression levels of these sequences were measured in Escherichia coli and found to be highly correlated (R2 = 0.87 with their estimated translational efficiencies. Moreover, we used our computational method to successfully transform a low-expressing DsRed2 mRNA sequence into a high-expressing mRNA sequence by maximizing its translational efficiency through the modification of only eight nucleotides upstream of the start codon. Conclusions We herein describe a mathematical model that uses m

  6. Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA.

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    David J Leslie

    2015-07-01

    Full Text Available Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival. However, the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood. Here, we identify post-transcriptional mechanisms that help enforce a cell-cycle arrest in Caulobacter crescentus following nutrient limitation and during entry into stationary phase by limiting the accumulation of DnaA, the conserved replication initiator protein. DnaA is rapidly degraded by the Lon protease following nutrient limitation. However, the rate of DnaA degradation is not significantly altered by changes in nutrient availability. Instead, we demonstrate that decreased nutrient availability downregulates dnaA translation by a mechanism involving the 5' untranslated leader region of the dnaA transcript; Lon-dependent proteolysis of DnaA then outpaces synthesis, leading to the elimination of DnaA and the arrest of DNA replication. Our results demonstrate how regulated translation and constitutive degradation provide cells a means of precisely and rapidly modulating the concentration of key regulatory proteins in response to environmental inputs.

  7. Translation initiation factor (iso) 4E interacts with BTF3, the beta subunit of the nascent polypeptide-associated complex.

    Science.gov (United States)

    Freire, Miguel Angel

    2005-01-31

    A two-hybrid screen with the translation initiation factor, eIF(iso)4E from Arabidopsis, identified a clone encoding a lipoxygenase type 2 [Freire, M.A., et al., 2000. Plant lipoxygenase 2 is a translation initiation factor-4E-binding protein. Plant Molecular Biology 44, 129-140], and three cDNA clones encoding the homologue of the mammalian BTF3 factor, the beta subunit of the nascent polypeptide-associated complex (NAC). Here we report on the interaction between the translation initiation factor eIF(iso)4E and AtBTF3. AtBTF3 protein is able to interact with the wheat initiation factors eIF4E and eIF(iso)4E. AtBTF3 contains a sequence related to the prototypic motif found on most of the 4E-binding proteins, and competes with the translation initiation factor eIF(iso)4G for eIF4(iso)4E binding, in a two hybrid interference assay. These findings provide a molecular link between the translation initiation mechanism and the emergence of the nascent polypeptide chains.

  8. Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome.

    Science.gov (United States)

    Willemsen, Michèl A; Vissers, Lisenka Elm; Verbeek, Marcel M; van Bon, Bregje W; Geuer, Sinje; Gilissen, Christian; Klepper, Joerg; Kwint, Michael P; Leen, Wilhelmina G; Pennings, Maartje; Wevers, Ron A; Veltman, Joris A; Kamsteeg, Erik-Jan

    2017-06-01

    Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. The disorder is caused by impaired glucose transport into the brain resulting from variants in SCL2A1. In 10% of GLUT1DS patients, a genetic diagnosis can not be made. Using whole-genome sequencing, we identified a de novo 5'-UTR variant in SLC2A1, generating a novel translation initiation codon, severely compromising SLC2A1 function. This finding expands our understanding of the disease mechanisms underlying GLUT1DS and encourages further in-depth analysis of SLC2A1 non-coding regions in patients without variants in the coding region.

  9. 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.

  10. Androgen Signaling Promotes Translation of TMEFF2 in Prostate Cancer Cells via Phosphorylation of the α Subunit of the Translation Initiation Factor 2

    Science.gov (United States)

    Overcash, Ryan F.; Chappell, Vesna A.; Green, Thomas; Geyer, Christopher B.; Asch, Adam S.; Ruiz-Echevarría, Maria J.

    2013-01-01

    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. PMID:23405127

  11. PreTIS: A Tool to Predict Non-canonical 5’ UTR Translational Initiation Sites in Human and Mouse

    Science.gov (United States)

    Reuter, Kerstin; Helms, Volkhard

    2016-01-01

    Translation of mRNA sequences into proteins typically starts at an AUG triplet. In rare cases, translation may also start at alternative non–AUG codons located in the annotated 5’ UTR which leads to an increased regulatory complexity. Since ribosome profiling detects translational start sites at the nucleotide level, the properties of these start sites can then be used for the statistical evaluation of functional open reading frames. We developed a linear regression approach to predict in–frame and out–of–frame translational start sites within the 5’ UTR from mRNA sequence information together with their translation initiation confidence. Predicted start codons comprise AUG as well as near–cognate codons. The underlying datasets are based on published translational start sites for human HEK293 and mouse embryonic stem cells that were derived by the original authors from ribosome profiling data. The average prediction accuracy of true vs. false start sites for HEK293 cells was 80%. When applied to mouse mRNA sequences, the same model predicted translation initiation sites observed in mouse ES cells with an accuracy of 76%. Moreover, we illustrate the effect of in silico mutations in the flanking sequence context of a start site on the predicted initiation confidence. Our new webservice PreTIS visualizes alternative start sites and their respective ORFs and predicts their ability to initiate translation. Solely, the mRNA sequence is required as input. PreTIS is accessible at http://service.bioinformatik.uni-saarland.de/pretis. PMID:27768687

  12. Generating optimal initial conditions for smooth particle hydrodynamics (SPH) simulations

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, Steven [Los Alamos National Laboratory; Rockefeller, Gabriel M [Los Alamos National Laboratory; Fryer, Christopher L [Los Alamos National Laboratory

    2008-01-01

    We present a new optimal method to set up initial conditions for Smooth Particle Hydrodynamics Simulations, which may also be of interest for N-body simulations. This new method is based on weighted Voronoi tesselations (WVTs) and can meet arbitrarily complex spatial resolution requirements. We conduct a comprehensive review of existing SPH setup methods, and outline their advantages, limitations and drawbacks. A serial version of our WVT setup method is publicly available and we give detailed instruction on how to easily implement the new method on top of an existing parallel SPH code.

  13. CALCULATION OF INITIALS OPTIMAL PRODUCTION CAPACITIES CONSIDERING UNCERTAINTY ELEMENTS

    Directory of Open Access Journals (Sweden)

    Hilda Oquendo Ferrer

    2016-04-01

    Full Text Available In diversification, an attractive variant constitutes the projection of ethanol plants due to all the advantages that this represents and a crucial element for this to be effective is the existence of cane as a fundamental raw material for the sugar industry and therefore the derived productions. To project the initials optimal capacity of the plant, uncertainty in the raw material was considered. Mathematical models of capacity in time are obtained, choosing those that best fit, being the linear the simplest for future calculations. The initial capacity the plant should have is determined, also the time at which the first extension and the capacity of the plant should be done, which allows, considering other criteria, to make decisions about what should be the capacity of an ethanol plant in response to the current and future availability of sugar cane. It is presented a general method that can be used considering other tax sugar companies in a province or a region.

  14. Using Open Source Tools to Create a Mobile Optimized, Crowdsourced Translation Tool

    Directory of Open Access Journals (Sweden)

    Evviva Weinraub Lajoie

    2014-04-01

    Full Text Available In late 2012, OSU Libraries and Press partnered with Maria's Libraries, an NGO in Rural Kenya, to provide users the ability to crowdsource translations of folk tales and existing children's books into a variety of African languages, sub-languages, and dialects. Together, these two organizations have been creating a mobile optimized platform using open source libraries such as Wink Toolkit (a library which provides mobile-friendly interaction from a website and Globalize3 to allow for multiple translations of database entries in a Ruby on Rails application. Research regarding successes of similar tools has been utilized in providing a consistent user interface. The OSU Libraries & Press team delivered a proof-of-concept tool that has the opportunity to promote technology exploration, improve early childhood literacy, change the way we approach foreign language learning, and to provide opportunities for cost-effective, multi-language publishing.

  15. 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

  16. Inverse optimal sliding mode control of spacecraft with coupled translation and attitude dynamics

    Science.gov (United States)

    Pukdeboon, Chutiphon

    2015-10-01

    This paper proposes two robust inverse optimal control schemes for spacecraft with coupled translation and attitude dynamics in the presence of external disturbances. For the first controller, an inverse optimal control law is designed based on Sontag-type formula and the control Lyapunov function. Then a robust inverse optimal position and attitude controller is designed by using a new second-order integral sliding mode control method to combine a sliding mode control with the derived inverse optimal control. The global asymptotic stability of the proposed control law is proved by using the second method of Lyapunov. For the other control law, a nonlinear H∞ inverse optimal controller for spacecraft position and attitude tracking motion is developed to achieve the design conditions of controller gains that the control law becomes suboptimal H∞ state feedback control. The ultimate boundedness of system state is proved by using the Lyapunov stability theory. Both developed robust inverse optimal controllers can minimise a performance index and ensure the stability of the closed-loop system and external disturbance attenuation. An example of position and attitude tracking manoeuvres is presented and simulation results are included to show the performance of the proposed controllers.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

    Science.gov (United States)

    Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

    2015-01-01

    Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety.

  1. Optimal encoding on discrete lattice with translational invariant constrains using statistical algorithms

    CERN Document Server

    Duda, Jarek

    2007-01-01

    In this paper it is shown how to almost optimally encode information in valuations of discrete lattice with some translational invariant constrains. The method is based on finding statistical description of such valuations and changing it into statistical algorithm: which allow to construct deterministically valuation with given statistics. Optimal statistic allows to generate valuations with uniform distribution - we get this way maximum information capacity. It will be shown that in this approach we practically can get as close to capacity of the model as we want (found numerically: lost 1e-10 bit/node for Hard Square). There will be presented an alternative to Huffman coding too, which is more precise and practice with changing probability distributions.

  2. 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.

  3. Deciphering the Translation Initiation Factor 5A Modification Pathway in Halophilic Archaea

    Directory of Open Access Journals (Sweden)

    Laurence Prunetti

    2016-01-01

    Full Text Available Translation initiation factor 5A (IF5A is essential and highly conserved in Eukarya (eIF5A and Archaea (aIF5A. The activity of IF5A requires hypusine, a posttranslational modification synthesized in Eukarya from the polyamine precursor spermidine. Intracellular polyamine analyses revealed that agmatine and cadaverine were the main polyamines produced in Haloferax volcanii in minimal medium, raising the question of how hypusine is synthesized in this halophilic Archaea. Metabolic reconstruction led to a tentative picture of polyamine metabolism and aIF5A modification in Hfx. volcanii that was experimentally tested. Analysis of aIF5A from Hfx. volcanii by LC-MS/MS revealed it was exclusively deoxyhypusinylated. Genetic studies confirmed the role of the predicted arginine decarboxylase gene (HVO_1958 in agmatine synthesis. The agmatinase-like gene (HVO_2299 was found to be essential, consistent with a role in aIF5A modification predicted by physical clustering evidence. Recombinant deoxyhypusine synthase (DHS from S. cerevisiae was shown to transfer 4-aminobutyl moiety from spermidine to aIF5A from Hfx. volcanii in vitro. However, at least under conditions tested, this transfer was not observed with the Hfx. volcanii DHS. Furthermore, the growth of Hfx. volcanii was not inhibited by the classical DHS inhibitor GC7. We propose a model of deoxyhypusine synthesis in Hfx. volcanii that differs from the canonical eukaryotic pathway, paving the way for further studies.

  4. Deciphering the Translation Initiation Factor 5A Modification Pathway in Halophilic Archaea.

    Science.gov (United States)

    Prunetti, Laurence; Graf, Michael; Blaby, Ian K; Peil, Lauri; Makkay, Andrea M; Starosta, Agata L; Papke, R Thane; Oshima, Tairo; Wilson, Daniel N; de Crécy-Lagard, Valérie

    2016-01-01

    Translation initiation factor 5A (IF5A) is essential and highly conserved in Eukarya (eIF5A) and Archaea (aIF5A). The activity of IF5A requires hypusine, a posttranslational modification synthesized in Eukarya from the polyamine precursor spermidine. Intracellular polyamine analyses revealed that agmatine and cadaverine were the main polyamines produced in Haloferax volcanii in minimal medium, raising the question of how hypusine is synthesized in this halophilic Archaea. Metabolic reconstruction led to a tentative picture of polyamine metabolism and aIF5A modification in Hfx. volcanii that was experimentally tested. Analysis of aIF5A from Hfx. volcanii by LC-MS/MS revealed it was exclusively deoxyhypusinylated. Genetic studies confirmed the role of the predicted arginine decarboxylase gene (HVO_1958) in agmatine synthesis. The agmatinase-like gene (HVO_2299) was found to be essential, consistent with a role in aIF5A modification predicted by physical clustering evidence. Recombinant deoxyhypusine synthase (DHS) from S. cerevisiae was shown to transfer 4-aminobutyl moiety from spermidine to aIF5A from Hfx. volcanii in vitro. However, at least under conditions tested, this transfer was not observed with the Hfx. volcanii DHS. Furthermore, the growth of Hfx. volcanii was not inhibited by the classical DHS inhibitor GC7. We propose a model of deoxyhypusine synthesis in Hfx. volcanii that differs from the canonical eukaryotic pathway, paving the way for further studies.

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

    Science.gov (United States)

    Hashimoto, Masayoshi; Neriya, Yutaro; Yamaji, Yasuyuki; Namba, Shigetou

    2016-01-01

    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. PMID:27833593

  6. Relationship between Eukaryotic Translation Initiation Factor 4E and Malignant Angiogenesis in Non-Hodgkin Lymphoma

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yanxia; LIU Wenli; ZHOU Sheng; ZHOU Jianfeng; SUN Hanying

    2005-01-01

    The relationship between angiogenesis and eukaryotic translation initiation factor 4E (EIF4E) expression level in non-Hodgkin lymphoma (NHL) was studied. Mean microvessel density (MVD) and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3.1 (+) and transfected into Raji cells. A series of angiogenesis related factors,including vascular endothelial growth factor (VEGF), matrix metalloproteinases 9 (MMP-9)and tissue inhibitor of metalloproteinases-2 (TIMP-2) proteins were detected by Western blot. The results showed that: (1) The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas(P<0.05)and the expression of EIF4E was positively correlated with MVD in lymph node of NHL(r=0. 695, P<0.01). (2) Antisense EIF4E eukaryocytic expression vector (pcDNA3.1-EIF4Eas) was constructed successfully. (3) EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells ( NHPMC), and blockage of EIF4E expression brought down the expression of VEGF and MMP-9.However, TIMP-2 was undetectable in Raji cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL.

  7. Translation initiation factor eIF4G1 preferentially binds yeast transcript leaders containing conserved oligo-uridine motifs.

    Science.gov (United States)

    Zinshteyn, Boris; Rojas-Duran, Maria F; Gilbert, Wendy V

    2017-09-01

    Translational control of gene expression plays essential roles in cellular stress responses and organismal development by enabling rapid, selective, and localized control of protein production. Translational regulation depends on context-dependent differences in the protein output of mRNAs, but the key mRNA features that distinguish efficiently translated mRNAs are largely unknown. Here, we comprehensively determined the RNA-binding preferences of the eukaryotic initiation factor 4G (eIF4G) to assess whether this core translation initiation factor has intrinsic sequence preferences that may contribute to preferential translation of specific mRNAs. We identified a simple RNA sequence motif-oligo-uridine-that mediates high-affinity binding to eIF4G in vitro. Oligo(U) motifs occur naturally in the transcript leader (TL) of hundreds of yeast genes, and mRNAs with unstructured oligo(U) motifs were enriched in immunoprecipitations against eIF4G. Ribosome profiling following depletion of eIF4G in vivo showed preferentially reduced translation of mRNAs with long TLs, including those that contain oligo(U). Finally, TL oligo(U) elements are enriched in genes with regulatory roles and are conserved between yeast species, consistent with an important cellular function. Taken together, our results demonstrate RNA sequence preferences for a general initiation factor, which cells potentially exploit for translational control of specific mRNAs. © 2017 Zinshteyn et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  8. 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.

  9. A new role for translation initiation factor 2 in maintaining genome integrity.

    Directory of Open Access Journals (Sweden)

    K Elizabeth Madison

    Full Text Available Escherichia coli translation initiation factor 2 (IF2 performs the unexpected function of promoting transition from recombination to replication during bacteriophage Mu transposition in vitro, leading to initiation by replication restart proteins. This function has suggested a role of IF2 in engaging cellular restart mechanisms and regulating the maintenance of genome integrity. To examine the potential effect of IF2 on restart mechanisms, we characterized its influence on cellular recovery following DNA damage by methyl methanesulfonate (MMS and UV damage. Mutations that prevent expression of full-length IF2-1 or truncated IF2-2 and IF2-3 isoforms affected cellular growth or recovery following DNA damage differently, influencing different restart mechanisms. A deletion mutant (del1 expressing only IF2-2/3 was severely sensitive to growth in the presence of DNA-damaging agent MMS. Proficient as wild type in repairing DNA lesions and promoting replication restart upon removal of MMS, this mutant was nevertheless unable to sustain cell growth in the presence of MMS; however, growth in MMS could be partly restored by disruption of sulA, which encodes a cell division inhibitor induced during replication fork arrest. Moreover, such characteristics of del1 MMS sensitivity were shared by restart mutant priA300, which encodes a helicase-deficient restart protein. Epistasis analysis indicated that del1 in combination with priA300 had no further effects on cellular recovery from MMS and UV treatment; however, the del2/3 mutation, which allows expression of only IF2-1, synergistically increased UV sensitivity in combination with priA300. The results indicate that full-length IF2, in a function distinct from truncated forms, influences the engagement or activity of restart functions dependent on PriA helicase, allowing cellular growth when a DNA-damaging agent is present.

  10. Automating Initial Guess Generation for High Fidelity Trajectory Optimization Tools

    Science.gov (United States)

    Villa, Benjamin; Lantoine, Gregory; Sims, Jon; Whiffen, Gregory

    2013-01-01

    Many academic studies in spaceflight dynamics rely on simplified dynamical models, such as restricted three-body models or averaged forms of the equations of motion of an orbiter. In practice, the end result of these preliminary orbit studies needs to be transformed into more realistic models, in particular to generate good initial guesses for high-fidelity trajectory optimization tools like Mystic. This paper reviews and extends some of the approaches used in the literature to perform such a task, and explores the inherent trade-offs of such a transformation with a view toward automating it for the case of ballistic arcs. Sample test cases in the libration point regimes and small body orbiter transfers are presented.

  11. Improvements in Pain Outcomes in a Canadian Pediatric Teaching Hospital Following Implementation of a Multifaceted, Knowledge Translation Initiative

    Directory of Open Access Journals (Sweden)

    Lisa M Zhu

    2012-01-01

    Full Text Available BACKGROUND: A previous audit performed at a tertiary/quaternary pediatric hospital in Toronto, Ontario, demonstrated suboptimal assessment and treatment of children’s pain. Knowledge translation (KT initiatives (education, reminders, audit and feedback were implemented to address identified care gaps; however, the impact is unknown.

  12. Ribosomal Initiation Complex Assembly within the Wild-Strain of Coxsackievirus B3 and Live-Attenuated Sabin3-like IRESes during the Initiation of Translation

    Directory of Open Access Journals (Sweden)

    Nathalie Chamond

    2013-02-01

    Full Text Available Coxsackievirus B3 (CVB3 is an enterovirus of the family of Picornaviridae. The Group B coxsackieviruses include six serotypes (B1 to B6 that cause a variety of human diseases, including myocarditis, meningitis, and diabetes. Among the group B, the B3 strain is mostly studied for its cardiovirulence and its ability to cause acute and persistent infections. Translation initiation of CVB3 RNA has been shown to be mediated by a highly ordered structure of the 5’-untranslated region (5’UTR, which harbors an internal ribosome entry site (IRES. Translation initiation is a complex process in which initiator tRNA, 40S and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs into an 80S ribosome at the initiation codon of the mRNA. We have previously addressed the question of whether the attenuating mutations of domain V of the poliovirus IRES were specific for a given genomic context or whether they could be transposed and extrapolated to a genomic related virus, i.e., CVB3 wild-type strain. In this context, we have described that Sabin3-like mutation (U473→C introduced in CVB3 genome led to a defective mutant with a serious reduction in translation efficiency. In this study, we analyzed the efficiency of formation of ribosomal initiation complexes 48S and 80S through 10%–30% and 10%–50% sucrose gradients using rabbit reticulocyte lysates (RRLs and stage-specific translation inhibitors: 5'-Guanylyl-imidodiphosphate (GMP-PNP and Cycloheximide (CHX, respectively. We demonstrated that the interaction of 48S and 80S ribosomal complexes within the mutant CVB3 RNA was abolished compared with the wild-type RNA by ribosome assembly analysis. Taken together, it is possible that the mutant RNA was unable to interact with some trans-acting factors critical for enhanced IRES function.

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

    Science.gov (United States)

    Zhu, Jie; Wang, Binbin; Miao, Qiuhong; Tan, Yonggui; Li, Chuanfeng; Chen, Zongyan; Guo, Huimin; Liu, Guangqing

    2015-01-01

    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.

  14. 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.

  15. Role of hypusinated eukaryotic translation initiation factor 5A in polyamine depletion-induced cytostasis.

    Science.gov (United States)

    Hyvönen, Mervi T; Keinänen, Tuomo A; Cerrada-Gimenez, Marc; Sinervirta, Riitta; Grigorenko, Nikolay; Khomutov, Alex R; Vepsäläinen, Jouko; Alhonen, Leena; Jänne, Juhani

    2007-11-30

    We have earlier shown that alpha-methylated spermidine and spermine analogues rescue cells from polyamine depletion-induced growth inhibition and maintain pancreatic integrity under severe polyamine deprivation. However, because alpha-methylspermidine can serve as a precursor of hypusine, an integral part of functional eukaryotic translation initiation factor 5A required for cell proliferation, and because alpha, omega-bismethylspermine can be converted to methylspermidine, it is not entirely clear whether the restoration of cell growth is actually attributable to hypusine formed from these polyamine analogues. Here, we have used optically active isomers of methylated spermidine and spermine and show that polyamine depletion-induced acute cytostasis in cultured cells could be reversed by all the isomers of the methylpolyamines irrespective of whether they served or not as precursors of hypusine. In transgenic rats with activated polyamine catabolism, all the isomers similarly restored liver regeneration and reduced plasma alpha-amylase activity associated with induced pancreatitis. Under the above experimental conditions, the (S, S)- but not the (R, R)-isomer of bismethylspermine was converted to methylspermidine apparently through the action of spermine oxidase strongly preferring the (S, S)-isomer. Of the analogues, however, only (S)-methylspermidine sustained cell growth during prolonged (more than 1 week) inhibition of polyamine biosynthesis. It was also the only isomer efficiently converted to hypusine, indicating that deoxyhypusine synthase likewise possesses hidden stereospecificity. Taken together, the results show that growth inhibition in response to polyamine depletion involves two phases, an acute and a late hypusine-dependent phase.

  16. 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

  17. 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.

  18. Translational networks in healthcare? Evidence on the design and initiation of organizational networks for knowledge mobilization.

    Science.gov (United States)

    Fitzgerald, Louise; Harvey, Gill

    2015-08-01

    International attention has focussed on the variations between research evidence and practice in healthcare. This prompted the creation of formalized translational networks consisting of academic-service partnerships. The English Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) are one example of a translational network. Using longitudinal, archival case study data from one CLAHRC over a 3-year period (2008-11), this article explores the relationship between organizational form and the function(s) of a translational network. The article focuses on the research gaps on the effective structures and appropriate governance to support a translational network. Data analysis suggested that the policy of setting up translational networks is insufficient of itself to produce positive translational activity. The data indicate that to leverage the benefits of the whole network, attention must be paid to devising a structure which integrates research production and use and facilitates lateral cross-disciplinary and cross-organizational communication. Equally, appropriate governance arrangements are necessary, particularly in large, multi-stakeholder networks, where shared governance may be questionable. Inappropriate network structure and governance inhibits the potential of the translational network. Finally, the case provides insights into the movement of knowledge within and between network organizations. The data demonstrate that knowledge mobilization extends beyond knowledge translation; knowledge mobilization includes the negotiated utilization of knowledge - a balanced power form of collaboration. Whilst much translational effort is externally focused on the health system, our findings highlight the essential need for the internal negotiation and mobilization of knowledge within academia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Dual Mechanisms of Translation Initiation of the Full-Length HIV-1 mRNA Contribute to Gag Synthesis

    Science.gov (United States)

    Rivero, Matias; Cohen, Éric A.; Lopez-Lastra, Marcelo; Mouland, Andrew J.

    2013-01-01

    The precursor group-specific antigen (pr55Gag) is central to HIV-1 assembly. Its expression alone is sufficient to assemble into virus-like particles. It also selects the genomic RNA for encapsidation and is involved in several important virus-host interactions for viral assembly and restriction, making its synthesis essential for aspects of viral replication. Here, we show that the initiation of translation of the HIV-1 genomic RNA is mediated through both a cap-dependent and an internal ribosome entry site (IRES)-mediated mechanisms. In support of this notion, pr55Gag synthesis was maintained at 70% when cap-dependent translation initiation was blocked by the expression of eIF4G- and PABP targeting viral proteases in two in vitro systems and in HIV-1-expressing cells directly infected with poliovirus. While our data reveal that IRES-dependent translation of the viral genomic RNA ensures pr55Gag expression, the synthesis of other HIV-1 proteins, including that of pr160Gag/Pol, Vpr and Tat is suppressed early during progressive poliovirus infection. The data presented herein implies that the unspliced HIV-1 genomic RNA utilizes both cap-dependent and IRES-dependent translation initiation to supply pr55Gag for virus assembly and production. PMID:23861855

  20. Dual mechanisms of translation initiation of the full-length HIV-1 mRNA contribute to gag synthesis.

    Directory of Open Access Journals (Sweden)

    Anne Monette

    Full Text Available The precursor group-specific antigen (pr55(Gag is central to HIV-1 assembly. Its expression alone is sufficient to assemble into virus-like particles. It also selects the genomic RNA for encapsidation and is involved in several important virus-host interactions for viral assembly and restriction, making its synthesis essential for aspects of viral replication. Here, we show that the initiation of translation of the HIV-1 genomic RNA is mediated through both a cap-dependent and an internal ribosome entry site (IRES-mediated mechanisms. In support of this notion, pr55(Gag synthesis was maintained at 70% when cap-dependent translation initiation was blocked by the expression of eIF4G- and PABP targeting viral proteases in two in vitro systems and in HIV-1-expressing cells directly infected with poliovirus. While our data reveal that IRES-dependent translation of the viral genomic RNA ensures pr55(Gag expression, the synthesis of other HIV-1 proteins, including that of pr160(Gag/Pol, Vpr and Tat is suppressed early during progressive poliovirus infection. The data presented herein implies that the unspliced HIV-1 genomic RNA utilizes both cap-dependent and IRES-dependent translation initiation to supply pr55(Gag for virus assembly and production.

  1. Inactivation of the mTORC1-Eukaryotic Translation Initiation Factor 4E Pathway Alters Stress Granule Formation

    Science.gov (United States)

    Fournier, Marie-Josée; Coudert, Laetitia; Mellaoui, Samia; Adjibade, Pauline; Gareau, Cristina; Côté, Marie-France; Sonenberg, Nahum; Gaudreault, René C.

    2013-01-01

    Stress granules (SG) are cytoplasmic multimeric RNA bodies that form under stress conditions known to inhibit cap-dependent translation. SG contain translation initiation factors, RNA binding proteins, and signaling molecules. SG are known to inhibit apoptotic pathways, thus contributing to chemo- and radioresistance in tumor cells. However, whether stress granule formation involves oncogenic signaling pathways is currently unknown. Here, we report a novel role of the mTORC1-eukaryotic translation initiation factor 4E (eIF4E) pathway, a key regulator of cap-dependent translation initiation of oncogenic factors, in SG formation. mTORC1 specifically drives the eIF4E-mediated formation of SG through the phosphorylation of 4E-BP1, a key factor known to inhibit formation of the mTORC1-dependent eIF4E-eIF4GI interactions. Disrupting formation of SG by inactivation of mTOR with its specific inhibitor pp242 or by depletion of eIF4E or eIF4GI blocks the SG-associated antiapoptotic p21 pathway. Finally, pp242 sensitizes cancer cells to death in vitro and inhibits the growth of chemoresistant tumors in vivo. This work therefore highlights a novel role of the oncogenic mTORC1-eIF4E pathway, namely, the promotion of formation of antiapoptotic SG. PMID:23547259

  2. Structure and dimerization of translation initiation factor aIF5B in solution

    Energy Technology Data Exchange (ETDEWEB)

    Carø VohlanderRasmussen, Louise; Oliveira, Cristiano Luis Pinto; Byron, Olwyn; Jensen, Janni Mosgaard; Pedersen, Jan Skov; Sperling-Petersen, Hans Uffe; Mortensen, Kim Kusk (Aarhus); (Glasgow)

    2012-02-07

    Translation initiation factor 5B (IF5B) is required for initiation of protein synthesis. The solution structure of archaeal IF5B (aIF5B) was analysed by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS) and was indicated to be in both monomeric and dimeric form. Sedimentation equilibrium (SE) analytical ultracentrifugation (AUC) of aIF5B indicated that aIF5B forms irreversible dimers in solution but only to a maximum of 5.0-6.8% dimer. Sedimentation velocity (SV) AUC at higher speed also indicated the presence of two species, and the sedimentation coefficients s{sub 20,w}{sup 0} were determined to be 3.64 and 5.51 {+-} 0.29 S for monomer and dimer, respectively. The atomic resolution (crystallographic) structure of aIF5B (Roll-Mecak et al. [6]) was used to model monomer and dimer, and theoretical sedimentation coefficients for these models were computed (3.89 and 5.63 S, respectively) in good agreement with the sedimentation coefficients obtained from SV analysis. Thus, the structure of aIF5B in solution must be very similar to the atomic resolution structure of aIF5B. SAXS data were acquired in the same buffer with the addition of 2% glycerol to inhibit dimerization, and the resultant monomeric aIF5B in solution did indeed adopt a structure very similar to the one reported earlier for the protein in crystalline form. The p(r) function indicated an elongated conformation supported by a radius of gyration of 37.5 {+-} 0.2 {angstrom} and a maximum dimension of {approx}130 {angstrom}. The effects of glycerol on the formation of dimers are discussed. This new model of aIF5B in solution shows that there are universal structural differences between aIF5B and the homologous protein IF2 from Escherichia coli.

  3. Structure and dimerization of translation initiation factor aIF5B in solution

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Louise Caroe Vohlander [Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10, DK-8000 Aarhus C (Denmark); Oliveira, Cristiano Luis Pinto [Department of Chemistry, Centre for mRNP Biogenesis and Metabolism, and iNANO Interdisciplinary Nanoscience Center, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C (Denmark); Byron, Olwyn [Glasgow Biomedical Research Center, University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Jensen, Janni Mosgaard [Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10, DK-8000 Aarhus C (Denmark); Pedersen, Jan Skov [Department of Chemistry, Centre for mRNP Biogenesis and Metabolism, and iNANO Interdisciplinary Nanoscience Center, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C (Denmark); Sperling-Petersen, Hans Uffe [Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10, DK-8000 Aarhus C (Denmark); Mortensen, Kim Kusk, E-mail: kkm@science.au.dk [Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10, DK-8000 Aarhus C (Denmark)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer aIF5B forms maximum 5.0-6.8% irreversible dimers in solution. Black-Right-Pointing-Pointer Sedimentation coefficients for monomer and dimer are 3.64 and 5.51 {+-} 0.29 S. Black-Right-Pointing-Pointer Adding only 2% glycerol prevents dimerization. Black-Right-Pointing-Pointer SAXS on aIF5B monomer gave an R{sub g} of 37.5 {+-} 0.2 A and a D{sub max} of {approx}130 A. Black-Right-Pointing-Pointer There are universal structural differences between aIF5B and Escherichia coli IF2. -- Abstract: Translation initiation factor 5B (IF5B) is required for initiation of protein synthesis. The solution structure of archaeal IF5B (aIF5B) was analysed by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS) and was indicated to be in both monomeric and dimeric form. Sedimentation equilibrium (SE) analytical ultracentrifugation (AUC) of aIF5B indicated that aIF5B forms irreversible dimers in solution but only to a maximum of 5.0-6.8% dimer. Sedimentation velocity (SV) AUC at higher speed also indicated the presence of two species, and the sedimentation coefficients s{sub 20,w}{sup 0} were determined to be 3.64 and 5.51 {+-} 0.29 S for monomer and dimer, respectively. The atomic resolution (crystallographic) structure of aIF5B (Roll-Mecak et al. ) was used to model monomer and dimer, and theoretical sedimentation coefficients for these models were computed (3.89 and 5.63 S, respectively) in good agreement with the sedimentation coefficients obtained from SV analysis. Thus, the structure of aIF5B in solution must be very similar to the atomic resolution structure of aIF5B. SAXS data were acquired in the same buffer with the addition of 2% glycerol to inhibit dimerization, and the resultant monomeric aIF5B in solution did indeed adopt a structure very similar to the one reported earlier for the protein in crystalline form. The p(r) function indicated an elongated conformation supported by a radius of gyration of 37.5 {+-} 0.2 A

  4. The surprising negative correlation of gene length and optimal codon use--disentangling translational selection from GC-biased gene conversion in yeast.

    Science.gov (United States)

    Stoletzki, Nina

    2011-04-11

    Surprisingly, in several multi-cellular eukaryotes optimal codon use correlates negatively with gene length. This contrasts with the expectation under selection for translational accuracy. While suggested explanations focus on variation in strength and efficiency of translational selection, it has rarely been noticed that the negative correlation is reported only in organisms whose optimal codons are biased towards codons that end with G or C (-GC). This raises the question whether forces that affect base composition--such as GC-biased gene conversion--contribute to the negative correlation between optimal codon use and gene length. Yeast is a good organism to study this as equal numbers of optimal codons end in -GC and -AT and one may hence compare frequencies of optimal GC- with optimal AT-ending codons to disentangle the forces. Results of this study demonstrate in yeast frequencies of GC-ending (optimal AND non-optimal) codons decrease with gene length and increase with recombination. A decrease of GC-ending codons along genes contributes to the negative correlation with gene length. Correlations with recombination and gene expression differentiate between GC-ending and optimal codons, and also substitution patterns support effects of GC-biased gene conversion. While the general effect of GC-biased gene conversion is well known, the negative correlation of optimal codon use with gene length has not been considered in this context before. Initiation of gene conversion events in promoter regions and the presence of a gene conversion gradient most likely explain the observed decrease of GC-ending codons with gene length and gene position.

  5. 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.

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

    NARCIS (Netherlands)

    Mugavero, M.J.; May, M.; Harris, R.; Saag, M.S.; Costagliola, D.; Egger, M.; Phillips, A.; Gunthard, H.F.; Dabis, F.; Hogg, R.; Wolf, F. de; Fatkenheuer, G.; Gill, M.J.; Justice, A.; Monforte, A. D'Arminio; Lampe, F.; Miro, J.M.; Staszewski, S.; Sterne, J.A.

    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-naive patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between

  7. 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.

  8. Novel mutation involving the translation initiation codon of the growth hormone receptor gene (GHR) in a patient with Laron syndrome.

    Science.gov (United States)

    Quinteiro, Celsa; Castro-Feijoo, Lidia; Loidi, Lourdes; Barreiro, Jesus; de la Fuente, Maria; Dominguez, Fernando; Pombo, Manuel

    2002-01-01

    Laron syndrome (LS) or growth hormone (GH) insensitivity syndrome (GHIS) is an autosomal recessive disease due to molecular defects in the GH receptor gene (GHR). Most of the identified mutations are located on the extracelular domain of the receptor. We studied the GHR gene in a patient with LS and found a homozygous missense mutation in exon 2. The novel mutation is an A-->T transversion (ATG -->TTG) that abolishes the translation initiation codon of the GHR gene. This mutation is expected to prevent the translation of the protein. We present clinical, biochemical and molecular evidence of Laron syndrome as the result of a mutation (ATG-->TTG) in the codon for the initial methionine of the GHR gene.

  9. Adaptation and Diversification of an RNA Replication System under Initiation- or Termination-Impaired Translational Conditions.

    Science.gov (United States)

    Mizuuchi, Ryo; Ichihashi, Norikazu; Yomo, Tetsuya

    2016-07-01

    Adaptation to various environments is a remarkable characteristic of life. Is this limited to extant complex living organisms, or is it also possible for a simpler self-replication system to adapt? In this study, we addressed this question by using a translation-coupled RNA replication system that comprised a reconstituted translation system and an RNA "genome" that encoded a replicase gene. We performed RNA replication reactions under four conditions, under which different components of translation were partly inhibited. We found that replication efficiency increased with the number of rounds of replication under all the tested conditions. The types of dominant mutations differed depending on the condition, thus indicating that this simple system adapted to different environments in different ways. This suggests that even a primitive self-replication system composed of a small number of genes on the early earth could have had the ability to adapt to various environments.

  10. 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

    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...

  11. The post-translational synthesis of a polyamine-derived amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF5A).

    Science.gov (United States)

    Park, Myung Hee

    2006-02-01

    The eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein that contains the unique polyamine-derived amino acid, hypusine [Nepsilon-(4-amino-2-hydroxybutyl)lysine]. Hypusine is formed in eIF5A by a novel post-translational modification reaction that involves two enzymatic steps. In the first step, deoxyhypusine synthase catalyzes the cleavage of the polyamine spermidine and transfer of its 4-aminobutyl moiety to the epsilon-amino group of one specific lysine residue of the eIF5A precursor to form a deoxyhypusine intermediate. In the second step, deoxyhypusine hydroxylase converts the deoxyhypusine-containing intermediate to the hypusine-containing mature eIF5A. The structure and mechanism of deoxyhypusine synthase have been extensively characterized. Deoxyhypusine hydroxylase is a HEAT-repeat protein with a symmetrical superhelical structure consisting of 8 helical hairpins (HEAT motifs). It is a novel metalloenzyme containing tightly bound iron at the active sites. Four strictly conserved His-Glu pairs were identified as iron coordination sites. The structural fold of deoxyhypusine hydroxylase is entirely different from those of the other known protein hydroxylases such as prolyl 4-hydroxylase and lysyl hydroxylases. The eIF5A protein and deoxyhypusine/hypusine modification are essential for eukaryotic cell proliferation. Thus, hypusine synthesis represents the most specific protein modification known to date, and presents a novel target for intervention in mammalian cell proliferation.

  12. Alternative translational initiation of ATP sulfurylase underlying dual localization of sulfate assimilation pathways in plastids and cytosol in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Anne-Sophie eBohrer

    2015-01-01

    Full Text Available Plants assimilate inorganic sulfate into sulfur-containing vital metabolites. ATP sulfurylase (ATPS is the enzyme catalyzing the key entry step of the sulfate assimilation pathway in both plastids and cytosol in plants. Arabidopsis thaliana has four ATPS genes (ATPS1, -2, -3 and -4 encoding ATPS pre-proteins containing N-terminal transit peptide sequences for plastid targeting, however, the genetic identity of the cytosolic ATPS has remained unverified. Here we show that Arabidopsis ATPS2 dually encodes plastidic and cytosolic ATPS isoforms, differentiating their subcellular localizations by initiating translation at AUGMet1 to produce plastid-targeted ATPS2 pre-proteins or at AUGMet52 or AUGMet58 within the transit peptide to have ATPS2 stay in cytosol. Translational initiation of ATPS2 at AUGMet52 or AUGMet58 was verified by expressing a tandem-fused synthetic gene, ATPS2(5’UTR-His12:Renilla luciferase:ATPS2(Ile13-Val77:firefly luciferase, under a single constitutively active CaMV 35S promoter in Arabidopsis protoplasts and examining the activities of two different luciferases translated in-frame with split N-terminal portions of ATPS2. Introducing missense mutations at AUGMet52 and AUGMet58 significantly reduced the firefly luciferase activity, while AUGMet52 was a relatively preferred site for the alternative translational initiation. The activity of luciferase fusion protein starting at AUGMet52 or AUGMet58 was not modulated by changes in sulfate conditions. The dual localizations of ATPS2 in plastids and cytosol were further evidenced by expression of ATPS2-GFP fusion proteins in Arabidopsis protoplasts and transgenic lines, while they were also under control of tissue-specific ATPS2 promoter activity found predominantly in leaf epidermal cells, guard cells, vascular tissues and roots.

