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

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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.
Silibinin inhibits translation initiation: implications for anticancer therapy.

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Lin, Chen-Ju; Sukarieh, Rami; Pelletier, Jerry

2009-06-01

Silibinin is a nontoxic flavonoid reported to have anticancer properties. In this study, we show that silibinin exhibits antiproliferative activity on MCF-7 breast cancer cells. Exposure to silibinin leads to a concentration-dependent decrease in global protein synthesis associated with reduced levels of eukaryotic initiation factor 4F complex. Moreover, polysome profile analysis of silibinin-treated cells shows a decrease in polysome content and translation of cyclin D1 mRNA. Silibinin exerts its effects on translation initiation by inhibiting the mammalian target of rapamycin signaling pathway by acting upstream of TSC2. Our results show that silibinin blocks mammalian target of rapamycin signaling with a concomitant reduction in translation initiation, thus providing a possible molecular mechanism of how silibinin can inhibit growth of transformed cells.
Translation initiation on mRNAs bound by nuclear cap-binding protein complex CBP80/20 requires interaction between CBP80/20-dependent translation initiation factor and eukaryotic translation initiation factor 3g.

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Choe, Junho; Oh, Nara; Park, Sungjin; Lee, Ye Kyung; Song, Ok-Kyu; Locker, Nicolas; Chi, Sung-Gil; Kim, Yoon Ki

2012-05-25

In the cytoplasm of mammalian cells, either cap-binding proteins 80 and 20 (CBP80/20) or eukaryotic translation initiation factor (eIF) 4E can direct the initiation of translation. Although the recruitment of ribosomes to mRNAs during eIF4E-dependent translation (ET) is well characterized, the molecular mechanism for CBP80/20-dependent translation (CT) remains obscure. Here, we show that CBP80/20-dependent translation initiation factor (CTIF), which has been shown to be preferentially involved in CT but not ET, specifically interacts with eIF3g, a component of the eIF3 complex involved in ribosome recruitment. By interacting with eIF3g, CTIF serves as an adaptor protein to bridge the CBP80/20 and the eIF3 complex, leading to efficient ribosome recruitment during CT. Accordingly, down-regulation of CTIF using a small interfering RNA causes a redistribution of CBP80 from polysome fractions to subpolysome fractions, without significant consequence to eIF4E distribution. In addition, down-regulation of eIF3g inhibits the efficiency of nonsense-mediated mRNA decay, which is tightly coupled to CT but not to ET. Moreover, the artificial tethering of CTIF to an intercistronic region of dicistronic mRNA results in translation of the downstream cistron in an eIF3-dependent manner. These findings support the idea that CT mechanistically differs from ET.
Predicting Translation Initiation Rates for Designing Synthetic Biology

International Nuclear Information System (INIS)

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

2014-01-01

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

International Nuclear Information System (INIS)

Trivigno, Donatella; Bornes, Laura; Huber, Stephan M; Rudner, Justine

2013-01-01

Proliferating tumor cells require continuous protein synthesis. De novo synthesis of most proteins is regulated through cap-dependent translation. Cellular stress such as ionizing radiation (IR) blocks cap-dependent translation resulting in shut-down of global protein translation which saves resources and energy needed for the stress response. At the same time, levels of proteins required for stress response are maintained or even increased. The study aimed to analyze the regulation of signaling pathways controlling protein translation in response to IR and the impact on Mcl-1, an anti-apoptotic and radioprotective protein, which levels rapidly decline upon IR. Protein levels and processing were analyzed by Western blot. The assembly of the translational pre-initiation complex was examined by Immunoprecipitation and pull-down experiments with 7-methyl GTP agarose. To analyze IR-induced cell death, dissipation of the mitochondrial membrane potential and DNA fragmentation were determined by flow cytometry. Protein levels of the different initiation factors were down-regulated using RNA interference approach. IR induced caspase-dependent cleavage of the translational initiation factors eIF4G1, eIF3A, and eIF4B resulting in disassembly of the cap-dependent initiation complex. In addition, DAP5-dependent initiation complex that regulates IRES-dependent translation was disassembled in response to IR. Moreover, IR resulted in dephosphorylation of 4EBP1, an inhibitor of cap-dependent translation upstream of caspase activation. However, knock-down of eIF4G1, eIF4B, DAP5, or 4EBP1 did not affect IR-induced decline of the anti-apoptotic protein Mcl-1. Our data shows that cap-dependent translation is regulated at several levels in response to IR. However, the experiments indicate that IR-induced Mcl-1 decline is not a consequence of translational inhibition in Jurkat cells
Regulation of protein translation initiation in response to ionizing radiation

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Trivigno Donatella

2013-02-01

Full Text Available Abstract Background Proliferating tumor cells require continuous protein synthesis. De novo synthesis of most proteins is regulated through cap-dependent translation. Cellular stress such as ionizing radiation (IR blocks cap-dependent translation resulting in shut-down of global protein translation which saves resources and energy needed for the stress response. At the same time, levels of proteins required for stress response are maintained or even increased. The study aimed to analyze the regulation of signaling pathways controlling protein translation in response to IR and the impact on Mcl-1, an anti-apoptotic and radioprotective protein, which levels rapidly decline upon IR. Methods Protein levels and processing were analyzed by Western blot. The assembly of the translational pre-initiation complex was examined by Immunoprecipitation and pull-down experiments with 7-methyl GTP agarose. To analyze IR-induced cell death, dissipation of the mitochondrial membrane potential and DNA fragmentation were determined by flow cytometry. Protein levels of the different initiation factors were down-regulated using RNA interference approach. Results IR induced caspase-dependent cleavage of the translational initiation factors eIF4G1, eIF3A, and eIF4B resulting in disassembly of the cap-dependent initiation complex. In addition, DAP5-dependent initiation complex that regulates IRES-dependent translation was disassembled in response to IR. Moreover, IR resulted in dephosphorylation of 4EBP1, an inhibitor of cap-dependent translation upstream of caspase activation. However, knock-down of eIF4G1, eIF4B, DAP5, or 4EBP1 did not affect IR-induced decline of the anti-apoptotic protein Mcl-1. Conclusion Our data shows that cap-dependent translation is regulated at several levels in response to IR. However, the experiments indicate that IR-induced Mcl-1 decline is not a consequence of translational inhibition in Jurkat cells.
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.
Translation initiation mediated by nuclear cap-binding protein complex.

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Ryu, Incheol; Kim, Yoon Ki

2017-04-01

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

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

2010-03-01

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

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Landon, Mark; Perry, Ernest

2007-01-01

A software interface has been devised to facilitate optimization of the shapes of valves, elbows, fittings, and other components used to handle fluids under extreme conditions. This software interface translates data files generated by PLOT3D (a NASA grid-based plotting-and- data-display program) and by computational fluid dynamics (CFD) software into a format in which the files can be read by Sculptor, which is a shape-deformation- and-optimization program. Sculptor enables the user to interactively, smoothly, and arbitrarily deform the surfaces and volumes in two- and three-dimensional CFD models. Sculptor also includes design-optimization algorithms that can be used in conjunction with the arbitrary-shape-deformation components to perform automatic shape optimization. In the optimization process, the output of the CFD software is used as feedback while the optimizer strives to satisfy design criteria that could include, for example, improved values of pressure loss, velocity, flow quality, mass flow, etc.
Engineering bacterial translation initiation - Do we have all the tools we need?

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Vigar, Justin R J; Wieden, Hans-Joachim

2017-11-01

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

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Colussi, Timothy M; Costantino, David A; Zhu, Jianyu; Donohue, John Paul; Korostelev, Andrei A; Jaafar, Zane A; Plank, Terra-Dawn M; Noller, Harry F; Kieft, Jeffrey S

2015-03-05

The central dogma of gene expression (DNA to RNA to protein) is universal, but in different domains of life there are fundamental mechanistic differences within this pathway. For example, the canonical molecular signals used to initiate protein synthesis in bacteria and eukaryotes are mutually exclusive. However, the core structures and conformational dynamics of ribosomes that are responsible for the translation steps that take place after initiation are ancient and conserved across the domains of life. We wanted to explore whether an undiscovered RNA-based signal might be able to use these conserved features, bypassing mechanisms specific to each domain of life, and initiate protein synthesis in both bacteria and eukaryotes. Although structured internal ribosome entry site (IRES) RNAs can manipulate ribosomes to initiate translation in eukaryotic cells, an analogous RNA structure-based mechanism has not been observed in bacteria. Here we report our discovery that a eukaryotic viral IRES can initiate translation in live bacteria. We solved the crystal structure of this IRES bound to a bacterial ribosome to 3.8 Å resolution, revealing that despite differences between bacterial and eukaryotic ribosomes this IRES binds directly to both and occupies the space normally used by transfer RNAs. Initiation in both bacteria and eukaryotes depends on the structure of the IRES RNA, but in bacteria this RNA uses a different mechanism that includes a form of ribosome repositioning after initial recruitment. This IRES RNA bridges billions of years of evolutionary divergence and provides an example of an RNA structure-based translation initiation signal capable of operating in two domains of life.
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.
Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

DEFF Research Database (Denmark)

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

2012-01-01

Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, cDNAs corresponding to the wild type (wt) or mutant forms of the IRES of CSFV strain Paderborn were...... 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...... changes within the IRES. The growth characteristics of each rescued mutant virus were compared to that of the wt virus. It was shown that viable mutant viruses with reduced translation initiation efficiency can be designed and generated and that viruses containing mutations within domain IIIf of the IRES...
Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.

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

2014-08-01

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

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Helmle, Karmon E; Chacko, Sunita; Chan, Trevor; Drake, Alison; Edwards, Alun L; Moore, Glenda E; Philp, Leta C; Popeski, Naomi; Roedler, Rhonda L; Rogers, Edwin J R; Zimmermann, Gabrielle L; McKeen, Julie

2017-12-27

To develop and evaluate a Basal Bolus Insulin Therapy (BBIT) Knowledge Translation toolkit to address barriers to adoption of established best practice with BBIT in the care of adult inpatients. This study was conducted in 2 phases and focused on the hospitalist provider group across 4 acute care facilities in Calgary. Phase 1 involved a qualitative evaluation of provider and site specific barriers and facilitators, which were mapped to validated interventions using behaviour change theory. This informed the co-development and optimization of the BBIT Knowledge Translation toolkit, with each tool targeting a specific barrier to improved diabetes care practice, including BBIT ordering. In Phase 2, the BBIT Knowledge Translation toolkit was implemented and evaluated, focusing on BBIT ordering frequency, as well as secondary outcomes of hyperglycemia (patient-days with BG >14.0 mmol/L), hypoglycemia (patient-days with BG Knowledge Translation toolkit resulted in a significant 13% absolute increase in BBIT ordering. Hyperglycemic patient-days were significantly reduced, with no increase in hypoglycemia. There was a significant, absolute 14% reduction in length of stay. The implementation of an evidence-informed, multifaceted BBIT Knowledge Translation toolkit effectively reduced a deeply entrenched in-patient diabetes care gap. The resulting sustained practice change improved patient clinical and system resource utilization outcomes. This systemic approach to implementation will guide further scale and spread of glycemic optimization initiatives. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.
Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons.

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

2018-01-25

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

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

Czech Academy of Sciences Publication Activity Database

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

2013-01-01

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

OpenAIRE

Obermayer, Benedikt; Rajewsky, Nikolaus

2014-01-01

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

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Laura M McNamee

Full Text Available While timelines for clinical development have been extensively studied, there is little data on the broader path from initiation of research on novel drug targets, to approval of drugs based on this research. We examined timelines of translational science for 138 drugs and biologicals approved by the FDA from 2010-2014 using an analytical model of technology maturation. Research on targets for 102 products exhibited a characteristic (S-curve maturation pattern with exponential growth between statistically defined technology initiation and established points. The median initiation was 1974, with a median of 25 years to the established point, 28 years to first clinical trials, and 36 years to FDA approval. No products were approved before the established point, and development timelines were significantly longer when the clinical trials began before this point (11.5 vs 8.5 years, p<0.0005. Technological maturation represents the longest stage of translation, and significantly impacts the efficiency of drug development.
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.
Translational Geroscience: Emphasizing function to achieve optimal longevity

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Seals, Douglas R.; Melov, Simon

2014-01-01

Among individuals, biological aging leads to cellular and organismal dysfunction and an increased risk of chronic degenerative diseases and disability. This sequence of events in combination with the projected increases in the number of older adults will result in a worldwide healthcare burden with dire consequences. Superimposed on this setting are the adults now reaching traditional retirement ages--the baby boomers--a group that wishes to remain active, productive and physically and cognitively fit as they grow older. Together, these conditions are producing an unprecedented demand for increased healthspan or what might be termed “optimal longevity”—to live long, but well. To meet this demand, investigators with interests in the biological aspects of aging from model organisms to human epidemiology (population aging) must work together within an interactive process that we describe as translational geroscience. An essential goal of this new investigational platform should be the optimization and preservation of physiological function throughout the lifespan, including integrative physical and cognitive function, which would serve to increase healthspan, compress morbidity and disability into a shorter period of late-life, and help achieve optimal longevity. To most effectively utilize this new approach, we must rethink how investigators and administrators working at different levels of the translational research continuum communicate and collaborate with each other, how best to train the next generation of scientists in this new field, and how contemporary biological-biomedical aging research should be organized and funded. PMID:25324468
Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

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Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Li, Qiuping [Zhongshan Hospital of Fudan University, Shanghai 200032 (China); Yang, Zhiyuan; Wu, Guoqiang [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Gu, Jianxin [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences of Fudan University, Shanghai 200032 (China); Wei, Yuanyan, E-mail: yywei@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Jiang, Jianhai, E-mail: jianhaijiang@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China)

2010-07-09

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Science.gov (United States)

Kahvejian, Avak; Svitkin, Yuri V; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5'-end of the mRNA to promote the recruitment of the ribosome. Although the 3' poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (approximately 65% vs. approximately 35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5'-end of mRNA.
Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative.

Science.gov (United States)

Straus, Sharon E; Brouwers, Melissa; Johnson, David; Lavis, John N; Légaré, France; Majumdar, Sumit R; McKibbon, K Ann; Sales, Anne E; Stacey, Dawn; Klein, Gail; Grimshaw, Jeremy

2011-12-09

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

KAUST Repository

Nakagawa, So; Niimura, Yoshihito; Gojobori, Takashi

2017-01-01

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

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

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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.
Initiating statistical maintenance optimization

International Nuclear Information System (INIS)

Doyle, E. Kevin; Tuomi, Vesa; Rowley, Ian

2007-01-01

Since the 1980 s maintenance optimization has been centered around various formulations of Reliability Centered Maintenance (RCM). Several such optimization techniques have been implemented at the Bruce Nuclear Station. Further cost refinement of the Station preventive maintenance strategy includes evaluation of statistical optimization techniques. A review of successful pilot efforts in this direction is provided as well as initial work with graphical analysis. The present situation reguarding data sourcing, the principle impediment to use of stochastic methods in previous years, is discussed. The use of Crowe/AMSAA (Army Materials Systems Analysis Activity) plots is demonstrated from the point of view of justifying expenditures in optimization efforts. (author)
A proposed vestigial translation initiation motif in VP1 of hepatitis A virus.

Science.gov (United States)

Kang, Jeong-Ah; Funkhouser, Ann W

2002-07-01

The internal ribosome entry site (IRES) of picornaviruses has a 3' polypyrimidine tract (PPT) 16-24 bases upstream of an AUG triplet (PPT/AUG motif). This motif is critical in determining the efficiency of cap-independent translation. HAV has a conserved PPT/AUG motif consisting of a nine base sequence (AGGUUUUUC) 23 bases upstream of the preferred AUG start codon. This HAV-specific PPT/AUG motif is repeated and conserved in VP1 of HAV, but not of other picornaviruses. We proposed that the PPT/AUG motif in the open reading frame initiated translation and/or had an impact on the life cycle of the virus. In vitro translation of mutant bicistronic mRNAs and growth in cell culture of mutant viruses provided no evidence that the VP1 PPT/AUG motif had any impact on either translation or growth. HAV differs from other picornaviruses in its inefficient growth in cell culture. Since the HAV-specific PPT/AUG motif is found in only 1 in 300,000 reported viral sequences outside the hepatovirus genus, this motif may be a vestigial translation initiation element and may have played a role in determining the unusual phenotype of HAV.
Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative

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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.
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.
HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus

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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.
Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

DEFF Research Database (Denmark)

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

Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, the nucleotides 47 to 427, including the IRES region of the wt CSFV strain Paderborn, were amplified...... and inserted, under T7 promoter control, into mono- and dicistronic plasmids containing the reporter genes rLuc and fLuc. Mutant fragments of the IRES sequence were generated by overlap PCR and inserted into the reporter plasmids. To evaluate IRES functionality, translation of the rLUC was placed under...... 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...
Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity

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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.

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.

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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.
Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.

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Pelletier, Jerry; Graff, Jeremy; Ruggero, Davide; Sonenberg, Nahum

2015-01-15

Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor 4F (eIF4F), the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and preclinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes, such as cell growth and proliferation, enhanced cell survival and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion, and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g., Ras, PI3K/AKT/TOR, and MYC), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as antineoplastic agents. ©2014 American Association for Cancer Research.
Topology-optimized metasurfaces: impact of initial geometric layout.

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Yang, Jianji; Fan, Jonathan A

2017-08-15

Topology optimization is a powerful iterative inverse design technique in metasurface engineering and can transform an initial layout into a high-performance device. With this method, devices are optimized within a local design phase space, making the identification of suitable initial geometries essential. In this Letter, we examine the impact of initial geometric layout on the performance of large-angle (75 deg) topology-optimized metagrating deflectors. We find that when conventional metasurface designs based on dielectric nanoposts are used as initial layouts for topology optimization, the final devices have efficiencies around 65%. In contrast, when random initial layouts are used, the final devices have ultra-high efficiencies that can reach 94%. Our numerical experiments suggest that device topologies based on conventional metasurface designs may not be suitable to produce ultra-high-efficiency, large-angle metasurfaces. Rather, initial geometric layouts with non-trivial topologies and shapes are required.
Translation initiation in bacterial polysomes through ribosome loading on a standby site on a highly translated mRNA

Science.gov (United States)

Andreeva, Irena

2018-01-01

During translation, consecutive ribosomes load on an mRNA and form a polysome. The first ribosome binds to a single-stranded mRNA region and moves toward the start codon, unwinding potential mRNA structures on the way. In contrast, the following ribosomes can dock at the start codon only when the first ribosome has vacated the initiation site. Here we show that loading of the second ribosome on a natural 38-nt-long 5′ untranslated region of lpp mRNA, which codes for the outer membrane lipoprotein from Escherichia coli, takes place before the leading ribosome has moved away from the start codon. The rapid formation of this standby complex depends on the presence of ribosomal proteins S1/S2 in the leading ribosome. The early recruitment of the second ribosome to the standby site before translation by the leading ribosome and the tight coupling between translation elongation by the first ribosome and the accommodation of the second ribosome can contribute to high translational efficiency of the lpp mRNA. PMID:29632209
The Innovative Medicines Initiative moves translational immunology forward.

Science.gov (United States)

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.
Experimental Analysis of Mimivirus Translation Initiation Factor 4a Reveals Its Importance in Viral Protein Translation during Infection of Acanthamoeba polyphaga.

Science.gov (United States)

Bekliz, Meriem; Azza, Said; Seligmann, Hervé; Decloquement, Philippe; Raoult, Didier; La Scola, Bernard

2018-05-15

The Acanthamoeba polyphaga mimivirus is the first giant virus ever described, with a 1.2-Mb genome which encodes 979 proteins, including central components of the translation apparatus. One of these proteins, R458, was predicted to initiate translation, although its specific role remains unknown. We silenced the R458 gene using small interfering RNA (siRNA) and compared levels of viral fitness and protein expression in silenced versus wild-type mimivirus. Silencing decreased the growth rate, but viral particle production at the end of the viral cycle was unaffected. A comparative proteomic approach using two-dimensional difference-in-gel electrophoresis (2D-DIGE) revealed deregulation of the expression of 32 proteins in silenced mimivirus, which were defined as up- or downregulated. Besides revealing proteins with unknown functions, silencing R458 also revealed deregulation in proteins associated with viral particle structures, transcriptional machinery, oxidative pathways, modification of proteins/lipids, and DNA topology/repair. Most of these proteins belong to genes transcribed at the end of the viral cycle. Overall, our data suggest that the R458 protein regulates the expression of mimivirus proteins and, thus, that mimivirus translational proteins may not be strictly redundant in relation to those from the amoeba host. As is the case for eukaryotic initiation factor 4a (eIF4a), the R458 protein is the prototypical member of the ATP-dependent DEAD box RNA helicase mechanism. We suggest that the R458 protein is required to unwind the secondary structures at the 5' ends of mRNAs and to bind the mRNA to the ribosome, making it possible to scan for the start codon. These data are the first experimental evidence of mimivirus translation-related genes, predicted to initiate protein biosynthesis. IMPORTANCE The presence in the genome of a mimivirus of genes coding for many translational processes, with the exception of ribosome constituents, has been the subject of
The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon.