  13. More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer.

    Science.gov (United States)

    Lacerda, Rafaela; Menezes, Juliane; Romão, Luísa

    2017-05-01

    The scanning model for eukaryotic mRNA translation initiation states that the small ribosomal subunit, along with initiation factors, binds at the cap structure at the 5' end of the mRNA and scans the 5' untranslated region (5'UTR) until an initiation codon is found. However, under conditions that impair canonical cap-dependent translation, the synthesis of some proteins is kept by alternative mechanisms that are required for cell survival and stress recovery. Alternative modes of translation initiation include cap- and/or scanning-independent mechanisms of ribosomal recruitment. In most cap-independent translation initiation events there is a direct recruitment of the 40S ribosome into a position upstream, or directly at, the initiation codon via a specific internal ribosome entry site (IRES) element in the 5'UTR. Yet, in some cellular mRNAs, a different translation initiation mechanism that is neither cap- nor IRES-dependent seems to occur through a special RNA structure called cap-independent translational enhancer (CITE). Recent evidence uncovered a distinct mechanism through which mRNAs containing N (6)-methyladenosine (m(6)A) residues in their 5'UTR directly bind eukaryotic initiation factor 3 (eIF3) and the 40S ribosomal subunit in order to initiate translation in the absence of the cap-binding proteins. This review focuses on the important role of cap-independent translation mechanisms in human cells and how these alternative mechanisms can either act individually or cooperate with other cis-acting RNA regulons to orchestrate specific translational responses triggered upon several cellular stress states, and diseases such as cancer. Elucidation of these non-canonical mechanisms reveals the complexity of translational control and points out their potential as prospective novel therapeutic targets.

  14. Unique role for translation initiation factor 3 in the light color regulation of photosynthetic gene expression

    OpenAIRE

    Gutu, Andrian; Nesbit, April D.; Alverson, Andrew J.; Palmer, Jeffrey D.; Kehoe, David M.

    2013-01-01

    The regulation of photosynthesis is important, yet poorly understood. Our work reveals a previously undescribed form of photosynthesis gene regulation in cyanobacteria that apparently also controls gene expression in plants, including commercially important crops. This finding may provide a unique approach to modifying the environmental responses and developmental programs of agriculturally important species. In addition, translation is a key biological process, and many of its important feat...

  15. 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.

  16. Effect of the Flanking Sequence Architecture of Translation Initiation AUG Codon on Gene Expression Level in Rice

    Institute of Scientific and Technical Information of China (English)

    LIU Qing-po; TAN Jun; XUE Qing-zhong

    2004-01-01

    The relationship between the codon usage bias, gene expression level and the AUG context (from -20 to +6 positions relative to the initiator AUG codon) was examined in 541unigene sequences of rice. A significant correlation for CAI values (codon adaptation index) was observed at five nucleotide positions (-19, -18, -9, -4, +5), eight (-19, -18,-14, -9, -6, -4, -1, +5) for CPP (codon preference parameter), and seven (-18, -16, -15,-9, -7, -1, + 6) for mRNA abundance in the flanking sequence of the initiator AUG codon respectively, but a significantly positive correlation for both CAI and CPP at two positions (-4 and +5), indicating that both those positions are evolutionally under the natural selection constraint at the translational level. By site-directed mutagenesis at seven specific positions (-18, -16, -15, -9, -7, -1 and + 6) for allergenic protein that had the highest mRNA abundance in this study, its expression level decreased dramatically 63.3 and 72.5% respectively, indicating the importance of those 7 positions for gene expression. A highly positive correlation (r= 0.625, P< 0.01) between AUGCAI and GC content in the flanking sequence of the initiator AUG codon showed a more effective higher GC content on translation initiation efficiency. The strong preference for G or C at those 8 positions (-6, -5, -3, -2, -1, +4, +5 and +6) in the AUG context suggested that an important factor in modulation of the translation efficiency, as well as synonymous codon usage bias, particularly in highly expressed genes.

  17. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) induces initiation factor 2 alpha phosphorylation and translation inhibition in PC12 cells.

    Science.gov (United States)

    Muñoz, F; Martín, M E; Salinas, M; Fando, J L

    2001-03-09

    We have investigated the effect of the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) on protein synthesis rate and initiation factor 2 (eIF2) phosphorylation in PC12 cells differentiated with nerve growth factor. FCCP treatment induced a very rapid 2-fold increase in intracellular Ca(2+) concentration that was accompanied by a strong protein synthesis rate inhibition (68%). The translation inhibition correlated with an increased phosphorylation of the alpha subunit of eIF2 (eIF2 alpha) (25% vs. 7%, for FCCP-treated and control cells, respectively) and a 1.7-fold increase in the double-stranded RNA-dependent protein kinase activity. No changes in the PKR endoplasmic reticulum-related kinase or eIF2 alpha phosphatase were found. Translational regulation may play a significant role in the process triggered by mitochondrial calcium mobilization.

  18. 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.

  19. Initiation factor 2 crystal structure reveals a different domain organization from eukaryotic initiation factor 5B and mechanism among translational GTPases.

    Science.gov (United States)

    Eiler, Daniel; Lin, Jinzhong; Simonetti, Angelita; Klaholz, Bruno P; Steitz, Thomas A

    2013-09-24

    The initiation of protein synthesis uses initiation factor 2 (IF2) in prokaryotes and a related protein named eukaryotic initiation factor 5B (eIF5B) in eukaryotes. IF2 is a GTPase that positions the initiator tRNA on the 30S ribosomal initiation complex and stimulates its assembly to the 50S ribosomal subunit to make the 70S ribosome. The 3.1-Å resolution X-ray crystal structures of the full-length Thermus thermophilus apo IF2 and its complex with GDP presented here exhibit two different conformations (all of its domains except C2 domain are visible). Unlike all other translational GTPases, IF2 does not have an effecter domain that stably contacts the switch II region of the GTPase domain. The domain organization of IF2 is inconsistent with the "articulated lever" mechanism of communication between the GTPase and initiator tRNA binding domains that has been proposed for eIF5B. Previous cryo-electron microscopy reconstructions, NMR experiments, and this structure show that IF2 transitions from being flexible in solution to an extended conformation when interacting with ribosomal complexes.

  20. The nematode eukaryotic translation initiation factor 4E/G complex works with a trans-spliced leader stem-loop to enable efficient translation of trimethylguanosine-capped RNAs.

    Science.gov (United States)

    Wallace, Adam; Filbin, Megan E; Veo, Bethany; McFarland, Craig; Stepinski, Janusz; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Davis, Richard E

    2010-04-01

    Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5' end through the eIF4F initiation complex binding to the 5' m(7)G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5' end of mRNAs. Efficient translation of TMG-capped mRNAs in nematodes requires the SL sequence. Here we define a core set of nucleotides and a stem-loop within the 22-nucleotide nematode SL that stimulate translation of mRNAs with a TMG cap. The structure and core nucleotides are conserved in other nematode SLs and correspond to regions of SL1 required for early Caenorhabditis elegans development. These SL elements do not facilitate translation of m(7)G-capped RNAs in nematodes or TMG-capped mRNAs in mammalian or plant translation systems. Similar stem-loop structures in phylogenetically diverse SLs are predicted. We show that the nematode eukaryotic translation initiation factor 4E/G (eIF4E/G) complex enables efficient translation of the TMG-SL RNAs in diverse in vitro translation systems. TMG-capped mRNA translation is determined by eIF4E/G interaction with the cap and the SL RNA, although the SL does not increase the affinity of eIF4E/G for capped RNA. These results suggest that the mRNA 5' untranslated region (UTR) can play a positive and novel role in translation initiation through interaction with the eIF4E/G complex in nematodes and raise the issue of whether eIF4E/G-RNA interactions play a role in the translation of other eukaryotic mRNAs.

  1. Ab initio optimization principle for the ground states of translationally invariant strongly correlated quantum lattice models

    Science.gov (United States)

    Ran, Shi-Ju

    2016-05-01

    In this work, a simple and fundamental numeric scheme dubbed as ab initio optimization principle (AOP) is proposed for the ground states of translational invariant strongly correlated quantum lattice models. The idea is to transform a nondeterministic-polynomial-hard ground-state simulation with infinite degrees of freedom into a single optimization problem of a local function with finite number of physical and ancillary degrees of freedom. This work contributes mainly in the following aspects: (1) AOP provides a simple and efficient scheme to simulate the ground state by solving a local optimization problem. Its solution contains two kinds of boundary states, one of which play the role of the entanglement bath that mimics the interactions between a supercell and the infinite environment, and the other gives the ground state in a tensor network (TN) form. (2) In the sense of TN, a novel decomposition named as tensor ring decomposition (TRD) is proposed to implement AOP. Instead of following the contraction-truncation scheme used by many existing TN-based algorithms, TRD solves the contraction of a uniform TN in an opposite way by encoding the contraction in a set of self-consistent equations that automatically reconstruct the whole TN, making the simulation simple and unified; (3) AOP inherits and develops the ideas of different well-established methods, including the density matrix renormalization group (DMRG), infinite time-evolving block decimation (iTEBD), network contractor dynamics, density matrix embedding theory, etc., providing a unified perspective that is previously missing in this fields. (4) AOP as well as TRD give novel implications to existing TN-based algorithms: A modified iTEBD is suggested and the two-dimensional (2D) AOP is argued to be an intrinsic 2D extension of DMRG that is based on infinite projected entangled pair state. This paper is focused on one-dimensional quantum models to present AOP. The benchmark is given on a transverse Ising

  2. Reduction of initial stress stiffening by topology optimization

    DEFF Research Database (Denmark)

    Philippine, M. A.; Sigmund, Ole; Rebeiz, G. M.

    2012-01-01

    Topology optimization is a rigorous method of obtaining non-intuitive designs. We use it to obtain a capacitive RF switch that stiffens little in response to an increase of the in-plane biaxial stresses that typically develop during MEMS fabrication. The actuation voltage is closely related...

  3. Optimization of initial training military pilots in Ukraine

    Directory of Open Access Journals (Sweden)

    В.В. Шмаков

    2008-03-01

    Full Text Available  Began to attain adequacy of estimation of cost of primary preparation of pilots possible as a result of development in the Kharkov university of Aircraft of method which gave possibility to analyses the degree of influence on the cost of preparation of pilots of every constituent and define ways from optimization of preparation.

  4. 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

    2015-04-01

    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.

  5. 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.

  6. 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.

  7. Simulated annealing algorithm for the optimal translation sequence of the jth agent in rough communication

    Institute of Scientific and Technical Information of China (English)

    Wang Hongkai; Guan Yanyong; Xue Peijun

    2008-01-01

    In rough communication, because each agent has a different language and cannot provide precise communication to each other, the concept translated among multi-agents will loss some information and this results in a less or rougher concept. With different translation sequences, the problem of information loss is varied. To get the translation sequence, in which the jth agent taking part in rough communication gets maximum information, a simulated annealing algorithm is used. Analysis and simulation of this algorithm demonstrate its effectiveness.

  8. 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...

  9. [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.

  10. Structural determinant of human La protein critical for internal initiation of translation of hepatitis C virus RNA.

    Science.gov (United States)

    Mondal, Tanmoy; Ray, Upasana; Manna, Asit Kumar; Gupta, Romi; Roy, Siddhartha; Das, Saumitra

    2008-12-01

    Human La protein has been implicated in facilitating internal ribosome entry site (IRES)-mediated translation of hepatitis C virus (HCV). Earlier, we demonstrated that the RNA recognition motif (RRM) encompassing residues 112 to 184 of La protein [La (112-184)] interacts with the HCV IRES near the initiator AUG codon. A synthetic peptide, LaR2C (24-mer), derived from La RRM (112-184), retains RNA binding ability, competes with La protein binding to the HCV IRES, and inhibits translation. The peptide interferes with the assembly of 48S complexes, resulting in the accumulation of preinitiation complexes that are incompetent for the 60S ribosomal subunit joining. Here, nuclear magnetic resonance spectroscopy of the HCV IRES-bound peptide complex revealed putative contact points, mutations that showed reduced RNA binding and translation inhibitory activity. The residues responsible for RNA recognition were found to form a turn in the RRM (112-184) structure. A 7-mer peptide comprising this turn showed significant translation inhibitory activity. The bound structure of the peptide inferred from transferred nuclear Overhauser effect experiments suggests that it is a beta turn. This conformation is significantly different from that observed in the free RRM (112-184) NMR structure, suggesting paths toward a better-stabilized mimetic peptide. Interestingly, addition of hexa-arginine tag enabled the peptide to enter Huh7 cells and showed inhibition of HCV IRES function. More importantly, the peptide significantly inhibited replication of the HCV monocistronic replicon. Elucidation of the structural determinant of the peptide provides a basis for developing small peptidomimetic structures as potent anti-HCV therapeutics.

  11. Translation Regulation of the Glutamyl-prolyl-tRNA Synthetase Gene EPRS through Bypass of Upstream Open Reading Frames with Noncanonical Initiation Codons.

    Science.gov (United States)

    Young, Sara K; Baird, Thomas D; Wek, Ronald C

    2016-05-13

    In the integrated stress response, phosphorylation of eIF2α (eIF2α-P) reduces protein synthesis while concomitantly promoting preferential translation of specific transcripts associated with stress adaptation. Translation of the glutamyl-prolyl-tRNA synthetase gene EPRS is enhanced in response to eIF2α-P. To identify the underlying mechanism of translation control, we employed biochemical approaches to determine the regulatory features by which upstream ORFs (uORFs) direct downstream translation control and expression of the EPRS coding region. Our findings reveal that translation of two inhibitory uORFs encoded by noncanonical CUG and UUG initiation codons in the EPRS mRNA 5'-leader serve to dampen levels of translation initiation at the EPRS coding region. By a mechanism suggested to involve increased translation initiation stringency during stress-induced eIF2α-P, we observed facilitated ribosome bypass of these uORFs, allowing for increased translation of the EPRS coding region. Importantly, EPRS protein expression is enhanced through this preferential translation mechanism in response to multiple known activators of eIF2α-P and likely serves to facilitate stress adaptation in response to a variety of cellular stresses. The rules presented here for the regulated ribosome bypass of noncanonical initiation codons in the EPRS 5'-leader add complexity into the nature of uORF-mediated translation control mechanisms during eIF2α-P and additionally illustrate the roles that previously unexamined uORFs with noncanonical initiation codons can play in modulating gene expression.

  12. Design and Formative Evaluation of the Policy Liaison Initiative: A Long-Term Knowledge Translation Strategy to Encourage and Support the Use of Cochrane Systematic Reviews for Informing

    Science.gov (United States)

    Brennan, Sue E.; Cumpston, Miranda; Misso, Marie L.; McDonald, Steve; Murphy, Matthew J.; Green, Sally E.

    2016-01-01

    The Policy Liaison Initiative (PLI) is a long-term knowledge translation initiative designed to support the use of Cochrane systematic reviews in health policy. A joint initiative between the Australasian Cochrane Centre and Australian Government Department of Health and Ageing, the PLI includes: 1) a community of practice for evidence-informed…

  13. The role of mammalian initiation factor eIF-4D and its hypusine modification in translation.

    Science.gov (United States)

    Hershey, J W; Smit-McBride, Z; Schnier, J

    1990-08-27

    Initiation factor eIF-4D functions late in the initiation pathway, apparently during formation of the first peptide bond. The factor is post-translationally modified at a specific lysine residue by reaction with spermidine and subsequent hydroxylation to form hypusine. A precursor form lacking hypusine is inactive in the assay for methionyl-puromycin synthesis, but activity is restored following in vitro modification to deoxyhypusine, thereby suggesting that the modification is essential for function. Since formylated methionyl-tRNA is less dependent on eIF-4D in the puromycin assay, we postulate that eIF-4D and its hypusine modification may stabilize charged Met-tRNA binding to the peptidyl transferase center of the 60S ribosomal subunit. Analysis of eIF-4D genes in yeast indicate that eIF-4D and its hypusine modification are essential for cell growth.

  14. Identification of the hypusine-containing protein hy+ as translation initiation factor eIF-4D.

    Science.gov (United States)

    Cooper, H L; Park, M H; Folk, J E; Safer, B; Braverman, R

    1983-04-01

    A single protein of Mr 17,000-19,000 and pI approximately equal to 5.1, found in all animal cells we have studied to date, undergoes post-translational modification in growing cells to form the unusual amino acid hypusine. Because of the association of this modification with the increasing rate of protein synthesis during lymphocyte growth stimulation, its subcellular distribution, and its widespread occurrence and structural conservation among animal cells, we considered the possibility that this protein might be a translation initiation factor. Purified rabbit reticulocyte factors (eukaryote initiation factors) eIF-4C and eIF-4D were chosen for study because of their Mr (17,000-19,000) and acidic pI. The hypusine-containing protein and purified eIF-4D showed identity of electrophoretic mobility in both isoelectric focusing and NaDodSO4/polyacrylamide gel electrophoresis dimensions, while eIF-4C was clearly nonidentical. Purified eIF-4D contained approximately 1 mol of hypusine per mol of protein. Since only one protein has thus far been observed to contain hypusine, we conclude that eIF-4D is the hypusine-containing protein. On the basis of relative synthesis among lymphocyte proteins and detection by Coomassie blue staining, we also conclude that eIF-4D is a major cell protein. It is possible that the activity of this factor is modulated by It is possible that the activity of this factor is modulated by post-translational hypusine formation, which may play a role in regulation of protein synthesis during lymphocyte growth stimulation.

  15. Two isoforms of TALDO1 generated by alternative translational initiation show differential nucleocytoplasmic distribution to regulate the global metabolic network

    Science.gov (United States)

    Moriyama, Tetsuji; Tanaka, Shu; Nakayama, Yasumune; Fukumoto, Masahiro; Tsujimura, Kenji; Yamada, Kohji; Bamba, Takeshi; Yoneda, Yoshihiro; Fukusaki, Eiichiro; Oka, Masahiro

    2016-01-01

    Transaldolase 1 (TALDO1) is a rate-limiting enzyme involved in the pentose phosphate pathway, which is traditionally thought to occur in the cytoplasm. In this study, we found that the gene TALDO1 has two translational initiation sites, generating two isoforms that differ by the presence of the first 10 N-terminal amino acids. Notably, the long and short isoforms were differentially localised to the cell nucleus and cytoplasm, respectively. Pull-down and in vitro transport assays showed that the long isoform, unlike the short one, binds to importin α and is actively transported into the nucleus in an importin α/β-dependent manner, demonstrating that the 10 N-terminal amino acids are essential for its nuclear localisation. Additionally, we found that these two isoforms can form homo- and/or hetero-dimers with different localisation dynamics. A metabolite analysis revealed that the subcellular localisation of TALDO1 is not crucial for its activity in the pentose phosphate pathway. However, the expression of these two isoforms differentially affected the levels of various metabolites, including components of the tricarboxylic acid cycle, nucleotides, and sugars. These results demonstrate that the nucleocytoplasmic distribution of TALDO1, modulated via alternative translational initiation and dimer formation, plays an important role in a wide range of metabolic networks. PMID:27703206

  16. The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled.

    Science.gov (United States)

    Osborne, Michael J; Borden, Katherine L B

    2015-01-01

    The eukaryotic translation initiation factor eIF4E is a potent oncogene. Although eIF4E has traditional roles in translation initiation in the cytoplasm, it is also found in the nucleus, suggesting that it has activities beyond its role in protein synthesis. The road less traveled has been taken to study these nuclear activities and to understand their contribution to the oncogenic potential of eIF4E. The molecular features and biological pathways underpinning eIF4E's nuclear mRNA export are described. New classes of eIF4E regulators have been identified and their relevance to cancer shown. The studies presented here reveal the molecular, biophysical, and structural bases for eIF4E regulation. Finally, recent clinical work targeting eIF4E in acute myeloid leukemia patients with ribavirin is discussed. In summary, these findings provide a novel paradigm for eIF4E function and the molecular basis for targeting it in leukemia patients.

  17. 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

    In 1995, the Global Initiative for Asthma (GINA) published an evidence-based workshop report as a guide to clinicians managing asthma patients, and has updated it annually to ensure that recommendations remain current. Although the report has been widely disseminated and influenced clinical pract...

  18. Translation Sociology and Social Capital in Rural Development Initiatives. A Case Study from the Italian Alps

    Science.gov (United States)

    Magnani, Natalia; Struffi, Lauro

    2009-01-01

    This article analyses the results of a European "research and demonstration" project promoting multifunctional and sustainable agriculture in Alpine regions through a participatory approach. It focuses in particular on initiatives undertaken by a local farmers group in the Italian Alpine area of Val di Sole, the purpose being to draw…

  19. The DEAD-Box Protein Dhh1p Couples mRNA Decay and Translation by Monitoring Codon Optimality.

    Science.gov (United States)

    Radhakrishnan, Aditya; Chen, Ying-Hsin; Martin, Sophie; Alhusaini, Najwa; Green, Rachel; Coller, Jeff

    2016-09-22

    A major determinant of mRNA half-life is the codon-dependent rate of translational elongation. How the processes of translational elongation and mRNA decay communicate is unclear. Here, we establish that the DEAD-box protein Dhh1p is a sensor of codon optimality that targets an mRNA for decay. First, we find mRNAs whose translation elongation rate is slowed by inclusion of non-optimal codons are specifically degraded in a Dhh1p-dependent manner. Biochemical experiments show Dhh1p is preferentially associated with mRNAs with suboptimal codon choice. We find these effects on mRNA decay are sensitive to the number of slow-moving ribosomes on an mRNA. Moreover, we find Dhh1p overexpression leads to the accumulation of ribosomes specifically on mRNAs (and even codons) of low codon optimality. Lastly, Dhh1p physically interacts with ribosomes in vivo. Together, these data argue that Dhh1p is a sensor for ribosome speed, targeting an mRNA for repression and subsequent decay.

  20. Hypusine: its post-translational formation in eukaryotic initiation factor 5A and its potential role in cellular regulation.

    Science.gov (United States)

    Park, M H; Wolff, E C; Folk, J E

    1993-05-01

    The amino acid, hypusine [N epsilon-(4-amino-2-hydroxybutyl) lysine], a unique component of one cellular protein, eukaryotic translation initiation factor 5A (eIF-5A, old terminology eIF-4D), is formed post-translationally in two enzymatic steps: (i) transfer of the 4-aminobutyl moiety of the polyamine spermidine to the epsilon-amino group of a single specific lysine residue in the eIF-5A precursor protein to form an intermediate, deoxyhypusine, and (ii) subsequent hydroxylation in this 4-aminobutyl portion. Hypusine is produced soon after the translation of eIF-5A mRNA; the modification is essentially irreversible. Hypusine is found in all eukaryotes examined as well as in archaebacteria; it does not occur in eubacteria. The protein containing hypusine from each species displays a high degree of amino acid identity; the sequence of amino acids surrounding the hypusine residue is strictly conserved, suggesting the importance of the hypusine modification throughout evolution. Expression of one of the two yeast eIF-5A genes is required for survival and the lysine codon at the site of hypusine synthesis is vital for yeast growth. The precise cellular function of eIF-5A remains to be elucidated; however, eIF-5A stimulates methionyl-puromycin synthesis in a model assay for translation initiation and eIF-5A precursors containing lysine in place of hypusine are inactive in this assay. This provides evidence that the hypusine modification is needed for eIF-5A activity. In view of the important role of hypusine in eIF-5A and because of the narrow specificities of the enzymes involved in formation of this unusual amino acid, the hypusine biosynthetic steps offer promising targets for intervention in cellular proliferation. Spermidine analogs that are inhibitors of deoxyhypusine synthase in vitro also cause inhibition of hypusine formation in cells, together with a reduction in protein synthesis and in cell growth. In addition, certain metal chelating inhibitors of

  1. 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.

  2. Prediction of translation initiation sites in human mRNA sequences with AUG start codon in weak Kozak context: A neural network approach.

    Science.gov (United States)

    Tikole, Suhas; Sankararamakrishnan, Ramasubbu

    2008-05-16

    Translation of eukaryotic mRNAs is often regulated by nucleotides around the start codon. A purine at position -3 and a guanine at position +4 contribute significantly to enhance the translation efficiency. Algorithms to predict the translation initiation site often fail to predict the start site if the sequence context is not present. We have developed a neural network method to predict the initiation site of mRNA sequences that lack the preferred nucleotides at the positions -3 and +4 surrounding the translation initiation site. Neural networks of various architectures comprising different number of hidden layers were designed and tested for various sizes of windows of nucleotides surrounding translation initiation sites. We found that the neural network with two hidden layers showed a sensitivity of 83% and specificity of 73% indicating a vastly improved performance in successfully predicting the translation initiation site of mRNA sequences with weak Kozak context. WeakAUG server is freely available at http://bioinfo.iitk.ac.in/AUGPred/.

  3. [Just-in-time initiation of optimal dialysis].

    Science.gov (United States)

    Cornelis, Tom; Kooman, Jeroen P; van der Sande, Frank M

    2010-01-01

    The IDEAL trial shows that the decision to start renal replacement treatment should not depend on GFR alone, but should be taken on the basis of clinical parameters. Quality of Life (QoL) questionnaires and bio-impedance analysis are potential tools for detecting subtle changes in the predialysis clinic. Too early an initiation of dialysis may be deleterious for the patient and the healthcare system. We are convinced that ESRD patients should be informed about intensive haemodialysis (HD), especially nocturnal (home) HD, as the best available dialysis modality. There is substantial evidence which shows that intensive HD improves clinical, biochemical and biological parameters, and may even prolong survival. We believe that 'just-in-time delivery of intensive haemodialysis' may result in optimised QoL and reduced economic burden.

  4. The translation initiation factor 3f (eIF3f exhibits a deubiquitinase activity regulating Notch activation.

    Directory of Open Access Journals (Sweden)

    Julien Moretti

    Full Text Available Activation of the mammalian Notch receptor after ligand binding relies on a succession of events including metalloprotease-cleavage, endocytosis, monoubiquitination, and eventually processing by the gamma-secretase, giving rise to a soluble, transcriptionally active molecule. The Notch1 receptor was proposed to be monoubiquitinated before its gamma-secretase cleavage; the targeted lysine has been localized to its submembrane domain. Investigating how this step might be regulated by a deubiquitinase (DUB activity will provide new insight for understanding Notch receptor activation and downstream signaling. An immunofluorescence-based screening of an shRNA library allowed us to identify eIF3f, previously known as one of the subunits of the translation initiation factor eIF3, as a DUB targeting the activated Notch receptor. We show that eIF3f has an intrinsic DUB activity. Knocking down eIF3f leads to an accumulation of monoubiquitinated forms of activated Notch, an effect counteracted by murine WT eIF3f but not by a catalytically inactive mutant. We also show that eIF3f is recruited to activated Notch on endocytic vesicles by the putative E3 ubiquitin ligase Deltex1, which serves as a bridging factor. Finally, catalytically inactive forms of eIF3f as well as shRNAs targeting eIF3f repress Notch activation in a coculture assay, showing that eIF3f is a new positive regulator of the Notch pathway. Our results support two new and provocative conclusions: (1 The activated form of Notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. (2 The enzyme accounting for this deubiquitinase activity is eIF3f, known so far as a translation initiation factor. These data improve our knowledge of Notch signaling but also open new avenues of research on the Zomes family and the translation initiation factors.

  5. A computational-intelligence-based optimization of agents' initial positions in land combat simulation

    Institute of Scientific and Technical Information of China (English)

    WU Chunguo; LIANG Yanchun; GE Hongwei; CAO Lijuan; LEE Heow Pueh

    2003-01-01

    The optimization of agents' initial properties enables agents to perform their assigned tasks more perfectly. This paper presents an optimizing method using the combination of radial basis function (RBF) neural network and genetic algorithm (GA). In the land combat simulation, the method can ensure that the agents optimized defeat the agents not optimized absolutely. Compared with the optimization based on support vector machines (SVM), the proposed method improves the efficiency more than twenty times, so it suits the cases where the speed as well as performance is required.

  6. 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.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    He, Yangzi

    -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...... translates the genetic message encoded in mRNAs to synthesize proteins. Initiation of translation requires localization and recognition of the start codon at the P-site of the 40S small ribosomal subunit. On most eukaryotic mRNAs, the start codon is identified by a scanning mechanism, whereby a small subunit...

  9. Poly(A binding protein 1 enhances cap-independent translation initiation of neurovirulence factor from avian herpesvirus.

    Directory of Open Access Journals (Sweden)

    Abdessamad Tahiri-Alaoui

    Full Text Available Poly(A binding protein 1 (PABP1 plays a central role in mRNA translation and stability and is a target by many viruses in diverse manners. We report a novel viral translational control strategy involving the recruitment of PABP1 to the 5' leader internal ribosome entry site (5L IRES of an immediate-early (IE bicistronic mRNA that encodes the neurovirulence protein (pp14 from the avian herpesvirus Marek's disease virus serotype 1 (MDV1. We provide evidence for the interaction between an internal poly(A sequence within the 5L IRES and PABP1 which may occur concomitantly with the recruitment of PABP1 to the poly(A tail. RNA interference and reverse genetic mutagenesis results show that a subset of virally encoded-microRNAs (miRNAs targets the inhibitor of PABP1, known as paip2, and therefore plays an indirect role in PABP1 recruitment strategy by increasing the available pool of active PABP1. We propose a model that may offer a mechanistic explanation for the cap-independent enhancement of the activity of the 5L IRES by recruitment of a bona fide initiation protein to the 5' end of the message and that is, from the affinity binding data, still compatible with the formation of 'closed loop' structure of mRNA.

  10. The same allele of translation initiation factor 4E mediates resistance against two potyvirus species in Pisum sativum

    DEFF Research Database (Denmark)

    Bruun-Rasmussen, Marianne; 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...

  11. Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor

    Science.gov (United States)

    Huang, Yunfei; Higginson, Daniel S.; Hester, Lynda; Park, Myung Hee; Snyder, Solomon H.

    2007-01-01

    Eukaryotic translation initiation factor 5A (eIF5A), the only known protein containing the polyamine-derived amino acid hypusine, modulates protein synthesis. We show that neurotrophic and neuroprotective actions of nerve growth factor (NGF) are mediated by hypusinated eIF5A, which can account for the known roles of polyamines in cell growth and survival. NGF treatment of PC12 cells stimulates eIF5A formation. Moreover, prevention of hypusine formation by a selective inhibitor of deoxyhypusine synthase and by its depletion with RNA interference blocks the NGF-elicited augmentation of neurite outgrowth and cell survival of PC12 cells. In brain cultures, inhibition of hypusine formation also inhibits neuronal process extension. PMID:17360499

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

    Directory of Open Access Journals (Sweden)

    Mello Maria

    2007-03-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  13. 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 ...

  14. 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

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

    NARCIS (Netherlands)

    Mugavero, M.J.; May, M.; Harris, R.; Saag, M.S.; Costagliola, D.; Egger, M.; Phillips, A.; Gunthard, H.F.; Dabis, F.; Hogg, R.; Wolf, F. de; Fatkenheuer, G.; Gill, M.J.; Justice, A.; Monforte, A. D'Arminio; Lampe, F.; Miro, J.M.; Staszewski, S.; Sterne, J.A.

    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-naive patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between Jan

  16. Virtual couch shift (VCS) : accounting for patient translation and rotation by online IMRT re-optimization

    NARCIS (Netherlands)

    Bol, G.H.; Lagendijk, J. J. W.; Raaymakers, B. W.

    2013-01-01

    When delivering conventional intensity modulated radiotherapy (IMRT), discrepancies between the pre-treatment CT/MRI/PET based patient geometry and the daily patient geometry are minimized by performing couch translations and/or small rotations. However, full compensation of, in particular, rotation

  17. In silico analysis of 5'-UTRs highlights the prevalence of Shine-Dalgarno and leaderless-dependent mechanisms of translation initiation in bacteria and archaea, respectively.

    Science.gov (United States)

    Srivastava, Ambuj; Gogoi, Prerana; Deka, Bhagyashree; Goswami, Shrayanti; Kanaujia, Shankar Prasad

    2016-08-07

    In prokaryotes, a heterogeneous set of protein translation initiation mechanisms such as Shine-Dalgarno (SD) sequence-dependent, SD sequence-independent or ribosomal protein S1 mediated and leaderless transcript-dependent exists. To estimate the distribution of coding sequences employing a particular translation initiation mechanism, a total of 107 prokaryotic genomes were analysed using in silico approaches. Analysis of 5'-untranslated regions (UTRs) of genes reveals the existence of three types of mRNAs described as transcripts with and without SD motif and leaderless transcripts. Our results indicate that although all the three types of translation initiation mechanisms are widespread among prokaryotes, the number of SD-dependent genes in bacteria is higher than that of archaea. In contrast, archaea contain a significantly higher number of leaderless genes than SD-led genes. The correlation analysis between genome size and SD-led & leaderless genes suggests that the SD-led genes are decreasing (increasing) with genome size in bacteria (archaea). However, the leaderless genes are increasing (decreasing) in bacteria (archaea) with genome size. Moreover, an analysis of the start-codon biasness confirms that among ATG, GTG and TTG codons, ATG is indeed the most preferred codon at the translation initiation site in most of the coding sequences. In leaderless genes, however, the codons GTG and TTG are also observed at the translation initiation site in some species contradicting earlier studies which suggested the usage of only ATG codon. Henceforth, the conventional mechanism of translation initiation cannot be generalized as an exclusive way of initiating the process of protein biosynthesis in prokaryotes.

  18. Possible Involvement of a Mitochondrial Translation Initiation Factor 3 Variant Causing Decreased mRNA Levels in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Anna Anvret

    2010-01-01

    Full Text Available Genes important for mitochondrial function have been implicated in Parkinson's disease (PD. Mitochondrial translation initiation factor 3 (MTIF3 is a nuclear encoded protein required for the initiation of complex formation on mitochondrial ribosomes. Dysfunction of MTIF3 may impair mitochondrial function and dopamine neurons appear to be particularly vulnerable to oxidative stress, which may relate to their degeneration in PD. An association was recently reported between the synonymous rs7669(C>T in MTIF3 and PD in a German case-control material. We investigated rs7669 in a Swedish Parkinson case-control material. The study revealed no significant association of the individual genotypes or alleles with PD. When comparing the combined TT/CT-genotypes versus the CC-genotype, we observed a significant association (P=.0473 with PD. We also demonstrated that the TT-genotype causes a significant decrease in MTIF3 mRNA expression compared to the CC-genotype (P=.0163. Our findings support the hypothesis that MTIF3 may be involved in the etiology of PD.

  19. Translation and Initial Validation of the Chinese (Cantonese Version of Community Integration Measure for Use in Patients with Chronic Stroke

    Directory of Open Access Journals (Sweden)

    Tai-Wa Liu

    2014-01-01

    Full Text Available Objectives. To (1 translate and culturally adapt the English version Community Integration Measure into Chinese (Cantonese, (2 report the results of initial validation of the Chinese (Cantonese version of CIM (CIM-C including the content validity, internal consistency, test-retest reliability, and factor structure of CIM-C for use in stroke survivors in a Chinese community setting, and (3 investigate the level of community integration of stroke survivors living in Hong Kong. Design. Cross-sectional study. Setting. University-based rehabilitation centre. Participants. 62 (n=62 subjects with chronic stroke. Methods. The CIM-C was produced after forward-backward translation, expert panel review, and pretesting. 25 (n=25 of the same subjects were reassessed after a 1-week interval. Results. The items of the CIM-C demonstrated high internal consistency with a Cronbach’s α of 0.84. The CIM-C showed good test-retest reliability with an intraclass correlation coefficient (ICC of 0.84 (95% confidence interval, 0.64–0.93. A 3-factor structure of the CIM-C including “relationship and engagement,” “sense of knowing,” and “independent living,” was consistent with the original theoretical model. Hong Kong stroke survivors revealed a high level of community integration as measured by the CIM-C (mean (SD: 43.48 (5.79. Conclusions. The CIM-C is a valid and reliable measure for clinical use.

  20. The archaebacterial hypusine-containing protein. Structural features suggest common ancestry with eukaryotic translation initiation factor 5A.

    Science.gov (United States)

    Bartig, D; Lemkemeier, K; Frank, J; Lottspeich, F; Klink, F

    1992-03-01

    The amino acid hypusine is formed by post-translational modification of a lysine residue in eukaryotes and archaebacteria but up to now only the eukaryotic translation initiation factor eIF-5A has been known to contain this unique component. We isolated and purified a hypusine-containing protein from the thermophilic archaebacterium Sulfolobus acidocaldarius. The mainly cytosolic protein comprised about 0.03% of the post-ribosomal supernatant protein. No other hypusine-containing protein could be detected in S. acidocaldarius. The molar ratio of hypusine/hypusine-containing protein was 1:1. SDS/PAGE showed a molecular mass of 16.8 kDa; a pI of 7.8 for the native protein resulted from IEF. The N-terminus was blocked. Four cyanogen bromide fragments were partially sequenced and used to derive two 17-base oligonucleotide probes. A 3-kb HindIII fragment of genomic DNA hybridizing with both probes was cloned. By sequencing of exonuclease III deletion clones an open reading frame of 405 nucleotides was found coding for a protein of 135 amino acids with a molecular mass of 15 kDa. It contained all cyanogen bromide sequences analysed. Sequence alignment revealed that seven of eight residues around Lys40 in the Sulfolobus hypusine-containing protein were identical to the nonapeptides centered by hypusine in the three eIF-5A proteins sequenced so far. The Edman procedure gave no phenylthiohydantoin derivative for this position. For a central region of 44 residues a sequence similarity of 54% between the archaebacterial and eukaryotic proteins was calculated; for the total sequence about 33% similarity resulted. In addition, there were a number of conservative changes. The unique lysine modification surrounded by a conserved sequence strongly suggests a common ancestry of archaebacterial hypusine-containing protein and eIF-5A. Together with similarities in molecular mass and intracellular localization, it may point to an analogous biochemical function.

  1. Contribution of trans-splicing, 5' -leader length, cap-poly(A) synergism, and initiation factors to nematode translation in an Ascaris suum embryo cell-free system.

    Science.gov (United States)

    Lall, Sabbi; Friedman, Cassandra C; Jankowska-Anyszka, Marzena; Stepinski, Janusz; Darzynkiewicz, Edward; Davis, Richard E

    2004-10-29

    Trans-splicing introduces a common 5' 22-nucleotide sequence with an N-2,2,7-trimethylguanosine cap (m (2,2,7)(3)GpppG or TMG-cap) to more than 70% of transcripts in the nematodes Caenorhabditis elegans and Ascaris suum. Using an Ascaris embryo cell-free translation system, we found that the TMG-cap and spliced leader sequence synergistically collaborate to promote efficient translation, whereas addition of either a TMG-cap or spliced leader sequence alone decreased reporter activity. We cloned an A. suum embryo eIF4E homolog and demonstrate that this recombinant protein can bind m(7)G- and TMG-capped mRNAs in cross-linking assays and that binding is enhanced by eIF4G. Both the cap structure and the spliced leader (SL) sequence affect levels of A. suum eIF4E cross-linking to mRNA. Furthermore, the differential binding of eIF4E to a TMG-cap and to trans-spliced and non-trans-spliced RNAs is commensurate with the translational activity of reporter RNAs observed in the cell-free extract. Together, these binding data and translation assays with competitor cap analogs suggest that A. suum eIF4E-3 activity may be sufficient to mediate translation of both trans-spliced and non-trans-spliced mRNAs. Bioinformatic analyses demonstrate the SL sequence tends to trans-splice close to the start codon in a diversity of nematodes. This evolutionary conservation is functionally reflected in the optimal SL to AUG distance for reporter mRNA translation in the cell-free system. Therefore, trans-splicing of the SL1 leader sequence may serve at least two functions in nematodes, generation of an optimal 5'-untranslated region length and a specific sequence context (SL1) for optimal translation of trimethylguanosine capped transcripts.

  2. Biological insights into the expression of translation initiation factors from recombinant CHOK1SV cell lines and their relationship to enhanced productivity.

    Science.gov (United States)

    Mead, Emma J; Masterton, Rosalyn J; Feary, Marc; Obrezanova, Olga; Zhang, Lin; Young, Robert; Smales, C Mark

    2015-12-15

    Translation initiation is on the critical pathway for the production of monoclonal antibodies (mAbs) by mammalian cells. Formation of a closed loop structure comprised of mRNA, a number of eukaryotic initiation factors (eIFs) and ribosomal proteins has been proposed to aid re-initiation of translation and therefore increase global translational efficiency. We have determined mRNA and protein levels of the key components of the closed loop, eIFs (eIF3a, eIF3b, eIF3c, eIF3h, eIF3i and eIF4G1), poly(A)-binding protein (PABP) 1 and PABP-interacting protein 1 (PAIP1), across a panel of 30 recombinant mAb-producing GS-CHOK1SV cell lines with a broad range of growth characteristics and production levels of a model recombinant mAb. We have used a multi-level statistical approach to investigate the relationship between key performance indicators (cell growth and recombinant antibody productivity) and the intracellular amounts of target translation initiation factor proteins and the mRNAs encoding them. We show that high-producing cell lines maintain amounts of the translation initiation factors involved in the formation of the closed loop mRNA, maintaining these proteins at appropriate levels to deliver enhanced recombinant protein production. We then utilize knowledge of the amounts of these factors to build predictive models for and use cluster analysis to identify, high-producing cell lines. The present study therefore defines the translation initiation factor amounts that are associated with highly productive recombinant GS-CHOK1SV cell lines that may be targets for screening highly productive cell lines or to engineer new host cell lines with the potential for enhanced recombinant antibody productivity.

  3. Hybrid collaborative optimization based on selection strategy of initial point and adaptive relaxation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Aimin; Yin, Xu; Yuan, Minghai [Hohai University, Changzhou (China)

    2015-09-15

    There are two problems in Collaborative optimization (CO): (1) the local optima arising from the selection of an inappropriate initial point; (2) the low efficiency and accuracy root in inappropriate relaxation factors. To solve these problems, we first develop the Latin hypercube design (LHD) to determine an initial point of optimization, and then use the non-linear programming by quadratic Lagrangian (NLPQL) to search for the global solution. The effectiveness of the initial point selection strategy is verified by three benchmark functions with some dimensions and different complexities. Then we propose the Adaptive relaxation collaborative optimization (ARCO) algorithm to solve the inconsistency between the system level and the disciplines level, and in this method, the relaxation factors are determined according to the three separated stages of CO respectively. The performance of the ARCO algorithm is compared with the standard collaborative algorithm and the constant relaxation collaborative algorithm with a typical numerical example, which indicates that the ARCO algorithm is more efficient and accurate. Finally, we propose a Hybrid collaborative optimization (HCO) approach, which integrates the selection strategy of initial point with the ARCO algorithm. The results show that HCO can achieve the global optimal solution without the initial value and it also has advantages in convergence, accuracy and robustness. Therefore, the proposed HCO approach can solve the CO problems with applications in the spindle and the speed reducer.

  4. Humans make near-optimal adjustments of control to initial body configuration in vertical squat jumping.

    Science.gov (United States)

    Bobbert, Maarten F; Richard Casius, L J; Kistemaker, Dinant A

    2013-05-01

    We investigated adjustments of control to initial posture in squat jumping. Eleven male subjects jumped from three initial postures: preferred initial posture (PP), a posture in which the trunk was rotated 18° more backward (BP) and a posture in which it was rotated 15° more forward (FP) than in PP. Kinematics, ground reaction forces and electromyograms (EMG) were collected. EMG was rectified and smoothed to obtain smoothed rectified EMG (srEMG). Subjects showed adjustments in srEMG histories, most conspicuously a shift in srEMG-onset of rectus femoris (REC): from early in BP to late in FP. Jumps from the subjects' initial postures were simulated with a musculoskeletal model comprising four segments and six Hill-type muscles, which had muscle stimulation (STIM) over time as input. STIM of each muscle changed from initial to maximal at STIM-onset, and STIM-onsets were optimized using jump height as criterion. Optimal simulated jumps from BP, PP and FP were similar to jumps of the subjects. Optimal solutions primarily differed in STIM-onset of REC: from early in BP to late in FP. Because the subjects' adjustments in srEMG-onsets were similar to adjustments of the model's optimal STIM-onsets, it was concluded that the former were near-optimal. With the model we also showed that near-maximum jumps from BP, PP and FP could be achieved when STIM-onset of REC depended on initial hip joint angle and STIM-onsets of the other muscles were posture-independent. A control theory that relies on a mapping from initial posture to STIM-onsets seems a parsimonious alternative to theories relying on internal optimal control models. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. The translation initiation factor 3 subunit eIF3K interacts with PML and associates with PML nuclear bodies

    Energy Technology Data Exchange (ETDEWEB)

    Salsman, Jayme; Pinder, Jordan; Tse, Brenda [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Corkery, Dale [Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada); Dellaire, Graham, E-mail: dellaire@dal.ca [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada)

    2013-10-15

    The promyelocytic leukemia protein (PML) is a tumor suppressor protein that regulates a variety of important cellular processes, including gene expression, DNA repair and cell fate decisions. Integral to its function is the ability of PML to form nuclear bodies (NBs) that serve as hubs for the interaction and modification of over 90 cellular proteins. There are seven canonical isoforms of PML, which encode diverse C-termini generated by alternative pre-mRNA splicing. Recruitment of specific cellular proteins to PML NBs is mediated by protein–protein interactions with individual PML isoforms. Using a yeast two-hybrid screen employing peptide sequences unique to PML isoform I (PML-I), we identified an interaction with the eukaryotic initiation factor 3 subunit K (eIF3K), and in the process identified a novel eIF3K isoform, which we term eIF3K-2. We further demonstrate that eIF3K and PML interact both in vitro via pull-down assays, as well as in vivo within human cells by co-immunoprecipitation and co-immunofluorescence. In addition, eIF3K isoform 2 (eIF3K-2) colocalizes to PML bodies, particularly those enriched in PML-I, while eIF3K isoform 1 associates poorly with PML NBs. Thus, we report eIF3K as the first known subunit of the eIF3 translation pre-initiation complex to interact directly with the PML protein, and provide data implicating alternative splicing of both PML and eIF3K as a possible regulatory mechanism for eIF3K localization at PML NBs. - Highlights: • The PML-I C-terminus, encoded by exon 9, interacts with translation factor eIF3K. • We identify a novel eIF3K isoform that excludes exon 2 (eIF3K-2). • eIF3K-2 preferentially associates with PML bodies enriched in PML-I vs. PML-IV. • Alternative splicing of eIF3K regulates association with PML bodies.

  6. Carrots and Sticks as Incentive Mechanisms for the Optimal Initiation of Insolvency Proceedings

    Directory of Open Access Journals (Sweden)

    Cepec Jaka

    2016-06-01

    Full Text Available The pursuit of ex-ante efficiency in bankruptcy law has been widely discussed in recent law and economics literature. However, the exact incentive mechanisms inducing the optimal commencement of bankruptcy proceedings have generally been exempted from the current scholarly debate. Using the law and economics tools and comparative analysis, this paper seeks to identify insolvency-specific optimal incentive mechanisms, while using the general theory on carrots and sticks in legal regulations. The paper suggests the employment of mixed-sticks-and-carrots incentive mechanisms for managers’ prompt proposals of insolvency proceedings as an optimal regulatory response. Moreover, the article provides comparative evidence that exclusive use of sticks or carrots in French, German, US, English, and Slovenian legal systems results in sub-optimal initiation of insolvency proceedings and may also induce adverse effects on prompt initiation.

  7. A class of edit kernels for SVMs to predict translation initiation sites in eukaryotic mRNAs.

    Science.gov (United States)

    Li, Haifeng; Jiang, Tao

    2005-01-01

    The prediction of translation initiation sites (TISs) in eukaryotic mRNAs has been a challenging problem in computational molecular biology. In this paper, we present a new algorithm to recognize TISs with a very high accuracy. Our algorithm includes two novel ideas. First, we introduce a class of new sequence-similarity kernels based on string editing, called edit kernels, for use with support vector machines (SVMs) in a discriminative approach to predict TISs. The edit kernels are simple and have significant biological and probabilistic interpretations. Although the edit kernels are not positive definite, it is easy to make the kernel matrix positive definite by adjusting the parameters. Second, we convert the region of an input mRNA sequence downstream to a putative TIS into an amino acid sequence before applying SVMs to avoid the high redundancy in the genetic code. The algorithm has been implemented and tested on previously published data. Our experimental results on real mRNA data show that both ideas improve the prediction accuracy greatly and that our method performs significantly better than those based on neural networks and SVMs with polynomial kernels or Salzberg kernels.

  8. Differential expression of genes encoding the hypusine-containing translation initiation factor, eIF-5A, in tobacco.

    Science.gov (United States)

    Chamot, D; Kuhlemeier, C

    1992-01-01

    Two Nicotiana plumbaginifolia cDNA clones, NeIF-5A1 and NeIF-5A2, encoding eukaryotic translation initiation factor eIF-5A (formerly called eIF-4D) were cloned by heterologous screening with Dictyostelium and human eIF-5A probes. eIF-5A is the only protein known to contain a unique amino acid modification, hypusine. Comparison of the Nicotiana deduced amino acid sequences with those of other eIF-5A polypeptides reveals conservation throughout the coding sequence, especially in the region of the hypusine residue. Transcript analysis reveals that NeIF-5A1 is preferentially expressed in photosynthetic tissues, while NeIF-5A2 is constitutively expressed in all plant tissues examined. A polyclonal antibody was raised against NeIF-5A1 overexpressed in E. coli. NeIF-5A1 antiserum crossreacts with an 18 kDa polypeptide doublet in all tobacco tissues examined. At least one polypeptide of ca. 18 kDa from a diversity of higher and lower plants crossreacts with NeIF-5A1 antiserum. Images PMID:1542563

  9. The highly conserved human cytomegalovirus UL136 ORF generates multiple Golgi-localizing protein isoforms through differential translation initiation.

    Science.gov (United States)

    Liao, Huanan; Lee, Jung-Hyun; Kondo, Rikita; Katata, Marei; Imadome, Ken-Ichi; Miyado, Kenji; Inoue, Naoki; Fujiwara, Shigeyoshi; Nakamura, Hiroyuki

    2014-01-22

    The UL133-UL138 locus in the unique long b' (ULb') region of the human cytomegalovirus (HCMV) genome is considered to play certain roles in viral replication, dissemination and latency in a host cell type-dependent manner. Here we characterized the proteins encoded by UL136, one of the open reading frames (ORFs) in the locus. Comparative sequence analysis of UL136 among clinical isolates and laboratory strains indicates that its predicted amino-acid sequence is highly conserved. A polyclonal antibody against UL136 proteins (pUL136s) was raised against its carboxy-terminal region and this antibody specifically recognized at least five UL136-encoded protein isoforms of 29-17 kDa both in HCMV-infected cells and in cells transfected with a construct expressing pUL136. Immunofluorescence analysis with this antibody revealed localization of pUL136 in the Golgi apparatus. Analysis of several pUL136 mutants indicated that the putative transmembrane domain of pUL136 is required for its Golgi localization. Mutational analysis of multiple AUG codons in UL136 demonstrated that translation initiation from these AUG codons contributes in the generation of pUL136 isoforms.

  10. 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

  11. Optimal initial condition of passive tracers for their maximal mixing in finite time

    CERN Document Server

    Farazmand, Mohammad

    2016-01-01

    The efficiency of a fluid mixing device is often limited by fundamental laws and/or design constraints, such that a perfectly homogeneous mixture cannot be obtained in finite time. Here, we address the natural corollary question: Given the best available mixer, what is the optimal initial tracer pattern that leads to the most homogeneous mixture after a prescribed finite time? For ideal passive tracers, we show that this optimal initial condition coincides with the right singular vector (corresponding to the smallest singular value) of a suitably truncated Koopman operator. The truncation of the Koopman operator is made under the assumption that there is a small length-scale threshold $\\ell_\

  12. Study on optimization of agent initial positions in land combat simulation

    Institute of Scientific and Technical Information of China (English)

    WU Chunguo; LIANG Yanchun; LEE Heow Pueh; LU Chun; YANG Xiaowei

    2004-01-01

    The use of computational-intelligence-based techniques in the optimization of agent initial positions in land combat simulations is studied. A novel method for the reduction of support vectors in the support vector machine (SVM) is presented. The optimization on the width of the Gaussian kernel function and the combination of the SVM with the radial basis function neural network are performed in the proposed method. Simulation results show that the proposed method can improve the running efficiency drastically compared with that using the traditional SVM with the same precision. We also summarize and present some experiences and trends in the study on the optimization problem in land combat simulation.

  13. Observation of the Field, Current and Force Distributions in an Optimized Superconducting Levitation with Translational Symmetry

    Science.gov (United States)

    Ye, Chang-Qing; Ma, Guang-Tong; Liu, Kun; Wang, Jia-Su

    2016-08-01

    The superconducting levitation realized by immersing the high-temperature superconductors (HTSs) into nonuniform magnetic field is deemed promising in a wide range of industrial applications such as maglev transportation and kinetic energy storage. Using a well-established electromagnetic model to mathematically describe the HTS, we have developed an efficient scheme that is capable of intelligently and globally optimizing the permanent magnet guideway (PMG) with single or multiple HTSs levitated above for the maglev transportation applications. With maximizing the levitation force as the principal objective, we optimized the dimensions of a Halbach-derived PMG to observe how the field, current and force distribute inside the HTSs when the optimized situation is achieved. Using a pristine PMG as a reference, we have analyzed the critical issues for enhancing the levitation force through comparing the field, current and force distributions between the optimized and pristine PMGs. It was also found that the optimized dimensions of the PMG are highly dependent upon the levitated HTS. Moreover, the guidance force is not always contradictory to the levitation force and may also be enhanced when the levitation force is prescribed to be the principle objective, depending on the configuration of levitation system and lateral displacement.

  14. Observation of the Field, Current and Force Distributions in an Optimized Superconducting Levitation with Translational Symmetry

    Science.gov (United States)

    Ye, Chang-Qing; Ma, Guang-Tong; Liu, Kun; Wang, Jia-Su

    2017-01-01

    The superconducting levitation realized by immersing the high-temperature superconductors (HTSs) into nonuniform magnetic field is deemed promising in a wide range of industrial applications such as maglev transportation and kinetic energy storage. Using a well-established electromagnetic model to mathematically describe the HTS, we have developed an efficient scheme that is capable of intelligently and globally optimizing the permanent magnet guideway (PMG) with single or multiple HTSs levitated above for the maglev transportation applications. With maximizing the levitation force as the principal objective, we optimized the dimensions of a Halbach-derived PMG to observe how the field, current and force distribute inside the HTSs when the optimized situation is achieved. Using a pristine PMG as a reference, we have analyzed the critical issues for enhancing the levitation force through comparing the field, current and force distributions between the optimized and pristine PMGs. It was also found that the optimized dimensions of the PMG are highly dependent upon the levitated HTS. Moreover, the guidance force is not always contradictory to the levitation force and may also be enhanced when the levitation force is prescribed to be the principle objective, depending on the configuration of levitation system and lateral displacement.

  15. 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...

  16. Viral and cellular mRNA-specific activators harness PABP and eIF4G to promote translation initiation downstream of cap binding.

    Science.gov (United States)

    Smith, Richard W P; Anderson, Ross C; Larralde, Osmany; Smith, Joel W S; Gorgoni, Barbara; Richardson, William A; Malik, Poonam; Graham, Sheila V; Gray, Nicola K

    2017-06-13

    Regulation of mRNA translation is a major control point for gene expression and is critical for life. Of central importance is the complex between cap-bound eukaryotic initiation factor 4E (eIF4E), eIF4G, and poly(A) tail-binding protein (PABP) that circularizes mRNAs, promoting translation and stability. This complex is often targeted to regulate overall translation rates, and also by mRNA-specific translational repressors. However, the mechanisms of mRNA-specific translational activation by RNA-binding proteins remain poorly understood. Here, we address this deficit, focusing on a herpes simplex virus-1 protein, ICP27. We reveal a direct interaction with PABP that is sufficient to promote PABP recruitment and necessary for ICP27-mediated activation. PABP binds several translation factors but is primarily considered to activate translation initiation as part of the PABP-eIF4G-eIF4E complex that stimulates the initial cap-binding step. Importantly, we find that ICP27-PABP forms a complex with, and requires the activity of, eIF4G. Surprisingly, ICP27-PABP-eIF4G complexes act independently of the effects of PABP-eIF4G on cap binding to promote small ribosomal subunit recruitment. Moreover, we find that a cellular mRNA-specific regulator, Deleted in Azoospermia-like (Dazl), also employs the PABP-eIF4G interaction in a similar manner. We propose a mechanism whereby diverse RNA-binding proteins directly recruit PABP, in a non-poly(A) tail-dependent manner, to stimulate the small subunit recruitment step. This strategy may be particularly relevant to biological conditions associated with hypoadenylated mRNAs (e.g., germ cells/neurons) and/or limiting cytoplasmic PABP (e.g., viral infection, cell stress). This mechanism adds significant insight into our knowledge of mRNA-specific translational activation and the function of the PABP-eIF4G complex in translation initiation.

  17. Hinge-free topology optimization with embedded translation-invariant differentiable wavelet shrinkage

    DEFF Research Database (Denmark)

    Yoon, G. H.; Kim, Y. Y.; Bendsøe, Martin P.;

    2004-01-01

    In topology optimization applications for the design of compliant mechanisms, the formation of hinges is typically encountered. Often such hinges are unphysical artifacts that appear due to the choice of discretization spaces for design and analysis. The objective of this work is to present a new...... in the multiscale design space. To imbed the shrinkage method implicitly in the optimization formulation and thus facilitate sensitivity analysis, the shrinkage method is made differentiable by means of differentiable versions of logical operators. The validity of the present method is confirmed by solving typical...... two-dimensional compliant mechanism design problems....

  18. 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.

  19. Heat induction of a novel Rad9 variant from a cryptic translation initiation site reduces mitotic commitment.

    Science.gov (United States)

    Janes, Simon; Schmidt, Ulrike; Ashour Garrido, Karim; Ney, Nadja; Concilio, Susanna; Zekri, Mohamed; Caspari, Thomas

    2012-10-01

    Exposure of human cells to heat switches the activating signal of the DNA damage checkpoint from genotoxic to temperature stress. This change reduces mitotic commitment at the expense of DNA break repair. The thermal alterations behind this switch remain elusive despite the successful use of heat to sensitise cancer cells to DNA breaks. Rad9 is a highly conserved subunit of the Rad9-Rad1-Hus1 (9-1-1) checkpoint-clamp that is loaded by Rad17 onto damaged chromatin. At the DNA, Rad9 activates the checkpoint kinases Rad3(ATR) and Chk1 to arrest cells in G2. Using Schizosaccharomyces pombe as a model eukaryote, we discovered a new variant of Rad9, Rad9-M50, whose expression is specifically induced by heat. High temperatures promote alternative translation from a cryptic initiation codon at methionine-50. This process is restricted to cycling cells and is independent of the temperature-sensing mitogen-activated protein kinase (MAPK) pathway. While full-length Rad9 delays mitosis in the presence of DNA lesions, Rad9-M50 functions in a remodelled checkpoint pathway to reduce mitotic commitment at elevated temperatures. This remodelled pathway still relies on Rad1 and Hus1, but acts independently of Rad17. Heat-induction of Rad9-M50 ensures that the kinase Chk1 remains in a hypo-phosphorylated state. Elevated temperatures specifically reverse the DNA-damage-induced modification of Chk1 in a manner dependent on Rad9-M50. Taken together, heat reprogrammes the DNA damage checkpoint at the level of Chk1 by inducing a Rad9 variant that can act outside of the canonical 9-1-1 complex.

  20. Subdivision, Sampling, and Initialization Strategies for Simplical Branch and Bound in Global Optimization

    DEFF Research Database (Denmark)

    Clausen, Jens; Zilinskas, A,

    2002-01-01

    two schemes for sampling points of the function: midpoint sampling and vertex sampling. The convergence of the algorithm is proved, and numerical results are presented for the two dimensional case, for which also a special initial covering is presented. (C) 2002 Elsevier Science Ltd. All rights......We consider the problem of optimizing a Lipshitzian function. The branch and bound technique is a well-known solution method, and the key components for this are the subdivision scheme, the bound calculation scheme, and the initialization. For Lipschitzian optimization, the bound calculations...... are based on the sampling of function values. We propose a branch and bound algorithm based on regular simplexes. Initially, the domain in question is covered with regular simplexes, and our subdivision scheme maintains this property. The bound calculation becomes both simple and efficient, and we describe...

  1. The determination of optimal initial tension in rat coronary artery using wire myography.

    Science.gov (United States)

    Ping, N-N; Cao, L; Xiao, X; Li, S; Cao, Y-X

    2014-01-01

    The aim of the present study was to determine the optimal initial tension, i.e. initial stretch for rat coronary artery when using the multi-wire myograph system. We used the normalization procedure to mimic physiological conditions and to stretch the coronary arterial segments to normalized internal circumference (IC(1)). It is determined the internal circumference when the vessel relaxed under a transmural pressure of 100 mm Hg (IC(100)), and the IC(1) is calculated by multiplying the IC(100) by a factor k. The impact of different factor k on the initial stretch and agonist-induced tension of coronary arteries were investigated. The results showed that the maximal agonist-induced tension was achieved at the factor k value of 0.90 and the initial stretch tension was given 1.16+/-0.04 mN/mm. The most appropriate factor k value was 0.90-0.95 and the most appropriate initial tension was 1.16-1.52 mN/mm. The equilibration time of the coronary artery segments should be at least 1.0 h. In the same optimal initial tension, the agonist-induced tension increased as equilibration time lengthened.

  2. Internal initiation of translation from the human rhinovirus-2 internal ribosome entry site requires the binding of Unr to two distinct sites on the 5' untranslated region.

    Science.gov (United States)

    Anderson, Emma C; Hunt, Sarah L; Jackson, Richard J

    2007-11-01

    Internal initiation of translation from the human rhinovirus-2 (HRV-2) internal ribosome entry site (IRES) is dependent upon host cell trans-acting factors. The multiple cold shock domain protein Unr and the polypyrimidine tract-binding protein have been identified as synergistic activators of HRV-2 IRES-driven translation. In order to investigate the mechanism by which Unr acts in this process, we have mapped the binding sites of Unr to two distinct secondary structure domains of the HRV-2 IRES, and have identified specific nucleotides that are involved in the binding of Unr to the IRES. The data suggest that Unr acts as an RNA chaperone to maintain a complex tertiary IRES structure required for translational competency.

  3. Optimal initial condition of passive tracers for their maximal mixing in finite time

    Science.gov (United States)

    Farazmand, Mohammad

    2017-05-01

    The efficiency of fluid flow for mixing passive tracers is often limited by fundamental laws and/or design constraints, such that a perfectly homogeneous mixture cannot be obtained in finite time. Here we address the natural corollary question: Given a fluid flow, what is the optimal initial tracer pattern that leads to the most homogeneous mixture after a prescribed finite time? For ideal passive tracers, we show that this optimal initial condition coincides with the right singular vector (corresponding to the smallest singular value) of a suitably truncated Perron-Frobenius (PF) operator. The truncation of the PF operator is made under the assumption that there is a small length-scale threshold ℓν under which the tracer blobs are considered, for all practical purposes, completely mixed. We demonstrate our results on two examples: a prototypical model known as the sine flow and a direct numerical simulation of two-dimensional turbulence. Evaluating the optimal initial condition through this framework requires only the position of a dense grid of fluid particles at the final instance and their preimages at the initial instance of the prescribed time interval. As such, our framework can be readily applied to flows where such data are available through numerical simulations or experimental measurements.

  4. Is belief larger than fact: expectations, optimism and reality for translational stem cell research

    Directory of Open Access Journals (Sweden)

    Bubela Tania

    2012-11-01

    Full Text Available Abstract Background Stem cell (SC therapies hold remarkable promise for many diseases, but there is a significant gulf between public expectations and the reality of progress toward clinical application. Public expectations are fueled by stakeholder arguments for research and public funding, coupled with intense media coverage in an ethically charged arena. We examine media representations in light of the expanding global landscape of SC clinical trials, asking what patients may realistically expect by way of timelines for the therapeutic and curative potential of regenerative medicine? Methods We built 2 international datasets: (1 3,404 clinical trials (CT containing 'stem cell*' from ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Search Portal; and (2 13,249 newspaper articles on SC therapies using Factiva.com. We compared word frequencies between the CT descriptions and full-text newspaper articles for the number containing terms for SC type and diseases/conditions. We also developed inclusion and exclusion criteria to identify novel SC CTs, mainly regenerative medicine applications. Results Newspaper articles focused on human embryonic SCs and neurological conditions with significant coverage as well of cardiovascular disease and diabetes. In contrast, CTs used primarily hematopoietic SCs, with an increase in CTs using mesenchymal SCs since 2007. The latter dominated our novel classification for CTs, most of which are in phases I and II. From the perspective of the public, expecting therapies for neurological conditions, there is limited activity in what may be considered novel applications of SC therapies. Conclusions Given the research, regulatory, and commercialization hurdles to the clinical translation of SC research, it seems likely that patients and political supporters will become disappointed and disillusioned. In this environment, proponents need to make a concerted effort to temper

  5. RAPID OPTIMAL SPH PARTICLE DISTRIBUTIONS IN SPHERICAL GEOMETRIES FOR CREATING ASTROPHYSICAL INITIAL CONDITIONS

    Energy Technology Data Exchange (ETDEWEB)

    Raskin, Cody; Owen, J. Michael [Lawrence Livermore National Laboratory, P.O. Box 808, L-038, Livermore, CA 94550 (United States)

    2016-04-01

    Creating spherical initial conditions in smoothed particle hydrodynamics simulations that are spherically conformal is a difficult task. Here, we describe two algorithmic methods for evenly distributing points on surfaces that when paired can be used to build three-dimensional spherical objects with optimal equipartition of volume between particles, commensurate with an arbitrary radial density function. We demonstrate the efficacy of our method against stretched lattice arrangements on the metrics of hydrodynamic stability, spherical conformity, and the harmonic power distribution of gravitational settling oscillations. We further demonstrate how our method is highly optimized for simulating multi-material spheres, such as planets with core–mantle boundaries.

  6. Rapid Optimal SPH Particle Distributions in Spherical Geometries For Creating Astrophysical Initial Conditions

    CERN Document Server

    Raskin, Cody

    2016-01-01

    Creating spherical initial conditions in smoothed particle hydrodynamics simulations that are spherically conformal is a difficult task. Here, we describe two algorithmic methods for evenly distributing points on surfaces, that when paired can be used to build 3D spherical objects with optimal equipartition of volume between particles, commensurate with an arbitrary, radial density function. We demonstrate the efficacy of our method against stretched lattice arrangements on the metrics of hydrodynamic stability, spherical conformity, and the harmonic power distribution of gravitational settling oscillations. We further demonstrate how our method is highly optimized for simulating multi-material spheres, such as planets with core-mantle boundaries.

  7. Differential contribution of the m7G-cap to the 5' end-dependent translation initiation of mammalian mRNAs.

    Science.gov (United States)

    Andreev, Dmitri E; Dmitriev, Sergey E; Terenin, Ilya M; Prassolov, Vladimir S; Merrick, William C; Shatsky, Ivan N

    2009-10-01

    Many mammalian mRNAs possess long 5' UTRs with numerous stem-loop structures. For some of them, the presence of Internal Ribosome Entry Sites (IRESes) was suggested to explain their significant activity, especially when cap-dependent translation is compromised. To test this hypothesis, we have compared the translation initiation efficiencies of some cellular 5' UTRs reported to have IRES-activity with those lacking IRES-elements in RNA-transfected cells and cell-free systems. Unlike viral IRESes, the tested 5' UTRs with so-called 'cellular IRESes' demonstrate only background activities when placed in the intercistronic position of dicistronic RNAs. In contrast, they are very active in the monocistronic context and the cap is indispensable for their activities. Surprisingly, in cultured cells or cytoplasmic extracts both the level of stimulation with the cap and the overall translation activity do not correlate with the cumulative energy of the secondary structure of the tested 5' UTRs. The cap positive effect is still observed under profound inhibition of translation with eIF4E-BP1 but its magnitude varies for individual 5' UTRs irrespective of the cumulative energy of their secondary structures. Thus, it is not mandatory to invoke the IRES hypothesis, at least for some mRNAs, to explain their preferential translation when eIF4E is partially inactivated.

  8. Differential contribution of the m7G-cap to the 5′ end-dependent translation initiation of mammalian mRNAs

    Science.gov (United States)

    Andreev, Dmitri E.; Dmitriev, Sergey E.; Terenin, Ilya M.; Prassolov, Vladimir S.; Merrick, William C.; Shatsky, Ivan N.

    2009-01-01

    Many mammalian mRNAs possess long 5′ UTRs with numerous stem-loop structures. For some of them, the presence of Internal Ribosome Entry Sites (IRESes) was suggested to explain their significant activity, especially when cap-dependent translation is compromised. To test this hypothesis, we have compared the translation initiation efficiencies of some cellular 5′ UTRs reported to have IRES-activity with those lacking IRES-elements in RNA-transfected cells and cell-free systems. Unlike viral IRESes, the tested 5′ UTRs with so-called ‘cellular IRESes’ demonstrate only background activities when placed in the intercistronic position of dicistronic RNAs. In contrast, they are very active in the monocistronic context and the cap is indispensable for their activities. Surprisingly, in cultured cells or cytoplasmic extracts both the level of stimulation with the cap and the overall translation activity do not correlate with the cumulative energy of the secondary structure of the tested 5′ UTRs. The cap positive effect is still observed under profound inhibition of translation with eIF4E-BP1 but its magnitude varies for individual 5′ UTRs irrespective of the cumulative energy of their secondary structures. Thus, it is not mandatory to invoke the IRES hypothesis, at least for some mRNAs, to explain their preferential translation when eIF4E is partially inactivated. PMID:19696074

  9. 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.

  10. Initial billet and forging dies shape optimization: Application on an axisymetrical forging with a hammer

    Science.gov (United States)

    Meng, Fanjuan; Labergere, Carl; Lafon, Pascal

    2011-05-01

    In metal forming process, the forging die design is the most important step for products quality control. Reasonable dies shape can not only reduce raw material cost but also improving material flow and eliminating defects. The main objective of this paper is to obtain some optimal parameters of the initial billet and forging dies shape according to the simulation results of a two-step metal forming process (platting step and forging step). To develop this metal forming process optimization system several numerical tools are required: geometric modelling (CATIA V5™), FEM analysis (ABAQUS®), work-flow control and optimization computation (MODEFRONTIER®). This study is done in three stages: simulating the two-step metal forming process, building surrogate meta-models to relate response and variables and optimizing the process by using advanced optimization algorithms. In this paper, a two-step axisymmetric metal forming project was studied as an example. By using our simulation model, we get 581 correct real simulation results totally. According to all these real values, we build the surrogate meta-models and obtain Pareto points for a two-objective optimization process. The choice of a solution in all Pareto points will be done by the engineer who can choose his best values according to their criterions of project.

  11. 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.

  12. Optimal control of the initiation of a pericyclic reaction in the electronic ground state

    Indian Academy of Sciences (India)

    Timm Bredtmann; Jörn Manz

    2012-01-01

    Pericyclic reactions in the electronic ground state may be initiated by down-chirped pump-dump sub-pulses of an optimal laser pulse, in the ultraviolet (UV) frequency and sub-10 femtosecond (fs) time domain. This is demonstrated by means of a quantum dynamics model simulation of the Cope rearrangement of Semibullvalene. The laser pulse is designed by means of optimal control theory, with detailed analysis of the mechanism. The theoretical results support the recent experimental initiation of a pericyclic reaction. The present approach provides an important step towards monitoring asynchronous electronic fluxes during synchronous nuclear pericyclic reaction dynamics, with femto-to-attosecond time resolution, as motivated by the recent prediction of our group.

  13. Direct Method for Resolution of Optimal Control Problem with Free Initial Condition

    Directory of Open Access Journals (Sweden)

    Louadj Kahina

    2012-01-01

    Full Text Available The theory of control analyzes the proprieties of commanded systems. Problems of optimal control (OC have been intensively investigated in the world literature for over forty years. During this period, series of fundamental results have been obtained, among which should be noted the maximum principle (Pontryagin et al., 1962 and dynamic programming (Bellman, 1963. For many of the problems of the optimal control theory (OCT, adequate solutions are found (Bryson and Yu-chi, 1969, Lee and Markus, 1967, Gabasov and Kirillova, 1977, 1978, 1980. Results of the theory were taken up in various fields of science, engineering, and economics. The present paper aims at extending the constructive methods of Balashevich et al., (2000 that were developed for the problems of optimal control with the bounded initial state is not fixed are considered.

  14. Left ventricular mass and incident hypertension in individuals with initial optimal blood pressure

    Science.gov (United States)

    de Simone, Giovanni; Devereux, Richard B.; Chinali, Marcello; Roman, Mary J.; Welty, Thomas K.; Lee, Elisa T.; Howard, Barbara V.

    2008-01-01

    Objective Metabolic abnormalities have been shown to predict 8-year incident arterial hypertension in individuals with optimal blood pressure. As echocardiographic left ventricular mass has also been reported to predict incident hypertension in individuals with baseline blood pressure of less than 140/90 mmHg, we determined whether left ventricular mass predicts 4-year incident hypertension also in individuals with initial optimal blood pressure (<120/80 mmHg), independent of metabolic factors influencing blood pressure. Methods We studied 777 of 3257 members of the American Indian population-based Strong Heart Study cohort with optimal blood pressure (34% men, 45% obese, and 35% diabetic), aged 57 ± 7 years, and without prevalent cardiovascular disease. Results Over 4 years, 159 individuals (20%, group H) developed hypertension (blood pressure ≥140/90 mmHg). They had a greater baseline BMI, waist girth, and blood pressure (112/69 vs. 109/68 mmHg, all P<0.03) than those remaining normotensive (group N), with similar lipid profile and renal function. At baseline, left ventricular mass was significantly greater in group H than in group N (P<0.004). The difference in left ventricular mass was confirmed after controlling for initial BMI, systolic blood pressure, homeostatic model assessment index, and diabetes. The probability of incident hypertension increased by 36% for each standard deviation of left ventricular mass index (P=0.006), independent of covariates. Participants with left ventricular mass of more than 159 g (75th percentile of distribution) had 2.5-fold (95% confidence interval, 1.4-3.6; P<0.001) higher adjusted risk of incident hypertension than those below this value. Conclusion Left ventricular mass predicts incident arterial hypertension in individuals with initially optimal blood pressure. This association is independent of body build, prevalent diabetes, and initial blood pressure. PMID:18698223

  15. Applicability of initial optimal maternal and fetal electrocardiogram combination vectors to subsequent recordings

    Science.gov (United States)

    Yan, Hua-Wen; Huang, Xiao-Lin; Zhao, Ying; Si, Jun-Feng; Liu, Tie-Bing; Liu, Hong-Xing

    2014-11-01

    A series of experiments are conducted to confirm whether the vectors calculated for an early section of a continuous non-invasive fetal electrocardiogram (fECG) recording can be directly applied to subsequent sections in order to reduce the computation required for real-time monitoring. Our results suggest that it is generally feasible to apply the initial optimal maternal and fetal ECG combination vectors to extract the fECG and maternal ECG in subsequent recorded sections.

  16. Variational data assimilation for the optimized ozone initial state and the short-time forecasting

    Science.gov (United States)

    Park, Soon-Young; Kim, Dong-Hyeok; Lee, Soon-Hwan; Lee, Hwa Woon

    2016-04-01

    In this study, we apply the four-dimensional variational (4D-Var) data assimilation to optimize initial ozone state and to improve the predictability of air quality. The numerical modeling systems used for simulations of atmospheric condition and chemical formation are the Weather Research and Forecasting (WRF) model and the Community Multiscale Air Quality (CMAQ) model . The study area covers the capital region of South Korea, where the surface measurement sites are relatively evenly distributed. The 4D-Var code previously developed for the CMAQ model is modified to consider background error in matrix form, and various numerical tests are conducted. The results are evaluated with an idealized covariance function for the appropriateness of the modified codes. The background error is then constructed using the NMC method with long-term modeling results, and the characteristics of the spatial correlation scale related to local circulation is analyzed. The background error is applied in the 4D-Var research, and a surface observational assimilation is conducted to optimize the initial concentration of ozone. The statistical results for the 12-hour assimilation periods and the 120 observatory sites show a 49.4% decrease in the root mean squred error (RMSE), and a 59.9% increase in the index of agreement (IOA). The temporal variation of spatial distribution of the analysis increments indicates that the optimized initial state of ozone concentration is transported to inland areas by the clockwise-rotating local circulation during the assimilation windows. To investigate the predictability of ozone concentration after the assimilation window, a short-time forecasting is carried out. The ratios of the RMSE with assimilation versus that without assimilation are 8% and 13% for the +24 and +12 hours, respectively. Such a significant improvement in the forecast accuracy is obtained solely by using the optimized initial state. The potential improvement in ozone prediction for

  17. ERK1/2 map kinase metabolic pathway is responsible for phosphorylation of translation initiation factor eIF4E during in vitro maturation of pig oocytes.

    Science.gov (United States)

    Ellederová, Zdenka; Cais, Ondrej; Susor, Andrej; Uhlírová, Katka; Kovárová, Hana; Jelínková, Lucie; Tomek, Wolfgang; Kubelka, Michal

    2008-02-01

    Eukaryotic initiation factor 4E (eIF4E) plays an important role in mRNA translation by binding the 5'-cap structure of the mRNA and facilitating the recruitment to the mRNA of other translation factors and the 40S ribosomal subunit. eIF4E undergoes regulated phosphorylation on Ser-209 and this phosphorylation is believed to be important for its binding to mRNA and to other initiation factors. The findings showing that the translation initiation factor eIF4E becomes gradually phosphorylated during in vitro maturation (IVM) of pig oocytes with a maximum in metaphase II (M II) stage oocytes have been documented by us recently (Ellederova et al., 2006). The aim of this work was to study in details the metabolic pathways involved in this process. Using inhibitors of cyclin-dependent kinases, Butyrolactone I (BL I) and protein phosphatases, okadaic acid (OA) we show that ERK1/2 MAP kinase pathway is involved in this phosphorylation. We also demonstrate that activation and phosphorylation of ERK1/2 MAP kinase and eIF4E is associated with the activating phosphorylation of Mnk1 kinase, one of the two main kinases phosphorylating eIF4E in somatic cells.

  18. 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

    2016-01-01

    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. PMID:27325740

  19. 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.

  20. Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cox, James D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael; Mohan, Radhe [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Garden, Adam S.; Rosenthal, David I.; Gunn, G. Brandon [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Weber, Randal S. [Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kies, Merrill S. [Department of Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lewin, Jan S. [Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Palmer, Matthew B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Sahoo, Narayan; Zhang, Xiaodong; Liu, Wei; Zhu, X. Ronald [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-07-15

    Background: We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials: Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results: Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions: To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.

  1. The effects of initial conditions and control time on optimal actuator placement via a max-min Genetic Algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Redmond, J. [Sandia National Labs., Albuquerque, NM (United States); Parker, G. [State Univ. of New York, Buffalo, NY (United States)

    1993-07-01

    This paper examines the role of the control objective and the control time in determining fuel-optimal actuator placement for structural vibration suppression. A general theory is developed that can be easily extended to include alternative performance metrics such as energy and time-optimal control. The performance metric defines a convex admissible control set which leads to a max-min optimization problem expressing optimal location as a function of initial conditions and control time. A solution procedure based on a nested Genetic Algorithm is presented and applied to an example problem. Results indicate that the optimal locations vary widely as a function of control time and initial conditions.

  2. 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.

  3. SU-C-BRB-02: Symmetric and Asymmetric MLC Based Lung Shielding and Dose Optimization During Translating Bed TBI

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, S; Kakakhel, MB [Pakistan Institute of Engineering & Applied Sciences (PIEAS), Islamabad (Pakistan); Ahmed, SBS; Hussain, A [Aga Khan University Hospital (AKUH), Karachi (Pakistan)

    2015-06-15

    Purpose: The primary aim was to introduce a dose optimization method for translating bed total body irradiation technique that ensures lung shielding dynamically. Symmetric and asymmetric dynamic MLC apertures were employed for this purpose. Methods: The MLC aperture sizes were defined based on the radiological depth values along the divergent ray lines passing through the individual CT slices. Based on these RD values, asymmetrically shaped MLC apertures were defined every 9 mm of the phantom in superior-inferior direction. Individual MLC files were created with MATLAB™ and were imported into Eclipse™ treatment planning system for dose calculations. Lungs can be shielded to an optimum level by reducing the MLC aperture width over the lungs. The process was repeated with symmetrically shaped apertures. Results: Dose-volume histogram (DVH) analysis shows that the asymmetric MLC based technique provides better dose coverage to the body and optimum shielding of the lungs compared to symmetrically shaped beam apertures. Midline dose homogeneity is within ±3% with asymmetric MLC apertures whereas it remains within ±4.5% with symmetric ones (except head region where it drops down to −7%). The substantial over and under dosage of ±5% at tissue interfaces has been reduced to ±2% with asymmetric MLC technique. Lungs dose can be reduced to any desired limit. In this experiment lungs dose was reduced to 80% of the prescribed dose, as was desired. Conclusion: The novel asymmetric MLC based technique assures optimum shielding of OARs (e.g. lungs) and better 3-D dose homogeneity and body-dose coverage in comparison with the symmetric MLC aperture optimization. The authors acknowledge the financial and infrastructural support provided by Pakistan Institute of Engineering & Applied Sciences (PIEAS), Islamabad and Aga Khan University Hospital (AKUH), Karachi during the course of this research project. Authors have no conflict of interest with any national / international

  4. An Ad-Hoc Initial Solution Heuristic for Metaheuristic Optimization of Energy Market Participation Portfolios

    Directory of Open Access Journals (Sweden)

    Ricardo Faia

    2017-06-01

    Full Text Available The deregulation of the electricity sector has culminated in the introduction of competitive markets. In addition, the emergence of new forms of electric energy production, namely the production of renewable energy, has brought additional changes in electricity market operation. Renewable energy has significant advantages, but at the cost of an intermittent character. The generation variability adds new challenges for negotiating players, as they have to deal with a new level of uncertainty. In order to assist players in their decisions, decision support tools enabling assisting players in their negotiations are crucial. Artificial intelligence techniques play an important role in this decision support, as they can provide valuable results in rather small execution times, namely regarding the problem of optimizing the electricity markets participation portfolio. This paper proposes a heuristic method that provides an initial solution that allows metaheuristic techniques to improve their results through a good initialization of the optimization process. Results show that by using the proposed heuristic, multiple metaheuristic optimization methods are able to improve their solutions in a faster execution time, thus providing a valuable contribution for players support in energy markets negotiations.