Science.gov (United States)

Moes, Lorin; Wirth, Manfred

2007-11-22

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. 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 swine fever virus, a pestivirus, and the
The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon

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

Science.gov (United States)

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

2014-05-06

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

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Roswani Siregar

2017-09-01

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

2010-01-01

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′ m7G-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 m7G-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. PMID:20154140
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...
Identification of the translational start site of codon-optimized mCherry in Mycobacterium tuberculosis

OpenAIRE

Carroll, Paul; Muwanguzi-Karugaba, Julian; Melief, Eduard; Files, Megan; Parish, Tanya

2014-01-01

Background Fluorescent proteins are used widely as reporter genes in many organisms. We previously codon-optimized mCherry for Mycobacterium tuberculosis and generated expression constructs with high level expression in mycobacteria with multiple uses in vitro and in vivo. However, little is known about the expression of fluorescent proteins in mycobacteria and the translational start codon for mCherry has not been experimentally determined. Results We determined the translational start site ...
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.
The Impact of Machine Translation and Computer-aided Translation on Translators

Science.gov (United States)

Peng, Hao

2018-03-01

Under the context of globalization, communications between countries and cultures are becoming increasingly frequent, which make it imperative to use some techniques to help translate. This paper is to explore the influence of computer-aided translation on translators, which is derived from the field of the computer-aided translation (CAT) and machine translation (MT). Followed by an introduction to the development of machine and computer-aided translation, it then depicts the technologies practicable to translators, which are trying to analyze the demand of designing the computer-aided translation so far in translation practice, and optimize the designation of computer-aided translation techniques, and analyze its operability in translation. The findings underline the advantages and disadvantages of MT and CAT tools, and the serviceability and future development of MT and CAT technologies. Finally, this thesis probes into the impact of these new technologies on translators in hope that more translators and translation researchers can learn to use such tools to improve their productivity.
Dragon TIS Spotter: An Arabidopsis-derived predictor of translation initiation sites in plants

KAUST Repository

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

2012-01-01

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

Science.gov (United States)

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

2013-10-01

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

Science.gov (United States)

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

2017-11-01

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

OpenAIRE

Kahvejian, Avak; Svitkin, Yuri V.; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for ...

Modulation of translation-initiation in CHO-K1 cells by rapamycin-induced heterodimerization of engineered eIF4G fusion proteins.

Science.gov (United States)

Schlatter, Stefan; Senn, Claudia; Fussenegger, Martin

2003-07-20

Translation-initiation is a predominant checkpoint in mammalian cells which controls protein synthesis and fine-tunes the flow of information from gene to protein. In eukaryotes, translation-initiation is typically initiated at a 7-methyl-guanylic acid cap posttranscriptionally linked to the 5' end of mRNAs. Alternative cap-independent translation-initiation involves 5' untranslated regions (UTR) known as internal ribosome entry sites, which adopt a particular secondary structure. Translation-initiating ribosome assembly at cap or IRES elements is mediated by a multiprotein complex of which the initiation factor 4F (eIF4F) consisting of eIF4A (helicase), eIF4E (cap-binding protein), and eIF4G is a major constituent. eIF4G is a key target of picornaviral protease 2A, which cleaves this initiation factor into eIF4G(Delta) and (Delta)eIF4G to redirect the cellular translation machinery exclusively to its own IRES-containing transcripts. We have designed a novel translation control system (TCS) for conditional as well as adjustable translation of cap- and IRES-dependent transgene mRNAs in mammalian cells. eIF4G(Delta) and (Delta)eIF4G were fused C- and N-terminally to the FK506-binding protein (FKBP) and the FKBP-rapamycin-binding domain (FRB) of the human FKBP-rapamycin-associated protein (FRAP), respectively. Rapamycin-induced heterodimerization of eIF4G(Delta)-FKBP and FRB-(Delta)eIF4G fusion proteins reconstituted a functional chimeric elongation factor 4G in a dose-dependent manner. Rigorous quantitative expression analysis of cap- and IRES-dependent SEAP- (human placental secreted alkaline phosphatase) and luc- (Photinus pyralis luciferase) encoding reporter constructs confirmed adjustable translation control and revealed increased production of desired proteins in response to dimerization-induced heterologous eIF4G in Chinese hamster ovary (CHO-K1) cells. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 210-225, 2003.
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...
Regulation of cap-dependent translation initiation in the early stage porcine parthenotes

Czech Academy of Sciences Publication Activity Database

Šušor, Andrej; Jelínková, Lucie; Karabínová, Pavla; Torner, H.; Tomek, W.; Kovářová, Hana; Kubelka, Michal

2008-01-01

Roč. 75, č. 12 (2008), s. 1716-1725 ISSN 1040-452X R&D Projects: GA ČR GA524/04/0104; GA ČR GA524/07/1087 Institutional research plan: CEZ:AV0Z50450515 Keywords : meiosis * translation initiation * porcine parthenotes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.287, year: 2008
Dragon TIS Spotter: an Arabidopsis-derived predictor of translation initiation sites in plants.

Science.gov (United States)

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

2013-01-01

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

International Nuclear Information System (INIS)

Ilic, A. Z.; Ristic-Djurovic, J. L.; Cirkovic, S. T.

2007-01-01

The quality of a beam in a cyclotron depends a lot on the choice of initial conditions for acceleration. The criteria defining optimal acceleration as well as the choice of the corresponding initial conditions have been outlined. The results of beam dynamics simulations with optimal and non-optimal initial conditions are compared. (author)
A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

Directory of Open Access Journals (Sweden)

Wanjun Gu

2010-02-01

Full Text Available Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evidence for reduced mRNA stability near the start codon. The reduction in stability generally increases with increasing genomic GC content. In prokaryotes, the reduction also increases with decreasing optimal growth temperature. Within genomes, there is variation in the stability among genes, and this variation correlates with gene GC content, codon bias, and gene expression level. For birds and mammals, however, we do not find a genome-wide trend of reduced mRNA stability near the start codon. Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start codon by initiator-tRNA.
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...... practice and research, its major objective, of forming the basis for local and national initiatives to improve services for asthma patients, remains to be achieved. Over recent years, the science of guideline implementation has progressed, and encouraging examples of successful asthma programmes have been...... published. This report is intended to draw on this experience and assist with the translation of asthma guideline recommendations into quality programmes for patients with asthma using current knowledge translation principles. It also provides examples of successful initiatives in various socioeconomic...
ER stress inducer tunicamycin suppresses the self-renewal of glioma-initiating cell partly through inhibiting Sox2 translation.

Science.gov (United States)

Xing, Yang; Ge, Yuqing; Liu, Chanjuan; Zhang, Xiaobiao; Jiang, Jianhai; Wei, Yuanyan

2016-06-14

Glioma-initiating cells possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Therefore, their elimination is an essential factor for the development of efficient therapy. Here, we report that endoplasmic reticulum (ER) stress inducer tunicamycin inhibits glioma-initiating cell self-renewal as determined by neurosphere formation assay. Moreover, tunicamycin decreases the efficiency of glioma-initiating cell to initiate tumor formation. Although tunicamycin induces glioma-initiating cell apoptosis, apoptosis inhibitor z-VAD-fmk only partly abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Indeed, tunicamycin reduces the expression of self-renewal regulator Sox2 at translation level. Overexpression of Sox2 obviously abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Taken together, tunicamycin suppresses the self-renewal and tumorigenic potential of glioma-initiating cell partly through reducing Sox2 translation. This finding provides a cue to potential effective treatment of glioblastoma through controlling stem cells.
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.
Beyond initiation-limited translational bursting: the effects of burst size distributions on the stability of gene expression

KAUST Repository

Kuwahara, Hiroyuki; Arold, Stefan T.; Gao, Xin

2015-01-01

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
A translationally optimized AAV-UGT1A1 vector drives safe and long-lasting correction of Crigler-Najjar syndrome

Directory of Open Access Journals (Sweden)

Giuseppe Ronzitti

2016-01-01

Full Text Available Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1 enzyme. In an effort to translate to the clinic an adeno-associated virus vector mediated liver gene transfer approach to treat Crigler-Najjar syndrome, we developed and optimized a vector expressing the UGT1A1 transgene. For this purpose, we designed and tested in vitro and in vivo multiple codon-optimized UGT1A1 transgene cDNAs. We also optimized noncoding sequences in the transgene expression cassette. Our results indicate that transgene codon-optimization is a strategy that can improve efficacy of gene transfer but needs to be carefully tested in vitro and in vivo. Additionally, while inclusion of introns can enhance gene expression, optimization of these introns, and in particular removal of cryptic ATGs and splice sites, is an important maneuver to enhance safety and efficacy of gene transfer. Finally, using a translationally optimized adeno-associated virus vector expressing the UGT1A1 transgene, we demonstrated rescue of the phenotype of Crigler-Najjar syndrome in two animal models of the disease, Gunn rats and Ugt1a1-/- mice. We also showed long-term (>1 year correction of the disease in Gunn rats. These results support further translation of the approach to humans.
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.
HIV-1 transcripts use IRES-initiation under conditions where Cap-dependent translation is restricted by poliovirus 2A protease.

Directory of Open Access Journals (Sweden)

Raquel Amorim

Full Text Available The 30 different species of mRNAs synthesized during the HIV-1 replication cycle are all capped and polyadenilated. Internal ribosome entry sites have been recognized in the 5' untranslated region of some mRNA species of HIV-1, which would contribute to an alternative mechanism of initiation of mRNA translation. However, the Cap-dependent translation is assumed to be the main mechanism driving the initiation of HIV-1 protein synthesis. In this work, we describe a cell system in which lower to higher levels of transient expression of the poliovirus 2A protease strongly inhibited cellular Cap-dependent translation with no toxic effect to the cells during a 72-hour time frame. In this system, the synthesis of HIV-1 proteins was inhibited in a temporal dose-dependent way. Higher levels of 2A protease expression severely inhibited HIV-1 protein synthesis during the first 24 hours of infection consequently inhibiting viral production and infectivity. Intermediate to lower levels of 2A Protease expression caused the inhibition of viral protein synthesis only during the first 48 hours of viral replication. After this period both protein synthesis and viral release were recovered to the control levels. However, the infectivity of viral progeny was still partially inhibited. These results indicate that two mechanisms of mRNA translation initiation contribute to the synthesis of HIV-1 proteins; during the first 24-48 hours of viral replication HIV-1 protein synthesis is strongly dependent on Cap-initiation, while at later time points IRES-driven translation initiation is sufficient to produce high amounts of viral particles.
Translation initiation factor AteIF(iso4E is involved in selective mRNA translation in Arabidopsis thaliana seedlings.

Directory of Open Access Journals (Sweden)

Ana Valeria Martínez-Silva

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

Science.gov (United States)

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

2017-06-16

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

International Nuclear Information System (INIS)

Oliver, Mike; Jensen, Michael; Chen, Jeff; Wong, Eugene

2009-01-01

Intensity-modulated arc therapy (IMAT) is a rotational variant of intensity-modulated radiation therapy (IMRT) that can be implemented with or without angular dose rate variation. The purpose of this study is to assess optimization strategies and initial conditions using a leaf position optimization (LPO) algorithm altered for variable dose rate IMAT. A concave planning target volume (PTV) with a central cylindrical organ at risk (OAR) was used in this study. The initial IMAT arcs were approximated by multiple static beams at 5 deg. angular increments where multi-leaf collimator (MLC) leaf positions were determined from the beam's eye view to irradiate the PTV but avoid the OAR. For the optimization strategy, two arcs with arc ranges of 280 deg. and 150 deg. were employed and plans were created using LPO alone, variable dose rate optimization (VDRO) alone, simultaneous LPO and VDRO and sequential combinations of these strategies. To assess the MLC initialization effect, three single 360 deg. arc plans with different initial MLC configurations were generated using the simultaneous LPO and VDRO. The effect of changing optimization degrees of freedom was investigated by employing 3 deg., 5 deg. and 10 deg. angular sampling intervals for the two 280 deg., two 150 deg. and single arc plans using LPO and VDRO. The objective function value, a conformity index, a dose homogeneity index, mean dose to OAR and normal tissues were computed and used to evaluate the treatment plans. This study shows that the best optimization strategy for a concave target is to use simultaneous MLC LPO and VDRO. We found that the optimization result is sensitive to the choice of initial MLC aperture shapes suggesting that an LPO-based IMAT plan may not be able to overcome local minima for this geometry. In conclusion, simultaneous MLC leaf position and VDRO are needed with the most appropriate initial conditions (MLC positions, arc ranges and number of arcs) for IMAT.
Knowledge Translation Interventions to Improve the Timing of Dialysis Initiation: Protocol for a Cluster Randomized Trial.