  5. Optimized and Automated Radiosynthesis of [18F]DHMT for Translational Imaging of Reactive Oxygen Species with Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Wenjie Zhang

    2016-12-01

    Full Text Available Reactive oxygen species (ROS play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET imaging of ROS can assist in the detection of these diseases. For the purpose of clinical translation of [18F]6-(4-((1-(2-fluoroethyl-1H-1,2,3-triazol-4-ylmethoxyphenyl-5-methyl-5,6-dihydrophenanthridine-3,8-diamine ([18F]DHMT, a promising ROS PET radiotracer, we first manually optimized the large-scale radiosynthesis conditions and then implemented them in an automated synthesis module. Our manual synthesis procedure afforded [18F]DHMT in 120 min with overall radiochemical yield (RCY of 31.6% ± 9.3% (n = 2, decay-uncorrected and specific activity of 426 ± 272 GBq/µmol (n = 2. Fully automated radiosynthesis of [18F]DHMT was achieved within 77 min with overall isolated RCY of 6.9% ± 2.8% (n = 7, decay-uncorrected and specific activity of 155 ± 153 GBq/µmol (n = 7 at the end of synthesis. This study is the first demonstration of producing 2-[18F]fluoroethyl azide by an automated module, which can be used for a variety of PET tracers through click chemistry. It is also the first time that [18F]DHMT was successfully tested for PET imaging in a healthy beagle dog.

  6. The translation initiation factor eIF1A is an important determinant in the tolerance to NaCl stress in yeast and plants.

    Science.gov (United States)

    Rausell, Antonio; Kanhonou, Rodolphe; Yenush, Lynne; Serrano, Ramon; Ros, Roc

    2003-05-01

    Protein synthesis is very sensitive to NaCl. However, the molecular targets responsible for this sensitivity have not been described. A cDNA library of the halotolerant plant sugar beet was functionally screened in a sodium-sensitive yeast strain. We obtained a cDNA clone (BveIF1A) encoding the eukaryotic translation initiation factor eIF1A. BveIF1A was able to partially complement the yeast eIF1A-deficient strain. Overexpression of the sugar beet eIF1A specifically increased the sodium and lithium salt tolerance of yeast. This phenotype was not accompanied by changes in sodium or potassium homeostasis. Under salt stress conditions, yeast cells expressing BveIF1A presented a higher rate of amino acid incorporation into proteins than control cells. In an in vitro protein synthesis system from wheat germ, the BveIF1A recombinant protein improved translation in the presence of NaCl. Finally, transgenic Arabidopsis plants expressing BveIF1A exhibited increased tolerance to NaCl. These results suggest that the translation initiation factor eIF1A is an important determinant of sodium tolerance in yeast and plants.

  7. Chronic improvement of amino acid nutrition stimulates initiation of global messenger ribonucleic acid translation in tissues of sheep without affecting protein elongation.

    Science.gov (United States)

    Connors, M T; Poppi, D P; Cant, J P

    2010-02-01

    Initiation of mRNA translation and elongation of the polypeptide chain are 2 regulated processes responsible for the short-term postprandial acceleration of protein synthesis in animal tissues. It is known that a chronic increase in the absorptive supply of AA stimulates protein synthesis in ruminant animals, but effects on translation initiation and elongation are unknown. To determine whether initiation or elongation phases of global mRNA translation are affected by chronic elevation of AA supply, 24 ewe lambs of 25.9 +/- 2.5 kg of BW were randomly allocated to 4 treatment groups of 6 lambs each. All lambs received a basal diet of barley and hay at 1.2 times maintenance ME intake. Treatments were an intravenous (i.v.) saline infusion as a control, i.v. infusion of 6 essential AA (EAA; Arg, Lys, His, Thr, Met, Cys) for 10 d, i.v. infusion of the same EAA excluding Met and Cys (EAA-SAA) for 10 d, and an oral drench of fishmeal twice daily for 17 d. Fishmeal supplementation supplied an extra 719 mg of N x kg(-0.75) x d(-1) and N retention was increased 519 mg x kg(-0.75) x d(-1) over the control. The EAA treatment supplied an extra 343 mg of N x kg(-0.75) x d(-1) directly into the blood, and N balance was increased by 268 mg x kg(-0.75) x d(-1). Deletion of Met plus Cys from EAA had no effect on N balance. The results indicate that Met plus Cys did not limit body protein gain on the basal diet alone or the basal diet plus 6 AA. Protein fractional synthesis rates in liver, duodenum, skin, rumen, semimembranosus, and LM were measured by a flooding dose procedure using L-[ring-2,6-(3)H]-Phe. Ribosome transit times were estimated from the ratio of nascent to total protein-bound radioactivities. Fishmeal and EAA treatments had no effect on RNA, DNA, or protein contents of tissues, but fractional synthesis rate, translational efficiency, and concentrations of active ribosomes were consistently elevated. Ribosome transit time was not affected by long-term AA supply. We

  8. Partial Overhaul and Initial Parallel Optimization of KINETICS, a Coupled Dynamics and Chemistry Atmosphere Model

    Science.gov (United States)

    Nguyen, Howard; Willacy, Karen; Allen, Mark

    2012-01-01

    KINETICS is a coupled dynamics and chemistry atmosphere model that is data intensive and computationally demanding. The potential performance gain from using a supercomputer motivates the adaptation from a serial version to a parallelized one. Although the initial parallelization had been done, bottlenecks caused by an abundance of communication calls between processors led to an unfavorable drop in performance. Before starting on the parallel optimization process, a partial overhaul was required because a large emphasis was placed on streamlining the code for user convenience and revising the program to accommodate the new supercomputers at Caltech and JPL. After the first round of optimizations, the partial runtime was reduced by a factor of 23; however, performance gains are dependent on the size of the data, the number of processors requested, and the computer used.

  9. PKCδ Regulates Translation Initiation through PKR and eIF2α in Response to Retinoic Acid in Acute Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Bulent Ozpolat

    2012-01-01

    Full Text Available Translation initiation and activity of eukaryotic initiation factor-alpha (eIF2α, the rate-limiting step of translation initiation, is often overactivated in malignant cells. Here, we investigated the regulation and role of eIF2α in acute promyelocytic (APL and acute myeloid leukemia (AML cells in response to all-trans retinoic acid (ATRA and arsenic trioxide (ATO, the front-line therapies in APL. ATRA and ATO induce Ser-51 phosphorylation (inactivation of eIF2α, through the induction of protein kinase C delta (PKCδ and PKR, but not other eIF2α kinases, such as GCN2 and PERK in APL (NB4 and AML cells (HL60, U937, and THP-1. Inhibition of eIF2α reduced the expression of cellular proteins that are involved in apoptosis (DAP5/p97, cell cycle (p21Waf1/Cip1, differentiation (TG2 and induced those regulating proliferation (c-myc and survival (p70S6K. PI3K/Akt/mTOR pathway is involved in regulation of eIF2α through PKCδ/PKR axis. PKCδ and p-eIF2α protein expression levels revealed a significant association between the reduced levels of PKCδ (P=0.0378 and peIF2 (P=0.0041 and relapses in AML patients (n=47. In conclusion, our study provides the first evidence that PKCδ regulates/inhibits eIF2α through induction of PKR in AML cells and reveals a novel signaling mechanism regulating translation initiation.

  10. Initial state-specific photodissociation dynamics of pyrrole via 1 π σ ∗/ S 0 conical intersection initiated with optimally controlled UV-laser pulses

    Science.gov (United States)

    Nandipati, K. R.; Kanakati, Arun Kumar; Singh, H.; Lan, Z.; Mahapatra, S.

    2017-09-01

    Optimal initiation of quantum dynamics of N-H photodissociation of pyrrole on the S 0-1 π σ ∗(1 A 2) coupled electronic states by UV-laser pulses in an effort to guide the subsequent dynamics to dissociation limits is studied theoretically. Specifically, the task of designing optimal laser pulses that act on initial vibrational states of the system for an effective UV-photodissociation is considered by employing optimal control theory. The associated control mechanism(s) for the initial state dependent photodissociation dynamics of pyrrole in the presence of control pulses is examined and discussed in detail. The initial conditions determine implicitly the variation in the dissociation probabilities for the two channels, upon interaction with the field. The optimal pulse corresponds to the objective fixed as maximization of overall reactive flux subject to constraints of reasonable fluence and quantum dynamics. The simple optimal pulses obtained by the use of genetic algorithm based optimization are worth an experimental implementation given the experimental relevance of π σ ∗-photochemistry in recent times.

  11. Optimizing congestion and emissions via tradable credit charge and reward scheme without initial credit allocations

    Science.gov (United States)

    Zhu, Wenlong; Ma, Shoufeng; Tian, Junfang

    2017-01-01

    This paper investigates the revenue-neutral tradable credit charge and reward scheme without initial credit allocations that can reassign network traffic flow patterns to optimize congestion and emissions. First, we prove the existence of the proposed schemes and further decentralize the minimum emission flow pattern to user equilibrium. Moreover, we design the solving method of the proposed credit scheme for minimum emission problem. Second, we investigate the revenue-neutral tradable credit charge and reward scheme without initial credit allocations for bi-objectives to obtain the Pareto system optimum flow patterns of congestion and emissions; and present the corresponding solutions are located in the polyhedron constituted by some inequalities and equalities system. Last, numerical example based on a simple traffic network is adopted to obtain the proposed credit schemes and verify they are revenue-neutral.

  12. KVSA VERTAALPRYS / CASA TRANSLATION PRIZE

    Directory of Open Access Journals (Sweden)

    Annemarie De Villiers

    2012-03-01

    Full Text Available A translation competition was initiated and sponsored by theClassical Association of South Africa in 2011. This translation wasjudged to be the best student translation submitted to CASA duringthis past year.

  13. The 5′-untranslated region of the mouse mammary tumor virus mRNA exhibits cap-independent translation initiation

    Science.gov (United States)

    Vallejos, Maricarmen; Ramdohr, Pablo; Valiente-Echeverría, Fernando; Tapia, Karla; Rodriguez, Felipe E.; Lowy, Fernando; Huidobro-Toro, J. Pablo; Dangerfield, John A.; López-Lastra, Marcelo

    2010-01-01

    In this study, we demonstrate the identification of an internal ribosome entry site (IRES) within the 5′-untranslated region (5′-UTR) of the mouse mammary tumor virus (MMTV). The 5′-UTR of the full-length mRNA derived from the infectious, complete MMTV genome was cloned into a dual luciferase reporter construct containing an upstream Renilla luciferase gene (RLuc) and a downstream firefly luciferase gene (FLuc). In rabbit reticulocyte lysate, the MMTV 5′-UTR was capable of driving translation of the second cistron. In vitro translational activity from the MMTV 5′-UTR was resistant to the addition of m7GpppG cap-analog and cleavage of eIF4G by foot-and-mouth disease virus (FMDV) L-protease. IRES activity was also demonstrated in the Xenopus laevis oocyte by micro-injection of capped and polyadenylated bicistronic RNAs harboring the MMTV-5′-UTR. Finally, transfection assays showed that the MMTV-IRES exhibits cell type-dependent translational activity, suggesting a requirement for as yet unidentified cellular factors for its optimal function. PMID:19889724

  14. Translations and Translators.

    Science.gov (United States)

    Nida, Eugene A.

    1979-01-01

    The necessity for stylistic appropriateness in translation as well as correct content is discussed. To acquire this skill, translators must be trained in stylistics through close examination of their own language and must have practice in translating for different audiences at different levels. (PMJ)

  15. Optimizing management in autoimmune hepatitis with liver failure at initial presentation

    Institute of Scientific and Technical Information of China (English)

    Jonathan R Potts; Sumita Verma

    2011-01-01

    Autoimmune hepatitis (AIH) is a disease of unknown etiology, its hallmark being ongoing hepatic inflamma-tion. By its very nature, it is a chronic condition, al-though increasingly, we are becoming aware of patients with acute presentations, some of whom may have liver failure. There are very limited published data on patients with AIH with liver failure at initial diagnosis, which consist mostly of small retrospective studies. As a consequence, the clinical features and optimal management of this cohort remain poorly defined. A subset of patients with AIH who present with liver failure do respond to corticosteroids, but for the vast majority, an urgent liver transplantation may offer the only hope of long-term survival. At present, there is uncertainty on how best to stratify such a cohort into responders and non-responders to corticosteroids as soon as possible after hospitalization, thus optimizing their management. This editorial attempts to answer some of the unre-solved issues relating to management of patients with AIH with liver failure at initial presentation. However, it must be emphasized that, at present, this editorial is based mostly on small retrospective studies, and it is an understatement that multicenter prospective studies are urgently needed to address this important clinical issue.

  16. Effects of optimal initial errors on predicting the seasonal reduction of the upstream Kuroshio transport

    Science.gov (United States)

    Zhang, Kun; Wang, Qiang; Mu, Mu; Liang, Peng

    2016-10-01

    With the Regional Ocean Modeling System (ROMS), we realistically simulated the transport variations of the upstream Kuroshio (referring to the Kuroshio from its origin to the south of Taiwan), particularly for the seasonal transport reduction. Then, we investigated the effects of the optimal initial errors estimated by the conditional nonlinear optimal perturbation (CNOP) approach on predicting the seasonal transport reduction. Two transport reduction events (denoted as Event 1 and Event 2) were chosen, and CNOP1 and CNOP2 were obtained for each event. By examining the spatial structures of the two types of CNOPs, we found that the dominant amplitudes are located around (128°E, 17°N) horizontally and in the upper 1000 m vertically. For each event, the two CNOPs caused large prediction errors. Specifically, at the prediction time, CNOP1 (CNOP2) develops into an anticyclonic (cyclonic) eddy-like structure centered around 124°E, leading to the increase (decrease) of the upstream Kuroshio transport. By investigating the time evolution of the CNOPs in Event 1, we found that the eddy-like structures originating from east of Luzon gradually grow and simultaneously propagate westward. The eddy-energetic analysis indicated that the errors obtain energy from the background state through barotropic and baroclinic instabilities and that the latter plays a more important role. These results suggest that improving the initial conditions in east of Luzon could lead to better prediction of the upstream Kuroshio transport variation.

  17. Translating Words, Translating Cultures

    Directory of Open Access Journals (Sweden)

    Richard Whitaker

    2012-03-01

    Full Text Available What exactly does (or should translation from one language into another try to do? Attempt to convey to readers of the target language (the language into which one is translating something of the strangeness, difference and historicity of the original in the source language (the language from which one is translating? Or must translation try to bridge the gap between source and target language, by rendering the original in a thoroughly contemporary style and diction, as if this were a work being written now for the first time? And related to these the further questions: how closely should a translation render the genre, language, metre, style and content of the original? How far can a translation depart from the original without ceasing to be a translation – in other words, where is one to situate the border between “translation”, “version” and “adaptation”?

  18. A Discussion of Initiative Faithfulness and Creative Treason in Translation%翻译中的能动性忠实与创造性叛逆

    Institute of Scientific and Technical Information of China (English)

    叶晓玲

    2016-01-01

    Translation is the communication of meaning from one language to another. The difference between two languages will cause some deviations from the source text. The translators should attach importance to the relationship between initiative faithfulness and creative treason as well as their functions. By grasping the creative space and seeking balance between faithful-ness and treason, translators are able to serve the target audience better with the extending vitality, expressiveness and appeal.%翻译就是语言“转换变易”的活动。由于语言间的差异,翻译中的“走样”与“失真”在所难免。译者在翻译过程中应重视能动性忠实与创造性叛逆的关系和作用,把握创造性空间的大小,在忠实与背叛间寻求平衡,利用一定程度的“走样”与“失真”使原作延伸生命力,扩大表现力,增强感染力,更好地为读者服务。

  19. 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.

  20. The Optimize Heart Failure Care Program: Initial lessons from global implementation.

    Science.gov (United States)

    Cowie, Martin R; Lopatin, Yuri M; Saldarriaga, Clara; Fonseca, Cândida; Sim, David; Magaña, Jose Antonio; Albuquerque, Denilson; Trivi, Marcelo; Moncada, Gustavo; González Castillo, Baldomero A; Sánchez, Mario Osvaldo Speranza; Chung, Edward

    2017-06-01

    Hospitalization for heart failure (HF) places a major burden on healthcare services worldwide, and is a strong predictor of increased mortality especially in the first three months after discharge. Though undesirable, hospitalization is an opportunity to optimize HF therapy and advise clinicians and patients about the importance of continued adherence to HF medication and regular monitoring. The Optimize Heart Failure Care Program (www.optimize-hf.com), which has been implemented in 45 countries, is designed to improve outcomes following HF hospitalization through inexpensive initiatives to improve prescription of appropriate drug therapies, patient education and engagement, and post-discharge planning. It includes best practice clinical protocols for local adaptation, pre- and post-discharge checklists, and 'My HF Passport', a printed and smart phone application to improve patient understanding of HF and encourage involvement in care and treatment adherence. Early experience of the Program suggests that factors leading to successful implementation include support from HF specialists or 'local leaders', regular educational meetings for participating healthcare professionals, multidisciplinary collaboration, and full integration of pre- and post-hospital discharge checklists across care services. The Program is helping to raise awareness of HF and generate useful data on current practice. It is showing how good evidence-based care can be achieved through the use of simple clinician and patient-focused tools. Preliminary results suggest that optimization of HF pharmacological therapy is achievable through the Program, with little new investment. Further data collection will lead to a greater understanding of the impact of the Program on HF care and key indicators of success. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. 翻译起始因子与肿瘤翻译调控异常研究进展%Translation initiation factors and abnormalities of translation control in tumors

    Institute of Scientific and Technical Information of China (English)

    沈杰; 谢海棠; 刘昭前

    2013-01-01

    Maintenance of cell homeostasis and regulation of cell proliferation depend importantly on regulating the process of protein synthesis. Most translational controls occur during the initiation phase of protein synthesis recruiting several translation initiation factors (eIFs), with the initiation factors being the major target of regulation through their phosphorylation. When the process of protein synthesis is hyper-activated, abnormalities in the phosphorylation, expression and degradation were frequently observed, leading to an imbalance of cellular proteins that promotes cell proliferation and malignant transformation. This occurs, for example, when the cap-binding protein, eIF4E, is overex-pressed, or when the methionyl-tRNAi-binding factor, eIF2, is too active, and when eIF3 hyper-activated. The importance of elFs as regulators of protein synthesis and cell proliferation makes them potential therapeutic targets for the treatment of cancer. This review focuses on elFs and mechanisms of translational control and how disregulation results in cell malignancy.%蛋白合成是维持细胞稳态和细胞增殖的关键步骤.翻译过程的调控多发生在蛋白合成起始过程,多种翻译起始因子(eIFs)参与此过程.在细胞恶性袁型转化过程中,常伴随这些因子的磷酸化、过表达及降解过程异常.如帽结合蛋白eIF4E高表达,甲硫氨酸-tRNA结合蛋白eIF2过度活跃,eIF3的活性增高等现象.eIFs在蛋白合成及细胞增殖过程中的重要地位使得其成为抗肿瘤研究的热点及潜在的治疗靶点.本文对eIFs及肿瘤翻译调控的研究进展及研究方法进行综述.

  2. Establishment and Application of a High Throughput Screening System Targeting the Interaction between HCV Internal Ribosome Entry Site and Human Eukaryotic Translation Initiation Factor 3

    Directory of Open Access Journals (Sweden)

    Yuying Zhu

    2017-05-01

    Full Text Available Viruses are intracellular obligate parasites and the host cellular machinery is usually recruited for their replication. Human eukaryotic translation initiation factor 3 (eIF3 could be directly recruited by the hepatitis C virus (HCV internal ribosome entry site (IRES to promote the translation of viral proteins. In this study, we establish a fluorescence polarization (FP based high throughput screening (HTS system targeting the interaction between HCV IRES and eIF3. By screening a total of 894 compounds with this HTS system, two compounds (Mucl39526 and NP39 are found to disturb the interaction between HCV IRES and eIF3. And these two compounds are further demonstrated to inhibit the HCV IRES-dependent translation in vitro. Thus, this HTS system is functional to screen the potential HCV replication inhibitors targeting human eIF3, which is helpful to overcome the problem of viral resistance. Surprisingly, one compound HP-3, a kind of oxytocin antagonist, is discovered to significantly enhance the interaction between HCV IRES and eIF3 by this HTS system. HP-3 is demonstrated to directly interact with HCV IRES and promote the HCV IRES-dependent translation both in vitro and in vivo, which strongly suggests that HP-3 has potentials to promote HCV replication. Therefore, this HTS system is also useful to screen the potential HCV replication enhancers, which is meaningful for understanding the viral replication and screening novel antiviral drugs. To our knowledge, this is the first HTS system targeting the interaction between eIF3 and HCV IRES, which could be applied to screen both potential HCV replication inhibitors and enhancers.

  3. Mitochondrial Respiration Inhibitors Suppress Protein Translation and Hypoxic Signaling via the Hyperphosphorylation and Inactivation of Translation Initiation Factor eIF2α and Elongation Factor eEF2

    Science.gov (United States)

    Li, Jun; Mahdi, Fakhri; Du, Lin; Datta, Sandipan; Nagle, Dale G.; Zhou, Yu-Dong

    2011-01-01

    Over 20000 lipid extracts of plants and marine organisms were evaluated in a human breast tumor T47D cell-based reporter assay for hypoxia-inducible factor-1 (HIF-1) inhibitory activity. Bioassay-guided isolation and dereplication-based structure elucidation of an active extract from the Bael tree (Aegle marmelos) afforded two protolimonoids, skimmiarepin A (1) and skimmiarepin C (2). In T47D cells, 1 and 2 inhibited hypoxia-induced HIF-1 activation with IC50 values of 0.063 µM and 0.068 µM, respectively. Compounds 1 and 2 also suppressed hypoxic induction of the HIF-1 target genes GLUT-1 and VEGF. Mechanistic studies revealed that 1 and 2 inhibited HIF-1 activation by blocking the hypoxia-induced accumulation of HIF-1α protein. At the range of concentrations that inhibited HIF-1 activation, 1 and 2 suppressed cellular respiration by selectively inhibiting the mitochondrial electron transport chain at complex I (NADH dehydrogenase). Further investigation indicated that mitochondrial respiration inhibitors such as 1 and rotenone induced the rapid hyperphosphorylation and inhibition of translation initiation factor eIF2α and elongation factor eEF2. The inhibition of protein translation may account for the short-term exposure effects exerted by mitochondrial inhibitors on cellular signaling, while the suppression of cellular ATP production may contribute to the inhibitory effects following extended treatment periods. PMID:21875114

  4. Physical and biochemical properties of mammalian DNase X proteins: non-AUG translation initiation of porcine and bovine mRNAs for DNase X.

    Science.gov (United States)

    Shiokawa, Daisuke; Shika, Yukari; Saito, Kazuki; Yamazaki, Kosuke; Tanuma, Sei-ichi

    2005-12-15

    DNase X is the first human DNase protein identified as being homologous with DNase I. In the present study we describe the isolation of several mammalian DNase X cDNAs and the molecular characterization of their coding proteins. A sequence comparison reveals some conserved characteristics: all the mammalian DNase X proteins have an N-terminal signal peptide, a potential N-linked glycosylation site and a C-terminal hydrophobic domain. Human DNase X, ectopically expressed in HeLa S3 cells, is located in the ER (endoplasmic reticulum) and is modified by an N-linked glycosylation at Asn-243. Gene expression analyses show that the high expression level in muscular tissues, a known feature of human DNASE X, is also observed in mouse DNase X. Interestingly, the translation of porcine and bovine DNase X proteins occurs in the absence of an in-frame AUG initiation codon. We show that their mRNAs utilize a conserved CUG triplet for translation initiation.

  5. An algorithm of sequential systems of linear equations for nonlinear optimization problems with arbitrary initial point

    Institute of Scientific and Technical Information of China (English)

    高自友; 贺国平; 吴方

    1997-01-01

    For current sequential quadratic programming (SQP) type algorithms, there exist two problems; (i) in order to obtain a search direction, one must solve one or more quadratic programming subproblems per iteration, and the computation amount of this algorithm is very large. So they are not suitable for the large-scale problems; (ii) the SQP algorithms require that the related quadratic programming subproblems be solvable per iteration, but it is difficult to be satisfied. By using e-active set procedure with a special penalty function as the merit function, a new algorithm of sequential systems of linear equations for general nonlinear optimization problems with arbitrary initial point is presented This new algorithm only needs to solve three systems of linear equations having the same coefficient matrix per iteration, and has global convergence and local superlinear convergence. To some extent, the new algorithm can overcome the shortcomings of the SQP algorithms mentioned above.

  6. Exploring How Knowledge Translation Can Improve Sustainability of Community-Based Health Initiatives for People with Intellectual/Developmental Disabilities

    Science.gov (United States)

    Spassiani, Natasha A.; Parker Harris, Sarah; Hammel, Joy

    2016-01-01

    Community-based health initiatives (CBHI) play an important role in maintaining the health, function and participation of people with intellectual/developmental disabilities (I/DD) living in the community. However, implementation and long-term sustainability of CBHI is challenging. The Promoting Action on Research Implementation in Health Services…

  7. 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

  8. Reconstructing Networks from Profit Sequences in Evolutionary Games via a Multiobjective Optimization Approach with Lasso Initialization

    Science.gov (United States)

    Wu, Kai; Liu, Jing; Wang, Shuai

    2016-11-01

    Evolutionary games (EG) model a common type of interactions in various complex, networked, natural and social systems. Given such a system with only profit sequences being available, reconstructing the interacting structure of EG networks is fundamental to understand and control its collective dynamics. Existing approaches used to handle this problem, such as the lasso, a convex optimization method, need a user-defined constant to control the tradeoff between the natural sparsity of networks and measurement error (the difference between observed data and simulated data). However, a shortcoming of these approaches is that it is not easy to determine these key parameters which can maximize the performance. In contrast to these approaches, we first model the EG network reconstruction problem as a multiobjective optimization problem (MOP), and then develop a framework which involves multiobjective evolutionary algorithm (MOEA), followed by solution selection based on knee regions, termed as MOEANet, to solve this MOP. We also design an effective initialization operator based on the lasso for MOEA. We apply the proposed method to reconstruct various types of synthetic and real-world networks, and the results show that our approach is effective to avoid the above parameter selecting problem and can reconstruct EG networks with high accuracy.

  9. Initialization and self-organized optimization of recurrent neural network connectivity.

    Science.gov (United States)

    Boedecker, Joschka; Obst, Oliver; Mayer, N Michael; Asada, Minoru

    2009-10-01

    Reservoir computing (RC) is a recent paradigm in the field of recurrent neural networks. Networks in RC have a sparsely and randomly connected fixed hidden layer, and only output connections are trained. RC networks have recently received increased attention as a mathematical model for generic neural microcircuits to investigate and explain computations in neocortical columns. Applied to specific tasks, their fixed random connectivity, however, leads to significant variation in performance. Few problem-specific optimization procedures are known, which would be important for engineering applications, but also in order to understand how networks in biology are shaped to be optimally adapted to requirements of their environment. We study a general network initialization method using permutation matrices and derive a new unsupervised learning rule based on intrinsic plasticity (IP). The IP-based learning uses only local learning, and its aim is to improve network performance in a self-organized way. Using three different benchmarks, we show that networks with permutation matrices for the reservoir connectivity have much more persistent memory than the other methods but are also able to perform highly nonlinear mappings. We also show that IP-based on sigmoid transfer functions is limited concerning the output distributions that can be achieved.

  10. Genes optimized by evolution for accurate and fast translation encode in Archaea and Bacteria a broad and characteristic spectrum of protein functions

    Directory of Open Access Journals (Sweden)

    Merkl Rainer

    2010-11-01

    Full Text Available Abstract Background In many microbial genomes, a strong preference for a small number of codons can be observed in genes whose products are needed by the cell in large quantities. This codon usage bias (CUB improves translational accuracy and speed and is one of several factors optimizing cell growth. Whereas CUB and the overrepresentation of individual proteins have been studied in detail, it is still unclear which high-level metabolic categories are subject to translational optimization in different habitats. Results In a systematic study of 388 microbial species, we have identified for each genome a specific subset of genes characterized by a marked CUB, which we named the effectome. As expected, gene products related to protein synthesis are abundant in both archaeal and bacterial effectomes. In addition, enzymes contributing to energy production and gene products involved in protein folding and stabilization are overrepresented. The comparison of genomes from eleven habitats shows that the environment has only a minor effect on the composition of the effectomes. As a paradigmatic example, we detailed the effectome content of 37 bacterial genomes that are most likely exposed to strongest selective pressure towards translational optimization. These effectomes accommodate a broad range of protein functions like enzymes related to glycolysis/gluconeogenesis and the TCA cycle, ATP synthases, aminoacyl-tRNA synthetases, chaperones, proteases that degrade misfolded proteins, protectants against oxidative damage, as well as cold shock and outer membrane proteins. Conclusions We made clear that effectomes consist of specific subsets of the proteome being involved in several cellular functions. As expected, some functions are related to cell growth and affect speed and quality of protein synthesis. Additionally, the effectomes contain enzymes of central metabolic pathways and cellular functions sustaining microbial life under stress situations. These

  11. 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.

  12. 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.

  13. 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.

  14. A Conserved Interaction between a C-Terminal Motif in Norovirus VPg and the HEAT-1 Domain of eIF4G Is Essential for Translation Initiation.

    Directory of Open Access Journals (Sweden)

    Eoin N Leen

    2016-01-01

    Full Text Available Translation initiation is a critical early step in the replication cycle of the positive-sense, single-stranded RNA genome of noroviruses, a major cause of gastroenteritis in humans. Norovirus RNA, which has neither a 5´ m7G cap nor an internal ribosome entry site (IRES, adopts an unusual mechanism to initiate protein synthesis that relies on interactions between the VPg protein covalently attached to the 5´-end of the viral RNA and eukaryotic initiation factors (eIFs in the host cell. For murine norovirus (MNV we previously showed that VPg binds to the middle fragment of eIF4G (4GM; residues 652-1132. Here we have used pull-down assays, fluorescence anisotropy, and isothermal titration calorimetry (ITC to demonstrate that a stretch of ~20 amino acids at the C terminus of MNV VPg mediates direct and specific binding to the HEAT-1 domain within the 4GM fragment of eIF4G. Our analysis further reveals that the MNV C terminus binds to eIF4G HEAT-1 via a motif that is conserved in all known noroviruses. Fine mutagenic mapping suggests that the MNV VPg C terminus may interact with eIF4G in a helical conformation. NMR spectroscopy was used to define the VPg binding site on eIF4G HEAT-1, which was confirmed by mutagenesis and binding assays. We have found that this site is non-overlapping with the binding site for eIF4A on eIF4G HEAT-1 by demonstrating that norovirus VPg can form ternary VPg-eIF4G-eIF4A complexes. The functional significance of the VPg-eIF4G interaction was shown by the ability of fusion proteins containing the C-terminal peptide of MNV VPg to inhibit in vitro translation of norovirus RNA but not cap- or IRES-dependent translation. These observations define important structural details of a functional interaction between norovirus VPg and eIF4G and reveal a binding interface that might be exploited as a target for antiviral therapy.

  15. Translation initiation factor 5A and its hypusine modification are essential for cell viability in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Schnier, J; Schwelberger, H G; Smit-McBride, Z; Kang, H A; Hershey, J W

    1991-06-01

    Translation intitiation factor eIF-5A (previously named eIF-4D) is a highly conserved protein that promotes formation of the first peptide bond. One of its lysine residues is modified by spermidine to form hypusine, a posttranslational modification unique to eIF-5A. To elucidate the function of eIF-5A and determine the role of its hypusine modification, the cDNA encoding human eIF-5A was used as a probe to identify and clone the corresponding genes from the yeast Saccharomyces cerevisiae. Two genes named TIF51A and TIF51B were cloned and sequenced. The two yeast proteins are closely related, sharing 90% sequence identity, and each is ca. 63% identical to the human protein. The purified protein expressed from the TIF51A gene substitutes for HeLa eIF-5A in the mammalian methionyl-puromycin synthesis assay. Strains lacking the A form of eIF-5A, constructed by disruption of TIF51A with LEU2, grow slowly, whereas strains lacking the B form, in which HIS3 was used to disrupt TIF51B, show no growth rate phenotype. However, strains with both TIF51A and TIF51B disrupted are not viable, indicating that eIF-5a is essential for cell growth in yeast cells. Northern (RNA) blot analysis shows two mRNA species, a larger mRNA (0.9 kb) transcribed from TIF51A and a smaller mRNA (0.8 kb) encoded by TIF51B. Under the aerobic growth conditions of this study, the 0.8-kb TIF51B transcript is not detected in the wild-type strain and is expressed only when TIF51A is disrupted. The TIF51A gene was altered by site-directed mutagenesis at the site of hypusination by changing the Lys codon to that for Arg, thereby producing a stable protein that retains the positive charge but is not modified to the hypusine derivative. The plasmid shuffle technique was used to replace the wild-type gene with the mutant form, resulting in failure of the yeast cells to grow. This result indicates that hypusine very likely is required for the vital in vivo function of eIF-5A and suggests a precise, essential

  16. Translating China

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    sidney Shapiro, an American-born translator famous for his translation of Chinese literary works, received the Lifetime Achievement Award in Translation by the Translators Association of China on December 2, 2010.

  17. Optimization of Thermal Aspects of Friction Stir Welding – Initial Studies Using a Space Mapping Technique

    DEFF Research Database (Denmark)

    Larsen, Anders Astrup; Bendsøe, Martin P.; Schmidt, Henrik Nikolaj Blicher;

    2007-01-01

    The aim of this paper is to optimize a thermal model of a friction stir welding process. The optimization is performed using a space mapping technique in which an analytical model is used along with the FEM model to be optimized. The results are compared to traditional gradient based optimization...

  18. Optimization of Thermal Aspects of Friction Stir Welding – Initial Studies Using a Space Mapping Technique

    DEFF Research Database (Denmark)

    Larsen, Anders Astrup; Bendsøe, Martin P.; Schmidt, Henrik Nikolaj Blicher

    2007-01-01

    The aim of this paper is to optimize a thermal model of a friction stir welding process. The optimization is performed using a space mapping technique in which an analytical model is used along with the FEM model to be optimized. The results are compared to traditional gradient based optimization...

  19. Translation Theory 'Translated'

    DEFF Research Database (Denmark)

    Wæraas, Arild; Nielsen, Jeppe

    2016-01-01

    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 mo......, 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.......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...... 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...

  20. Eukaryotic translation initiation factor 4E (eIF4E) expression is associated with breast cancer tumor phenotype and predicts survival after anthracycline chemotherapy treatment.

    Science.gov (United States)

    Heikkinen, Tuomas; Korpela, Taina; Fagerholm, Rainer; Khan, Sofia; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Carpén, Olli; Nevanlinna, Heli

    2013-08-01

    Abnormal translation of mRNAs frequently occurring during carcinogenesis is among the mechanisms that can affect the expression of proteins involved in tumor development and progression. Eukaryotic initiation factor eIF4E is a key regulator of translation of many cancer-related transcripts and its expression is altered in various cancers and has been associated with worse survival. We determined the eIF4E protein levels using immunohistochemistry (IHC) in 1,233 breast tumors on tissue microarrays. We analyzed the effects of the IHC expression level on tumor characteristics and patient survival, also with stratification by adjuvant chemotherapy treatment. In 1,085 successfully stained tumors, high level of eIF4E protein expression was associated with features of aggressive tumor phenotype, namely grade, estrogen and progesterone receptor negativity, HER2 receptor positivity, and high expression of p53 and Ki67, and with triple negative subtype (p effect was strongest among patients treated with anthracycline chemotherapy (HR = 3.34, 95 % CI 1.72-6.48, p = 0.0002), whereas no such effect was seen among patients who had not received anthracycline with significant difference in heterogeneity between the two groups (p = 0.0358). High expression of eIF4E is associated with adverse tumor characteristics and predicts poor breast cancer-specific survival. This effect is emphasized in patients treated with anthracycline chemotherapy. eIF4E as a treatment predictive factor warrants further studies.

  1. 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...... - translators, language teachers, translation users and literary, TV and film critics, for instance. Discussions focus on translation between Danish and English....

  2. 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...... - translators, language teachers, translation users and literary, TV and film critics, for instance. Discussions focus on translation between Danish and English....

  3. Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis

    Science.gov (United States)

    Meng, Xiang; Firczuk, Helena; Pietroni, Paola; Westbrook, Richard; Dacheux, Estelle; Mendes, Pedro; McCarthy, John E.G.

    2017-01-01

    Gene expression noise influences organism evolution and fitness. The mechanisms determining the relationship between stochasticity and the functional role of translation machinery components are critical to viability. eIF4G is an essential translation factor that exerts strong control over protein synthesis. We observe an asymmetric, approximately bell-shaped, relationship between the average intracellular abundance of eIF4G and rates of cell population growth and global mRNA translation, with peak rates occurring at normal physiological abundance. This relationship fits a computational model in which eIF4G is at the core of a multi-component–complex assembly pathway. This model also correctly predicts a plateau-like response of translation to super-physiological increases in abundance of the other cap-complex factors, eIF4E and eIF4A. Engineered changes in eIF4G abundance amplify noise, demonstrating that minimum stochasticity coincides with physiological abundance of this factor. Noise is not increased when eIF4E is overproduced. Plasmid-mediated synthesis of eIF4G imposes increased global gene expression stochasticity and reduced viability because the intrinsic noise for this factor influences total cellular gene noise. The naturally evolved eIF4G gene expression noise minimum maps within the optimal activity zone dictated by eIF4G's mechanistic role. Rate control and noise are therefore interdependent and have co-evolved to share an optimal physiological abundance point. PMID:27928055

  4. Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines

    Science.gov (United States)

    2011-01-01

    required for the adhesion of platelets to inflamed ECs. Because platelet adhesion to an inflamed endothelium is crucial for plaque formation in non-denuded blood vessels, we conclude that the de-novo translation of F11R is a crucial early step in the initiation of atherogenesis, leading to atherosclerosis, heart attacks and stroke. PMID:21703019

  5. Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines

    Directory of Open Access Journals (Sweden)

    Kornecki Elizabeth

    2011-06-01

    of F11R in ECs is required for the adhesion of platelets to inflamed ECs. Because platelet adhesion to an inflamed endothelium is crucial for plaque formation in non-denuded blood vessels, we conclude that the de-novo translation of F11R is a crucial early step in the initiation of atherogenesis, leading to atherosclerosis, heart attacks and stroke.

  6. Optimization approach of background value and initial item for improving prediction precision of GM(1,1) model

    Institute of Scientific and Technical Information of China (English)

    Yuhong Wang; Qin Liu; Jianrong Tang; Wenbin Cao; Xiaozhong Li

    2014-01-01

    A combination method of optimization of the back-ground value and optimization of the initial item is proposed. The sequences of the unbiased exponential distribution are simulated and predicted through the optimization of the background value in grey differential equations. The principle of the new information priority in the grey system theory and the rationality of the initial item in the original GM(1,1) model are ful y expressed through the improvement of the initial item in the proposed time response function. A numerical example is employed to il ustrate that the proposed method is able to simulate and predict sequences of raw data with the unbiased exponential distribution and has better simulation performance and prediction precision than the original GM(1,1) model relatively.

  7. Effects of novel C-methylated spermidine analogs on cell growth via hypusination of eukaryotic translation initiation factor 5A.

    Science.gov (United States)

    Hyvönen, Mervi T; Keinänen, Tuomo A; Khomutov, Maxim; Simonian, Alina; Vepsäläinen, Jouko; Park, Jong Hwan; Khomutov, Alex R; Alhonen, Leena; Park, Myung Hee

    2012-02-01

    The polyamines, putrescine, spermidine, and spermine, are ubiquitous multifunctional cations essential for cellular proliferation. One specific function of spermidine in cell growth is its role as a butylamine donor for hypusine synthesis in the eukaryotic initiation factor 5A (eIF5A). Here, we report the ability of novel mono-methylated spermidine analogs (α-MeSpd, β-MeSpd, γ-MeSpd, and ω-MeSpd) to function in the hypusination of eIF5A and in supporting the growth of DFMO-treated DU145 cells. We also tested them as substrates and inhibitors for deoxyhypusine synthase (DHS) in vitro. Of these compounds, α-MeSpd, β-MeSpd, and γ-MeSpd (but not ω-MeSpd) were substrates for DHS in vitro, while they all inhibited the enzyme reaction. As racemic mixtures, only α-MeSpd and β-MeSpd supported long-term growth (9-18 days) of spermidine-depleted DU145 cells, whereas γ-MeSpd and ω-MeSpd did not. The S-enantiomer of α-MeSpd, which supported long-term growth, was a good substrate for DHS in vitro, whereas the R-isomer was not. The long-term growth of DFMO-treated cells correlated with the hypusine modification of eIF5A by intracellular methylated spermidine analogs. These results underscore the critical requirement for hypusine modification in mammalian cell proliferation and provide new insights into the specificity of the deoxyhypusine synthase reaction.

  8. Cap-dependent and cap-independent translation by internal initiation of mRNAs in cell extracts prepared from Saccharomyces cerevisiae.

    OpenAIRE

    Iizuka, N; Najita, L; Franzusoff, A; Sarnow, P

    1994-01-01

    Translation extracts were prepared from various strains of Saccharomyces cerevisiae. The translation of mRNA molecules in these extracts were cooperatively enhanced by the presence of 5'-terminal cap structures and 3'-terminal poly(A) sequences. These cooperative effects could not be observed in other translation systems such as those prepared from rabbit reticulocytes, wheat germ, and human HeLa cells. Because the yeast translation system mimicked the effects of the cap structure and poly(A)...

  9. Optimizing selection of training and auxiliary data for operational land cover classification for the LCMAP initiative

    Science.gov (United States)

    Zhu, Zhe; Gallant, Alisa L.; Woodcock, Curtis E.; Pengra, Bruce; Olofsson, Pontus; Loveland, Thomas R.; Jin, Suming; Dahal, Devendra; Yang, Limin; Auch, Roger F.

    2016-12-01

    The U.S. Geological Survey's Land Change Monitoring, Assessment, and Projection (LCMAP) initiative is a new end-to-end capability to continuously track and characterize changes in land cover, use, and condition to better support research and applications relevant to resource management and environmental change. Among the LCMAP product suite are annual land cover maps that will be available to the public. This paper describes an approach to optimize the selection of training and auxiliary data for deriving the thematic land cover maps based on all available clear observations from Landsats 4-8. Training data were selected from map products of the U.S. Geological Survey's Land Cover Trends project. The Random Forest classifier was applied for different classification scenarios based on the Continuous Change Detection and Classification (CCDC) algorithm. We found that extracting training data proportionally to the occurrence of land cover classes was superior to an equal distribution of training data per class, and suggest using a total of 20,000 training pixels to classify an area about the size of a Landsat scene. The problem of unbalanced training data was alleviated by extracting a minimum of 600 training pixels and a maximum of 8000 training pixels per class. We additionally explored removing outliers contained within the training data based on their spectral and spatial criteria, but observed no significant improvement in classification results. We also tested the importance of different types of auxiliary data that were available for the conterminous United States, including: (a) five variables used by the National Land Cover Database, (b) three variables from the cloud screening "Function of mask" (Fmask) statistics, and (c) two variables from the change detection results of CCDC. We found that auxiliary variables such as a Digital Elevation Model and its derivatives (aspect, position index, and slope), potential wetland index, water probability, snow

  10. Increased literacy of the best evidence base optimizes patient-clinician communication in convergent translational health care: Relevance for patient-centered modalities

    Directory of Open Access Journals (Sweden)

    Allen Khakshooy

    2015-01-01

    Full Text Available Introduction: Dentistry in particular and biomedicine in general have undergone a fundamental transformation over the recent decades, which have been formalized by the Affordable Care Act, 2010. In brief, modern contemporary health care has evolved from procedure-driven and intervention-centered care based on research evidence to the administration and delivery of care that is patient-centered, effectiveness-focused, and that utilizes the best evidence base generated by systematic research synthesis (i.e., evidence-based. The present conceptualization of health care integrates translational research and translational effectiveness, and allows convergence of the multiple specialization fields of biomedicine (e.g., dentistry, internal medicine, and psychiatry as well as the various medical traditions globally (i.e., Western, Ayurvedic, and Chinese medical traditions, etc.. The Hypothesis: Here, we propose the hypothesis that increased literacy of the best evidence base optimizes patient-clinician communication in the current convergent translational health care model including dental care. Evaluation of the Hypothesis: We discuss the salient points of this proposition, and outline the relevance of certain salient convergent patient-centered modalities of health care that intimately intertwine medicine and dentistry.

  11. 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.

  12. The DEAD-box helicase DDX3 substitutes for the cap-binding protein eIF4E to promote compartmentalized translation initiation of the HIV-1 genomic RNA.

    Science.gov (United States)

    Soto-Rifo, Ricardo; Rubilar, Paulina S; Ohlmann, Théophile

    2013-07-01

    Here, we show a novel molecular mechanism promoted by the DEAD-box RNA helicase DDX3 for translation of the HIV-1 genomic RNA. This occurs through the adenosine triphosphate-dependent formation of a translation initiation complex that is assembled at the 5' m(7)GTP cap of the HIV-1 mRNA. This is due to the property of DDX3 to substitute for the initiation factor eIF4E in the binding of the HIV-1 m(7)GTP 5' cap structure where it nucleates the formation of a core DDX3/PABP/eIF4G trimeric complex on the HIV-1 genomic RNA. By using RNA fluorescence in situ hybridization coupled to indirect immunofluorescence, we further show that this viral ribonucleoprotein complex is addressed to compartmentalized cytoplasmic foci where the translation initiation complex is assembled.

  13. Optimizing Quality of Care and Patient Safety in Malaysia: The Current Global Initiatives, Gaps and Suggested Solutions.

    Science.gov (United States)

    Jarrar, Mu'taman; Abdul Rahman, Hamzah; Don, Mohammad Sobri

    2015-10-20

    Demand for health care service has significantly increased, while the quality of healthcare and patient safety has become national and international priorities. This paper aims to identify the gaps and the current initiatives for optimizing the quality of care and patient safety in Malaysia. Review of the current literature. Highly cited articles were used as the basis to retrieve and review the current initiatives for optimizing the quality of care and patient safety. The country health plan of Ministry of Health (MOH) Malaysia and the MOH Malaysia Annual Reports were reviewed. The MOH has set four strategies for optimizing quality and sustaining quality of life. The 10th Malaysia Health Plan promotes the theme "1 Care for 1 Malaysia" in order to sustain the quality of care. Despite of these efforts, the total number of complaints received by the medico-legal section of the MOH Malaysia is increasing. The current global initiatives indicted that quality performance generally belong to three main categories: patient; staffing; and working environment related factors. There is no single intervention for optimizing quality of care to maintain patient safety. Multidimensional efforts and interventions are recommended in order to optimize the quality of care and patient safety in Malaysia.

  14. Structural modeling and mutational analysis of yeast eukaryotic translation initiation factor 5A reveal new critical residues and reinforce its involvement in protein synthesis

    Science.gov (United States)

    Dias, Camila A. O.; Cano, Veridiana S. P.; Rangel, Suzana M.; Apponi, Luciano H.; Frigieri, Mariana C.; Muniz, João R. C.; Garcia, Wanius; Park, Myung H.; Garratt, Richard C.; Zanelli, Cleslei F.; Valentini, Sandro R.

    2017-01-01

    Eukaryotic translation initiation factor 5A (eIF5A) is a protein that is highly conserved and essential for cell viability. This factor is the only protein known to contain the unique and essential amino acid residue hypusine. This work focused on the structural and functional characterization of Saccharomyces cerevisiae eIF5A. The tertiary structure of yeast eIF5A was modeled based on the structure of its Leishmania mexicana homologue and this model was used to predict the structural localization of new site-directed and randomly generated mutations. Most of the 40 new mutants exhibited phenotypes that resulted from eIF-5A protein-folding defects. Our data provided evidence that the C-terminal α-helix present in yeast eIF5A is an essential structural element, whereas the eIF5A N-terminal 10 amino acid extension not present in archaeal eIF5A homologs, is not. Moreover, the mutants containing substitutions at or in the vicinity of the hypusine modification site displayed nonviable or temperature-sensitive phenotypes and were defective in hypusine modification. Interestingly, two of the temperature-sensitive strains produced stable mutant eIF5A proteins – eIF5AK56A and eIF5AQ22H,L93F – and showed defects in protein synthesis at the restrictive temperature. Our data revealed important structural features of eIF5A that are required for its vital role in cell viability and underscored an essential function of eIF5A in the translation step of gene expression. PMID:18341589

  15. Structural basis for nematode eIF4E binding an m(2,2,7)G-Cap and its implications for translation initiation.

    Science.gov (United States)

    Liu, Weizhi; Jankowska-Anyszka, Marzena; Piecyk, Karolina; Dickson, Laura; Wallace, Adam; Niedzwiecka, Anna; Stepinski, Janusz; Stolarski, Ryszard; Darzynkiewicz, Edward; Kieft, Jeffrey; Zhao, Rui; Jones, David N M; Davis, Richard E

    2011-11-01

    Metazoan spliced leader (SL) trans-splicing generates mRNAs with an m(2,2,7)G-cap and a common downstream SL RNA sequence. The mechanism for eIF4E binding an m²²⁷G-cap is unknown. Here, we describe the first structure of an eIF4E with an m(2,2,7)G-cap and compare it to the cognate m⁷G-eIF4E complex. These structures and Nuclear Magnetic Resonance (NMR) data indicate that the nematode Ascaris suum eIF4E binds the two different caps in a similar manner except for the loss of a single hydrogen bond on binding the m(2,2,7)G-cap. Nematode and mammalian eIF4E both have a low affinity for m(2,2,7)G-cap compared with the m⁷G-cap. Nematode eIF4E binding to the m⁷G-cap, m(2,2,7)G-cap and the m(2,2,7)G-SL 22-nt RNA leads to distinct eIF4E conformational changes. Additional interactions occur between Ascaris eIF4E and the SL on binding the m(2,2,7)G-SL. We propose interactions between Ascaris eIF4E and the SL impact eIF4G and contribute to translation initiation, whereas these interactions do not occur when only the m(2,2,7)G-cap is present. These data have implications for the contribution of 5'-UTRs in mRNA translation and the function of different eIF4E isoforms.

  16. Tandem affinity purification revealed the hypusine-dependent binding of eukaryotic initiation factor 5A to the translating 80S ribosomal complex.

    Science.gov (United States)

    Jao, David Li-En; Chen, Kuang Yu

    2006-02-15

    Eukaryotic initiation factor 5A (eIF5A) is the only protein in nature that contains hypusine, an unusual amino acid formed post-translationally in two steps by deoxyhypusine synthase and deoxyhypusine hydroxylase. Genes encoding eIF5A or deoxyhypusine synthase are essential for cell survival and proliferation. To determine the physiological function of eIF5A, we have employed the tandem affinity purification (TAP) method and mass spectrometry to search for and identify the potential eIF5A-interacting proteins. The TAP-tag was fused in-frame to chromosomal TIF51A gene and eIF5A-TAP fusion protein expressed at its natural level was used as the bait to fish out its interacting partners. At salt concentrations of 150 mM, deoxyhypusine synthase was the only protein bound to eIF5A. As salt concentrations were lowered to 125 mM or less, eIF5A interacted with a set of proteins, which were identified as the components of the 80S ribosome complex. The eIF5A-ribosome interaction was sensitive to RNase and EDTA treatments, indicating the requirement of RNA and the joining of 40S and 60S ribosomal subunits for the interaction. Importantly, a single mutation of hypusine to arginine completely abolished the eIF5A-ribosome interaction. Sucrose gradient sedimentation analysis of log versus stationary phase cells and eIF3 mutant strain showed that the endogenous eIF5A co-sedimented with the actively translating 80S ribosomes and polyribosomes in an RNase- and EDTA-sensitive manner. Our study demonstrates for the first time that eIF5A interacts in a hypusine-dependent manner with a molecular complex rather than a single protein, suggesting that the essential function of eIF5A is mostly likely mediated through its interaction with the actively translating ribosomes. (c) 2005 Wiley-Liss, Inc.

  17. Translating Means Translating Meaning

    Institute of Scientific and Technical Information of China (English)

    李海燕

    2000-01-01

    美国著名翻译理论家尤金·奈达说 :“翻译即译意 (Translating m eans translating m eaning)。”就实质而言 ,翻译即译意。就是把一种语言表达的意义用另一种语言表达出来。翻译分理解与表达两个步骤。理解是翻译的基础 ,表达直接决定译文的成败与优劣 ,两者缺一不可

  18. Human Translator and Translation Technology

    Institute of Scientific and Technical Information of China (English)

    李辰

    2016-01-01

    With the great development of technology, translation technology exerts great influence on human translators because during their translation process, they may use many computer-aided translation tools, such as TRADOS, Snowman, WordFisher and etc. However, they always misunderstand the concept of computer-aided translation, so this thesis managed to providedetails about some translation technology and human translators' strengths so as to help them improve the productivity and the quality of theirtranslation works effectively and efficiently.

  19. Simplified Analytical Method for Optimized Initial Shape Analysis of Self-Anchored Suspension Bridges and Its Verification

    Directory of Open Access Journals (Sweden)

    Myung-Rag Jung

    2015-01-01

    Full Text Available A simplified analytical method providing accurate unstrained lengths of all structural elements is proposed to find the optimized initial state of self-anchored suspension bridges under dead loads. For this, equilibrium equations of the main girder and the main cable system are derived and solved by evaluating the self-weights of cable members using unstrained cable lengths and iteratively updating both the horizontal tension component and the vertical profile of the main cable. Furthermore, to demonstrate the validity of the simplified analytical method, the unstrained element length method (ULM is applied to suspension bridge models based on the unstressed lengths of both cable and frame members calculated from the analytical method. Through numerical examples, it is demonstrated that the proposed analytical method can indeed provide an optimized initial solution by showing that both the simplified method and the nonlinear FE procedure lead to practically identical initial configurations with only localized small bending moment distributions.

  20. Machine Translation

    Institute of Scientific and Technical Information of China (English)

    张严心

    2015-01-01

    As a kind of ancillary translation tool, Machine Translation has been paid increasing attention to and received different kinds of study by a great deal of researchers and scholars for a long time. To know the definition of Machine Translation and to analyse its benefits and problems are significant for translators in order to make good use of Machine Translation, and helpful to develop and consummate Machine Translation Systems in the future.

  1. Optimal control for systems governed by parabolic equations without initial conditions with controls in the coefficients

    Directory of Open Access Journals (Sweden)

    Mykola Bokalo

    2017-03-01

    Full Text Available We consider an optimal control problem for systems described by a Fourier problem for parabolic equations. We prove the existence of solutions, and obtain necessary conditions of the optimal control in the case of final observation when the control functions occur in the coefficients.

  2. Inhibition of Translation Initiation by Protein 169: A Vaccinia Virus Strategy to Suppress Innate and Adaptive Immunity and Alter Virus Virulence.

    Directory of Open Access Journals (Sweden)

    Pavla Strnadova

    2015-09-01

    Full Text Available Vaccinia virus (VACV is the prototypic orthopoxvirus and the vaccine used to eradicate smallpox. Here we show that VACV strain Western Reserve protein 169 is a cytoplasmic polypeptide expressed early during infection that is excluded from virus factories and inhibits the initiation of cap-dependent and cap-independent translation. Ectopic expression of protein 169 causes the accumulation of 80S ribosomes, a reduction of polysomes, and inhibition of protein expression deriving from activation of multiple innate immune signaling pathways. A virus lacking 169 (vΔ169 replicates and spreads normally in cell culture but is more virulent than parental and revertant control viruses in intranasal and intradermal murine models of infection. Intranasal infection by vΔ169 caused increased pro-inflammatory cytokines and chemokines, infiltration of pulmonary leukocytes, and lung weight. These alterations in innate immunity resulted in a stronger CD8+ T-cell memory response and better protection against virus challenge. This work illustrates how inhibition of host protein synthesis can be a strategy for virus suppression of innate and adaptive immunity.

  3. 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

    Rhopalosiphum padi virus (RhPV) is a member of the family Dicistroviridae. The genomes of viruses in this family contain two open reading frames, each preceded by distinct internal ribosome entry site (IRES) elements. The RhPV 5' IRES is functional in mammalian, insect and plant translation systems...... (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...

  4. Optimism, Cynical Hostility, Falls, and Fractures: The Women's Health Initiative Observational Study (WHI-OS).

    Science.gov (United States)

    Cauley, Jane A; Smagula, Stephen F; Hovey, Kathleen M; Wactawski-Wende, Jean; Andrews, Christopher A; Crandall, Carolyn J; LeBoff, Meryl S; Li, Wenjun; Coday, Mace; Sattari, Maryam; Tindle, Hilary A

    2017-02-01

    Traits of optimism and cynical hostility are features of personality that could influence the risk of falls and fractures by influencing risk-taking behaviors, health behaviors, or inflammation. To test the hypothesis that personality influences falls and fracture risk, we studied 87,342 women enrolled in WHI-OS. Optimism was assessed by the Life Orientation Test-Revised and cynical hostility, the cynicism subscale of the Cook-Medley questionnaire. Higher scores indicate greater optimism and hostility. Optimism and hostility were correlated at r = -0. 31, p optimism and hostility with tests for trends; Q1 formed the referent group. The average follow-up for fractures was 11.4 years and for falls was 7.6 years. In multivariable (MV)-adjusted models, women with the highest optimism scores (Q4) were 11% less likely to report ≥2 falls in the past year (odds ratio [OR] = 0.89; 95% confidence intervals [CI] 0.85-0.90). Women in Q4 for hostility had a 12% higher risk of ≥2 falls (OR = 1.12; 95% CI 1.07-1.17). Higher optimism scores were also associated with a 10% lower risk of fractures, but this association was attenuated in MV models. Women with the greatest hostility (Q4) had a modest increased risk of any fracture (MV-adjusted hazard ratio = 1. 05; 95% CI 1.01-1.09), but there was no association with specific fracture sites. In conclusion, optimism was independently associated with a decreased risk of ≥2 falls, and hostility with an increased risk of ≥2 falls, independent of traditional risk factors. The magnitude of the association was similar to aging 5 years. Whether interventions aimed at attitudes could reduce fall risks remains to be determined. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  5. Optimal Error Estimates of Two Mixed Finite Element Methods for Parabolic Integro-Differential Equations with Nonsmooth Initial Data

    KAUST Repository

    Goswami, Deepjyoti

    2013-05-01

    In the first part of this article, a new mixed method is proposed and analyzed for parabolic integro-differential equations (PIDE) with nonsmooth initial data. Compared to the standard mixed method for PIDE, the present method does not bank on a reformulation using a resolvent operator. Based on energy arguments combined with a repeated use of an integral operator and without using parabolic type duality technique, optimal L2 L2-error estimates are derived for semidiscrete approximations, when the initial condition is in L2 L2. Due to the presence of the integral term, it is, further, observed that a negative norm estimate plays a crucial role in our error analysis. Moreover, the proposed analysis follows the spirit of the proof techniques used in deriving optimal error estimates for finite element approximations to PIDE with smooth data and therefore, it unifies both the theories, i.e., one for smooth data and other for nonsmooth data. Finally, we extend the proposed analysis to the standard mixed method for PIDE with rough initial data and provide an optimal error estimate in L2, L 2, which improves upon the results available in the literature. © 2013 Springer Science+Business Media New York.

  6. Translation Initiation Factor eIF4E and eIFiso4E Are Both Required for Peanut stripe virus Infection in Peanut (Arachis hypogaea L.)

    Science.gov (United States)

    Xu, Manlin; Xie, Hongfeng; Wu, Juxiang; Xie, Lianhui; Yang, Jinguang; Chi, Yucheng

    2017-01-01

    Peanut stripe virus (PStV) belongs to the genus Potyvirus and is the most important viral pathogen of cultivated peanut (Arachis hypogaea L.). The eukaryotic translation initiation factor, eIF4E, and its isoform, eIF(iso)4E, play key roles during virus infection in plants, particularly Potyvirus. In the present study, we cloned the eIF4E and eIF(iso)4E homologs in peanut and named these as PeaeIF4E and PeaeIF(iso)4E, respectively. Quantitative real-time PCR (qRT-PCR) analysis showed that these two genes were expressed during all growth periods and in all peanut organs, but were especially abundant in young leaves and roots. These also had similar expression levels. Yeast two-hybrid analysis showed that PStV multifunctional helper component proteinase (HC-Pro) and viral protein genome-linked (VPg) both interacted with PeaeIF4E and PeaeIF(iso)4E. Bimolecular fluorescence complementation assay showed that there was an interaction between HC-Pro and PeaeIF4E/PeaeIF(iso)4E in the cytoplasm and between VPg and PeaeIF4E/PeaeIF(iso)4E in the nucleus. Silencing either PeaeIF4E or PeaeIF(iso)4E using a virus-induced gene silencing system did not significantly affect PStV accumulation. However, silencing both PeaeIF4E and PeaeIF(iso)4E genes significantly weakened PStV accumulation. The findings of the present study suggest that PeaeIF4E and PeaeIF(iso)4E play important roles in the PStV infection cycle and may potentially contribute to PStV resistance.

  7. Cis-motifs upstream of the transcription and translation initiation sites are effectively revealed by their positional disequilibrium in eukaryote genomes using frequency distribution curves

    Directory of Open Access Journals (Sweden)

    Harter Klaus

    2006-11-01

    Full Text Available Abstract Background The discovery of cis-regulatory motifs still remains a challenging task even though the number of sequenced genomes is constantly growing. Computational analyses using pattern search algorithms have been valuable in phylogenetic footprinting approaches as have expression profile experiments to predict co-occurring motifs. Surprisingly little is known about the nature of cis-regulatory element (CRE distribution in promoters. Results In this paper we used the Motif Mapper open-source collection of visual basic scripts for the analysis of motifs in any aligned set of DNA sequences. We focused on promoter motif distribution curves to identify positional over-representation of DNA motifs. Using differentially aligned datasets from the model species Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster and Saccharomyces cerevisiae, we convincingly demonstrated the importance of the position and orientation for motif discovery. Analysis with known CREs and all possible hexanucleotides showed that some functional elements gather close to the transcription and translation initiation sites and that elements other than the TATA-box motif are conserved between eukaryote promoters. While a high background frequency usually decreases the effectiveness of such an enumerative investigation, we improved our analysis by conducting motif distribution maps using large datasets. Conclusion This is the first study to reveal positional over-representation of CREs and promoter motifs in a cross-species approach. CREs and motifs shared between eukaryotic promoters support the observation that an eukaryotic promoter structure has been conserved throughout evolutionary time. Furthermore, with the information on positional enrichment of a motif or a known functional CRE, it is possible to get a more detailed insight into where an element appears to function. This in turn might accelerate the in depth examination of known and yet unknown

  8. 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.

  9. A point mutation in translation initiation factor 2B leads to a continuous hyper stress state in oligodendroglial-derived cells.

    Directory of Open Access Journals (Sweden)

    Liraz Kantor

    Full Text Available BACKGROUND: Mutations in eukaryotic translation initiation factor 2B (eIF2B cause Childhood Ataxia with CNS Hypomyelination (CACH, also known as Vanishing White Matter disease (VWM. The disease is manifested by loss of brain myelin upon physiological stress. In a previous study, we showed that fibroblasts isolated from CACH/VWM patients are hypersensitive to pharmacologically-induced endoplasmic reticulum (ER stress. Since brain cells from affected individuals are not available for research, we wished to assess the effect of eIF2B mutation on oligodendroglial-derived cells. METHODOLOGY/PRINCIPAL FINDINGS: A rat oligodendroglial-derived cell line was used for a stable knock-down of eIF2B5 followed by stable expression of mutated eIF2B5(R195H cDNA. In response to a pharmacological ER-stress agent, eIF2B5(R195H expressing cells exhibited heightened ER-stress response demonstrated by hyper induction of ATF4, GADD34, Bip, PDIA1, PDIA3, PDIA4 and PDIA6 proteins. Moreover, even in the absence of a pharmacological stress agent, eIF2B5(R195H-expressing cells exhibited high basal levels of ATF4, GADD34 and ER-associated Bip, PDIA1 and PDIA3. SIGNIFICANCE: The data provide evidence that oligodendroglial-derived cells expressing a mutated eIF2B constantly use their stress response mechanism as an adaptation mean in order to survive. The current study is the first to demonstrate the effects of eIF2B5 mutation on ER homeostasis in oligodendroglial-derived cells.

  10. Translational Creativity

    DEFF Research Database (Denmark)

    Nielsen, Sandro

    2010-01-01

    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...... 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...

  11. A generalized computationally efficient inverse characterization approach combining direct inversion solution initialization with gradient-based optimization

    Science.gov (United States)

    Wang, Mengyu; Brigham, John C.

    2017-03-01

    A computationally efficient gradient-based optimization approach for inverse material characterization from incomplete system response measurements that can utilize a generally applicable parameterization (e.g., finite element-type parameterization) is presented and evaluated. The key to this inverse characterization algorithm is the use of a direct inversion strategy with Gappy proper orthogonal decomposition (POD) response field estimation to initialize the inverse solution estimate prior to gradient-based optimization. Gappy POD is used to estimate the complete (i.e., all components over the entire spatial domain) system response field from incomplete (e.g., partial spatial distribution) measurements obtained from some type of system testing along with some amount of a priori information regarding the potential distribution of the unknown material property. The estimated complete system response is used within a physics-based direct inversion procedure with a finite element-type parameterization to estimate the spatial distribution of the desired unknown material property with minimal computational expense. Then, this estimated spatial distribution of the unknown material property is used to initialize a gradient-based optimization approach, which uses the adjoint method for computationally efficient gradient calculations, to produce the final estimate of the material property distribution. The three-step [(1) Gappy POD, (2) direct inversion, and (3) gradient-based optimization] inverse characterization approach is evaluated through simulated test problems based on the characterization of elastic modulus distributions with localized variations (e.g., inclusions) within simple structures. Overall, this inverse characterization approach is shown to efficiently and consistently provide accurate inverse characterization estimates for material property distributions from incomplete response field measurements. Moreover, the solution procedure is shown to be capable

  12. CHALLENGES AND OPPORTUNITIES--INTEGRATED LIFE-CYCLE OPTIMIZATION INITIATIVES FOR THE HANFORD RIVER PROTECTION PROJECT--WASTE TREATMENT PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Auclair, K. D.

    2002-02-25

    of issues across contract boundaries is a more difficult matter. This aspect, one of a seamless systems approach to the treatment of tank wastes at the Hanford site, is the focus of the Optimization Studies. This ''big O''Optimization of Life-Cycle operations is what is meant when the term ''optimization'' is used on the River Protection Project and initiatives cited in this paper. From the early contractor centric methods and processes used to move toward an integrated solution, through extensive partnering approaches, to the current quality initiatives with multi-organizational participation, significant progress is being made towards achieving the goal of truly integrated life-cycle optimization for the Department of Energy's River Protection Project and Waste Treatment Plant.

  13. The FERMI @ Elettra Technical Optimization Study: PreliminaryParameter Set and Initial Studies

    Energy Technology Data Exchange (ETDEWEB)

    Byrd, John; Corlett, John; Doolittle, Larry; Fawley, William; Lidia, Steven; Penn, Gregory; Ratti, Alex; Staples, John; Wilcox,Russell; Wurtele, Jonathan; Zholents, Alexander

    2005-08-01

    The goal of the FERMI {at} Elettra Technical Optimization Study is to produce a machine design and layout consistent with user needs for radiation in the approximate ranges 100 nm to 40 nm, and 40 nm to 10 nm, using seeded FEL's. The Study will involve collaboration between Italian and US physicists and engineers, and will form the basis for the engineering design and the cost estimation.

  14. Optimal descriptor as a translator of eclectic data into endpoint prediction: mutagenicity of fullerene as a mathematical function of conditions.

    Science.gov (United States)

    Toropov, Andrey A; Toropova, Alla P

    2014-06-01

    The experimental data on the bacterial reverse mutation test on C60 nanoparticles (TA100) is examined as an endpoint. By means of the optimal descriptors calculated with the Monte Carlo method a mathematical model of the endpoint has been built up. The model is the mathematical function of (i) dose (g/plate); (ii) metabolic activation (i.e. with S9 mix or without S9 mix); and (iii) illumination (i.e. dark or irradiation). The statistical quality of the model is the following: n=10, r(2)=0.7549, q(2)=0.5709, s=7.67, F=25 (Training set); n=5, r(2)=0.8987, s=18.4 (Calibration set); and n=5, r(2)=0.6968, s=10.9 (Validation set). Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. The 3′ Untranslated Region of the Andes Hantavirus Small mRNA Functionally Replaces the Poly(A) Tail and Stimulates Cap-Dependent Translation Initiation from the Viral mRNA ▿

    Science.gov (United States)

    Vera-Otarola, Jorge; Soto-Rifo, Ricardo; Ricci, Emiliano P.; Ohlmann, Théophile; Darlix, Jean-Luc; López-Lastra, Marcelo

    2010-01-01

    In the process of translation of eukaryotic mRNAs, the 5′ cap and the 3′ poly(A) tail interact synergistically to stimulate protein synthesis. Unlike its cellular counterparts, the small mRNA (SmRNA) of Andes hantavirus (ANDV), a member of the Bunyaviridae, lacks a 3′ poly(A) tail. Here we report that the 3′ untranslated region (3′UTR) of the ANDV SmRNA functionally replaces a poly(A) tail and synergistically stimulates cap-dependent translation initiation from the viral mRNA. Stimulation of translation by the 3′UTR of the ANDV SmRNA was found to be independent of viral proteins and of host poly(A)-binding protein. PMID:20660206

  16. Translation Nation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The International Federation of Translators will hold its largest ever world congress in China on the eve of 2008 Olympic Games china’ s position as a powerhouse of the translation industry is to be cemented,

  17. Translating Europe

    Directory of Open Access Journals (Sweden)

    Yves Chevrel

    2007-07-01

    Europe thinks in many languages and Europe is a land of translation. Translation is a means of transmitting culture, a means of making it available to others and an invitation to share. It is a cement which binds Europe together.

  18. teaching translation

    Directory of Open Access Journals (Sweden)

    Sergio Bolaños Cuéllar

    2007-01-01

    Full Text Available The advance in cultural-oriented perspectives in Translation Studies has sometimes played down the text linguistic nature of translation. A pilot study in teaching translation was carried out to make students aware of the text linguistic character of translating and help them to improve their translation skills, particularly with an emphasis on self-awareness and self-correcting strategies. The theoretical background is provided by the Dynamic Translation Model (2004, 2005 proposed by the author, with relevant and important contributions taken from Genette’s (1982 transtextuality phenomena (hypertext, hypotext, metatext, paratext, intertext and House and Kasper’s (1981 pragmatic modality markers (downgraders, upgraders. The key conceptual role of equivalence as a defining feature of translation is also dealt with. The textual relationship between Source Language Text (slt is deemed to be pivotal for performing translation and correction tasks in the classroom. Finally, results of the pilot study are discussed and some conclusions are drawn.

  19. Literal Translation and Free Translation

    Institute of Scientific and Technical Information of China (English)

    彭佼

    2011-01-01

    @@ Dispute over the method of literal translation and that of free translation had a long history in China, in East Jin Dynasty Daoan(道安314-385),a well-known monk, was the representative of those who firmly advocated literal translation.Since he feared that free translation might not be true to the original, he advocated strict literal translation so as to preserve the true features.Works under his direction were typical of word-for-word translation, in which no alteration was made except accidental changes in word order.

  20. The 5' untranslated region and Gag product of Idefix, a long terminal repeat-retrotransposon from Drosophila melanogaster, act together to initiate a switch between translated and untranslated states of the genomic mRNA.

    Science.gov (United States)

    Meignin, Carine; Bailly, Jean-Luc; Arnaud, Frédérick; Dastugue, Bernard; Vaury, Chantal

    2003-11-01

    Idefix is a long terminal repeat (LTR)-retrotransposon present in Drosophila melanogaster which shares similarities with vertebrates retroviruses both in its genomic arrangement and in the mechanism of transposition. Like in retroviruses, its two LTRs flank a long 5' untranslated region (5'UTR) and three open reading frames referred to as the gag, pol, and env genes. Here we report that its 5'UTR, located upstream of the gag gene, can fold into highly structured domains that are known to be incompatible with efficient translation by ribosome scanning. Using dicistronic plasmids analyzed by both (i) in vitro transcription and translation in rabbit reticulocyte or wheat germ lysates and (ii) in vivo expression in transgenic flies, we show that the 5'UTR of Idefix exhibits an internal ribosome entry site (IRES) activity that is able to promote translation of a downstream cistron in a cap-independent manner. The functional state of this novel IRES depends on eukaryotic factors that are independent of their host origin. However, in vivo, its function can be down-regulated by trans-acting factors specific to tissues or developmental stages of its host. We identify one of these trans-acting factors as the Gag protein encoded by Idefix itself. Our data support a model in which nascent Gag is able to block translation initiated from the viral mRNA and thus its own translation. These data highlight the fact that LTR-retrotransposons may autoregulate their replication cycle through their Gag production.

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

    Science.gov (United States)

    Ghosh, Sanjay; Lasko, Paul

    2015-01-01

    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.

  2. An Initial Survey of the Course Reform of Multilingual Translation%多语种笔译课程改革初探

    Institute of Scientific and Technical Information of China (English)

    陈影

    2015-01-01

    有效的课程改革可以促进教学质量的提高。在本文的教学情境中,笔译课程是一门针对大学四年级双语专业学生的必修课。学生在学习英语笔译的同时,还学习专业方向的小语种笔译。重复学习浪费了一定的教学资源,而且没能充分利用出双语特色和优势。该文主要探讨了笔译课程改革的背景、目的、意义和具体内容,对多语种笔译课程建设进行了探索。%The effective course reform contributes to the improvement of teaching quality. In this teaching context, translation is a compulsory course for junior students in bilingual school. While students learn English translation, they also have translation courses of their second foreign languages. Undoubtedly, repetitive study wastes the teaching resources and does not make use of the advantages and features of the major. This paper mainly inquires into the background, purpose, significance and content of the course reform of translation so as to explore the course construction of multilingual translation.

  3. Optimization of Skill Retention in the U. S. Army through Initial Training Analysis and Design: Skill Sustainment Exercises. Volume 3.

    Science.gov (United States)

    1983-05-01

    well. 3. Screws the M605 fuze into fuze well. 4. Buries the mine up to the bottom of the release pin ring. S. Removes the locking safety pin . 6...positive safety pin . MGA SSE-3 TRIAL "- d 7D-Rl31 988 OPTIMIZATION OF SKILL RETENTION IN THE U S RRMY THROUJGH 216 INITIAL TRAINING..(U) MCFANN GRAY...DATE: TASK NO.: 051-192-1012 PAGE I OF I GO NO GO I. Checks mine for boobytraps. 2. Uncovers top of mine. 3. Inserts original safety pin , if available

  4. OPTIMAL PARAMETERS OF BLASTING IN TUNNELS USING PATRONED AND PUMPED EXPLOSIVES WITH ELECTRIC AND NON-ELECTRIC INITIATION

    Directory of Open Access Journals (Sweden)

    Zvonimir Deković

    2003-12-01

    Full Text Available The parameters of drilling and blasting procedures during excavation of Grič and mala Kapela Tunnels are presented in this work. The tunnels are being constructed according to NATM (New Austrian Tunneling Method in two parallel tubes. By Comparison of blasting with patroned and pumped explosives and electric and non-electric mode of initiation, optimal technological parameters have been defined concerning duration of blasting working cycle, progress, tunnel category and seismic effects of blasting on the tunnel support system of the parallel tunnel tube.

  5. Translation Techniques

    Directory of Open Access Journals (Sweden)

    Marcia Pinheiro

    2015-05-01

    Full Text Available In this paper, we discuss three translation techniques: literal, cultural, and artistic. Literal translation is a well-known technique, which means that it is quite easy to find sources on the topic. Cultural and artistic translation may be new terms. Whilst cultural translation focuses on matching contexts, artistic translation focuses on matching reactions. Because literal translation matches only words, it is not hard to find situations in which we should not use this technique.  Because artistic translation focuses on reactions, judging the quality of an artistic translation work is one of the most difficult things one can do. We end up having a score of complexity and humanity for each one of the mentioned techniques: Literal translation would be the closest thing we have to the machines world and artistic translation would be the closest thing we have to the purely human world. By creating these classifications and studying the subtleties of each one of them, we are adding degrees of quality to our courses and to translation as a professional field. The main contribution of this paper is then the formalization of such a piece of knowledge. We, however, also lay the foundations for studies of this type.

  6. New Solutions of Translation Initiation Site Prediction for Prokaryotic Genomes%原核基因翻译起始位点预测的新方法

    Institute of Scientific and Technical Information of China (English)

    胡钢清; 刘永初; 郑晓斌; 杨一帆; 余振苏; 朱怀球

    2008-01-01

    翻译起始位点(TIS,即基因5′端)的精确定位是原核生物基因预测的一个关键问题,而基因组GC含量和翻译起始机制的多样性是影响当前TIS预测水平的重要因素.结合基因组结构的复杂信息(包括GC含量、TIS邻近序列及上游调控信号、序列编码潜能、操纵子结构等),发展刻画翻译起始机制的数学统计模型,据此设计TIS预测的新算法MED-StartPlus.并将MED-StartPlus与同类方法RBSfinder、GS-Finder、MED-Start、TiCo和Hon-yaku等进行系统地比较和评价.测试针对两种数据集进行:当前14个已知的TIS被确认的基因数据集,以及300个物种中功能已知的基因数据集.测试结果表明,MED-StartPlus的预测精度在总体上超过同类方法.尤其是对高GC含量基因组以及具有复杂翻译起始机制的基因组,MED-StartPlus具有明显的优势.%Accurate prediction of the translation initiation site (TIS) is an important issue for prokaryotic genome annotation. However, it is still a challenge for the existing methods to predict the TIS in the genomes over a wide variety of GC content. Besides, the existing methods have not yet undergone a comprehensive evaluation, leaving prediction reliability as a largely open problem. A new algorithm MED-StartPlus, a tool that predicts TIS in prokaryotic genomes with a wide variety of GC content was presented. It makes several efforts to model the nucleotide composition bias, the regulatory motifs upstream of the TIS, the sequence patterns around the TIS, and the operon structure. Tests on hundreds of reliable data sets, with TISs confirmed by experiments or having annotated functions, show that the new method achieves a totally high accuracy of TIS prediction. Compared with existing TIS predictors, the method reports a totally higher performance, especially for genomes that are GC-rich or have complex initiation mechanisms. The potential application of the method to improve the TIS annotation

  7. An optimized initialization algorithm to ensure accuracy in quantum Monte Carlo calculations.

    Science.gov (United States)

    Fisher, Daniel R; Kent, David R; Feldmann, Michael T; Goddard, William A

    2008-11-15

    Quantum Monte Carlo (QMC) calculations require the generation of random electronic configurations with respect to a desired probability density, usually the square of the magnitude of the wavefunction. In most cases, the Metropolis algorithm is used to generate a sequence of configurations in a Markov chain. This method has an inherent equilibration phase, during which the configurations are not representative of the desired density and must be discarded. If statistics are gathered before the walkers have equilibrated, contamination by nonequilibrated configurations can greatly reduce the accuracy of the results. Because separate Markov chains must be equilibrated for the walkers on each processor, the use of a long equilibration phase has a profoundly detrimental effect on the efficiency of large parallel calculations. The stratified atomic walker initialization (STRAW) shortens the equilibration phase of QMC calculations by generating statistically independent electronic configurations in regions of high probability density. This ensures the accuracy of calculations by avoiding contamination by nonequilibrated configurations. Shortening the length of the equilibration phase also results in significant improvements in the efficiency of parallel calculations, which reduces the total computational run time. For example, using STRAW rather than a standard initialization method in 512 processor calculations reduces the amount of time needed to calculate the energy expectation value of a trial function for a molecule of the energetic material RDX to within 0.01 au by 33%.