Science.gov (United States)

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

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. 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. This study is a multicenter, 2-arm parallel, cluster randomized trial. The study involves 55 advanced chronic kidney disease clinics across Canada. 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. 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 m 2 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. 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-person medical detailing visit. Control clinics are only exposed to guideline
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.
Optimal Damping of Perturbations of Moving Thermoelastic Panel

Science.gov (United States)

Banichuk, N. V.; Ivanova, S. Yu.

2018-01-01

The translational motion of a thermoelastic web subject to transverse vibrations caused by initial perturbations is considered. It is assumed that a web moving with a constant translational velocity is described by the model of a thermoelastic panel simply supported at its ends. The problem of optimal damping of vibrations when applying active transverse actions is formulated. For solving the optimization problem, modern methods developed in control theory for systems with distributed parameters described by partial differential equations are used.
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.

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

African Journals Online (AJOL)

Drawing on the Bourdieusian concept of habitus and its applicability in the field of translation, this article discusses Antjie Krog's profile in the practice of translation in. South Africa. Bourdieu's conceptualisation of the relationship between the initiating activities of translators and the structures which constrain and enable ...
Using Open Source Tools to Create a Mobile Optimized, Crowdsourced Translation Tool

OpenAIRE

Evviva Weinraub Lajoie; Trey Terrell; Susan McEvoy; Eva Kaplan; Ariel Schwartz; Esther Ajambo

2014-01-01

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

International Nuclear Information System (INIS)

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

Science.gov (United States)

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

2018-05-14

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

NARCIS (Netherlands)

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

2015-01-01

The identification of translation initiation sites (TISs) constitutes an important aspect of sequence-based genome analysis. An erroneous TIS annotation can impair the identification of regulatory elements and N-terminal signal peptides, and also may flaw the determination of descent, for any
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. © 2015 Authors; published by Portland Press Limited.
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.
Initiatives and evaluation of teaching-learning process in translation training

OpenAIRE

Olvera Lobo, Mar??a Dolores; Guti??rrez-Artacho, Juncal

2010-01-01

The ability to manage information and communication technologies (ICT) is a professional prerequisite for translators. The translation discipline is aware of this trend because ICTs have changed and developed the translation profession. Translation training is more than just learning a proficient command of languages, and translators must also develop other important skills ??? such as accessing and managing information resources. A group of teachers from various departments of the Univers...
Genome-Scale Analysis of Translation Elongation with a Ribosome Flow Model

Science.gov (United States)

Meilijson, Isaac; Kupiec, Martin; Ruppin, Eytan

2011-01-01

We describe the first large scale analysis of gene translation that is based on a model that takes into account the physical and dynamical nature of this process. The Ribosomal Flow Model (RFM) predicts fundamental features of the translation process, including translation rates, protein abundance levels, ribosomal densities and the relation between all these variables, better than alternative (‘non-physical’) approaches. In addition, we show that the RFM can be used for accurate inference of various other quantities including genes' initiation rates and translation costs. These quantities could not be inferred by previous predictors. We find that increasing the number of available ribosomes (or equivalently the initiation rate) increases the genomic translation rate and the mean ribosome density only up to a certain point, beyond which both saturate. Strikingly, assuming that the translation system is tuned to work at the pre-saturation point maximizes the predictive power of the model with respect to experimental data. This result suggests that in all organisms that were analyzed (from bacteria to Human), the global initiation rate is optimized to attain the pre-saturation point. The fact that similar results were not observed for heterologous genes indicates that this feature is under selection. Remarkably, the gap between the performance of the RFM and alternative predictors is strikingly large in the case of heterologous genes, testifying to the model's promising biotechnological value in predicting the abundance of heterologous proteins before expressing them in the desired host. PMID:21909250
PKC δ Regulates Translation Initiation through PKR and eIF2 α in Response to Retinoic Acid in Acute Myeloid Leukemia Cells

OpenAIRE

Ozpolat, Bulent; Akar, Ugur; Tekedereli, Ibrahim; Alpay, S. Neslihan; Barria, Magaly; Gezgen, Baki; Zhang, Nianxiang; Coombes, Kevin; Kornblau, Steve; Lopez-Berestein, Gabriel

2012-01-01

Translation initiation and activity of eukaryotic initiation factor-alpha (eIF2 α ), the rate-limiting step of translation initiation, is often overactivated in malignant cells. Here, we investigated the regulation and role of eIF2 α 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 eIF2 α , through the induct...
N-terminal Proteomics Assisted Profiling of the Unexplored Translation Initiation Landscape in Arabidopsis thaliana.

Science.gov (United States)

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

2017-06-01

Proteogenomics is an emerging research field yet lacking a uniform method of analysis. Proteogenomic studies in which N-terminal proteomics and ribosome profiling are combined, suggest that a high number of protein start sites are currently missing in genome annotations. We constructed a proteogenomic pipeline specific for the analysis of N-terminal proteomics data, with the aim of discovering novel translational start sites outside annotated protein coding regions. In summary, unidentified MS/MS spectra were matched to a specific N-terminal peptide library encompassing protein N termini encoded in the Arabidopsis thaliana genome. After a stringent false discovery rate filtering, 117 protein N termini compliant with N-terminal methionine excision specificity and indicative of translation initiation were found. These include N-terminal protein extensions and translation from transposable elements and pseudogenes. Gene prediction provided supporting protein-coding models for approximately half of the protein N termini. Besides the prediction of functional domains (partially) contained within the newly predicted ORFs, further supporting evidence of translation was found in the recently released Araport11 genome re-annotation of Arabidopsis and computational translations of sequences stored in public repositories. Most interestingly, complementary evidence by ribosome profiling was found for 23 protein N termini. Finally, by analyzing protein N-terminal peptides, an in silico analysis demonstrates the applicability of our N-terminal proteogenomics strategy in revealing protein-coding potential in species with well- and poorly-annotated genomes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein

International Nuclear Information System (INIS)

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

2012-01-01

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

Science.gov (United States)

Luijten, Peter R; van Dongen, Guus A M S; Moonen, Chrit T; Storm, Gert; Crommelin, Daan J A

2012-07-20

The way forward in multidisciplinary research according to former NIH's director Elias Zerhouni is to engage in predictive, personalized, preemptive and participatory medicine. For the creation of the optimal innovation climate that would allow for such a strategy, public-private partnerships have been widely proposed as an important instrument. Public-private partnerships have become an important instrument to expedite translational research in medicine. The Netherlands have initiated three large public-private partnerships in the life sciences and health area to facilitate the translation of valuable basic scientific concepts to new products and services in medicine. The focus of these partnerships has been on drug development, improved diagnosis and regenerative medicine. The Dutch model of public-private partnership forms the blueprint of a much larger European initiative called EATRIS. This paper will provide practical examples of public-private partnerships initiated to expedite the translation of new technology for drug development towards the clinic. Three specific technologies are in focus: companion diagnostics using nuclear medicine, the use of ultra high field MRI to generate sensitive surrogate endpoints based on endogenous contrast, and MRI guidance for High Intensity Focused Ultrasound mediated drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.
The triplet repeats of the Sin Nombre hantavirus 5' untranslated region are sufficient in cis for nucleocapsid-mediated translation initiation.

Science.gov (United States)

Mir, Mohammad A; Panganiban, Antonito T

2010-09-01

Hantavirus nucleocapsid protein (N) can replace the cellular cap-binding complex, eukaryotic initiation factor 4F (eIF4F), to mediate translation initiation. Although N can augment translation initiation of nonviral mRNA, initiation of viral mRNA by N is superior. All members of the Bunyaviridae family, including the species of the hantavirus genus, express either three or four primary mRNAs from their tripartite negative-sense genomes. The 5' ends of the mRNAs contain nonviral heterologous oligonucleotides that originate from endonucleolytic cleavage of cellular mRNA during the process of cap snatching. In the hantaviruses these caps terminate with a 3' G residue followed by nucleotides arising from the viral template. Further, the 5' untranslated region (UTR) of viral mRNA uniformly contains, near the 5' end, either two or three copies of the triplet repeat sequence, UAGUAG or UAGUAGUAG. Through analysis of a panel of mutants with mutations in the viral UTR, we found that the sequence GUAGUAG is sufficient for preferential N-mediated translation initiation and for high-affinity binding of N to the UTR. This heptanucleotide sequence is present in viral mRNA containing either two or three copies of the triplet repeat.
Switch from cap- to factorless IRES-dependent 0 and +1 frame translation during cellular stress and dicistrovirus infection.

Directory of Open Access Journals (Sweden)

Qing S Wang

Full Text Available Internal ribosome entry sites (IRES are utilized by a subset of cellular and viral mRNAs to initiate translation during cellular stress and virus infection when canonical cap-dependent translation is compromised. The intergenic region (IGR IRES of the Dicistroviridae uses a streamlined mechanism in which it can directly recruit the ribosome in the absence of initiation factors and initiates translation using a non-AUG codon. A subset of IGR IRESs including that from the honey bee viruses can also direct translation of an overlapping +1 frame gene. In this study, we systematically examined cellular conditions that lead to IGR IRES-mediated 0 and +1 frame translation in Drosophila S2 cells. Towards this, a novel bicistronic reporter that exploits the 2A "stop-go" peptide was developed to allow the detection of IRES-mediated translation in vivo. Both 0 and +1 frame translation by the IGR IRES are stimulated under a number of cellular stresses and in S2 cells infected by cricket paralysis virus, demonstrating a switch from cap-dependent to IRES-dependent translation. The regulation of the IGR IRES mechanism ensures that both 0 frame viral structural proteins and +1 frame ORFx protein are optimally expressed during virus infection.
The NS1 Protein from Influenza Virus Stimulates Translation Initiation by Enhancing Ribosome Recruitment to mRNAs.

Science.gov (United States)

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

2017-10-27

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

International Nuclear Information System (INIS)

Thakur, Amit; Singh, Baltej; Gupta, Anurag; Duggal, Vibhuti; Bhatt, Kislay; Krishnani, P.D.

2016-01-01

Highlights: • EDA has been applied to optimize initial core of AHWR-LEU. • Suitable value of weighing factor ‘α’ and population size in EDA was estimated. • The effect of varying initial distribution function on optimized solution was studied. • For comparison, Genetic algorithm was also applied. - Abstract: Population based evolutionary algorithms now form an integral part of fuel management in nuclear reactors and are frequently being used for fuel loading pattern optimization (LPO) problems. In this paper we have applied Estimation of distribution algorithm (EDA) to optimize initial core loading pattern (LP) of AHWR-LEU. In EDA, new solutions are generated by sampling the probability distribution model estimated from the selected best candidate solutions. The weighing factor ‘α’ decides the fraction of current best solution for updating the probability distribution function after each generation. A wider use of EDA warrants a comprehensive study on parameters like population size, weighing factor ‘α’ and initial probability distribution function. In the present study, we have done an extensive analysis on these parameters (population size, weighing factor ‘α’ and initial probability distribution function) in EDA. It is observed that choosing a very small value of ‘α’ may limit the search of optimized solutions in the near vicinity of initial probability distribution function and better loading patterns which are away from initial distribution function may not be considered with due weightage. It is also observed that increasing the population size improves the optimized loading pattern, however the algorithm still fails if the initial distribution function is not close to the expected optimized solution. We have tried to find out the suitable values for ‘α’ and population size to be considered for AHWR-LEU initial core loading pattern optimization problem. For sake of comparison and completeness, we have also addressed the
Initial ratio optimization for the ejector cooling system with thermal pumping effect (ECSTPE)

International Nuclear Information System (INIS)

He, Yijian; Sun, Yongjun; Zhang, Sheng; Lyu, Yuanli; Chen, Guangming

2016-01-01

Graphical abstract: The existing ejector cooling systems with thermal pumping effect (ECSTPEs) have severe problems of thermal energy and chilling load waste. The deviations of the initial ratio from its optimal value would lead to the deviations of the time length of cooling stage (TLCS), and finally, result in the performance deteriorations of the ECSTPEs. The results of the case study showed that, for an ECSTPE with R134a, a 10-second deviation from the optimal TLCS led to a decrease of 5.6% in the COP value and an increase of 23.7% in the chilling load, when the generation temperature, the condensing temperature and the evaporation temperature were 85 °C, 35 °C and 10 °C, respectively. Therefore, accurately controlling the TLCS corresponding to the optimal TLCS, which is derived on the basis of the optimal initial ratio, can effectively improve the performance of ECSPTEs. - Highlights: • ECSTPEs encounter challenges for a great waste of heat and chilling water. • Initial ratio optimization is proposed to improve the performance of ECSTPEs. • Based on the optimal initial ratio, the optimal TLCS control strategy is obtained. • With the optimal TLCS control, COP values of the ECSTPEs are effectively enhanced. • Accordingly, the chilling loads of the ECSTPEs are greatly reduced. - Abstract: An ejector cooling system with thermal pumping effect (ECSTPE) could operate without consumption of electric power, but it discards a great amount of thermal energy, which generally results in a lower COP value and a greater chilling load. An innovative concept for the optimal initial ratio is therefore proposed to develop the optimal time length of cooling stage (TLCS) control method. The optimal TLCS control method effectively improves the ECSTPE performance. First, in this context, it was theoretically proven that the optimal initial ratio could be used to reduce the energy loss and the chilling load. Second, it was formulated how to achieve the optimal initial
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

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
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...
A Protocol of Japanese-English Translation

OpenAIRE

三浦, 勲夫; MIURA, Isao

1999-01-01

Every year I translate Japanes enewspaper articles into English and publish them in book form containing 12 or more translations. In translating there are regular procedures I go through:1)initial translation done by me and 2) corrected translation done through discussion between a native English speaker and me.
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.
A genome-scale integration and analysis of Lactococcus lactis translation data.

Directory of Open Access Journals (Sweden)

Julien Racle

Full Text Available Protein synthesis is a template polymerization process composed by three main steps: initiation, elongation, and termination. During translation, ribosomes are engaged into polysomes whose size is used for the quantitative characterization of translatome. However, simultaneous transcription and translation in the bacterial cytosol complicates the analysis of translatome data. We established a procedure for robust estimation of the ribosomal density in hundreds of genes from Lactococcus lactis polysome size measurements. We used a mechanistic model of translation to integrate the information about the ribosomal density and for the first time we estimated the protein synthesis rate for each gene and identified the rate limiting steps. Contrary to conventional considerations, we find significant number of genes to be elongation limited. This number increases during stress conditions compared to optimal growth and proteins synthesized at maximum rate are predominantly elongation limited. Consistent with bacterial physiology, we found proteins with similar rate and control characteristics belonging to the same functional categories. Under stress conditions, we found that synthesis rate of regulatory proteins is becoming comparable to proteins favored under optimal growth. These findings suggest that the coupling of metabolic states and protein synthesis is more important than previously thought.
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.
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. © 2014 American Society for Clinical Pharmacology and Therapeutics.
Performance limitations of translationally symmetric nonimaging devices

Science.gov (United States)

Bortz, John C.; Shatz, Narkis E.; Winston, Roland

2001-11-01

The component of the optical direction vector along the symmetry axis is conserved for all rays propagated through a translationally symmetric optical device. This quality, referred to herein as the translational skew invariant, is analogous to the conventional skew invariant, which is conserved in rotationally symmetric optical systems. The invariance of both of these quantities is a consequence of Noether's theorem. We show how performance limits for translationally symmetric nonimaging optical devices can be derived from the distributions of the translational skew invariant for the optical source and for the target to which flux is to be transferred. Examples of computed performance limits are provided. In addition, we show that a numerically optimized non-tracking solar concentrator utilizing symmetry-breaking surface microstructure can overcome the performance limits associated with translational symmetry. The optimized design provides a 47.4% increase in efficiency and concentration relative to an ideal translationally symmetric concentrator.
The Jigsaw Puzzle of mRNA Translation Initiation in Eukaryotes: A Decade of Structures Unraveling the Mechanics of the Process.

Science.gov (United States)

Hashem, Yaser; Frank, Joachim

2018-03-01

Translation initiation in eukaryotes is a highly regulated and rate-limiting process. It results in the assembly and disassembly of numerous transient and intermediate complexes involving over a dozen eukaryotic initiation factors (eIFs). This process culminates in the accommodation of a start codon marking the beginning of an open reading frame at the appropriate ribosomal site. Although this process has been extensively studied by hundreds of groups for nearly half a century, it has been only recently, especially during the last decade, that we have gained deeper insight into the mechanics of the eukaryotic translation initiation process. This advance in knowledge is due in part to the contributions of structural biology, which have shed light on the molecular mechanics underlying the different functions of various eukaryotic initiation factors. In this review, we focus exclusively on the contribution of structural biology to the understanding of the eukaryotic initiation process, a long-standing jigsaw puzzle that is just starting to yield the bigger picture. Expected final online publication date for the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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.
Hybrid collaborative optimization based on selection strategy of initial point and adaptive relaxation

International Nuclear Information System (INIS)

Ji, Aimin; Yin, Xu; Yuan, Minghai

2015-01-01

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

NARCIS (Netherlands)

Daiber, J.

2018-01-01

Machine translation systems often incorporate modeling assumptions motivated by properties of the language pairs they initially target. When such systems are applied to language families with considerably different properties, translation quality can deteriorate. Phrase-based machine translation
Phosphorylation and interactions associated with the control of the Leishmania Poly-A Binding Protein 1 (PABP1) function during translation initiation.

Science.gov (United States)

de Melo Neto, Osvaldo P; da Costa Lima, Tamara D C; Merlo, Kleison C; Romão, Tatiany P; Rocha, Pollyanna O; Assis, Ludmila A; Nascimento, Larissa M; Xavier, Camila C; Rezende, Antonio M; Reis, Christian R S; Papadopoulou, Barbara

2018-03-23

The Poly-A Binding Protein (PABP) is a conserved eukaryotic polypeptide involved in many aspects of mRNA metabolism. During translation initiation, PABP interacts with the translation initiation complex eIF4F and enhances the translation of polyadenylated mRNAs. Schematically, most PABPs can be divided into an N-terminal RNA-binding region, a non-conserved linker segment and the C-terminal MLLE domain. In pathogenic Leishmania protozoans, three PABP homologues have been identified, with the first one (PABP1) targeted by phosphorylation and shown to co-immunoprecipitate with an eIF4F-like complex (EIF4E4/EIF4G3) implicated in translation initiation. Here, PABP1 phosphorylation was shown to be linked to logarithmic cell growth, reminiscent of EIF4E4 phosphorylation, and coincides with polysomal association. Phosphorylation targets multiple serine-proline (SP) or threonine-proline (TP) residues within the PABP1 linker region. This is an essential protein, but phosphorylation is not needed for its association with polysomes or cell viability. Mutations which do impair PABP1 polysomal association and are required for viability do not prevent phosphorylation, although further mutations lead to a presumed inactive protein largely lacking phosphorylated isoforms. Co-immunoprecipitation experiments were carried out to investigate PABP1 function further, identifying several novel protein partners and the EIF4E4/EIF4G3 complex, but no other eIF4F-like complex or subunit. A novel, direct interaction between PABP1 and EIF4E4 was also investigated and found to be mediated by the PABP1 MLLE binding to PABP Interacting Motifs (PAM2) within the EIF4E4 N-terminus. The results shown here are consistent with phosphorylation of PABP1 being part of a novel pathway controlling its function and possibly translation in Leishmania.
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.
Entrainment to periodic initiation and transition rates in a computational model for gene translation.

Directory of Open Access Journals (Sweden)

Michael Margaliot

Full Text Available Periodic oscillations play an important role in many biomedical systems. Proper functioning of biological systems that respond to periodic signals requires the ability to synchronize with the periodic excitation. For example, the sleep/wake cycle is a manifestation of an internal timing system that synchronizes to the solar day. In the terminology of systems theory, the biological system must entrain or phase-lock to the periodic excitation. Entrainment is also important in synthetic biology. For example, connecting several artificial biological systems that entrain to a common clock may lead to a well-functioning modular system. The cell-cycle is a periodic program that regulates DNA synthesis and cell division. Recent biological studies suggest that cell-cycle related genes entrain to this periodic program at the gene translation level, leading to periodically-varying protein levels of these genes. The ribosome flow model (RFM is a deterministic model obtained via a mean-field approximation of a stochastic model from statistical physics that has been used to model numerous processes including ribosome flow along the mRNA. Here we analyze the RFM under the assumption that the initiation and/or transition rates vary periodically with a common period T. We show that the ribosome distribution profile in the RFM entrains to this periodic excitation. In particular, the protein synthesis pattern converges to a unique periodic solution with period T. To the best of our knowledge, this is the first proof of entrainment in a mathematical model for translation that encapsulates aspects such as initiation and termination rates, ribosomal movement and interactions, and non-homogeneous elongation speeds along the mRNA. Our results support the conjecture that periodic oscillations in tRNA levels and other factors related to the translation process can induce periodic oscillations in protein levels, and may suggest a new approach for re-engineering genetic
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.
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.
RACK1-mediated translation control promotes liver fibrogenesis

International Nuclear Information System (INIS)

Liu, Min; Peng, Peike; Wang, Jiajun; Wang, Lan; Duan, Fangfang; Jia, Dongwei; Ruan, Yuanyuan; Gu, Jianxin

2015-01-01

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
Initiative Optimization Operation Strategy and Multi-objective Energy Management Method for Combined Cooling Heating and Power

Institute of Scientific and Technical Information of China (English)

Feng Zhao; Chenghui Zhang; Bo Sun

2016-01-01

This paper proposed an initiative optimization operation strategy and multi-objective energy management method for combined cooling heating and power(CCHP) with storage systems.Initially,the initiative optimization operation strategy of CCHP system in the cooling season,the heating season and the transition season was formulated.The energy management of CCHP system was optimized by the multi-objective optimization model with maximum daily energy efficiency,minimum daily carbon emissions and minimum daily operation cost based on the proposed initiative optimization operation strategy.Furthermore,the pareto optimal solution set was solved by using the niche particle swarm multi-objective optimization algorithm.Ultimately,the most satisfactory energy management scheme was obtained by using the technique for order preference by similarity to ideal solution(TOPSIS) method.A case study of CCHP system used in a hospital in the north of China validated the effectiveness of this method.The results showed that the satisfactory energy management scheme of CCHP system was obtained based on this initiative optimization operation strategy and multi-objective energy management method.The CCHP system has achieved better energy efficiency,environmental protection and economic benefits.
Nurturing and Testing Translation Competence for Text-Translating

Science.gov (United States)

Aubakirova, Karlygash Adilkhanovna

2016-01-01

The article analyzes the problems of contemporary professional education. As its instance, we examine the developmental scheme for training professional translators. Optimal ways of organizing the learning process are suggested from the point of view of the competence approach, which is widely recognized for training a modern specialist. The…

Optimal control of distributed parameter system with incomplete information about the initial condition

International Nuclear Information System (INIS)

Kotarski, W.; Kowalewski, A.