  8. Optimization the Initial Weights of Artificial Neural Networks via Genetic Algorithm Applied to Hip Bone Fracture Prediction

    Directory of Open Access Journals (Sweden)

    Yu-Tzu Chang

    2012-01-01

    Full Text Available This paper aims to find the optimal set of initial weights to enhance the accuracy of artificial neural networks (ANNs by using genetic algorithms (GA. The sample in this study included 228 patients with first low-trauma hip fracture and 215 patients without hip fracture, both of them were interviewed with 78 questions. We used logistic regression to select 5 important factors (i.e., bone mineral density, experience of fracture, average hand grip strength, intake of coffee, and peak expiratory flow rate for building artificial neural networks to predict the probabilities of hip fractures. Three-layer (one hidden layer ANNs models with back-propagation training algorithms were adopted. The purpose in this paper is to find the optimal initial weights of neural networks via genetic algorithm to improve the predictability. Area under the ROC curve (AUC was used to assess the performance of neural networks. The study results showed the genetic algorithm obtained an AUC of 0.858±0.00493 on modeling data and 0.802 ± 0.03318 on testing data. They were slightly better than the results of our previous study (0.868±0.00387 and 0.796±0.02559, resp.. Thus, the preliminary study for only using simple GA has been proved to be effective for improving the accuracy of artificial neural networks.

  9. A conceptual model of optimal international service-learning and its application to global health initiatives in rehabilitation.

    Science.gov (United States)

    Pechak, Celia M; Thompson, Mary

    2009-11-01

    There is growing involvement by US clinicians, faculty members, and students in global health initiatives, including international service-learning (ISL). Limited research has been done to examine the profession's increasing global engagement, or the ISL phenomenon in particular, and no research has been done to determine best practices. This study was intended as an early step in the examination of the physical therapy profession's role and activities in the global health arena within and beyond academics. The purposes of this study were: (1) to identify and analyze the common structures and processes among established ISL programs within physical therapist education programs and (2) to develop a conceptual model of optimal ISL within physical therapist education programs. A descriptive, exploratory study was completed using grounded theory. Telephone interviews were completed with 14 faculty members who had been involved in international service, international learning, or ISL in physical therapist education programs. Interviews were transcribed, and transcriptions were analyzed using the grounded theory method. Four major themes emerged from the data: structure, reciprocity, relationship, and sustainability. A conceptual model of and a proposed definition for optimal ISL in physical therapist education were developed. Seven essential components of the conceptual model are: a partner that understands the role of physical therapy, community-identified needs, explicit service and learning objectives, reflection, preparation, risk management, and service and learning outcome measures. Essential consequences are positive effects on students and community. The conceptual model and definition of optimal ISL can be used to direct development of new ISL programs and to improve existing programs. In addition, they can offer substantive guidance to any physical therapist involved in global health initiatives.

  10. Genetic inhibition of phosphorylation of the translation initiation factor eIF2α does not block Aβ-dependent elevation of BACE1 and APP levels or reduce amyloid pathology in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Katherine R Sadleir

    Full Text Available β-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1 initiates the production of β-amyloid (Aβ, the major constituent of amyloid plaques in Alzheimer's disease (AD. BACE1 is elevated ∼2-3 fold in AD brain and is concentrated in dystrophic neurites near plaques, suggesting BACE1 elevation is Aβ-dependent. Previously, we showed that phosphorylation of the translation initiation factor eIF2α de-represses translation of BACE1 mRNA following stress such as energy deprivation. We hypothesized that stress induced by Aβ might increase BACE1 levels by the same translational mechanism involving eIF2α phosphorylation. To test this hypothesis, we used three different genetic strategies to determine the effects of reducing eIF2α phosphorylation on Aβ-dependent BACE1 elevation in vitro and in vivo: 1 a two-vector adeno-associated virus (AAV system to express constitutively active GADD34, the regulatory subunit of PP1c eIF2α phosphatase; 2 a non-phosphorylatable eIF2α S51A knockin mutation; 3 a BACE1-YFP transgene lacking the BACE1 mRNA 5' untranslated region (UTR required for eIF2α translational regulation. The first two strategies were used in primary neurons and 5XFAD transgenic mice, while the third strategy was employed only in 5XFAD mice. Despite very effective reduction of eIF2α phosphorylation in both primary neurons and 5XFAD brains, or elimination of eIF2α-mediated regulation of BACE1-YFP mRNA translation in 5XFAD brains, Aβ-dependent BACE1 elevation was not decreased. Additionally, robust inhibition of eIF2α phosphorylation did not block Aβ-dependent APP elevation in primary neurons, nor did it reduce amyloid pathology in 5XFAD mice. We conclude that amyloid-associated BACE1 elevation is not caused by translational de-repression via eIF2α phosphorylation, but instead appears to involve a post-translational mechanism. These definitive genetic results exclude a role for eIF2α phosphorylation in Aβ-dependent BACE1 and

  11. Genetic inhibition of phosphorylation of the translation initiation factor eIF2α does not block Aβ-dependent elevation of BACE1 and APP levels or reduce amyloid pathology in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Sadleir, Katherine R; Eimer, William A; Kaufman, Randal J; Osten, Pavel; Vassar, Robert

    2014-01-01

    β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) initiates the production of β-amyloid (Aβ), the major constituent of amyloid plaques in Alzheimer's disease (AD). BACE1 is elevated ∼2-3 fold in AD brain and is concentrated in dystrophic neurites near plaques, suggesting BACE1 elevation is Aβ-dependent. Previously, we showed that phosphorylation of the translation initiation factor eIF2α de-represses translation of BACE1 mRNA following stress such as energy deprivation. We hypothesized that stress induced by Aβ might increase BACE1 levels by the same translational mechanism involving eIF2α phosphorylation. To test this hypothesis, we used three different genetic strategies to determine the effects of reducing eIF2α phosphorylation on Aβ-dependent BACE1 elevation in vitro and in vivo: 1) a two-vector adeno-associated virus (AAV) system to express constitutively active GADD34, the regulatory subunit of PP1c eIF2α phosphatase; 2) a non-phosphorylatable eIF2α S51A knockin mutation; 3) a BACE1-YFP transgene lacking the BACE1 mRNA 5' untranslated region (UTR) required for eIF2α translational regulation. The first two strategies were used in primary neurons and 5XFAD transgenic mice, while the third strategy was employed only in 5XFAD mice. Despite very effective reduction of eIF2α phosphorylation in both primary neurons and 5XFAD brains, or elimination of eIF2α-mediated regulation of BACE1-YFP mRNA translation in 5XFAD brains, Aβ-dependent BACE1 elevation was not decreased. Additionally, robust inhibition of eIF2α phosphorylation did not block Aβ-dependent APP elevation in primary neurons, nor did it reduce amyloid pathology in 5XFAD mice. We conclude that amyloid-associated BACE1 elevation is not caused by translational de-repression via eIF2α phosphorylation, but instead appears to involve a post-translational mechanism. These definitive genetic results exclude a role for eIF2α phosphorylation in Aβ-dependent BACE1 and APP elevation

  12. 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......) way. Most respondents and interviewees are worried about increasing pressures on the translation market, which, combined with customers’ general lack of understanding of the translation process, mean that systematic, all-encompassing quality assurance is rarely financially viable....

  13. Efficient Translation Initiation Directed by the 900-Nucleotide-Long and GC-Rich 5′ Untranslated Region of the Human Retrotransposon LINE-1 mRNA Is Strictly Cap Dependent Rather than Internal Ribosome Entry Site Mediated▿

    Science.gov (United States)

    Dmitriev, Sergey E.; Andreev, Dmitri E.; Terenin, Ilya M.; Olovnikov, Ivan A.; Prassolov, Vladimir S.; Merrick, William C.; Shatsky, Ivan N.

    2007-01-01

    Retrotransposon L1 is a mobile genetic element of the LINE family that is extremely widespread in the mammalian genome. It encodes a dicistronic mRNA, which is exceptionally rare among eukaryotic cellular mRNAs. The extremely long and GC-rich L1 5′ untranslated region (5′UTR) directs synthesis of numerous copies of RNA-binding protein ORF1p per mRNA. One could suggest that the 5′UTR of L1 mRNA contained a powerful internal ribosome entry site (IRES) element. Using transfection of cultured cells with the polyadenylated monocistronic (L1 5′UTR-Fluc) or bicistronic (Rluc-L1 5′UTR-Fluc) RNA constructs, capped or uncapped, it has been firmly established that the 5′UTR of L1 does not contain an IRES. Uncapping reduces the initiation activity of the L1 5′UTR to that of background. Moreover, the translation is inhibited by upstream AUG codons in the 5′UTR. Nevertheless, this cap-dependent initiation activity of the L1 5′UTR was unexpectedly high and resembles that of the beta-actin 5′UTR (84 nucleotides long). Strikingly, the deletion of up to 80% of the nucleotide sequence of the L1 5′UTR, with most of its stem loops, does not significantly change its translation initiation efficiency. These data can modify current ideas on mechanisms used by 40S ribosomal subunits to cope with complex 5′UTRs and call into question the conception that every long GC-rich 5′UTR working with a high efficiency has to contain an IRES. Our data also demonstrate that the ORF2 translation initiation is not directed by internal initiation, either. It is very inefficient and presumably based on a reinitiation event. PMID:17470553

  14. Efficient translation initiation directed by the 900-nucleotide-long and GC-rich 5' untranslated region of the human retrotransposon LINE-1 mRNA is strictly cap dependent rather than internal ribosome entry site mediated.

    Science.gov (United States)

    Dmitriev, Sergey E; Andreev, Dmitri E; Terenin, Ilya M; Olovnikov, Ivan A; Prassolov, Vladimir S; Merrick, William C; Shatsky, Ivan N

    2007-07-01

    Retrotransposon L1 is a mobile genetic element of the LINE family that is extremely widespread in the mammalian genome. It encodes a dicistronic mRNA, which is exceptionally rare among eukaryotic cellular mRNAs. The extremely long and GC-rich L1 5' untranslated region (5'UTR) directs synthesis of numerous copies of RNA-binding protein ORF1p per mRNA. One could suggest that the 5'UTR of L1 mRNA contained a powerful internal ribosome entry site (IRES) element. Using transfection of cultured cells with the polyadenylated monocistronic (L1 5'UTR-Fluc) or bicistronic (Rluc-L1 5'UTR-Fluc) RNA constructs, capped or uncapped, it has been firmly established that the 5'UTR of L1 does not contain an IRES. Uncapping reduces the initiation activity of the L1 5'UTR to that of background. Moreover, the translation is inhibited by upstream AUG codons in the 5'UTR. Nevertheless, this cap-dependent initiation activity of the L1 5'UTR was unexpectedly high and resembles that of the beta-actin 5'UTR (84 nucleotides long). Strikingly, the deletion of up to 80% of the nucleotide sequence of the L1 5'UTR, with most of its stem loops, does not significantly change its translation initiation efficiency. These data can modify current ideas on mechanisms used by 40S ribosomal subunits to cope with complex 5'UTRs and call into question the conception that every long GC-rich 5'UTR working with a high efficiency has to contain an IRES. Our data also demonstrate that the ORF2 translation initiation is not directed by internal initiation, either. It is very inefficient and presumably based on a reinitiation event.

  15. Expression of truncated eukaryotic initiation factor 3e (eIF3e) resulting from integration of mouse mammary tumor virus (MMTV) causes a shift from cap-dependent to cap-independent translation.

    Science.gov (United States)

    Chiluiza, David; Bargo, Sharon; Callahan, Robert; Rhoads, Robert E

    2011-09-09

    Integration of mouse mammary tumor virus (MMTV) at the common integration site Int6 occurs in the gene encoding eIF3e, the p48 subunit of translation initiation factor eIF3. Integration is at any of several introns of the Eif3e gene and causes the expression of truncated Eif3e mRNAs. Ectopic expression of the truncated eIF3e protein resulting from integration at intron 5 (3e5) induces malignant transformation, but by an unknown mechanism. Because eIF3e makes up at least part of the binding site for eIF4G, we examined the effects of 3e5 expression on protein synthesis. We developed an NIH3T3 cell line that contains a single copy of the 3e5 sequence at a predetermined genomic site. Co-immunoprecipitation indicated diminished binding of eIF3 to eIF4G, signifying a reduction in recruitment of the mRNA-unwinding machinery to the 43 S preinitiation complex. Cell growth and overall protein synthesis were decreased. Translation driven by the eIF4G-independent hepatitis C virus internal ribosome entry sequence (HCV IRES) in a bicistronic mRNA was increased relative to cap-dependent translation. Endogenous mRNAs encoding XIAP, c-Myc, CYR61, and Pim-1, which are translated in a cap-independent manner, were shifted to heavier polysomes whereas mRNAs encoding GAPDH, actin, L32, and L34, which are translated in a cap-dependent manner, were shifted to lighter polysomes. We propose that expression of 3e5 diminishes eIF4G interaction with eIF3 and causes abnormal gene expression at the translational level. The correlation between up-regulation of cap-independent translation and MMTV-induced tumorigenesis contrasts with the well established model for malignant transformation involving up-regulation of highly cap-dependent translation.

  16. 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...

  17. An Alternate Approach to Optimal L 2 -Error Analysis of Semidiscrete Galerkin Methods for Linear Parabolic Problems with Nonsmooth Initial Data

    KAUST Repository

    Goswami, Deepjyoti

    2011-09-01

    In this article, we propose and analyze an alternate proof of a priori error estimates for semidiscrete Galerkin approximations to a general second order linear parabolic initial and boundary value problem with rough initial data. Our analysis is based on energy arguments without using parabolic duality. Further, it follows the spirit of the proof technique used for deriving optimal error estimates for finite element approximations to parabolic problems with smooth initial data and hence, it unifies both theories, that is, one for smooth initial data and other for nonsmooth data. Moreover, the proposed technique is also extended to a semidiscrete mixed method for linear parabolic problems. In both cases, optimal L2-error estimates are derived, when the initial data is in L2. A superconvergence phenomenon is also observed, which is then used to prove L∞-estimates for linear parabolic problems defined on two-dimensional spatial domain again with rough initial data. Copyright © Taylor & Francis Group, LLC.

  18. Optimal timing for initiation of biofeedback-assisted relaxation training in hospitalized coronary heart disease patients with sleep disturbances.

    Science.gov (United States)

    Wang, Li-Na; Tao, Hong; Zhao, Yue; Zhou, Yu-Qiu; Jiang, Xiu-Rong

    2014-07-01

    Clinical studies have shown that biofeedback-assisted relaxation positively influences the treatment outcomes of sleep disturbance. However, there are only few studies reporting the timing of relaxation training initiation, and the relationships between the timing of initiation and the effectiveness of relaxation remain unclear. The aim of this study was to determine the optimal timing for initiating nurse-led biofeedback-assisted relaxation on hospitalized coronary heart disease patients with sleep disturbance. An experimental pretest and repeated posttest design was used to compare the effectiveness of nurse-led biofeedback-assisted relaxation. A total of 128 patients with coronary heart disease were randomly assigned to 1 of 4 groups: morning group, night group, morning-night group, or control group. Outcome measures included self-report of sleep-related indicators, the scores of the Pittsburgh Sleep Quality Index (PSQI) and the Zung's Self-rating Anxiety Scale (SAS), and the dosage of sleep medication used. A 2-way analysis of variance and a simple effect test were used to analyze the differences among the 4 groups. No significant differences could be detected at baseline. Compared with the control group, the nurse-led biofeedback-assisted relaxation yielded a greater benefit for patients in the 3 intervention groups. Group and time factors (pretest-protest) could explain the variation in the effectiveness of this program (main effect P sleep latency, experienced fewer awakenings, reported higher sleep quality, and used significantly fewer sleep medications than the morning group did (F = 32.97, P sleep quality and decrease the need for of sleep medications in hospitalized patients with sleep disturbance.

  19. 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.

  20. Translation initiation factor eIF-5A, the hypusine-containing protein, is phosphorylated on serine and tyrosine and O-glycosylated in Trichomonas vaginalis.

    Science.gov (United States)

    Carvajal-Gamez, Bertha Isabel; Quintas-Granados, Laura Itzel; Arroyo, Rossana; Mendoza-Hernández, Guillermo; Alvarez-Sánchez, Maria Elizbeth

    2012-03-01

    The eukaryotic translation factor eIF-5A is highly conserved throughout eukaryotes and undergoes an unusual polyamine-dependent post-translational modification called hypusination. Trichomonas vaginalis has two tveif-5a genes (tveif-5a1 and tveif-5a2), each encoding a 19-kDa protein. In this report, we describe the detection of two forms with different isoelectric points (5.2 and 5.5) that correspond to the precursor and mature TveIF-5A, respectively. In addition, we demonstrated that only the mature form of TveIF-5A is phosphorylated and glycosylated via two-dimensional gel electrophoresis-western blot (2DE-WB) assays using anti-phosphoserine and anti-phosphotyrosine antibodies and the SNA, ConA and MAA lectins. Interestingly, when the protozoa were grown in 1,4-diamino-2-butanone (DAB), an inhibitor of putrescine biosynthesis, and transferred to medium containing exogenous putrescine, a new spot with an isoelectric point of 5.3 was observed, presumably corresponding to a phosphorylated intermediate or deoxyhypusine form. Our data indicate that, in T. vaginalis, phosphorylations and glycosylations are necessary to obtain the mature TveIF-5A, and we confirm the identity of the precursor, intermediate and mature forms of TveIF-5A by mass spectrometry analysis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Optimism

    Science.gov (United States)

    Carver, Charles S.; Scheier, Michael F.; Segerstrom, Suzanne C.

    2010-01-01

    Optimism is an individual difference variable that reflects the extent to which people hold generalized favorable expectancies for their future. Higher levels of optimism have been related prospectively to better subjective well-being in times of adversity or difficulty (i.e., controlling for previous well-being). Consistent with such findings, optimism has been linked to higher levels of engagement coping and lower levels of avoidance, or disengagement, coping. There is evidence that optimism is associated with taking proactive steps to protect one's health, whereas pessimism is associated with health-damaging behaviors. Consistent with such findings, optimism is also related to indicators of better physical health. The energetic, task-focused approach that optimists take to goals also relates to benefits in the socioeconomic world. Some evidence suggests that optimism relates to more persistence in educational efforts and to higher later income. Optimists also appear to fare better than pessimists in relationships. Although there are instances in which optimism fails to convey an advantage, and instances in which it may convey a disadvantage, those instances are relatively rare. In sum, the behavioral patterns of optimists appear to provide models of living for others to learn from. PMID:20170998

  2. Optimization

    CERN Document Server

    Pearce, Charles

    2009-01-01

    Focuses on mathematical structure, and on real-world applications. This book includes developments in several optimization-related topics such as decision theory, linear programming, turnpike theory, duality theory, convex analysis, and queuing theory.

  3. Advertisement Translation within the Context of"the Belt and Road"Initiative%"一带一路"战略构想下的广告翻译研究

    Institute of Scientific and Technical Information of China (English)

    王巧宁; 张焱

    2015-01-01

    中国国家主席习近平在2013 年提出的"一带一路"(丝绸之路经济带和21 世纪海上丝绸之路)战略构想无疑给各国之间的经济贸易活动带来了新的发展契机. 新的发展契机下,众多试图跻身国际市场的商品则面临语言翻译.广告翻译的处理、策略的选择在很大程度上取决于其语言效果在海外市场上所带来的经济价值.本文拟结合一些具体的广告文本探讨"一带一路"构想下语言经济学如何在广告翻译实践中的体现和应用.%The "One Belt One Road" (Silk Road Economic Belt and the twenty-first Century Maritime Silk Road) initiative put forward by Chinese President Xi Jinping in 2013 undoubtedly brings new opportunities for numerous economic activities between countries. This is where translation leads many products attempting to enter the international market within such a new context. The choice of techniques and strategies in advertisement translation is largely a matter of potential profits brought by the translated versions in the overseas market. This paper aims at exploring how Economics of Language represents and applies itself in advertisement translation.

  4. The essential role of hypusine in eukaryotic translation initiation factor 4D (eIF-4D). Purification of eIF-4D and its precursors and comparison of their activities.

    Science.gov (United States)

    Park, M H

    1989-11-05

    Eukaryotic translation initiation factor 4D (eIF-4D) is the only protein known to contain the amino acid, hypusine [N epsilon-(4-amino-2-hydroxybutyl)lysine]. This unusual amino acid is formed post-translationally by modification of a single specific lysine residue in an eIF-4D precursor protein. Two separate eIF-4D precursors, each of which contains a lysine residue in place of the hypusine residue and each of which thereby serves as a protein substrate for the hypusine modification, were purified from DL-2-difluoromethylornithine-treated Chinese hamster ovary cells by means of a five-step procedure. These two precursors termed PI and PII both have apparent molecular masses of approximately 17 kDa, indistinguishable from that of eIF-4D, but exhibit more acidic isoelectric points (5.1 and 5.25 for PI and PII, respectively, compared with 5.37 for eIF-4D). These physical characteristics, together with other properties, indicate that eIF-4D differs from PII only in possessing the hypusine residue in place of a lysine residue, whereas an additional structural difference exists between PI and eIF-4D. eIF-4D from CHO cells provides a significant enhancement of methionyl-puromycin synthesis, a model assay for translation initiation. Neither PI nor PII stimulates this in vitro system. These findings are the first direct evidence that hypusine is essential for the biological activity of eIF-4D.

  5. 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…

  6. Application of translation strategies in the translation of trademark

    Institute of Scientific and Technical Information of China (English)

    曾丽晔

    2014-01-01

    The trademark propaganda is an important means of sel ing goods and way of competition in international market. Cultivating famous brand serves as an important links in opening up the international market. So the importance of a good trademark translation is evident. Through discussing the importance of the Chinese-English trademark translation, the translation of the principles, tactics, errors and trademark translation of cultural taboos, this paper studies initial y several aspects about how to translate the Chinese trademark into English, which is in order to make the translation of the original brand names and the products match perfectly in the sound, shape, meaning, and beauty. Thus, commodity exchanges and cultural exchanges both can be achieved.

  7. 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...... 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...

  8. Optimization of friction stir welding using space mapping and manifold mapping-an initial study of thermal aspects

    DEFF Research Database (Denmark)

    Larsen, Anders Astrup; Bendsøe, Martin P.; Hattel, Jesper Henri

    2009-01-01

    The aim of this paper is to optimize a thermal model of a friction stir welding process by finding optimal welding parameters. The optimization is performed using space mapping and manifold mapping techniques in which a coarse model is used along with the fine model to be optimized. Different...... coarse models are applied and the results and computation time are compared to gradient based optimization using the full model. It is found that the use of space and manifold mapping reduces the computational cost significantly due to the fact that fewer function evaluations and no fine model gradient...

  9. 40S recruitment in the absence of eIF4G/4A by EMCV IRES refines the model for translation initiation on the archetype of Type II IRESs.

    Science.gov (United States)

    Chamond, Nathalie; Deforges, Jules; Ulryck, Nathalie; Sargueil, Bruno

    2014-01-01

    Initiation of translation on Type II IRESs, such as those of EMCV and FMDV viruses, has been well documented in the recent years. For EMCV, the current model argues for a mechanism in which the key interaction necessary for the pre-initiation complex recruitment is eIF4G binding to the central J-K domains of EMCV-IRES. Here we demonstrate that, in contrast with the current model, the molecular mechanism of EMCV-IRES involves direct recruitment of the 40S subunit. Importantly, we identified a specific structural element that prevents the correct positioning of the initiation codon in the close vicinity of the ribosomal P site. This work clarifies how this interaction could not be anticipated by earlier studies and allows us to propose a new model for initiation complex assembly on EMCV-IRES. The role attributed to eIF4G/4A can thus be refined as stabilizing/promoting the conformational changes that are necessary for IRES function, thus resembling the role conventionally assigned to ITAFs. This raises the interesting possibility that IRESs are primarily ribosome binders, some of which having partly lost the ability to fold into the active structure without the help of proteins.

  10. A Stable Upstream Stem-loop Structure Enhances Selection of the First 5′-ORF-AUG as a Main Start Codon for Translation Initiation of Human ACAT1 mRNA

    Institute of Scientific and Technical Information of China (English)

    Li YANG; Jiang CHEN; Catherine C. Y. CHANG; Xin-Ying YANG; Zhen-Zhen WANG; Ta-Yuan CHANG; Bo-Liang LI

    2004-01-01

    Human ACAT1 cDNA K1 was first cloned and functionally expressed in 1993. There are two adjacent in-frame AUG codons, AUG1397-1399 and AUG1415-1417, at 5′-terminus of the open reading frame (ORF,nt 1397-3049) of human ACAT1 mRNA corresponding to cDNA K1. In current work, these two adjacent inframe AUGs at 5 ′-terminus of the predicted ORF (5′-ORF-AUGs) as start codons for translation initiation of human ACAT1 mRNA were characterized in detail. Codon mutations indicated that both of these two adjacent 5′-ORF-AUGs can be selected as start codons but the first 5′-ORF-AUG1397-1399 is a main start codon consistent with that of the predicted ORF of human ACAT1 mRNA. Further deletion and mutation analyses demonstrated that a stable upstream stem-loop structure enhanced the selection of the first 5 ′-ORF-AUG1397-1399 as a main start codon, in addition to upstream nucleotide A in the -3 position, which is a key site of Kozak sequence. In addition, result of ACAT1 enzymatic activity assay showed no obvious difference between these two ACAT1 proteins respectively initiated from the two adjacent 5′-ORF-AUGs. This work showed that a stable upstream stem-loop structure could modulate the start codon selection during translation initiation of mRNAs that contain adjacent multi-5′-ORF-AUGs.

  11. Conserved TAAATG sequence at the transcriptional and translational initiation sites of vaccinia virus late genes deduced by structural and functional analysis of the HindIII H genome fragment.

    Science.gov (United States)

    Rosel, J L; Earl, P L; Weir, J P; Moss, B

    1986-11-01

    The sequence of the 8,600-base-pair HindIII H fragment, located at the center of the vaccinia virus genome, was determined to analyze several late genes. Seven major complete open reading frames (ORFs) and two that started from or continued into adjacent DNA segments were identified. ORFs were closely spaced and present on both DNA strands. Some adjacent ORFs had oppositely oriented overlapping termination codons or contiguous stop and start codons. Nucleotide compositional analysis indicated that the A-T frequency was consistently lowest in the first codon position. The sizes of the polypeptides predicted from the DNA sequence were compared with those determined by polyacrylamide gel electrophoresis of cell-free translation products of mRNAs selected by hybridization to cloned single-stranded DNA segments or synthesized in vitro by bacteriophage T7 RNA polymerase. Six transcripts that initiated within the HindIII H DNA fragment were detected, and of these, four were synthesized only at late times, one was synthesized only early, and one was synthesized early and late. The sites on the genome corresponding to the 5' ends of the transcripts were located by high-resolution nuclease S1 analysis. For late genes, the transcriptional and translational initiation sites mapped within a few nucleotides of each other, and in each case the sequence TAAATGG occurred at the start of the ORF. The extremely short leader and the absence of A or G in the -3 position, relative to the first nucleotide of the initiation codon, distinguishes the majority of vaccinia virus late genes from eucaryotic and vaccinia virus early genes.

  12. Educational intervention to reduce disease related to sub-optimal basic hygiene in Rwanda: initial evaluation and feasibility study.

    Science.gov (United States)

    Stone, Margaret A; Ndagijimana, Hormisdas

    2018-01-01

    Despite a global reduction in morbidity related to sub-optimal water, sanitation and hygiene, the incidence of such diseases remains a significant problem in sub-Saharan Africa. This study aimed to initially assess the potential effectiveness (primarily in terms of impact on morbidity) of a simple educational intervention delivered in Rwanda. Additionally, we sought to explore feasibility relating to the practicality of evaluating and implementing this type of intervention in a low- and middle-income country. Two districts in Northern Province were purposively selected; one was randomly allocated to receive the intervention, with the other acting as control. The intervention was based on an interactive DVD about basic hygiene. Baseline and follow-up data for incident cases of relevant morbidities were collected from health centre records. Changes were compared between the two districts using descriptive statistics and chi-squared tests. Qualitative data were obtained through observations, discussions and feedback and were analysed thematically. Cases of infection with intestinal worms and parasites were frequently recorded in both districts. For these morbidities, there was a 39% decrease in cases between baseline and follow-up in the intervention district (4995 reduced to 3069), compared to 13% (5002 reduced to 4356) in the control district (p evaluation and implementation, whilst also highlighting problems encountered and possible solutions, in particular, the potential advantages of training local personnel to deliver this type of intervention. This small-scale study has a number of acknowledged limitations which would need to be addressed in a larger study in order to confidently confirm the effectiveness of the intervention. It nevertheless provides evidence suggesting that the educational intervention is promising in terms of a potential impact on health and feasible to deliver and evaluate. These findings indicate that further evaluation and possibly early

  13. Optimal cutoffs of obesity measures in relation to cancer risk in postmenopausal women in the Women's Health Initiative Study.

    Science.gov (United States)

    Heo, Moonseong; Kabat, Geoffrey C; Strickler, Howard D; Lin, Juan; Hou, Lifang; Stefanick, Marcia L; Anderson, Garnet L; Rohan, Thomas E

    2015-03-01

    Obesity is a risk factor for several cancers in postmenopausal women. We attempted to determine cutoffs of adiposity measures in relation to risk of obesity-related cancers among postmenopausal women and to examine the effects of hormone therapy (HT) use on the cutoffs, neither of which has been broadly studied. We used data from the Women's Health Initiative cohort (n=144,701) and applied Cox-proportional hazards regressions to each combination of 17 cancer types and 6 anthropometric measures (weight, body mass index [BMI], weight to height ratio, waist circumference, waist to hip ratio [WHR], and waist to height ratio). Interactions between the anthropometric measures and HT use were also examined. Cutoffs were determined by applying a grid search followed by a two-fold cross validation method. Survival ROC analysis of 5- and 10-year incidence followed. Breast, colorectal, colon, endometrium, kidney, and all cancers combined were significantly positively associated with all six anthropometric measures, whereas lung cancer among ever smokers was significantly inversely associated with all measures except WHR. The derived cutoffs of each obesity measure varied across cancers (e.g., BMI cutoffs for breast and endometrium cancers were 30 kg/m(2) and 34 kg/m(2), respectively), and also depended on HT use. The Youden indices of the cutoffs for predicting 5- and 10-year cancer incidence were higher among HT never users. Using a panel of different anthropometric measures, we derived optimal cut-offs categorizing populations into high- and low-risk groups, which differed by cancer type and HT use. Although the discrimination abilities of these risk categories were generally poor, the results of this study could serve as a starting point from which to determine adiposity cutoffs for inclusion in risk prediction models for specific cancer types.

  14. Optimal escape theory predicts escape behaviors beyond flight initiation distance: risk assessment and escape by striped plateau lizards Sceloporus virgatus

    Institute of Scientific and Technical Information of China (English)

    William E.COOPER Jr

    2009-01-01

    Escape theory predicts that flight initiation distance (FID=distance between predator and prey when escape begins) is longer when risk is greater and shorter when escape is more costly. A few tests suggest that escape theory applies to distance fled. Escape models have not addressed stochastic variables, such as probability of fleeing and of entering refuge, but their economic logic might be applicable. Experiments on several risk factors in the lizard Sceloporus virgatus confirmed all predictions for the above escape variables. FID was greater when approach was faster and more direct, for lizards on ground than on trees, for lizards rarely exposed to humans, for the second of two approaches, and when the predator turned toward lizards rather than away. Lizards fled further during rapid and second consecutive approaches. They were more likely to flee when approached directly, when a predator turned toward them, and during second approaches. They were more likely to enter refuge when approached rapidly. A novel finding is that perch height in trees was unrelated to FID because lizards escaped by moving out of sight, then moving up or down unpredictably. These findings add to a growing body of evidence supporting predictions of escape theory for FID and distance fled. They show that two probabilistic aspects of escape are predictable based on relative predation risk levels. Because individuals differ in boldness, the assessed optimal FID and threshold risks for fleeing and entering refuge are exceeded for an increasing proportion of individuals as risk increases[Current Zoology 55(2):123-131,2009].

  15. Optimal Cutoffs of Obesity Measures in Relation to Cancer Risk in Postmenopausal Women in the Women's Health Initiative Study

    Science.gov (United States)

    Kabat, Geoffrey C.; Strickler, Howard D.; Lin, Juan; Hou, Lifang; Stefanick, Marcia L.; Anderson, Garnet L.; Rohan, Thomas E.

    2015-01-01

    Abstract Background: Obesity is a risk factor for several cancers in postmenopausal women. We attempted to determine cutoffs of adiposity measures in relation to risk of obesity-related cancers among postmenopausal women and to examine the effects of hormone therapy (HT) use on the cutoffs, neither of which has been broadly studied. Methods: We used data from the Women's Health Initiative cohort (n=144,701) and applied Cox-proportional hazards regressions to each combination of 17 cancer types and 6 anthropometric measures (weight, body mass index [BMI], weight to height ratio, waist circumference, waist to hip ratio [WHR], and waist to height ratio). Interactions between the anthropometric measures and HT use were also examined. Cutoffs were determined by applying a grid search followed by a two-fold cross validation method. Survival ROC analysis of 5- and 10-year incidence followed. Results: Breast, colorectal, colon, endometrium, kidney, and all cancers combined were significantly positively associated with all six anthropometric measures, whereas lung cancer among ever smokers was significantly inversely associated with all measures except WHR. The derived cutoffs of each obesity measure varied across cancers (e.g., BMI cutoffs for breast and endometrium cancers were 30 kg/m2 and 34 kg/m2, respectively), and also depended on HT use. The Youden indices of the cutoffs for predicting 5- and 10-year cancer incidence were higher among HT never users. Conclusion: Using a panel of different anthropometric measures, we derived optimal cut-offs categorizing populations into high- and low-risk groups, which differed by cancer type and HT use. Although the discrimination abilities of these risk categories were generally poor, the results of this study could serve as a starting point from which to determine adiposity cutoffs for inclusion in risk prediction models for specific cancer types. PMID:25587642

  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. Putting Translational Science onto a Global Stage

    Science.gov (United States)

    Gilliland, C. Taylor; Zuk, Dorit; Kocis, Petr; Johnson, Mike; Hay, Stewart; Bietrix, Florence; Aversa, Gregorio; Austin, Christopher P.; Ussi, Anton E.

    2017-01-01

    Global collaboration in translational science promises to accelerate the discovery, development and dissemination of new medical interventions. In this article, we introduce a new international collaboration of translational science organizations and highlight our initial strategy to reduce or remove bottlenecks in translation. A first step in this process is increasing the awareness and understanding of the field among key stakeholder groups. PMID:27032820

  18. 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.

  19. Recognition of Translator Expertise using Sequences of Fixations and Keystrokes

    DEFF Research Database (Denmark)

    Gómez, Pascual Martínez; Minocha, Akshay; Huang, Jin

    2014-01-01

    Professional human translation is necessary to meet high quality standards in industry and governmental agencies. Translators engage in multiple activities during their task, and there is a need to model their behavior, with the objective to understand and optimize the translation process. In rec...... and keystrokes into activities and model translation sessions with the objective to recognize translator expertise. We show significant error reductions in the task of recognizing certified translators and their years of experience, and analyze the characterizing patterns....

  20. 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....

  1. 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.

  2. Conformational transitions of the catalytic domain of heme-regulated eukaryotic initiation factor 2α kinase, a key translational regulatory molecule.

    Science.gov (United States)

    Sreejith, R K; Suresh, C G; Bhosale, Siddharth H; Bhavnani, Varsha; Kumar, Avinash; Gaikwad, Sushama M; Pal, Jayanta K

    2012-01-01

    In mammalian cells, the heme-regulated inhibitor (HRI) plays a critical role in the regulation of protein synthesis at the initiation step through phosphorylation of α-subunit of the eukaryotic initiation factor 2 (eIF2). In this study we have cloned and performed biophysical characterization of the kinase catalytic domain (KD) of rabbit HRI. The KD described here comprises kinase 1, the kinase insertion domain (KI) and kinase 2. We report here the existence of an active and stable monomer of HRI (KD). The HRI (KD) containing three tryptophan residues was examined for its conformational transitions occurring under various denaturing conditions using steady-state and time-resolved tryptophan fluorescence, circular dichroism (CD) and hydrophobic dye binding. The parameter A and phase diagram analysis revealed multi-state unfolding and existence of three stable intermediates during guanidine hydrochloride (Gdn-HCl) induced unfolding of HRI (KD). The protein treated with 6 M Gdn-HCl showed collisional and static mechanism of acrylamide quenching and the constants (K(sv) = 3.08 M(-1) and K(s)= 5.62 M(-1)) were resolved using time resolved fluorescence titration. Based on pH, guanidine hydrochloride and temperature mediated transitions, HRI (KD) appears to exemplify a rigid molten globule-like intermediate with compact secondary structure, altered tertiary structure and exposed hydrophobic patches at pH 3.0. The results indicate the inherent structural stability of HRI (KD), a member of the class of stress response proteins.

  3. Evidence of Parallel Processing During Translation

    DEFF Research Database (Denmark)

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

    2014-01-01

    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......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...

  4. Functional characterization of the Arabidopsis eukaryotic translation initiation factor 5A-2 that plays a crucial role in plant growth and development by regulating cell division, cell growth, and cell death.

    Science.gov (United States)

    Feng, Haizhong; Chen, Qingguo; Feng, Jian; Zhang, Jian; Yang, Xiaohui; Zuo, Jianru

    2007-07-01

    The eukaryotic translation initiation factor 5A (eIF-5A) is a highly conserved protein found in all eukaryotic organisms. Although originally identified as a translation initiation factor, recent studies in mammalian and yeast (Saccharomyces cerevisiae) cells suggest that eIF-5A is mainly involved in RNA metabolism and trafficking, thereby regulating cell proliferation, cell growth, and programmed cell death. In higher plants, the physiological function of eIF-5A remains largely unknown. Here, we report the identification and characterization of an Arabidopsis (Arabidopsis thaliana) mutant fumonisin B(1)-resistant12 (fbr12). The fbr12 mutant shows an antiapoptotic phenotype and has reduced dark-induced leaf senescence. Moreover, fbr12 displays severe defects in plant growth and development. The fbr12 mutant plant is extreme dwarf with substantially reduced size and number of all adult organs. During reproductive development, fbr12 causes abnormal development of floral organs and defective sporogenesis, leading to the abortion of both female and male germline cells. Microscopic studies revealed that these developmental defects are associated with abnormal cell division and cell growth. Genetic and molecular analyses indicated that FBR12 encodes a putative eIF-5A-2 protein. When expressed in a yeast mutant strain carrying a mutation in the eIF-5A gene, FBR12 cDNA is able to rescue the lethal phenotype of the yeast mutant, indicating that FBR12 is a functional eIF-5A. We propose that FBR12/eIF-5A-2 is fundamental for plant growth and development by regulating cell division, cell growth, and cell death.

  5. The small molecule '1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate' and its derivatives regulate global protein synthesis by inactivating eukaryotic translation initiation factor 2-alpha.

    Science.gov (United States)

    Hong, Mi-Na; Nam, Ky-Youb; Kim, Kyung Kon; Kim, So-Young; Kim, InKi

    2016-05-01

    By environmental stresses, cells can initiate a signaling pathway in which eukaryotic translation initiation factor 2-alpha (eIF2-α) is involved to regulate the response. Phosphorylation of eIF2-α results in the reduction of overall protein neogenesis, which allows cells to conserve resources and to reprogram energy usage for effective stress control. To investigate the role of eIF2-α in cell stress responses, we conducted a viability-based compound screen under endoplasmic reticulum (ER) stress condition, and identified 1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate (AMC-01) and its derivatives as eIF2-α-inactivating chemical. Molecular characterization of this signaling pathway revealed that AMC-01 induced inactivation of eIF2-α by phosphorylating serine residue 51 in a dose- and time-dependent manner, while the negative control compounds did not affect eIF2-α phosphorylation. In contrast with ER stress induction by thapsigargin, phosphorylation of eIF2-α persisted for the duration of incubation with AMC-01. By pathway analysis, AMC-01 clearly induced the activation of protein kinase RNA-activated (PKR) kinase and nuclear factor-κB (NF-κB), whereas it did not modulate the activity of PERK or heme-regulated inhibitor (HRI). Finally, we could detect a lower protein translation rate in cells incubated with AMC-01, establishing AMC-01 as a potent chemical probe that can regulate eIF2-α activity. We suggest from these data that AMC-01 and its derivative compounds can be used as chemical probes in future studies of the role of eIF2-α in protein synthesis-related cell physiology.