1982-03-01

In this paper we consider an optimal control problem for a system described by a linear partial differential equation of the parabolic type with Dirichlet's boundary condition. We impose some constraints on the control. The performance functional has the integral form. The control time T is fixed. The initial condition is not given by a known function but belongs to a certain set (incomplete information about the initial state). The problem formulated in this paper describes the process of optimal heating, of which we do not have exact information about the initial temperature on the heated object. We present an example in which the set of admissible controls and one of initial conditions are given by means of the norm constraints too. The application of the well-known projective gradient method in the Hilbert space allows us to obtain the numerical solution for our optimization problem. (author)
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.
Preventive maintenance optimization for a stochastically degrading system with a random initial age

International Nuclear Information System (INIS)

Sidibe, I.B.; Khatab, A.; Diallo, C.; Kassambara, A.

2017-01-01

This paper investigates the optimal age replacement policy for used systems, such as second-hand products, which start their second life-cycle in a more severe environment with an initial age that is uncertain. This uncertain age is modelled as a random variable following continuous probability distributions. A mathematical model is developed to minimize the total expected cost per unit of time for these systems on an infinite time horizon. Optimality and existence conditions for a unique optimal solution are derived and used in a numerical procedure to solve the problem. Numerical experiments are provided to demonstrate the added value and the impacts of the random initial age on the optimal replacement policy.
Pharmacogenetic diversification by alternative translation initiation: background channels to the fore.

Science.gov (United States)

Abbott, G W

2014-02-15

Unanticipated complexity of drug-target interactions creates a headache for those attempting to rationalize and create simple models of antiarrhythmic action, but can also introduce opportunities for increased drug specificity, or for potentially advantageous spatial and temporal variation in drug effects. The newest findings reported by Kisselbach et al. in this issue are a case in point. Building upon previous pioneering work demonstrating that neuronal K 2P 2.1 potassium-selective "background" channels can become permeable to sodium ions depending upon alternative translation initiation (ATI) (Thomas et al., 2008), the Thomas lab now shows that ATI of K 2P 2.1 and K 2P 10.1, which are also expressed in the heart, can cause a fivefold shift in sensitivity to block by the β-receptor (and potassium channel) antagonist, carvedilol (Kisselbach et al., 2014). This article is protected by copyright. All rights reserved.
Expression of the Eukaryotic Translation Initiation Factors 4E and 2α in Non-Hodgkin’s Lymphomas

Science.gov (United States)

Wang, Songtao; Rosenwald, Igor B.; Hutzler, Michael J.; Pihan, German A.; Savas, Lou; Chen, Jane-Jane; Woda, Bruce A.

1999-01-01

Transition of cells from quiescence to proliferation requires an increase in the rate of protein synthesis, which is regulated in part by two key translation initiation factors, 4E and 2α. The expression and activity of both factors are increased transiently when normal resting cells are stimulated to proliferate. They are constitutively elevated in oncogene transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study we investigate an association between the expression of translation initiation factors and lymphomagenesis. We have analyzed the expression of the protein synthesis initiation factors 4E and 2α by immunohistochemistry in reactive lymph nodes and several types of non-Hodgkin’s lymphoma representing a wide range of clinical behaviors based on the Revised European-American Lymphoma behavioral classification. The study included 7 benign lymph nodes with follicular hyperplasia, 26 indolent lymphomas (6 marginal zone lymphomas, 7 small lymphocytic lymphomas, and 13 follicular lymphomas, grades 1 and 2), 16 moderately aggressive lymphomas (8 mantle cell lymphomas and 8 follicular lymphomas, grade 3), 24 aggressive lymphomas (14 large-B-cell lymphomas and 10 anaplastic large-cell lymphomas), and 15 highly aggressive lymphomas (7 lymphoblastic lymphomas and 8 Burkitt’s lymphomas). Strong expression of initiation factors 4E and 2α was demonstrated in the germinal centers of reactive follicles. Minimal or no expression was seen in the mantle zones and surrounding paracortices, indicating that high expression of initiation factors 4E and 2α is associated with the active proliferation of lymphocytes. Most cases of aggressive and highly aggressive lymphomas showed strong expression of initiation factors 4E and 2α, in contrast to the cases of indolent and moderately aggressive lymphoma, in which their expression was intermediate between the germinal centers and the mantles of reactive
Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

International Nuclear Information System (INIS)

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

2013-01-01

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

KAUST Repository

Ketcheson, David I.; Ahmadia, Aron

2013-01-01

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
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.
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.
Specific Increase of Protein Levels by Enhancing Translation Using Antisense Oligonucleotides Targeting Upstream Open Frames.

Science.gov (United States)

Liang, Xue-Hai; Shen, Wen; Crooke, Stanley T

2017-01-01

A number of diseases are caused by low levels of key proteins; therefore, increasing the amount of specific proteins in human bodies is of therapeutic interest. Protein expression is downregulated by some structural or sequence elements present in the 5' UTR of mRNAs, such as upstream open reading frames (uORF). Translation initiation from uORF(s) reduces translation from the downstream primary ORF encoding the main protein product in the same mRNA, leading to a less efficient protein expression. Therefore, it is possible to use antisense oligonucleotides (ASOs) to specifically inhibit translation of the uORF by base-pairing with the uAUG region of the mRNA, redirecting translation machinery to initiate from the primary AUG site. Here we review the recent findings that translation of specific mRNAs can be enhanced using ASOs targeting uORF regions. Appropriately designed and optimized ASOs are highly specific, and they act in a sequence- and position-dependent manner, with very minor off-target effects. Protein levels can be increased using this approach in different types of human and mouse cells, and, importantly, also in mice. Since uORFs are present in around half of human mRNAs, the uORF-targeting ASOs may thus have valuable potential as research tools and as therapeutics to increase the levels of proteins for a variety of genes.
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.
Translating Alcohol Research

Science.gov (United States)

Batman, Angela M.; Miles, Michael F.

2015-01-01

Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of streamlining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD. PMID:26259085
Eukaryotic translation initiation factor 2B-beta (eIF2Bβ), a new class of plant virus resistance gene.

Science.gov (United States)

Shopan, Jannat; Mou, Haipeng; Zhang, Lili; Zhang, Changtong; Ma, Weiwei; Walsh, John A; Hu, Zhongyuan; Yang, Jinghua; Zhang, Mingfang

2017-06-01

Recessive resistances to plant viruses in the Potyvirus genus have been found to be based on mutations in the plant eukaryotic translation initiation factors, eIF4E and eIF4G or their isoforms. Here we report that natural, monogenic recessive resistance to the Potyvirus Turnip mosaic virus (TuMV) has been found in a number of mustard (Brassica juncea) accessions. Bulked segregant analysis and sequencing of resistant and susceptible plant lines indicated the resistance is controlled by a single recessive gene, recessive TuMV resistance 03 (retr03), an allele of the eukaryotic translation initiation factor 2B-beta (eIF2Bβ). Silencing of eIF2Bβ in a TuMV-susceptible mustard plant line and expression of eIF2Bβ from a TuMV-susceptible line in a TuMV-resistant mustard plant line confirmed the new resistance mechanism. A functional copy of a specific allele of eIF2Bβ is required for efficient TuMV infection. eIF2Bβ represents a new class of virus resistance gene conferring resistance to any pathogen. eIF2B acts as a guanine nucleotide exchange factor (GEF) for its GTP-binding protein partner eIF2 via interaction with eIF2·GTP at an early step in translation initiation. Further genotyping indicated that a single non-synonymous substitution (A120G) in the N-terminal region of eIF2Bβ was responsible for the TuMV resistance. A reproducible marker has been developed, facilitating marker-assisted selection for TuMV resistance in B. juncea. Our findings provide a new target for seeking natural resistance to potyviruses and new opportunities for the control of potyviruses using genome editing techniques targeted on eIF2Bβ. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.
Pioneer round of translation occurs during serum starvation

International Nuclear Information System (INIS)

Oh, Nara; Kim, Kyoung Mi; Cho, Hana; Choe, Junho; Kim, Yoon Ki

2007-01-01

The pioneer round of translation plays a role in translation initiation of newly spliced and exon junction complex (EJC)-bound mRNAs. Nuclear cap-binding protein complex CBP80/20 binds to those mRNAs at the 5'-end, recruiting translation initiation complex. As a consequence of the pioneer round of translation, the bound EJCs are dissociated from mRNAs and CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E. Steady-state translation directed by eIF4E allows for an immediate and rapid response to changes in physiological conditions. Here, we show that nonsense-mediated mRNA decay (NMD), which restricts only to the pioneer round of translation but not to steady-state translation, efficiently occurs even during serum starvation, in which steady-state translation is drastically abolished. Accordingly, CBP80 remains in the nucleus and processing bodies are unaffected in their abundance and number in serum-starved conditions. These results suggest that mRNAs enter the pioneer round of translation during serum starvation and are targeted for NMD if they contain premature termination codons
Subdivision, Sampling, and Initialization Strategies for Simplical Branch and Bound in Global Optimization

DEFF Research Database (Denmark)

Clausen, Jens; Zilinskas, A,

2002-01-01

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...
On Translators' Cultural Frame of Functionist Reference

Science.gov (United States)

Fu, Zhiyi

2009-01-01

A deep cognition with translators' cultural frame of functionist reference can help instructors and teachers adjust and extend patterns and schemes of translation and generate the optimal classroom conditions for acquisition of the target language. The author of the paper, in the perspectives of motivational, cognitive and communicative…
Establishing a national knowledge translation and generation network in kidney disease: the CAnadian KidNey KNowledge TraNslation and GEneration NeTwork.

Science.gov (United States)

Manns, Braden; Barrett, Brendan; Evans, Michael; Garg, Amit; Hemmelgarn, Brenda; Kappel, Joanne; Klarenbach, Scott; Madore, Francois; Parfrey, Patrick; Samuel, Susan; Soroka, Steven; Suri, Rita; Tonelli, Marcello; Wald, Ron; Walsh, Michael; Zappitelli, Michael

2014-01-01

Patients with chronic kidney disease (CKD) do not always receive care consistent with guidelines, in part due to complexities in CKD management, lack of randomized trial data to inform care, and a failure to disseminate best practice. At a 2007 conference of key Canadian stakeholders in kidney disease, attendees noted that the impact of Canadian Society of Nephrology (CSN) guidelines was attenuated given limited formal linkages between the CSN Clinical Practice Guidelines Group, kidney researchers, decision makers and knowledge users, and that further knowledge was required to guide care in patients with kidney disease. The idea for the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) developed from this meeting. CANN-NET is a pan-Canadian network established in partnership with CSN, the Kidney Foundation of Canada and other professional societies to improve the care and outcomes of patients with and at risk for kidney disease. The initial priority areas for knowledge translation include improving optimal timing of dialysis initiation, and increasing the appropriate use of home dialysis. Given the urgent need for new knowledge, CANN-NET has also brought together a national group of experienced Canadian researchers to address knowledge gaps by encouraging and supporting multicentre randomized trials in priority areas, including management of cardiovascular disease in patients with kidney failure.
Codon usage regulates protein structure and function by affecting translation elongation speed in Drosophila cells.

Science.gov (United States)

Zhao, Fangzhou; Yu, Chien-Hung; Liu, Yi

2017-08-21

Codon usage biases are found in all eukaryotic and prokaryotic genomes and have been proposed to regulate different aspects of translation process. Codon optimality has been shown to regulate translation elongation speed in fungal systems, but its effect on translation elongation speed in animal systems is not clear. In this study, we used a Drosophila cell-free translation system to directly compare the velocity of mRNA translation elongation. Our results demonstrate that optimal synonymous codons speed up translation elongation while non-optimal codons slow down translation. In addition, codon usage regulates ribosome movement and stalling on mRNA during translation. Finally, we show that codon usage affects protein structure and function in vitro and in Drosophila cells. Together, these results suggest that the effect of codon usage on translation elongation speed is a conserved mechanism from fungi to animals that can affect protein folding in eukaryotic organisms. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Eukaryotic translation initiation factor 3 subunit e controls intracellular calcium homeostasis by regulation of cav1.2 surface expression.

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Pawel Buda

Full Text Available Inappropriate surface expression of voltage-gated Ca(2+channels (CaV in pancreatic ß-cells may contribute to the development of type 2 diabetes. First, failure to increase intracellular Ca(2+ concentrations at the sites of exocytosis impedes insulin release. Furthermore, excessive Ca(2+ influx may trigger cytotoxic effects. The regulation of surface expression of CaV channels in the pancreatic β-cells remains unknown. Here, we used real-time 3D confocal and TIRFM imaging, immunocytochemistry, cellular fractionation, immunoprecipitation and electrophysiology to study trafficking of L-type CaV1.2 channels upon β-cell stimulation. We found decreased surface expression of CaV1.2 and a corresponding reduction in L-type whole-cell Ca(2+ currents in insulin-secreting INS-1 832/13 cells upon protracted (15-30 min stimulation. This internalization occurs by clathrin-dependent endocytosis and could be prevented by microtubule or dynamin inhibitors. eIF3e (Eukaryotic translation initiation factor 3 subunit E is part of the protein translation initiation complex, but its effect on translation are modest and effects in ion channel trafficking have been suggested. The factor interacted with CaV1.2 and regulated CaV1.2 traffic bidirectionally. eIF3e silencing impaired CaV1.2 internalization, which resulted in an increased intracellular Ca(2+ load upon stimulation. These findings provide a mechanism for regulation of L-type CaV channel surface expression with consequences for β-cell calcium homeostasis, which will affect pancreatic β-cell function and insulin production.
The Continuing Challenges of Translational Research: Clinician-Scientists’ Perspective

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Shervanthi Homer-Vanniasinkam

2012-01-01

Full Text Available Over the last twenty years, revolutionary advances in biomedicine including gene therapy, stem cell research, proteomics, genomics and nanotechnology have highlighted the progressive need to restructure traditional approaches to basic and clinical research in order to facilitate the rapid, efficient integration and translation of these new technologies into novel effective therapeutics. Over the past ten years, funding bodies in the USA and UK such as the National Institutes of Health (NIH and the Medical Research Council (MRC have been driving translational research by defining and tackling the hurdles but more still remains to be achieved. This article discusses the ongoing challenges translational researchers face and outlines recent initiatives to tackle these including the new changes to translational funding schemes proposed by the NIH and the MRC and the launch of the “European Advanced Translational Research InfraStructure in Medicine” (EATRIS. It is anticipated that initiatives such as these will not only strengthen translational biomedical research programmes already initiated but should lead to rapid benefits to patients and society.
Optimal initial fuel distribution in a thermal reactor for maximum energy production

International Nuclear Information System (INIS)

Moran-Lopez, J.M.

1983-01-01

Using the fuel burnup as objective function, it is desired to determine the initial distribution of the fuel in a reactor in order to obtain the maximum energy possible, for which, without changing a fixed initial fuel mass, the results for different initial fuel and control poison configurations are analyzed and the corresponding running times compared. One-dimensional, two energy-group theory is applied to a reflected cylindrical reactor using U-235 as fuel and light water as moderator and reflector. Fissions in both fast and thermal groups are considered. The reactor is divided into several annular regions, and the constant flux approximation in each depletion step is then used to solve the fuel and fission-product poisons differential equations in each region. The computer code OPTIME was developed to determine the time variation of core properties during the fuel cycle. At each depletion step, OPTIME calls ODMUG, [12] a criticality search program, from which the spatially-averaged neutron fluxes and control poison cross sections are obtained
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…
The eukaryotic translation initiation factor 3 subunit E binds to classical swine fever virus NS5A and facilitates viral replication.

Science.gov (United States)

Liu, Xiaofeng; Wang, Xiaoyu; Wang, Qian; Luo, Mingyang; Guo, Huancheng; Gong, Wenjie; Tu, Changchun; Sun, Jinfu

2018-02-01

Classical swine fever virus (CSFV) NS5A protein is a multifunctional protein, playing critical roles in viral RNA replication, translation and assembly. To further explore its functions in viral replication, interaction of NS5A with host factors was assayed using a his-tag "pull down" assay coupled with shotgun LC-MS/MS. Host protein translation initiation factor 3 subunit E was identified as a binding partner of NS5A, and confirmed by co-immunoprecipitation and co-localization analysis. Overexpression of eIF3E markedly enhanced CSFV genomic replication, viral protein expression and production of progeny virus, and downregulation of eIF3E by siRNA significantly decreased viral proliferation in PK-15 cells. Luciferase reporter assay showed an enhancement of translational activity of the internal ribosome entry site of CSFV by eIF3E and a decrease in cellular translation by NS5A. These data indicate that eIF3E plays an important role in CSFV replication, thereby identifying it as a potential target for inhibition of the virus. Copyright © 2017 Elsevier Inc. All rights reserved.
Control of protein synthesis in Escherichia coli: strain differences in control of translational initiation after energy source shift-down.

Science.gov (United States)

Jacobson, L A; Jen-Jacobson, L

1980-06-01

We have studied the parameters of protein synthesis in a number of Escherichia coli strains after a shift-down from glucose-minimal to succinate-minimal medium. One group of strains, including K-12(lambda) (ATCC 10798) and NF162, showed a postshift translational yield of 50 to 65% and a 2- to 2.5-fold increase in the functional lifetime of general messenger ribonucleic acid. There was no change in the lag time for beta-galactosidase induction in these strains after the shift-down. A second group, including W1 and W2, showed no reduction in translational yield, no change in the functional lifetime of messenger ribonucleic acid, and a 50% increase in the lag time for beta-galactosidase induction. Evidence is presented which indicates that this increased lag time is not the result of a decreased rate of polypeptide chain propagation. A third group of strains, including NF161, CP78, and NF859, showed an intermediate pattern: translational yield was reduced to about 75% of normal, and the messenger ribonucleic acid functional lifetime was increased by about 50%. Calculation of the relative postshift rates of translational initiation gave about 0.2, 1.0, and 0.5, respectively, for the three groups. There was no apparent correlation between the ability to control translation and the genotypes of these strains at the relA, relX, or spoT loci. Measurements of the induction lag for beta-galactosidase during short-term glucose starvation or after a down-shift induced by alpha-methylglucoside indicated that these regimens elicit responses that are physiologically distinct from those elicited by a glucose-to-succinate shift-down.
Translational Research from an Informatics Perspective

Science.gov (United States)

Bernstam, Elmer; Meric-Bernstam, Funda; Johnson-Throop, Kathy A.; Turley, James P.; Smith, Jack W.

2007-01-01

Clinical and translational research (CTR) is an essential part of a sustainable global health system. Informatics is now recognized as an important en-abler of CTR and informaticians are increasingly called upon to help CTR efforts. The US National Institutes of Health mandated biomedical informatics activity as part of its new national CTR grant initiative, the Clinical and Translational Science Award (CTSA). Traditionally, translational re-search was defined as the translation of laboratory discoveries to patient care (bench to bedside). We argue, however, that there are many other kinds of translational research. Indeed, translational re-search requires the translation of knowledge dis-covered in one domain to another domain and is therefore an information-based activity. In this panel, we will expand upon this view of translational research and present three different examples of translation to illustrate the point: 1) bench to bedside, 2) Earth to space and 3) academia to community. We will conclude with a discussion of our local translational research efforts that draw on each of the three examples.
Establishing a National Knowledge Translation and Generation Network in Kidney Disease: The CAnadian KidNey KNowledge TraNslation and GEneration NeTwork

Directory of Open Access Journals (Sweden)

Braden Manns

2014-04-01

Full Text Available Patients with chronic kidney disease (CKD do not always receive care consistent with guidelines, in part due to complexities in CKD management, lack of randomized trial data to inform care, and a failure to disseminate best practice. At a 2007 conference of key Canadian stakeholders in kidney disease, attendees noted that the impact of Canadian Society of Nephrology (CSN guidelines was attenuated given limited formal linkages between the CSN Clinical Practice Guidelines Group, kidney researchers, decision makers and knowledge users, and that further knowledge was required to guide care in patients with kidney disease. The idea for the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET developed from this meeting. CANN-NET is a pan-Canadian network established in partnership with CSN, the Kidney Foundation of Canada and other professional societies to improve the care and outcomes of patients with and at risk for kidney disease. The initial priority areas for knowledge translation include improving optimal timing of dialysis initiation, and increasing the appropriate use of home dialysis. Given the urgent need for new knowledge, CANN-NET has also brought together a national group of experienced Canadian researchers to address knowledge gaps by encouraging and supporting multicentre randomized trials in priority areas, including management of cardiovascular disease in patients with kidney failure.
IRES-dependent translational control during virus-induced endoplasmic reticulum stress and apoptosis

Directory of Open Access Journals (Sweden)

Paul eHanson

2012-03-01

Full Text Available Many virus infections and stresses can induce endoplasmic reticulum (ER stress response, a host self defense mechanism against viral invasion and stress. During this event, viral and cellular gene expression is actively regulated and often encounters a switching of the translation initiation from cap-dependent to IRES (internal ribosome entry sites-dependent. This switching is largely dependent on the mRNA structure of the 5’untranslated region (5’UTR and on the particular stress stimuli. Picornviruses and some other viruses contain an IRES within their 5’UTR of viral genome and employ an IRES-driven mechanism for translation initiation. Recently, a growing number of cellular genes involved in growth control, cell cycle progression and apoptosis were also found to contain one or more IRES within their long highly structured 5’UTRs. These genes initiate translation usually by a cap-dependent mechanism under normal physiological conditions; however, in certain environments, such as infection, starvation and heat shock they shift translation initiation to an IRES-dependent modality. Although the molecular mechanism is not entirely understood, a number of studies have revealed that several cellular biochemical processes are responsible for the switching of translation initiation to IRES-dependent. These include the cleavage of translation initiation factors by viral and/or host proteases, phosphorylation (inactivation of host factors for translation initiation, over-production of homologous proteins of cap-binding protein eIF4E, suppression of cap-binding protein eIF4E expression by specific microRNA, activation of enzymes for mRNA decapping, as well as others. Here, we summarize the recent advances in our understanding of the molecular mechanisms for the switching of translation initiation, particularly for the proteins involved in cell survival and apoptosis in the ER stress pathways during viral infections.
Calculation of depletion with optimal distribution of initial control poison

International Nuclear Information System (INIS)

Castro Lobo, P.D. de.