  6. 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

  7. Translation techniques for distributed-shared memory programming models

    Energy Technology Data Exchange (ETDEWEB)

    Fuller, Douglas James [Iowa State Univ., Ames, IA (United States)

    2005-01-01

    The high performance computing community has experienced an explosive improvement in distributed-shared memory hardware. Driven by increasing real-world problem complexity, this explosion has ushered in vast numbers of new systems. Each new system presents new challenges to programmers and application developers. Part of the challenge is adapting to new architectures with new performance characteristics. Different vendors release systems with widely varying architectures that perform differently in different situations. Furthermore, since vendors need only provide a single performance number (total MFLOPS, typically for a single benchmark), they only have strong incentive initially to optimize the API of their choice. Consequently, only a fraction of the available APIs are well optimized on most systems. This causes issues porting and writing maintainable software, let alone issues for programmers burdened with mastering each new API as it is released. Also, programmers wishing to use a certain machine must choose their API based on the underlying hardware instead of the application. This thesis argues that a flexible, extensible translator for distributed-shared memory APIs can help address some of these issues. For example, a translator might take as input code in one API and output an equivalent program in another. Such a translator could provide instant porting for applications to new systems that do not support the application's library or language natively. While open-source APIs are abundant, they do not perform optimally everywhere. A translator would also allow performance testing using a single base code translated to a number of different APIs. Most significantly, this type of translator frees programmers to select the most appropriate API for a given application based on the application (and developer) itself instead of the underlying hardware.

  8. Translation techniques for distributed-shared memory programming models

    Energy Technology Data Exchange (ETDEWEB)

    Fuller, Douglas James

    2005-08-01

    The high performance computing community has experienced an explosive improvement in distributed-shared memory hardware. Driven by increasing real-world problem complexity, this explosion has ushered in vast numbers of new systems. Each new system presents new challenges to programmers and application developers. Part of the challenge is adapting to new architectures with new performance characteristics. Different vendors release systems with widely varying architectures that perform differently in different situations. Furthermore, since vendors need only provide a single performance number (total MFLOPS, typically for a single benchmark), they only have strong incentive initially to optimize the API of their choice. Consequently, only a fraction of the available APIs are well optimized on most systems. This causes issues porting and writing maintainable software, let alone issues for programmers burdened with mastering each new API as it is released. Also, programmers wishing to use a certain machine must choose their API based on the underlying hardware instead of the application. This thesis argues that a flexible, extensible translator for distributed-shared memory APIs can help address some of these issues. For example, a translator might take as input code in one API and output an equivalent program in another. Such a translator could provide instant porting for applications to new systems that do not support the application's library or language natively. While open-source APIs are abundant, they do not perform optimally everywhere. A translator would also allow performance testing using a single base code translated to a number of different APIs. Most significantly, this type of translator frees programmers to select the most appropriate API for a given application based on the application (and developer) itself instead of the underlying hardware.

  9. Theorizing About Translation and Translation Studies

    OpenAIRE

    Williams, Mukesh

    2012-01-01

    The act of translation between languages and cultures has been going on for centuries, but the act of theorizing about-translation is of recent origin. In the last forty years translation scholars have attempted to understand the process of translation and evaluate its merits giving rise to a whole range of conceptualizing which is now called translation studies. Translation studies , therefore, has grown within important scholastic enclosures of the west attempting to conduct political and i...

  10. Co-Optimization of Fuels & Engines (Co-Optima) Initiative: Recent Progress on Light-Duty Boosted Spark-Ignition Fuels/Engines

    Energy Technology Data Exchange (ETDEWEB)

    Farrell, John

    2017-07-03

    This presentation reports recent progress on light-duty boosted spark-ignition fuels/engines being developed under the Co-Optimization of Fuels and Engines initiative (Co-Optima). Co-Optima is focused on identifying fuel properties that optimize engine performance, independent of composition, allowing the market to define the best means to blend and provide these fuels. However, in support of this, we are pursuing a systematic study of blendstocks to identify a broad range of feasible options, with the objective of identifying blendstocks that can provide target ranges of key fuel properties, identifying trade-offs on consistent and comprehensive basis, and sharing information with stakeholders.

  11. Case study: technology initiative led to advanced lead optimization screening processes at Bristol-Myers Squibb, 2004-2009.

    Science.gov (United States)

    Zhang, Litao; Cvijic, Mary Ellen; Lippy, Jonathan; Myslik, James; Brenner, Stephen L; Binnie, Alastair; Houston, John G

    2012-07-01

    In this paper, we review the key solutions that enabled evolution of the lead optimization screening support process at Bristol-Myers Squibb (BMS) between 2004 and 2009. During this time, technology infrastructure investment and scientific expertise integration laid the foundations to build and tailor lead optimization screening support models across all therapeutic groups at BMS. Together, harnessing advanced screening technology platforms and expanding panel screening strategy led to a paradigm shift at BMS in supporting lead optimization screening capability. Parallel SAR and structure liability relationship (SLR) screening approaches were first and broadly introduced to empower more-rapid and -informed decisions about chemical synthesis strategy and to broaden options for identifying high-quality drug candidates during lead optimization.

  12. Discussion on the Management of Collaborative Translation Project

    Institute of Scientific and Technical Information of China (English)

    陈意

    2015-01-01

    With the rapidly increasing demands for translating, the number of translation projects is soaring and the scope of the project is expending to a large extent.Therefore, collaborative translation came into fashion breeding the needs for corresponding management which alters the traditional individual translation mode.The study of translation project management becomes necessary and is of great significance to MTI students.This paper makes a discussion on the management of collaborative translation projects standing in the position of a MTI student, composed of project analyzing and planning, translators organizing, translation quality optimizing and project schedule controlling.

  13. A dedicated cone-beam CT system for musculoskeletal extremities imaging: Design, optimization, and initial performance characterization

    Energy Technology Data Exchange (ETDEWEB)

    Zbijewski, W.; De Jean, P.; Prakash, P.; Ding, Y.; Stayman, J. W.; Packard, N.; Senn, R.; Yang, D.; Yorkston, J.; Machado, A.; Carrino, J. A.; Siewerdsen, J. H. [Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Carestream Health, Rochester, New York 14615 (United States); The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland 21287 (United States); Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States)

    2011-08-15

    Purpose: This paper reports on the design and initial imaging performance of a dedicated cone-beam CT (CBCT) system for musculoskeletal (MSK) extremities. The system complements conventional CT and MR and offers a variety of potential clinical and logistical advantages that are likely to be of benefit to diagnosis, treatment planning, and assessment of therapy response in MSK radiology, orthopaedic surgery, and rheumatology. Methods: The scanner design incorporated a host of clinical requirements (e.g., ability to scan the weight-bearing knee in a natural stance) and was guided by theoretical and experimental analysis of image quality and dose. Such criteria identified the following basic scanner components and system configuration: a flat-panel detector (FPD, Varian 3030+, 0.194 mm pixels); and a low-power, fixed anode x-ray source with 0.5 mm focal spot (SourceRay XRS-125-7K-P, 0.875 kW) mounted on a retractable C-arm allowing for two scanning orientations with the capability for side entry, viz. a standing configuration for imaging of weight-bearing lower extremities and a sitting configuration for imaging of tensioned upper extremity and unloaded lower extremity. Theoretical modeling employed cascaded systems analysis of modulation transfer function (MTF) and detective quantum efficiency (DQE) computed as a function of system geometry, kVp and filtration, dose, source power, etc. Physical experimentation utilized an imaging bench simulating the scanner geometry for verification of theoretical results and investigation of other factors, such as antiscatter grid selection and 3D image quality in phantom and cadaver, including qualitative comparison to conventional CT. Results: Theoretical modeling and benchtop experimentation confirmed the basic suitability of the FPD and x-ray source mentioned above. Clinical requirements combined with analysis of MTF and DQE yielded the following system geometry: a {approx}55 cm source-to-detector distance; 1.3 magnification; a

  14. Improved Fuzzy C-Means based Particle Swarm Optimization (PSO) initialization and outlier rejection with level set methods for MR brain image segmentation.

    Science.gov (United States)

    Mekhmoukh, Abdenour; Mokrani, Karim

    2015-11-01

    In this paper, a new image segmentation method based on Particle Swarm Optimization (PSO) and outlier rejection combined with level set is proposed. A traditional approach to the segmentation of Magnetic Resonance (MR) images is the Fuzzy C-Means (FCM) clustering algorithm. The membership function of this conventional algorithm is sensitive to the outlier and does not integrate the spatial information in the image. The algorithm is very sensitive to noise and in-homogeneities in the image, moreover, it depends on cluster centers initialization. To improve the outlier rejection and to reduce the noise sensitivity of conventional FCM clustering algorithm, a novel extended FCM algorithm for image segmentation is presented. In general, in the FCM algorithm the initial cluster centers are chosen randomly, with the help of PSO algorithm the clusters centers are chosen optimally. Our algorithm takes also into consideration the spatial neighborhood information. These a priori are used in the cost function to be optimized. For MR images, the resulting fuzzy clustering is used to set the initial level set contour. The results confirm the effectiveness of the proposed algorithm.

  15. Maximizing Protein Translation Rate in the Ribosome Flow Model: The Homogeneous Case.

    Science.gov (United States)

    Zarai, Yoram; Margaliot, Michael; Tuller, Tamir

    2014-01-01

    Gene translation is the process in which intracellular macro-molecules, called ribosomes, decode genetic information in the mRNA chain into the corresponding proteins. Gene translation includes several steps. During the elongation step, ribosomes move along the mRNA in a sequential manner and link amino-acids together in the corresponding order to produce the proteins. The homogeneous ribosome flow model (HRFM) is a deterministic computational model for translation-elongation under the assumption of constant elongation rates along the mRNA chain. The HRFM is described by a set of n first-order nonlinear ordinary differential equations, where n represents the number of sites along the mRNA chain. The HRFM also includes two positive parameters: ribosomal initiation rate and the (constant) elongation rate. In this paper, we show that the steady-state translation rate in the HRFM is a concave function of its parameters. This means that the problem of determining the parameter values that maximize the translation rate is relatively simple. Our results may contribute to a better understanding of the mechanisms and evolution of translation-elongation. We demonstrate this by using the theoretical results to estimate the initiation rate in M. musculus embryonic stem cell. The underlying assumption is that evolution optimized the translation mechanism. For the infinite-dimensional HRFM, we derive a closed-form solution to the problem of determining the initiation and transition rates that maximize the protein translation rate. We show that these expressions provide good approximations for the optimal values in the n-dimensional HRFM already for relatively small values of n. These results may have applications for synthetic biology where an important problem is to re-engineer genomic systems in order to maximize the protein production rate.

  16. Non-equal-interval direct optimizing Verhulst model that x(n) be taken as initial value and its application

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    To overcome the deficiencies of the existing Verhulst GM(1,1) model, based on the existing grey theory, a non-equal-interval direct optimum Verhulst GM(1,1) model is built which chooses a modified n-th component x(n) of X(0) as the starting condition of the grey differential model. It optimizes a modified β value and the background value, and takes two times fitting optimization. The new model extends equal intervals to non-equal-intervals and is suitable for general data modelling and estimating parameters...

  17. Translator's preface.

    Science.gov (United States)

    Lamiell, James T

    2013-08-01

    Presents a preface from James T. Lamiell, who translates Wilhelm Wundt's Psychology's Struggle for Existence (Die Psychologie im Kampf ums Dasein), in which Wundt advised against the impending divorce of psychology from philosophy, into English. Lamiell comments that more than a decade into the 21st century, it appears that very few psychologists have any interest at all in work at the interface of psychology and philosophy. He notes that one clear indication of this is that the Society for Theoretical and Philosophical Psychology, which is Division 24 of the American Psychological Association (APA), remains one of the smallest of the APA's nearly 60 divisions. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  18. Intravascular ultrasound radiofrequency analysis after optimal coronary stenting with initial quantitative coronary angiography guidance: An ATHEROREMO sub-study

    NARCIS (Netherlands)

    G. Sarno (Giovanna); S.A. Garg (Scot); J. Gomez-Lara (Josep); H.M. Garcia-Garcia (Hector); J.M.R. Ligthart (Jürgen); N. Bruining (Nico); Y. Onuma (Yoshinobu); K. Witberg (Karen); R.J.M. van Geuns (Robert Jan); S.P.M. de Boer (Sanneke); J.J. Wykrzykowska (Joanna); C.J. Schultz (Carl); H.J. Duckers (Henricus); E.S. Regar (Eveline); P.P.T. de Jaegere (Peter); P.J. de Feyter (Pim); G.A. van Es (Gerrit Anne); H. Boersma (Eric); W.J. van der Giessen (Wim); P.W.J.C. Serruys (Patrick)

    2011-01-01

    textabstractAims: To investigate whether the use of intravascular ultrasound virtual histology (IVUS-VH) leads to any improvements in stent deployment, when performed in patients considered to have had an optimal percutaneous coronary intervention (PCI) by quantitative coronary angiography (QCA). Me

  19. On Feminist Translation Theory and Literary Translation

    Institute of Scientific and Technical Information of China (English)

    狄东睿

    2015-01-01

    Feminist translation theory emerged in the late 70s and early 80s of 20th Century. It is the combination of the feminist movement and the“cultural turn”of translation. It was introduced to China in the 1980s, and with the development of the transla⁃tion theory and translation practice, more and more Chinese translators want to study the feminist translation theory from the deep levels.

  20. Optimal production lot size and reorder point of a two-stage supply chain while random demand is sensitive with sales teams' initiatives

    Science.gov (United States)

    Sankar Sana, Shib

    2016-01-01

    The paper develops a production-inventory model of a two-stage supply chain consisting of one manufacturer and one retailer to study production lot size/order quantity, reorder point sales teams' initiatives where demand of the end customers is dependent on random variable and sales teams' initiatives simultaneously. The manufacturer produces the order quantity of the retailer at one lot in which the procurement cost per unit quantity follows a realistic convex function of production lot size. In the chain, the cost of sales team's initiatives/promotion efforts and wholesale price of the manufacturer are negotiated at the points such that their optimum profits reached nearer to their target profits. This study suggests to the management of firms to determine the optimal order quantity/production quantity, reorder point and sales teams' initiatives/promotional effort in order to achieve their maximum profits. An analytical method is applied to determine the optimal values of the decision variables. Finally, numerical examples with its graphical presentation and sensitivity analysis of the key parameters are presented to illustrate more insights of the model.

  1. Optimization of Initial pH and Total Sugar Concentration Variables on Citric Acid Production from Pineapple Waste with Aspergillus niger Yeast by Using Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Widayat Widayat

    2011-06-01

    Full Text Available Citric acid can be produced from pineapple waste by using fermentation process. This process is done in bubble column reactor with Aspergillus niger yeast. The objective of this research is to find the optimum conditions of initial pH and total sugar concentration. The optimization method used was response surface methodology. This research was carried out at a temperature of 30 oC, spore concentration of 1.23 x 109 spore/ml, total volume 2.0 liter, flow rate of air 58.07 cc/sec and a 5% antifoam concentration. The fermentation process lasted 7 days and the citric acid concentration was analyzed by High Pressure Liquid Cromatography (HPLC method. Statistica 6 software was used for the data treatment. The mathematical model for the optimization citric acid fermentation in bubble column reactor is Y = 54.507 + 2.9851X - 8.987X12 - 2.581X2 - 15.446X22 - 7.989X1X2 The parameter of Y is citric acid yield, X1 is a coding initial pH and X2 is a coding total sugar concentration. The results has given an initial pH optimum 3.61 and total sugar concentration 19,285% w/v with optimum an yield of 55.03 % . Keywords: Bubble column bioreactor, Citric acid fermentation, Initial pH, Total sugar concentration, Response surface methodology

  2. A community of practice for knowledge translation trainees: an innovative approach for learning and collaboration.

    Science.gov (United States)

    Urquhart, Robin; Cornelissen, Evelyn; Lal, Shalini; Colquhoun, Heather; Klein, Gail; Richmond, Sarah; Witteman, Holly O

    2013-01-01

    A growing number of researchers and trainees identify knowledge translation (KT) as their field of study or practice. Yet, KT educational and professional development opportunities and established KT networks remain relatively uncommon, making it challenging for trainees to develop the necessary skills, networks, and collaborations to optimally work in this area. The Knowledge Translation Trainee Collaborative is a trainee-initiated and trainee-led community of practice established by junior knowledge translation researchers and practitioners to: examine the diversity of knowledge translation research and practice, build networks with other knowledge translation trainees, and advance the field through knowledge generation activities. In this article, we describe how the collaborative serves as an innovative community of practice for continuing education and professional development in knowledge translation and present a logic model that provides a framework for designing an evaluation of its impact as a community of practice. The expectation is that formal and informal networking will lead to knowledge sharing and knowledge generation opportunities that improve individual members' competencies (eg, combination of skills, abilities, and knowledge) in knowledge translation research and practice and contribute to the development and advancement of the knowledge translation field.

  3. STUDY OF TOURY'S THREE NORMS OF TRANSLATION

    Institute of Scientific and Technical Information of China (English)

    刘星

    2008-01-01

    Norms can be expected to operate not only in transLation of all kinds,nut also at every stage in the translating event,and hence to be reflected on every level of its product.Gideon Toury's most famous research-Descriptive Translation Study introduces us three norms of translation-preliminary norms;initial norms;operational norms,which are of vital importance in the field of translation theory study.In this essay,the author illustrates them to Chinese readers.

  4. 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...

  5. The eukaryotic translation initiation factor 5, eIF-5, a protein from Zea mays, containing a zinc-finger structure, binds nucleic acids in a zinc-dependent manner.

    Science.gov (United States)

    López Ribera, I; Ruiz-Avila, L; Puigdomènech, P

    1997-07-18

    A maize cDNA encoding the eukaryotic translation initiation factor 5 (eIF-5) has been isolated from an 8-day-old seedling cDNA library. The 1975 bp cDNA encodes a protein of 451 amino acids, with a predicted molecular weight of 49.04 kDa, and hybridizes to a single sequence in the maize genome. The deduced sequence contains motifs characteristic of proteins belonging to the GPTase superfamily, a zinc finger well conserved in all the protein sequences for eIF-5 reported so far, and a fragment also present in prokaryotic and chloroplast L11 ribosomal protein. Polymer-binding assays have been used to assess the predicted RNA binding property of the protein and to characterize its function. It is shown that the eIF-5-encoded protein binds to single-stranded DNA and to polyuridylic acid and that the binding is dependent on the presence of Zn2+ ions. These results suggest that the zinc-finger structure is involved in the binding of the eIF-5 protein to RNA.

  6. 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.

  7. N1-Guanyl-1,7-Diaminoheptane Sensitizes Estrogen Receptor Negative Breast Cancer Cells to Doxorubicin by Preventing Epithelial-Mesenchymal Transition through Inhibition of Eukaryotic Translation Initiation Factor 5A2 Activation

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2015-08-01

    Full Text Available Background: Approximately 30% of breast cancer does not express the estrogen receptor (ER, which is necessary for endocrine-based therapy approaches. Many studies demonstrated that eukaryotic translation initiation factor 5A2 (eIF5A2 serves as a proliferation-related oncogene in tumorigenic processes. Methods: The present study used cell viability assays, EdU incorporation assays, western blot, and immunofluorescence to explore whether N1-guanyl-1,7-diaminoheptane (GC7, which inhibits eIF5A2 activation, exerts synergistic cytotoxicity with doxorubicin in breast cancer. Results: We found that GC7 enhanced doxorubicin cytotoxicity in ER-negative HCC1937 cells but had little effect in ER-positive MCF-7 and Bcap-37 cells. Administration of GC7 reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT in ER-negative breast cancer cells. Knockdown of eIF5A2 by siRNA inhibited the doxorubicin-induced EMT in ER-negative HCC1937 cells. Conclusion: These data demonstrated that GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in estrogen negative breast cancer cells by preventing EMT through inhibition of eIF5A2 activation.

  8. Knowledge translation of research findings

    Directory of Open Access Journals (Sweden)

    Grimshaw Jeremy M

    2012-05-01

    Full Text Available Abstract Background One of the most consistent findings from clinical and health services research is the failure to translate research into practice and policy. As a result of these evidence-practice and policy gaps, patients fail to benefit optimally from advances in healthcare and are exposed to unnecessary risks of iatrogenic harms, and healthcare systems are exposed to unnecessary expenditure resulting in significant opportunity costs. Over the last decade, there has been increasing international policy and research attention on how to reduce the evidence-practice and policy gap. In this paper, we summarise the current concepts and evidence to guide knowledge translation activities, defined as T2 research (the translation of new clinical knowledge into improved health. We structure the article around five key questions: what should be transferred; to whom should research knowledge be transferred; by whom should research knowledge be transferred; how should research knowledge be transferred; and, with what effect should research knowledge be transferred? Discussion We suggest that the basic unit of knowledge translation should usually be up-to-date systematic reviews or other syntheses of research findings. Knowledge translators need to identify the key messages for different target audiences and to fashion these in language and knowledge translation products that are easily assimilated by different audiences. The relative importance of knowledge translation to different target audiences will vary by the type of research and appropriate endpoints of knowledge translation may vary across different stakeholder groups. There are a large number of planned knowledge translation models, derived from different disciplinary, contextual (i.e., setting, and target audience viewpoints. Most of these suggest that planned knowledge translation for healthcare professionals and consumers is more likely to be successful if the choice of knowledge

  9. RACK1-mediated translation control promotes liver fibrogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Min; Peng, Peike; Wang, Jiajun [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Wang, Lan; Duan, Fangfang [Institute of Biomedical Science, Fudan University, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Ruan, Yuanyuan, E-mail: yuanyuanruan@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Institute of Biomedical Science, Fudan University, Shanghai 200032 (China)

    2015-07-31

    Activation of quiescent hepatic stellate cells (HSCs) is the central event of liver fibrosis. The translational machinery is an optimized molecular network that affects cellular homoeostasis and diseases, whereas the role of protein translation in HSCs activation and liver fibrosis is little defined. Our previous report suggests that up-regulation of receptor for activated C-kinase 1(RACK1) in HSCs is critical for liver fibrogenesis. In this study, we found that RACK1 promoted macrophage conditioned medium (MCM)-induced assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. RACK1 enhanced the translation and expression of pro-fibrogenic factors collagen 1α1, snail and cyclin E1 induced by MCM. Administration of PP242 or knock-down of eIF4E suppressed RACK1-stimulated collagen 1α1 production, proliferation and migration in primary HSCs. In addition, depletion of eIF4E attenuated thioacetamide (TAA)-induced liver fibrosis in vivo. Our data suggest that RACK1-mediated stimulation of cap-dependent translation plays crucial roles in HSCs activation and liver fibrogenesis, and targeting translation initiation could be a promising strategy for the treatment of liver fibrosis. - Highlights: • RACK1 induces the assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. • RACK1 stimulates the translation of collagen 1α1, snail and cyclin E1 in HSCs. • RACK1 promotes HSCs activation via cap-mediated translation. • Depletion of eIF4E suppresses liver fibrogenesis in vivo.

  10. Discovery and initial optimization of 5,5'-disubstituted aminohydantoins as potent beta-secretase (BACE1) inhibitors.

    Science.gov (United States)

    Nowak, Pawel; Cole, Derek C; Aulabaugh, Ann; Bard, Jonathan; Chopra, Rajiv; Cowling, Rebecca; Fan, Kristi Y; Hu, Baihua; Jacobsen, Steve; Jani, Minakshi; Jin, Guixan; Lo, Mei-Chu; Malamas, Michael S; Manas, Eric S; Narasimhan, Rani; Reinhart, Peter; Robichaud, Albert J; Stock, Joseph R; Subrath, Joan; Svenson, Kristine; Turner, Jim; Wagner, Erik; Zhou, Ping; Ellingboe, John W

    2010-01-15

    8,8-Diphenyl-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-amine (1) was identified through HTS, as a weak (micromolar) inhibitor of BACE1. X-Ray crystallographic studies indicate the 2-aminoimidazole ring forms key H-bonding interactions with Asp32 and Asp228 in the catalytic site of BACE1. Lead optimization using structure-based focused libraries led to the identification of low nanomolar BACE1 inhibitors such as 20b with substituents which extend from the S(1) to the S(3) pocket. Copyright 2009 Elsevier Ltd. All rights reserved.

  11. Deconstructive Reconsideration of Translation

    Institute of Scientific and Technical Information of China (English)

    刘艳清

    2014-01-01

    This paper is on the deconstructive reconsideration of the definition of translation, the relation of source text and translation, as well as the relation of translator and author. It also points out the differences between tranditioanal concepts of translation and deconstructive reconsideration of translation.

  12. On Becoming a Translator

    Institute of Scientific and Technical Information of China (English)

    王莹

    2015-01-01

    Douglas Robinson's Becoming a Translator:An Introduction to the Theory and Practice of Translation has been well received around the world.Fusing translation theory with advice and information about the practicalities of translating,it is an essential resource for novice and practicing translators.

  13. Translator Studies in Retrospect

    Institute of Scientific and Technical Information of China (English)

    郭勤

    2009-01-01

    The concern about translator has run for thousands of years on which many translators and translation scholars have made comments.A rough examination of the translator within translation studies at home and abroad is expounded in a loosely chronological way as follows.

  14. On Becoming a Translator

    Institute of Scientific and Technical Information of China (English)

    王莹

    2015-01-01

    Douglas Robinson’s Becoming a Translator:An Introduction to the Theory and Practice of Translation has been well received around the world.Fusing translation theory with advice and information about the practicalities of translating,it is an essential resource for novice and practicing translators.

  15. 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...

  16. Equivalence in Translation

    Institute of Scientific and Technical Information of China (English)

    李良杰

    2013-01-01

    There are many researches about translation theories and methods in western translation history. Equivalence in transla⁃tion has always been the central issue for discussion. This paper gives a general review and comment on equivalence in translation in terms of three representative translation theorists and their views about equivalence in translation.

  17. optimal control

    Directory of Open Access Journals (Sweden)

    L. I. Rozonoer

    1999-01-01

    Full Text Available Necessary and sufficient conditions for existence of optimal control for all initial data are proved for LQ-optimization problem. If these conditions are fulfilled, necessary and sufficient conditions of optimality are formulated. Basing on the results, some general hypotheses on optimal control in terms of Pontryagin's maximum condition and Bellman's equation are proposed.

  18. 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…

  19. Effect of the nucleotides surrounding the start codon on the translation of foot-and-mouth disease virus RNA.

    Science.gov (United States)

    Ma, X X; Feng, Y P; Gu, Y X; Zhou, J H; Ma, Z R

    2016-06-01

    As for the alternative AUGs in foot-and-mouth disease virus (FMDV), nucleotide bias of the context flanking the AUG(2nd) could be used as a strong signal to initiate translation. To determine the role of the specific nucleotide context, dicistronic reporter constructs were engineered to contain different versions of nucleotide context linking between internal ribosome entry site (IRES) and downstream gene. The results indicate that under FMDV IRES-dependent mechanism, the nucleotide contexts flanking start codon can influence the translation initiation efficiencies. The most optimal sequences for both start codons have proved to be UUU AUG(1st) AAC and AAG AUG(2nd) GAA.

  20. Translational Influence on Messenger Stability

    DEFF Research Database (Denmark)

    Eriksen, Mette

    , on messenger stability was examined. Depending on the translation initiation frequency, the chance of an initial ribosome trailing the RNA polymerase get better for better initiation sites, thus protecting transcription from termination by Rho. A polarity assay in which the activity of the downstream lac......A in the lac operon was measured, demonstrated that Rho dependent transcriptional pre-termination correlated with ribosome translation initiation frequency. It was further shown that Rho terminates RNA polymerases during transcription on messengers normally considered stable, suggesting Rho transcriptional pre...... pulls out the nascent transcript. Finally this thesis also focussed on the cell stress caused by an artificial and very strong RNA psudoknot used in a fusion gene. The technique of ribosomal foot printing and whole transcriptome deep sequencing was employed to facilitate an overview of the changes...

  1. 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....

  2. 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...... output and keystrokes were recorded. Oral and written translation data were examined in order to investigate if task times and translation quality differed in the three modalities. Although task times were found to be highest in written translation, the quality was not consistently better. In addition...

  3. Optimal nano-descriptors as translators of eclectic data into prediction of the cell membrane damage by means of nano metal-oxides.

    Science.gov (United States)

    Toropova, Alla P; Toropov, Andrey A; Benfenati, Emilio; Korenstein, Rafi; Leszczynska, Danuta; Leszczynski, Jerzy

    2015-01-01

    Systematization of knowledge on nanomaterials has become a necessity with the fast growth of applications of these species. Building up predictive models that describe properties (both beneficial and hazardous) of nanomaterials is vital for computational sciences. Classic quantitative structure-property/activity relationships (QSPR/QSAR) are not suitable for investigating nanomaterials because of the complexity of their molecular architecture. However, some characteristics such as size, concentration, and exposure time can influence endpoints (beneficial or hazardous) related to nanoparticles and they can therefore be involved in building a model. Application of the optimal descriptors calculated with the so-called correlation weights of various concentrations and different exposure times are suggested in order to build up a predictive model for cell membrane damage caused by a series of nano metal-oxides. The numerical data on correlation weights are calculated by the Monte Carlo method. The obtained results are in good agreement with the experimental data.

  4. Development of ultrafine-grained 1100 aluminum alloy by cryorolling with the optimized initial heat treatment conditions

    Science.gov (United States)

    Zakaria, Siti Aminah; Hussain, Zuhailawati; Seman, Anasyida Abu

    2016-07-01

    The aims of this study to determine the suitable initial heat treatment for 1100 aluminum alloy prior to cryorolling process and the properties of annealed and cryorolled annealed sample. The samples were annealed at different annealing temperature of 200˚C, 250˚C, 300˚C, 350˚C and 400˚C for 2 hours soaking time before cryorolling. The annealing samples then were cryorolled up to 50% thickness reduction after dipping in liquid nitrogen for 30 minutes. The effect of annealing temperature on cryorolled sample was investigated by employing hardness measurements and tensile test. The highest hardness and tensile properties achieved for sample annealed at 250 °C. The entire cryorolled sample showed severely deformed grain which are elongated along and following the rolling direction.

  5. [Breastfeeding (part one): Frequency, benefits and drawbacks, optimal duration and factors influencing its initiation and prolongation. Clinical guidelines for practice].

    Science.gov (United States)

    Chantry, A A; Monier, I; Marcellin, L

    2015-12-01

    The objectives were to on assess the frequency and the duration of breastfeeding in France. On the other hand, the objectives were to identify its benefits and drawbacks, and to study the factors influencing its initiation and its extension. Bibliographic research in Medline, Google Scholar and in the Cochrane Library. Breastfeeding concerns in France about 70% of children at birth (EL2). Its median duration is about 15 weeks and 3 weeks ½ for exclusive breastfeeding. At three months, only one third of children breastfed at birth are still being breastfed (EL2). Whether this is due to the composition of breast milk or the behavior of mothers with their children or their socio-cultural level, or even by all these components at once, breastfeeding is associated with better cognitive development children (EL2). This effect is even more reinforced that mothers breastfeed exclusively and prolonged (EL2). As part of the prevention of many diseases (ear infections, gastrointestinal infections, atopic diseases, obesity and cardiovascular diseases…), exclusive and prolonged breastfeeding (grade B) between 4 to 6 months is recommended (professional consensus). Breastfeeding is not a means of preventing postpartum depression (professional consensus). To reduce the incidence of breast cancer, prolonged breastfeeding is recommended (grade B). In order to increase the rate of initiation of breastfeeding as well as its duration, it is recommended that health professionals work closely with mothers in their project (grade A), the breastfeeding promotion messages include message to husbands (grade B), and to promote breastfeeding on demand without fixed interval between feedings (grade B). However, there is not enough data to recommend the use of a specific position during breastfeeding, or the use of one or two breast or to early start breastfeeding or not (professional consensus). Exclusive and extended breastfeeding is recommended (grade B) between 4 to 6 months (professional

  6. Evaluation of optimal number of soil samples for detail reconstruction of initial field of 137Cs fallout in Chernobyl affected areas

    Directory of Open Access Journals (Sweden)

    Maxim Ivanov

    2015-10-01

    Full Text Available A Chernobyl-derived 137Cs- fallout was associated with one or two rainfalls Because of that vast areas of the Europe affected by Chernobyl-derived fallout are characterized by non-uniform field of radionuclide contamination. It was assessed after detailed field investigation within few river basins of the Central Russia located in areas with different levels of Chernobyl contamination, that existing maps of radionuclide contamination composed during last two decades are not enough detailed for assessment of initial contamination field transformation by the lateral migration processes of the Chernobyl-derived 137Cs. This problem can be overcomed if additional soil sampling are undertaken in reference locations for correction of exiting radionuclide contamination maps. However it is necessary to evaluate the optimal number of bulk samples which should be taken in each sampling point for receiving statistically correct results of radionuclide concentration. Special investigation was undertaken in few catchments (S= 2-50 km2 of the Central Russia, located in areas with different levels of initial Chernobyl contamination, for evaluation the optimal number of samples, which should be taken in each sampling point for the determination of Cs-137 concentrations error not exceed 30 % on 95 % confidence level.

  7. SU-E-T-500: Initial Implementation of GPU-Based Particle Swarm Optimization for 4D IMRT Planning in Lung SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Modiri, A; Hagan, A; Gu, X; Sawant, A [UT Southwestern Medical Center, Dallas, TX (United States)

    2015-06-15

    Purpose 4D-IMRT planning, combined with dynamic MLC tracking delivery, utilizes the temporal dimension as an additional degree of freedom to achieve improved OAR-sparing. The computational complexity for such optimization increases exponentially with increase in dimensionality. In order to accomplish this task in a clinically-feasible time frame, we present an initial implementation of GPU-based 4D-IMRT planning based on particle swarm optimization (PSO). Methods The target and normal structures were manually contoured on ten phases of a 4DCT scan of a NSCLC patient with a 54cm3 right-lower-lobe tumor (1.5cm motion). Corresponding ten 3D-IMRT plans were created in the Eclipse treatment planning system (Ver-13.6). A vendor-provided scripting interface was used to export 3D-dose matrices corresponding to each control point (10 phases × 9 beams × 166 control points = 14,940), which served as input to PSO. The optimization task was to iteratively adjust the weights of each control point and scale the corresponding dose matrices. In order to handle the large amount of data in GPU memory, dose matrices were sparsified and placed in contiguous memory blocks with the 14,940 weight-variables. PSO was implemented on CPU (dual-Xeon, 3.1GHz) and GPU (dual-K20 Tesla, 2496 cores, 3.52Tflops, each) platforms. NiftyReg, an open-source deformable image registration package, was used to calculate the summed dose. Results The 4D-PSO plan yielded PTV coverage comparable to the clinical ITV-based plan and significantly higher OAR-sparing, as follows: lung Dmean=33%; lung V20=27%; spinal cord Dmax=26%; esophagus Dmax=42%; heart Dmax=0%; heart Dmean=47%. The GPU-PSO processing time for 14940 variables and 7 PSO-particles was 41% that of CPU-PSO (199 vs. 488 minutes). Conclusion Truly 4D-IMRT planning can yield significant OAR dose-sparing while preserving PTV coverage. The corresponding optimization problem is large-scale, non-convex and computationally rigorous. Our initial results

  8. RAN translation-What makes it run?

    Science.gov (United States)

    Green, Katelyn M; Linsalata, Alexander E; Todd, Peter K

    2016-09-15

    Nucleotide-repeat expansions underlie a heterogeneous group of neurodegenerative and neuromuscular disorders for which there are currently no effective therapies. Recently, it was discovered that such repetitive RNA motifs can support translation initiation in the absence of an AUG start codon across a wide variety of sequence contexts, and that the products of these atypical translation initiation events contribute to neuronal toxicity. This review examines what we currently know and do not know about repeat associated non-AUG (RAN) translation in the context of established canonical and non-canonical mechanisms of translation initiation. We highlight recent findings related to RAN translation in three repeat expansion disorders: CGG repeats in fragile X-associated tremor ataxia syndrome (FXTAS), GGGGCC repeats in C9orf72 associated amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and CAG repeats in Huntington disease. These studies suggest that mechanistic differences may exist for RAN translation dependent on repeat type, repeat reading frame, and the surrounding sequence context, but that for at least some repeats, RAN translation retains a dependence on some of the canonical translational initiation machinery. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.

  9. [Initial management of advanced ovarian cancer: What radiological, pathological and surgical information are important for optimal therapeutic strategy?].

    Science.gov (United States)

    Heudel, Pierre-Etienne; Selle, Frédéric; Morice, Philippe; Rouzier, Roman; Taieb, Sophie; Devouassoux-Shisheboran, Mojgan; Genestie, Catherine; Balleyguier, Corinne; Ray-Coquard, Isabelle

    2015-09-01

    Because the majority of patients present advanced disease at diagnosis, the management of epithelial ovarian cancer needs specialist multidisciplinary teamwork. Expertise in surgery, chemotherapy, imaging and histopathology is essential to achieve optimum outcomes. Computed tomography scans are routinely used to determine the extent of disease and to aid in surgical planning. The histologic classification is crucial to plan the best therapeutic strategy and to define the prognosis of disease. Pathological prognostic factors, such as degree of differentiation, FIGO-stage, and histological type have to be described. This report is fundamental to assessing prognosis and selection of appropriate treatment strategy. An adequate staging procedure is an extensive staging by an experienced gynecological oncologist, exploring the entire upper abdomen, and the pelvic and para-aortic lymph node regions to define the Peritoneal Cancer Index (PCI). The final assessment is the completeness of cytoreduction (CC) score, which is an assessment of residual disease after a maximal surgical effort. Initial management of advanced ovarian cancer is best provided by a specialist multidisciplinary team, including a radiologist, a pathologist, a gynecologic oncologist and a medical oncologist.

  10. Diminished capability to recognize the optimal temperature for sleep initiation may contribute to poor sleep in elderly people.

    Science.gov (United States)

    Raymann, Roy J E M; Van Someren, Eus J W

    2008-09-01

    Sleep propensity and skin temperature are functionally related. In young adults, changes of skin temperature within the comfortable thermoneutral zone affect sleep-onset latency and vigilance performance. Aging is associated with both decreased thermosensitivity and poorer sleep. Our goal was to test whether subtle manipulations of core body and skin temperature affect sleep onset in elderly people without sleep complaints and in elderly insomniacs and whether the subjective perception of these mild body temperature manipulations is preserved with aging and insomnia. In a 2-day semiconstant-routine protocol, 288 sleep-onset latencies were polysomnographically determined while manipulating core body and skin temperatures differentially in warm and cold directions within a comfortable thermoneutral range. Sleep laboratory of the Netherlands Institute for Neuroscience. Eight elderly subjects without sleep complaints (65.8 +/- 2.8 years, mean +/- SEM) and 8 elderly insomniacs (59.1 +/- 1.9 years). Warming the proximal skin by 0.4 degrees C facilitates sleep onset equally effective in healthy elderly (by 18% ie, by 1.84 minutes [95% confidence interval [CI], 0.76-2.92]) and elderly insomniacs (28%, 2.85 minutes [CI: 2.55-3.18]). These effects were comparable to the results in healthy young subjects, in spite of a marked decrease in the subjective perception of temperature changes in elderly subjects, especially in insomniacs. The findings show that mild changes in skin temperature have an effect on sleep propensity in elderly and indicate that elderly insomniacs may have a diminished capability to recognize that a slight increase in bed temperature facilitates the initiation or reinitiation of sleep.

  11. Corpora and Translator

    Institute of Scientific and Technical Information of China (English)

    傅丽莉

    2010-01-01

    @@ 1 Introduction Recent years have witnessed a significant growth of corpora heat. One of the many fields where corpora have a growing impact is translation, both at a descriptive and a practical level. Chesterman pointed out that the focus of Translation Studies shifted from translation itself to translators, from regulative to descriptive studies, from philosophical to empirical studies (Chesterman, 1998).

  12. Lost in Translation

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The intricacies of language still eludes even the most sophisticated technology IT is no surprise Jost Zetzsche,an English-to-German translator,raised the question of whether machine translation would ever replace the human variety in front of 700 interpreters and translators who gathered in San Francisco to discuss topical issues in the translation industry.

  13. Translators and Tools

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Technology is not yet advanced enough to capture the nuances of language It is no surprise Jost Zetzsche,an English-to-German translator,raised the question of whether machine translation would ever replace the human variety in front of 700 interpreters and translators who gathered in San Francisco to discuss topical issues in the translation industry.

  14. Lost in Translation

    Institute of Scientific and Technical Information of China (English)

    Ding Zhitao; Chen Wen

    2011-01-01

    IT is no surprise Jost Zetzsche,an English-to-German translator,raised the question of whether machine translation would ever replace the human variety in front of 700 interpreters and translators who gathered in San Francisco to discuss topical issues in the translation industry.

  15. Sound Effects in Translation

    DEFF Research Database (Denmark)

    Mees, Inger M.; Dragsted, Barbara; Gorm Hansen, Inge

    2015-01-01

    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...

  16. On translation equivalence

    Institute of Scientific and Technical Information of China (English)

    石雏凤

    2009-01-01

    Nida's translation theories, especially for his "Dynamic equivalence theory", are highly praised and adopted in Chinese translation circle. Howev-er, there are a lot of criticism and misunderstanding at the same time. This paper explores the issue on translation equivalence so as to benefit our translation studies on both theory and practice level.

  17. Optimization of Acidothermus Celluloyticus Endoglucanase (E1) Production in Transgenic Tobacco Plants by Transcriptional, Post-transcription and Post-Translational Modification

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Ziyu; Hooker, Brian S.; Quesenberry, Ryan D.; Thomas, S. R.

    2005-10-01

    Biochemical characteristics of Acidothermus cellulolyticus endoglucanase (E1) and its physiological effects in transgenic tobacco (Nicotiana tabacum) has been studied previously. In an attempt to obtain a high level of production of intact E1 in transgenic plants, the E1 gene was expressed under the control of strong Mac promoter (a hybrid promoter of manopine synthase promoter and cauliflower mosaic virus 35S promoter enhancer region) or tomato Rubisco small subunit (RbcS-3C) promoter with different 5’ untranslated leader (UTL) sequence and targeted to different subcellular comartmentations with various transit peptides. The expression of E1 protein in transgenic tobacco plants was determined via E1 activity, protein immunobloting, and RNA gel-blotting analyses. Effects of different transit peptides on E1 protein production and its stability were examined in transgenic tobacco plants carrying one of six transgene expression vectors with the same (Mac) promoter and transcription terminator (Tmas). Transgenic tobacco plants with apoplast transit peptide (Mm-apo) had the highest average E1 activity and protein accumulation , while E1 protein was more stable in transgenic plants with no transit peptide (Mm) than others. The E1 expression under tomato RbcS-3C promoter was higher than that under Mac promoter based on the average E1 activity, E1 protein accumulation, and RNA gel-blotting. The E1 expression was increased more than two fold when the 5’-UTL of alfalfa mosaic virus RNA4 gene replaced the UTL of RbcS-3C promoter, while the UTL of alfalfa mosaic virus RNA4 gene was less effective than the UTL of Mac promoter. The optimal combination of promoter, 5’-UTL, and subcellular compartmentation (transit peptide) for E1 protein production in transgenic tobacco plants are discussed.

  18. FACTORS REGULATING LIBERAL TRANSLATION

    Institute of Scientific and Technical Information of China (English)

    龚海红

    2012-01-01

    Literal translation and liberal translation are two important methods and both play key roles in translation.However,some textbooks say that most translations are literal translations while others maintain most are liberal ones,besides,some others suggest a combination of the two.This paper focuses on the facts that regulate liberal translation.Because of the differences in culture,society,history,geography,and so on,there exists a great difference between Chinese language and English language,which does naturally lead to the liberal translation.

  19. Some Major Steps to Translation and Translator

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Hojat Shamami

    2012-09-01

    Full Text Available This work is an overview of the main issues at the core of theorizing translation practice and the features of a good translator or how to be a good translator and of course what are the Skills to become a Freelance Translator and Translation process. In this world of science and technology there is knowledge explosion every day. This knowledge which is generally written in the English language needs to be transmitted in various languages so that people who do not know how to speak and write the original language can get the knowledge necessary for industrial development and technological innovation to keep up with the rest of the world. To transmit this knowledge effectively, there is a need for competent translators in various languages.

  20. Cultural Context and Translation

    Institute of Scientific and Technical Information of China (English)

    张敏

    2009-01-01

    cultural context plays an important role in translation. Because translation is a cross-culture activity, the culture context that influ-ences translating is consisted of both the culture contexts of source language and target language. This article firstly analyzes the concept of context and cultural context, then according to the procedure of translating classifies cultural context into two stages and talks about how they respectively influence translating.

  1. Stylistic Requirement for Translation

    Institute of Scientific and Technical Information of China (English)

    HOU Yin-zhen

    2016-01-01

    Stylistic research is subordinate to language use research. The fast maturing modern stylistics has greatly boosted trans-lation studies. Translation has a close relationship with stylistics. Many problems can be solved in translation practice by stylis-tic theories and analysis methods. Based on a brief introduction of stylistics and the relationship between stylistics and transla-tion, this paper will give a specific analysis of the stylistic requirement for translation.

  2. 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.

  3. Translation-coupling systems

    Energy Technology Data Exchange (ETDEWEB)

    Pfleger, Brian; Mendez-Perez, Daniel

    2015-05-19

    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.

  4. Translational Influence on Messenger Stability

    DEFF Research Database (Denmark)

    Eriksen, Mette

    , on messenger stability was examined. Depending on the translation initiation frequency, the chance of an initial ribosome trailing the RNA polymerase get better for better initiation sites, thus protecting transcription from termination by Rho. A polarity assay in which the activity of the downstream lac......-termination to be a global phenomena in gene regulation. The influence of codon usage in the early coding region on messenger stability was examined, in order to establish how fast or slow the ribosome has to decode the sequence for it to protect the messenger from degradation. The experiments demonstrated that very fast...

  5. Translation Theory 'Translated': Three Perspectives on Translation in Organizational Research

    DEFF Research Database (Denmark)

    Wæraas, Arild; Nielsen, Jeppe

    2016-01-01

    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 mo......, 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.......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...... 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...

  6. 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

  7. 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...

  8. contemporary translation studies and bible translation

    African Journals Online (AJOL)

    the source text to the translation process, the product and/or reception of ... The methodological impact was a shift from normative linguistic-based ... ary Society Period, with formal-equivalent translations being made by mis- ... the theoretical foundation of the functional-equivalent approach problem- ... After a review of.

  9. Unbiased Quantitative Models of Protein Translation Derived from Ribosome Profiling Data.

    Directory of Open Access Journals (Sweden)

    Alexey A Gritsenko

    2015-08-01

    Full Text Available Translation of RNA to protein is a core process for any living organism. While for some steps of this process the effect on protein production is understood, a holistic understanding of translation still remains elusive. In silico modelling is a promising approach for elucidating the process of protein synthesis. Although a number of computational models of the process have been proposed, their application is limited by the assumptions they make. Ribosome profiling (RP, a relatively new sequencing-based technique capable of recording snapshots of the locations of actively translating ribosomes, is a promising source of information for deriving unbiased data-driven translation models. However, quantitative analysis of RP data is challenging due to high measurement variance and the inability to discriminate between the number of ribosomes measured on a gene and their speed of translation. We propose a solution in the form of a novel multi-scale interpretation of RP data that allows for deriving models with translation dynamics extracted from the snapshots. We demonstrate the usefulness of this approach by simultaneously determining for the first time per-codon translation elongation and per-gene translation initiation rates of Saccharomyces cerevisiae from RP data for two versions of the Totally Asymmetric Exclusion Process (TASEP model of translation. We do this in an unbiased fashion, by fitting the models using only RP data with a novel optimization scheme based on Monte Carlo simulation to keep the problem tractable. The fitted models match the data significantly better than existing models and their predictions show better agreement with several independent protein abundance datasets than existing models. Results additionally indicate that the tRNA pool adaptation hypothesis is incomplete, with evidence suggesting that tRNA post-transcriptional modifications and codon context may play a role in determining codon elongation rates.

  10. Unbiased Quantitative Models of Protein Translation Derived from Ribosome Profiling Data.

    Science.gov (United States)

    Gritsenko, Alexey A; Hulsman, Marc; Reinders, Marcel J T; de Ridder, Dick

    2015-08-01

    Translation of RNA to protein is a core process for any living organism. While for some steps of this process the effect on protein production is understood, a holistic understanding of translation still remains elusive. In silico modelling is a promising approach for elucidating the process of protein synthesis. Although a number of computational models of the process have been proposed, their application is limited by the assumptions they make. Ribosome profiling (RP), a relatively new sequencing-based technique capable of recording snapshots of the locations of actively translating ribosomes, is a promising source of information for deriving unbiased data-driven translation models. However, quantitative analysis of RP data is challenging due to high measurement variance and the inability to discriminate between the number of ribosomes measured on a gene and their speed of translation. We propose a solution in the form of a novel multi-scale interpretation of RP data that allows for deriving models with translation dynamics extracted from the snapshots. We demonstrate the usefulness of this approach by simultaneously determining for the first time per-codon translation elongation and per-gene translation initiation rates of Saccharomyces cerevisiae from RP data for two versions of the Totally Asymmetric Exclusion Process (TASEP) model of translation. We do this in an unbiased fashion, by fitting the models using only RP data with a novel optimization scheme based on Monte Carlo simulation to keep the problem tractable. The fitted models match the data significantly better than existing models and their predictions show better agreement with several independent protein abundance datasets than existing models. Results additionally indicate that the tRNA pool adaptation hypothesis is incomplete, with evidence suggesting that tRNA post-transcriptional modifications and codon context may play a role in determining codon elongation rates.

  11. Taguchi Optimization on the Initial Thickness and Pre-aging of Nano-/Ultrafine-Grained Al-0.2 wt.%Sc Alloy Produced by ARB

    Science.gov (United States)

    Yousefieh, Mohammad; Tamizifar, Morteza; Boutorabi, Seyed Mohammad Ali; Borhani, Ehsan

    2016-10-01

    In this study, Taguchi design method with L9 orthogonal array has been used to optimize the initial thickness and pre-aging parameters (temperature and time) for the mechanical properties of Al-0.2 wt.% Sc alloy heavily deformed by accumulative roll bonding (ARB) up to ten cycles. Analysis of variance was performed on the measured data and signal-to-noise ratios. It was found that the pre-aging temperature has the most significant parameter affecting the mechanical properties by percentage contribution of 64.51%. Pre-aging time (19.29%) has the next most significant effect, while initial thickness (5.31%) has statistically less significant effect. In order to confirm experimental conclusions, verification experiments were carried out at optimum working conditions. Under these conditions, the yield strength was 6.51 times higher and toughness was 6.86% lower compared with the starting Al-Sc material. Moreover, mean grain size was decreased to 220 nm by setting the control parameters, which was the lowest value obtained in this study. It was concluded that the Taguchi method was found to be a promising technique to obtain the optimum conditions for such studies. Consequently, by controlling the parameter levels, the high-strength and high-toughness Al-Sc samples were fabricated through pre-aging and subsequent ARB process.

  12. 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....

  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. On Advertisement Language Translation

    Institute of Scientific and Technical Information of China (English)

    LI Ya-lu

    2015-01-01

    Advertisement language is a special practical writing with abundant imagination, great creativity and instigation. During translation the diversity in social culture, language and ethnic psychology, etc. will be directly reflected into its effect, presenting both the trouble in business of translators and also significant influences on the business brand. Starting from the features of adver⁃tisement language itself, this paper integrates translation situations and measures from several schools over the latest 20 years, gives typical examples in advertising translation and analyzes from varies perspectives and points out some problems in today ’s ad⁃vertisement translation,aiming to provide some constructive opinions for translation of advertisements.

  15. Film Name Translation

    Institute of Scientific and Technical Information of China (English)

    师晓晓

    2014-01-01

    <正>1.Introduction A good translation of the name should convey the information of the film and attract the audience’s desire for going to the cinema.Translation of film names should have business,information,culture,aesthetic features,while a short eye-catching name aims to leave the audience an unforgettable impression.This thesis discusses the translation of English film names from the aspects of the importance of English film name translation,principles for translating English film names and methods of English film name translation.

  16. Translation between representation languages

    Science.gov (United States)

    Vanbaalen, Jeffrey

    1994-01-01

    A capability for translating between representation languages is critical for effective knowledge base reuse. A translation technology for knowledge representation languages based on the use of an interlingua for communicating knowledge is described. The interlingua-based translation process consists of three major steps: translation from the source language into a subset of the interlingua, translation between subsets of the interlingua, and translation from a subset of the interlingua into the target language. The first translation step into the interlingua can typically be specified in the form of a grammar that describes how each top-level form in the source language translates into the interlingua. In cases where the source language does not have a declarative semantics, such a grammar is also a specification of a declarative semantics for the language. A methodology for building translators that is currently under development is described. A 'translator shell' based on this methodology is also under development. The shell has been used to build translators for multiple representation languages and those translators have successfully translated nontrivial knowledge bases.

  17. 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 translation would be. To provide a backdrop against which the issue may be discussed, I present an overview of the two areas which seem most likely to hold potential answers, viz., that of translation theory and that of quality management. Section 1. gives a brief outline of some contributions to translation...... theory which would seem likely to be of interest in this connection and section 2. gives a linguist's introduction to the part of the area of quality management which I consider relevant for present purposes. Section 3. is devoted to the case study of a small translation firm which has been certified...

  18. Accommodating Translational Research

    Science.gov (United States)

    Giles, Howard

    2008-01-01

    This is an article in a series illustrating the way scholars in communication have pursued translating their research into practice. The translational nature of communication accommodation theory and examples of its application are the focus of this contribution.

  19. 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....

  20. Stylistics in Translation Teaching.

    Science.gov (United States)

    Malmkjaer, Kirsten

    1994-01-01

    Suggests that trainee translators can be helped to move between the basic and advanced stages of training through practice in collocational translational stylistics. Describes the method and outlines its differences from monolingual stylistics. Illustrates the method with an example. (HB)

  1. 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.

  2. 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.

  3. Bssiness Correspondence Translation

    Institute of Scientific and Technical Information of China (English)

    徐静

    2009-01-01

    It is widely-acknowtedged that business correspondence works as a bridge between the writer and the reader.Taking its characteristics into consideration,this essay illustrates how to do business correspondence translation.Only by abiding by all those fcatures can the translator achieve the aim of translation.

  4. Translation is Art

    Institute of Scientific and Technical Information of China (English)

    苟婧妤

    2004-01-01

    This paper focuses on the art in translation.First,the translation and art are defined and some historic views are illustrated.Then the author lays emphasis on how to convey the artistic information and provides some methods on how to achieve artistic effect in translation.

  5. Metaphor and Translation

    Institute of Scientific and Technical Information of China (English)

    坎曼丽·麦麦提; 朱毅

    2015-01-01

    In this paper, the author first analyzed the nature of metaphor and difficulties in metaphor translation, displayed the fac-tors that will influence the translation between English and Chinese metaphors, and then explored the metaphor translation strate-gies by taking some English and Chinese idioms as examples.

  6. Found in Translation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The 18th World Congress of the International Federation of Translators(FIT) is bound to increase China’s international exposure.Shortly before the congress,Guo Xiaoyong,Executive Vice President of the Translators Association of China(TAC),spoke to Beijing Review about his expectations for the event and his evaluation of translation and interpretation services in China.

  7. Using Pragmatic in Translation

    Institute of Scientific and Technical Information of China (English)

    井琳

    2013-01-01

    Translating process is coordination of the source language and target language. As the source language and translation language readers are in different cultural background, so their understanding of the environment is different. When the translator express their understanding in the receptor language, he must figure out the best relevance between source language and target language, which can achieve pragmatic equivalence.

  8. New insight into translation during yeast programmed cell death

    OpenAIRE

    Silva, Maria Alexandra Oliveira da

    2012-01-01

    Tese de doutoramento em Ciências da Saúde Global mRNA translation impairment has been described during the course of apoptosis in both mammalian and yeast. Nevertheless, the molecular pathways modulating translation during different scenarios of yeast apoptosis are still largely unexplored. Here we show by polysome profile analysis an impairment in capdependent translation initiation, correlated with alterations in translation machinery, such as the decrease in eIF4A levels ...

  9. Advanced Understanding of Convection Initiation and Optimizing Cloud Seeding by Advanced Remote Sensing and Land Cover Modification over the United Arab Emirates

    Science.gov (United States)

    Wulfmeyer, V.; Behrendt, A.; Branch, O.; Schwitalla, T.

    2016-12-01

    A prerequisite for significant precipitation amounts is the presence of convergence zones. These are due to land surface heterogeneity, orography as well as mesoscale and synoptic scale circulations. Only, if these convergence zones are strong enough and interact with an upper level instability, deep convection can be initiated. For the understanding of convection initiation (CI) and optimal cloud seeding deployment, it is essential that these convergence zones are detected before clouds are developing in order to preempt the decisive microphysical processes for liquid water and ice formation. In this presentation, a new project on Optimizing Cloud Seeding by Advanced Remote Sensing and Land Cover Modification (OCAL) is introduced, which is funded by the United Arab Emirates Rain Enhancement Program (UAEREP). This project has two research components. The first component focuses on an improved detection and forecasting of convergence zones and CI by a) operation of scanning Doppler lidar and cloud radar systems during two seasonal field campaigns in orographic terrain and over the desert in the UAE, and b) advanced forecasting of convergence zones and CI with the WRF-NOAHMP model system. Nowcasting to short-range forecasting of convection will be improved by the assimilation of Doppler lidar and the UAE radar network data. For the latter, we will apply a new model forward operator developed at our institute. Forecast uncertainties will be assessed by ensemble simulations driven by ECMWF boundaries. The second research component of OCAL will study whether artificial modifications of land surface heterogeneity are possible through plantations or changes of terrain, leading to an amplification of convergence zones. This is based on our pioneering work on high-resolution modeling of the impact of plantations on weather and climate in arid regions. A specific design of the shape and location of plantations can lead to the formation of convergence zones, which can

  10. OVERVIEW OF TRANSLATION- JAHIZ

    Directory of Open Access Journals (Sweden)

    Dr. Yuslina Mohamed

    2015-01-01

    Full Text Available This research tries to contrive Jahiz's stands and ideas in translation which he has discussed in his two books named "Al-Bayan Wal-Tabyeen" and "Al-Haiwan". As it was known this issue of translation was emergence since long period of time, and there was no need toward translation, however, after Arabian and Persian assembled with Greek philosophers had increasingly the need and concerned on Religion Sciences and others, for instances: Mathematics, Medicine, Logic, Engineering, Business and others which were existed during that time. The translation movement had gone by several stages in the different periods and being developed during Abassid period for example, the works of "Hanen Ibn Ishaq" and his own school which the translators had faced difficulties and problems in their translation. To summarize, this research has found a number of results that the "Jahiz" was precedence than others who had stated the conditions of translation before 12th century ago. Besides, these conditions appropriate till nowadays, he had also pointed these conditions cannot be applied in translation of literature texts and holy texts because its might be obliterated the savoir faire. "Jahiz" had looked through this issue seriously, he tried to help translators in this area and he had stated in his famous books the conditions of translation and he had given his ideas toward translation benefited from his previous experience in translation the ancient philosopher's books from Persian to Arabic. Though, the readers could benefit his ideas in translation generally and for the translator specifically, also his books became as a heritage references and cannot be neglected at all in translation work.

  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. A Writer, a Translator and a Translator

    OpenAIRE

    Katarina Marinčič

    2015-01-01

    The article deals with the French translation of the short story Amy by the Slovenian writer Mira Mihelič, made by Elza Jereb for the anthology Nouvelles slovènes (Paris, 1969). The original text, a classical narrative involving some modernist strategies, presents a syntactical feature rather unusual in Slovenian (although typical of the author Mira Mihelič): a very frequent use of participles and participial structures. Elza Jereb’s translation is accurate and precise, preserving not only th...

  13. 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.

  14. 霍乱毒素A基因内部翻译调控元件具有翻译起始功能%Translation Initiation Function of the Regulation Element in the Operon of Cholera Toxin A

    Institute of Scientific and Technical Information of China (English)

    曹诚; 李平; 李杰之; 石成华; 马清钧

    2000-01-01

    To demonstrate that there existed translation coupling between cholera toxin A subunit gene and B subunit gene, and give the answer why the expression level of B gene is five times more than that of A gene, α report system for the investigation of translation coupling was constructed by using lacZ gene as reporter. Frame-shift mutation was introduced near the C terminal of ctxA gene, and the ribosome would read through its normal stop codon. The report plasmid was constructed and it was found that the expression level of lacZ gene decreased five times after the frame-shift mutation. The translation of cholera toxin B subunit gene was translational coupled with A subunit gene, and was responsible for the differential expression level of the two genes.%通过大肠杆菌体外转录-体外翻译系统,证明霍乱毒素A基因内部的翻译调控元件具有翻译起始功能,且其翻译起始效率较ctxA基因高得多.当ctxA的起始密码突变时,从该元件起始的翻译效率下降,说明基因内翻译起始效率受ctxA翻译起始的调控。结果进一步证实了霍乱毒素A、B亚基比例表达调控的翻译弱化-翻译偶联机理。

  15. Foreignizing Translation and Domesticating Translation of Hong Kong Movie Titles

    Institute of Scientific and Technical Information of China (English)

    林慧韵

    2014-01-01

    Generally,the movie title translation strategy would be divided into two:domesticating translation strategy and foreignizing translation strategy.The movie title translation in Hong Kong is chosen to be the material for the analysis of the domesticating translation strategy and foreignizing translation strategy,compared with that of Mainland China.

  16. On Peter Newmark’s Semanic Translation & Communicative Translation

    Institute of Scientific and Technical Information of China (English)

    LI Xin; ZHANG Zhe

    2015-01-01

    Peter Newmark has written many preeminent works on translation theory. He classifies the translation texts into differ⁃ent types,and puts forward his great translation methods-communiative translation and semantic translation. This paper is aimed to explain the creative work by Peter Nwmark in the translation theory.

  17. Text Type and Translation Strategy

    Institute of Scientific and Technical Information of China (English)

    刘福娟

    2015-01-01

    Translation strategy and translation standards are undoubtedly the core problems translators are confronted with in translation. There have arisen many kinds of translation strategies in translation history, among which the text type theory is considered an important breakthrough and a significant complement of traditional translation standards. This essay attempts to demonstrate the value of text typology (informative, expressive, and operative) to translation strategy, emphasizing the importance of text types and their communicative functions.

  18. 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

  19. 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.

  20. 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....

  1. Translation domains in multiferroics

    OpenAIRE

    Meier, D; Leo, N; Jungk, T.; Soergel, E.; Becker, P.; Bohaty, L.; Fiebig, M.

    2010-01-01

    Translation domains differing in the phase but not in the orientation of the corresponding order parameter are resolved in two types of multiferroics. Hexagonal (h-) YMnO$_3$ is a split-order-parameter multiferroic in which commensurate ferroelectric translation domains are resolved by piezoresponse force microscopy whereas MnWO$_4$ is a joint-order-parameter multiferroic in which incommensurate magnetic translation domains are observed by optical second harmonic generation. The pronounced ma...

  2. Relevance Theory in Translation

    Institute of Scientific and Technical Information of China (English)

    Shao Jun; Jiang Min

    2008-01-01

    In perspective of relevance theory, translation is regarded as communication. According to relevance theory, communication not only requires encoding, transfer and decoding processes, but also involves inference in addition. As communication, translation decision-making is also based on the human beings' inferential mental faculty. Concentrating on relevance theory, this paper tries to analyze and explain some translation phenomena in two English versions of Cai Gen Tan-My Crude Philosophy of Life.

  3. Transliteration in EST Translation

    Institute of Scientific and Technical Information of China (English)

    王新然

    2016-01-01

    Firstly, this paper presents the definition of transliteration and its important position in EST translation. Secondly, in terms of the previous practice and experience in EST translation, four main transliteration techniques are concluded and analyzed. But meanwhile, there are still some negative issues and phenomena. As a result, it is worthy to make good use of the existing transliteration techniques and create more proper ones to remove the obstructions and promote the development of EST translation.

  4. 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.

  5. 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.

  6. Knowledge Translation in Audiology

    Science.gov (United States)

    Kothari, Anita; Bagatto, Marlene P.; Seewald, Richard; Miller, Linda T.; Scollie, Susan D.

    2011-01-01

    The impetus for evidence-based practice (EBP) has grown out of widespread concern with the quality, effectiveness (including cost-effectiveness), and efficiency of medical care received by the public. Although initially focused on medicine, EBP principles have been adopted by many of the health care professions and are often represented in practice through the development and use of clinical practice guidelines (CPGs). Audiology has been working on incorporating EBP principles into its mandate for professional practice since the mid-1990s. Despite widespread efforts to implement EBP and guidelines into audiology practice, gaps still exist between the best evidence based on research and what is being done in clinical practice. A collaborative dynamic and iterative integrated knowledge translation (KT) framework rather than a researcher-driven hierarchical approach to EBP and the development of CPGs has been shown to reduce the knowledge-to-clinical action gaps. This article provides a brief overview of EBP and CPGs, including a discussion of the barriers to implementing CPGs into clinical practice. It then offers a discussion of how an integrated KT process combined with a community of practice (CoP) might facilitate the development and dissemination of evidence for clinical audiology practice. Finally, a project that uses the knowledge-to-action (KTA) framework for the development of outcome measures in pediatric audiology is introduced. PMID:22194314

  7. Optimizing Clinical Operations as part of a Global Emergency Medicine Initiative in Kumasi, Ghana: Application of Lean Manufacturing Principals to Low Resource Health Systems

    Science.gov (United States)

    Carter, Patrick M.; Desmond, Jeffery S.; Akanbobnaab, Christopher; Oteng, Rockefeller A.; Rominski, Sarah; Barsan, William G.; Cunningham, Rebecca

    2012-01-01

    Background Although many global health programs focus on providing clinical care or medical education, improving clinical operations can have a significant effect on patient care delivery, especially in developing health systems without high-level operations management. Lean manufacturing techniques have been effective in decreasing emergency department (ED) length of stay, patient waiting times, numbers of patients leaving without being seen, and door-to-balloon times for ST-elevation myocardial infarction in developed health systems; but use of Lean in low to middle income countries with developing emergency medicine systems has not been well characterized. Objectives To describe the application of Lean manufacturing techniques to improve clinical operations at Komfo Anokye Teaching Hospital in Ghana and to identify key lessons learned to aid future global EM initiatives. Methods A three-week Lean improvement program focused on the hospital admissions process at Komfo Anokye Teaching Hospital was completed by a 14-person team in six stages: problem definition, scope of project planning, value stream mapping, root cause analysis, future state planning, and implementation planning. Results The authors identified eight lessons learned during our use of Lean to optimize the operations of an ED in a global health setting: 1) the Lean process aided in building a partnership with Ghanaian colleagues; 2) obtaining and maintaining senior institutional support is necessary and challenging; 3) addressing power differences among the team to obtain feedback from all team members is critical to successful Lean analysis; 4) choosing a manageable initial project is critical to influence long-term Lean use in a new environment; 5) data intensive Lean tools can be adapted and are effective in a less resourced health system; 6) several Lean tools focused on team problem solving techniques worked well in a low resource system without modification; 7) using Lean highlighted that

  8. Optimizing clinical operations as part of a global emergency medicine initiative in Kumasi, Ghana: application of Lean manufacturing principals to low-resource health systems.

    Science.gov (United States)

    Carter, Patrick M; Desmond, Jeffery S; Akanbobnaab, Christopher; Oteng, Rockefeller A; Rominski, Sarah D; Barsan, William G; Cunningham, Rebecca M

    2012-03-01

    Although many global health programs focus on providing clinical care or medical education, improving clinical operations can have a significant effect on patient care delivery, especially in developing health systems without high-level operations management. Lean manufacturing techniques have been effective in decreasing emergency department (ED) length of stay, patient waiting times, numbers of patients leaving without being seen, and door-to-balloon times for ST-elevation myocardial infarction in developed health systems, but use of Lean in low to middle income countries with developing emergency medicine (EM) systems has not been well characterized. To describe the application of Lean manufacturing techniques to improve clinical operations at Komfo Anokye Teaching Hospital (KATH) in Ghana and to identify key lessons learned to aid future global EM initiatives. A 3-week Lean improvement program focused on the hospital admissions process at KATH was completed by a 14-person team in six stages: problem definition, scope of project planning, value stream mapping, root cause analysis, future state planning, and implementation planning. The authors identified eight lessons learned during our use of Lean to optimize the operations of an ED in a global health setting: 1) the Lean process aided in building a partnership with Ghanaian colleagues; 2) obtaining and maintaining senior institutional support is necessary and challenging; 3) addressing power differences among the team to obtain feedback from all team members is critical to successful Lean analysis; 4) choosing a manageable initial project is critical to influence long-term Lean use in a new environment; 5) data intensive Lean tools can be adapted and are effective in a less resourced health system; 6) several Lean tools focused on team problem-solving techniques worked well in a low-resource system without modification; 7) using Lean highlighted that important changes do not require an influx of resources; and

  9. Cultural bridge: translation

    Institute of Scientific and Technical Information of China (English)

    易菲

    2009-01-01

    In recent years, many researchers study on the relation between culture and language, language and translation, or culture and translation. Indeed, the three subjects are inseparable. It's incomprehensive to look into just two of them for a linguist. It's more useful for us to study on the relation between them, because we can extend our eyesight and searching scope and propel our translation business. Moreover, studying on them provides a rich material for other fields, such as sociology, translation, cross-cultural communication as well as give other subjects a lead to deep further.

  10. Translational research in neuroanaesthesia

    Directory of Open Access Journals (Sweden)

    Ganne S Umamaheswara Rao

    2014-01-01

    Full Text Available Translational research in anaesthesia provided great solutions to medicine, well beyond its scope, in the past. Exciting opportunities exist for neuroanaesthesiologists to conduct translational research not just in anaesthesia alone but in the wider realm of neurosciences. This research is expected to provide solutions to clinical neuroscience questions and to help understand some of the complex neurocognitive functions. Despite several technical developments, progress in translational sciences has been rather slow in the recent years. Re-orientation of the research programmes to a translational format with the involvement of all the stakeholders is likely to conserve the cost and provide rapid solutions to the healthcare.

  11. Feminist Translation in China

    Institute of Scientific and Technical Information of China (English)

    韩伟

    2008-01-01

    Feminist translation studies have underg one rapid development in China in recent years.However,most of its research rema ins on the inquiry of the influence on the theoretical layer.In this thesis,I tr y to probe carefully into the translation of "Men and Women,Women and the City" done by Zhu Hong in an attempt to find out wh at is the difference that exits in the translation between the Chinese female tr anslators and the western feminist translators.

  12. 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 with...... without undermining basic exploratory research and academic freedom.......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...

  13. Trusted Translation Services

    Science.gov (United States)

    Atif, Yacine; Serhani, Mohamed Adel; Campbell, Piers; Mathew, Sujith Samuel

    Administering multilingual Web sites and applications reliably, involves interconnected and multipart tasks, where trust in the involved parties and content translation sources is paramount. Published Web sites may reflect content from databases, content management systems and other repositories to manage related Web content. But a Web site mirrored wholly or selectively onto a target language version requires streamlined trusted processes. Traditionally, files are translated and transferred via FTP, e-mail, or other communication means. Similarly, translation instructions are communicated between involved parties through verbal instruction, e-mail, and instruction files lead to a variety of inconsistencies and lack of trust in the translation process. This paper proposes a Web service approach to streamline the translation processes and an integration of trust properties in the proposed translation Web services. Web Services have been instrumental in handling problems inherent to systems integration, allowing web-based systems to converse and communicate data automatically. The OASIS Translation Web Services Technical Committee has released a standard way for Web Services to serve the translation and localization business. This article proposes a framework to centralize translation services at a reputable source providing a workflow and a mechanism to quantify service trust. An implementation of the framework is also described in the context of a localization case study.

  14. 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.

  15. Translating the Untranslatable

    Institute of Scientific and Technical Information of China (English)

    WANG Jie; WANG Ping

    2015-01-01

    Translations contribute to our knowledge and understanding in various fields of daily life, as they open us to a greater awareness of the world in which we live. The deeper we are delved into the meaning of the translation, the more questions are raised, among which, translatable/untranslatable argument strikes the most. In this article, factors including cultural vocabulary va⁃cancy and different image associations leading to temporary untranslatability are presented. Besides, the strategies to change this situation to relatively translatable are given as well.

  16. Study on C-E Translation of Advertisements Based on Relevance Theory

    Institute of Scientific and Technical Information of China (English)

    蔡琮瑶

    2014-01-01

    The main errors in translating Chinese advertisements into English are pragmatic failures in which target-language readers fail to find the optimal relevance between the target text and source text.The translation strategies proposed under the guidance of Relevance Theory can effectively help translators find out optimal relevance in the process of translating Chinese ad-vertisements into English to avoid pragmatic failures .

  17. sST2 translation is regulated by FGF2 via an hnRNP A1-mediated IRES-dependent mechanism.

    Science.gov (United States)

    Kunze, Michael M; Benz, Fabienne; Brauß, Thilo F; Lampe, Sebastian; Weigand, Julia E; Braun, Johannes; Richter, Florian M; Wittig, Ilka; Brüne, Bernhard; Schmid, Tobias

    2016-07-01

    Translation is an energy-intensive process and tightly regulated. Generally, translation is initiated in a cap-dependent manner. Under stress conditions, typically found within the tumor microenvironment in association with e.g. nutrient deprivation or hypoxia, cap-dependent translation decreases, and alternative modes of translation initiation become more important. Specifically, internal ribosome entry sites (IRES) facilitate translation of specific mRNAs under otherwise translation-inhibitory conditions. This mechanism is controlled by IRES trans-acting factors (ITAF), i.e. by RNA-binding proteins, which interact with and determine the activity of selected IRESs. We aimed at characterizing the translational regulation of the IL-33 decoy receptor sST2, which was enhanced by fibroblast growth factor 2 (FGF2). We identified and verified an IRES within the 5'UTR of sST2. Furthermore, we found that MEK/ERK signaling contributes to FGF2-induced, sST2-IRES activation and translation. Determination of the sST2-5'UTR structure by in-line probing followed by deletion analyses identified 23 nucleotides within the sST2-5'UTR to be required for optimal IRES activity. Finally, we show that the RNA-binding protein heterogeneous ribonucleoprotein A1 (hnRNP A1) binds to the sST2-5'UTR, acts as an ITAF, and thus controls the activity of the sST2-IRES and consequently sST2 translation. Specifically, FGF2 enhances nuclear-cytoplasmic translocation of hnRNP A1, which requires intact MEK/ERK activity. In summary, we provide evidence that the sST2-5'UTR contains an IRES element, which is activated by a MEK/ERK-dependent increase in cytoplasmic localization of hnRNP A1 in response to FGF2, enhancing the translation of sST2.

  18. Optimized Method of Aircraft Initial Spares Variety Based on Set Pair Analysis and Rough Set%飞机初始备件品种优化的集对-粗糙集方法

    Institute of Scientific and Technical Information of China (English)

    车飞; 陈云翔

    2011-01-01

    飞机初始备件品种的确定是飞机初始使用和维修工作的必要条件.本文针对初始备件品种影响因素信息不完备的特点,依据集对分析方法在系统中的某一特性上具有同异反定量刻画的优势,结合经典粗糙集理论,提出初始备件品种优化的集对-粗糙集方法,最终得到初始备件品种优化的决策规则.实例计算表明,该方法能够为军方优化初始备件清单提供科学合理的决策.%Determine the variety of aircraft initial spares is essential condition for initial use and maintenance. Aimed at the characteristic of incomplete information for initial spares variety factors, according to the set pair analysis(SPA), which have the advantage of rational depict identity-discrepancy-contrary in unsure system about certain specialty, and combined with the classical rough set theory, the paper put forward the optimized method of initial spares variety, and obtained optimal decision rules finally. Example showed that the method can provide scientific and rational decision-making for the military optimized the initial spares list.

  19. Influence of Cultural Differences on Advertisement Translation and Trademark Translation

    Institute of Scientific and Technical Information of China (English)

    于晓玮

    2014-01-01

    Advertisement translation and trademark translation are becoming more and more prevailing and influential under the increasing development of internationalization of business. This paper attempts to analyze the influence of cultural differences on advertisement translation and trademark translation. It finds that advertisement translation and trademark translation are under the impressive influence of the differences between Chinese and Western cultures. This paper aims to stress the cultural differences in advertisement translation and trademark translation and reminds translators of the importance of noticing cultural differences and finding a proper point between foreign cultures and native cultures.

  20. Translation as Literary Criticism.

    Science.gov (United States)

    di Stefano, B. Follkart

    1982-01-01

    It is proposed that literary translation is intrinsically an act of literary criticism. This theory is illustrated by discussion of specific problems in translating Sartre's "La Nausee" and Leonard Forest's "Le pays de la Sagouine," especially the use of verb tense. (MSE)

  1. Translations and dynamics

    CERN Document Server

    Tresguerres, Romualdo

    2007-01-01

    We analyze the role played by local translational symmetry in the context of gauge theories of fundamental interactions. Translational connections and fields are introduced, with special attention being paid to their universal coupling to other variables, as well as to their contributions to field equations and to conserved quantities.

  2. Text Coherence in Translation

    Science.gov (United States)

    Zheng, Yanping

    2009-01-01

    In the thesis a coherent text is defined as a continuity of senses of the outcome of combining concepts and relations into a network composed of knowledge space centered around main topics. And the author maintains that in order to obtain the coherence of a target language text from a source text during the process of translation, a translator can…

  3. 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…

  4. 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…

  5. 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…

  6. Translational Health Economics

    NARCIS (Netherlands)

    Rogowski, Wolf; John, Jürgen; IJzerman, Maarten; 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

  7. 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...

  8. Translation as Literary Criticism.

    Science.gov (United States)

    di Stefano, B. Follkart

    1982-01-01

    It is proposed that literary translation is intrinsically an act of literary criticism. This theory is illustrated by discussion of specific problems in translating Sartre's "La Nausee" and Leonard Forest's "Le pays de la Sagouine," especially the use of verb tense. (MSE)

  9. Culture Difference and Translation

    Institute of Scientific and Technical Information of China (English)

    何冬兰

    2012-01-01

    Culture difference is necessary to be paid attention to during the process of translating.Culture difference is caused by different history,regions,customs,religions and the modes of thinking.Having the awareness of the culture difference will make translation more accurate and successful.

  10. Lost in Translation?

    NARCIS (Netherlands)

    Jonkers, Peter

    2017-01-01

    Translating sacred scriptures is not only a praxis that is crucial for the fruitful, i.e. non-distorted and unbiased dialogue between different religious traditions, but also raises some fundamental theoretical questions when it comes to translating the sacred texts of the religious other or

  11. 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))...

  12. 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))...

  13. Terminology, a Translational Discipline.

    Science.gov (United States)

    Ahrens, Helga

    1994-01-01

    Discusses the importance of qualified terminology and its implications for terminological activity. Argues that students have to learn how to organize their terminological activity. Suggests that translation is a special kind of intercultural communication and is an indispensable part of translational action. Argues that terminology be examined…

  14. Translation between cultures

    Directory of Open Access Journals (Sweden)

    Henrique de Oliveira Lee

    2016-08-01

    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.

  15. Translations toward Connected Mathematics

    Science.gov (United States)

    Applebaum, Mark; Leikin, Roza

    2010-01-01

    The translation principle allows students to solve problems in different branches of mathematics and thus to develop connectedness in their mathematical knowledge. Successful application of the translation principle depends on the classroom mathematical norms for the development of discussions and the comparison of different solutions to one…

  16. A CASE FOR TRANSLATION.

    Science.gov (United States)

    THORNTON-SMITH, C.B.

    MOST OF THE CRITICISMS OF TRANSLATION IN SECONDARY SCHOOL LANGUAGE COURSES FOCUS ON THE SUPPOSEDLY DIFFICULT PROBLEMS OF SELECTING, USING, AND GRADING TRANSLATION TESTS AS OPPOSED TO THE OBJECTIVE TESTS GENERALLY USED BY ADVOCATES OF AUDIOLINGUALISM. BUT MOST OF THESE CRITICISMS FAIL TO RECOGNIZE THAT THE PROCESS OF LEARNING A FOREIGN LANGUAGE…

  17. 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…

  18. 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…

  19. 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…

  20. An Analysis of the English Translation of Xi JinPing:The Governance Of China-From The Perspective of Toury’s Translation Norms

    Institute of Scientific and Technical Information of China (English)

    XUE Zhong

    2016-01-01

    Xi Jinping:The Governance of China is of great significance in asserting to the world the fundamental policies and state-craft of CPC. Its English translation is analyzed on the basis of Toury’s translation norm theory, which guide and regulate all the processes in the translation activities. Based on preliminary norms, initial norms and initial norms, factors influencing the choice of source text, the attitude of translators as well as the specific translation strategies in the translation activity are explored with detailed cases.