1978-03-01

The spatial depletion equations are linearized within the time intervals and their solution is obtained by modal analysis. At the beginning of life an optimal poison distribution that maximizes neutron economy and the corresponding flux is determined. At the start of the subsequent time steps the flux distributions are obtained by pertubation method in relation to the start of the previous time steps. The problem was studied with constant poison distribution in order to evaluate the influence of the poison at the beginning of life. The results obtained by the modal expansion techniques are satisfactory. However, the optimization of the initial distribution of the control poison does not indicate any significant effect on the core life [pt
Translational Repression in Malaria Sporozoites

Science.gov (United States)

Turque, Oliver; Tsao, Tiffany; Li, Thomas; Zhang, Min

2016-01-01

Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1), is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host. PMID:28357358
Translational repression in malaria sporozoites

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Oliver Turque

2016-04-01

Full Text Available Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1, is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host.
Health technology assessment to optimize health technology utilization: using implementation initiatives and monitoring processes.

Science.gov (United States)

Frønsdal, Katrine B; Facey, Karen; Klemp, Marianne; Norderhaug, Inger Natvig; Mørland, Berit; Røttingen, John-Arne

2010-07-01

The way in which a health technology is used in any particular health system depends on the decisions and actions of a variety of stakeholders, the local culture, and context. In 2009, the HTAi Policy Forum considered how health technology assessment (HTA) could be improved to optimize the use of technologies (in terms of uptake, change in use, or disinvestment) in such complex systems. In scoping, it was agreed to focus on initiatives to implement evidence-based guidance and monitoring activities. A review identified systematic reviews of implementation initiatives and monitoring activities. A two-day deliberative workshop was held to discuss key papers, members' experiences, and collectively address key questions. This consensus paper was developed by email and finalized at a postworkshop meeting. Evidence suggests that the impact and use of HTA could be increased by ensuring timely delivery of relevant reports to clearly determined policy receptor (decision-making) points. To achieve this, the breadth of assessment, implementation initiatives such as incentives and targeted, intelligent dissemination of HTA result, needs to be considered. HTA stakeholders undertake a variety of monitoring activities, which could inform optimal use of a technology. However, the quality of these data varies and is often not submitted to an HTA. Monitoring data should be sufficiently robust so that they can be used in HTA to inform optimal use of technology. Evidence-based implementation initiatives should be developed for HTA, to better inform decision makers at all levels in a health system about the optimal use of technology.
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
Optimal time for initiating extracorporeal membrane oxygenation.

Science.gov (United States)

Haile, Dawit T; Schears, Gregory J

2009-09-01

The technical evolution of extracorporeal membrane oxygenation (ECMO) coincides with the vast improvement in intensive care medicine of the past 4 decades. Extracorporeal circulatory technology substitutes for acutely failed cardiac or pulmonary function until these organs regain sustainable function through goal-oriented intensive care practice. The technology has been validated to improve survival in select patients who would otherwise have 100% mortality. This is by far the most complex life-sustaining technology employed and thus can contribute significant risks such that the decision to institute ECMO requires prompt risk and benefit analysis. Delaying the institution of ECMO may cause irreversible pulmonary and cardiac injuries in addition to other organs. Therefore, the optimal time of initiating ECMO support is crucial to the survival of a critically ill patient.
Optimizing Filter-Probe Diffusion Weighting in the Rat Spinal Cord for Human Translation

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Matthew D. Budde

2017-12-01

Full Text Available Diffusion tensor imaging (DTI is a promising biomarker of spinal cord injury (SCI. In the acute aftermath, DTI in SCI animal models consistently demonstrates high sensitivity and prognostic performance, yet translation of DTI to acute human SCI has been limited. In addition to technical challenges, interpretation of the resulting metrics is ambiguous, with contributions in the acute setting from both axonal injury and edema. Novel diffusion MRI acquisition strategies such as double diffusion encoding (DDE have recently enabled detection of features not available with DTI or similar methods. In this work, we perform a systematic optimization of DDE using simulations and an in vivo rat model of SCI and subsequently implement the protocol to the healthy human spinal cord. First, two complementary DDE approaches were evaluated using an orientationally invariant or a filter-probe diffusion encoding approach. While the two methods were similar in their ability to detect acute SCI, the filter-probe DDE approach had greater predictive power for functional outcomes. Next, the filter-probe DDE was compared to an analogous single diffusion encoding (SDE approach, with the results indicating that in the spinal cord, SDE provides similar contrast with improved signal to noise. In the SCI rat model, the filter-probe SDE scheme was coupled with a reduced field of view (rFOV excitation, and the results demonstrate high quality maps of the spinal cord without contamination from edema and cerebrospinal fluid, thereby providing high sensitivity to injury severity. The optimized protocol was demonstrated in the healthy human spinal cord using the commercially-available diffusion MRI sequence with modifications only to the diffusion encoding directions. Maps of axial diffusivity devoid of CSF partial volume effects were obtained in a clinically feasible imaging time with a straightforward analysis and variability comparable to axial diffusivity derived from DTI
Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation.

Science.gov (United States)

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

2016-10-14

ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
4EGI-1 represses cap-dependent translation and regulates genome-wide translation in malignant pleural mesothelioma.

Science.gov (United States)

De, Arpita; Jacobson, Blake A; Peterson, Mark S; Jay-Dixon, Joe; Kratzke, Marian G; Sadiq, Ahad A; Patel, Manish R; Kratzke, Robert A

2018-04-01

Deregulation of cap-dependent translation has been implicated in the malignant transformation of numerous human tissues. 4EGI-1, a novel small-molecule inhibitor of cap-dependent translation, disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex. The effects of 4EGI-1-mediated inhibition of translation initiation in malignant pleural mesothelioma (MPM) were examined. 4EGI-1 preferentially inhibited cell viability and induced apoptosis in MPM cells compared to normal mesothelial (LP9) cells. This effect was associated with hypophosphorylation of 4E-binding protein 1 (4E-BP1) and decreased protein levels of the cancer-related genes, c-myc and osteopontin. 4EGI-1 showed enhanced cytotoxicity in combination with pemetrexed or gemcitabine. Translatome-wide polysome microarray analysis revealed a large cohort of genes that were translationally regulated upon treatment with 4EGI-1. The 4EGI-1-regulated translatome was negatively correlated to a previously published translatome regulated by eIF4E overexpression in human mammary epithelial cells, which is in agreement with the notion that 4EGI-1 inhibits the eIF4F complex. These data indicate that inhibition of the eIF4F complex by 4EGI-1 or similar translation inhibitors could be a strategy for treating mesothelioma. Genome wide translational profiling identified a large cohort of promising target genes that should be further evaluated for their potential significance in the treatment of MPM.
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...
Lost in translation? Role of metabolomics in solving translational problems in drug discovery and development

NARCIS (Netherlands)

Greef, J. van der; Adourian, A.; Muntendam, P.; McBurney, R.N.

2006-01-01

Too few drug discovery projects generate a marketed drug product, often because preclinical studies fail to predict the clinical experience with a drug candidate. Improving the success of preclinical-to-clinical translation is of paramount importance in optimizing the pharmaceutical value chain.

The significance of translation regulation in the stress response

OpenAIRE

Picard, Flora; Loubière, Pascal; Girbal, Laurence; Bousquet, Muriel

2013-01-01

Background: The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results: A genome-scale study of the translational response to nutritional limitation was performed in t...
Euphemism vs explicitness: A corpus-based analysis of translated ...

African Journals Online (AJOL)

This article examines the governing initial norms, namely explicitness and euphemism in English source texts and Ndebele translations, focusing on how these norms influenced the strategies chosen by the Ndebele translators in the translation of taboo terms. In the article, a corpus-based approach is used to identify head ...
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.
Evaluation of the "Foundations in Knowledge Translation" training initiative: preparing end users to practice KT.

Science.gov (United States)

Park, Jamie S; Moore, Julia E; Sayal, Radha; Holmes, Bev J; Scarrow, Gayle; Graham, Ian D; Jeffs, Lianne; Timmings, Caitlyn; Rashid, Shusmita; Johnson, Alekhya Mascarenhas; Straus, Sharon E

2018-04-25

Current knowledge translation (KT) training initiatives are primarily focused on preparing researchers to conduct KT research rather than on teaching KT practice to end users. Furthermore, training initiatives that focus on KT practice have not been rigorously evaluated and have focused on assessing short-term outcomes and participant satisfaction only. Thus, there is a need for longitudinal training evaluations that assess the sustainability of training outcomes and contextual factors that may influence outcomes. We evaluated the KT training initiative "Foundations in KT" using a mixed-methods longitudinal design. "Foundations in KT" provided training in KT practice and included three tailored in-person workshops, coaching, and an online platform for training materials and knowledge exchange. Two cohorts were included in the study (62 participants, including 46 "Foundations in KT" participants from 16 project teams and 16 decision-maker partners). Participants completed self-report questionnaires, focus groups, and interviews at baseline and at 6, 12, 18, and 24 months after the first workshop. Participant-level outcomes include survey results which indicated that participants' self-efficacy in evidence-based practice (F(1,8.9) = 23.7, p = 0.001, n = 45), KT activities (F(1,23.9) = 43.2, p training initiative helped participants achieve their KT project objectives, plan their projects, and solve problems over time. Contextual factors include teams with high self-reported organizational capacity and commitment to implement at the start of their project had buy-in from upper management that resulted in secured funding and resources for their project. Training initiative outcomes include participants who applied the KT knowledge and skills they learned to other projects by sharing their knowledge informally with coworkers. Sustained spread of KT practice was observed with five teams at 24 months. We completed a longitudinal evaluation of a KT
Translational initiation in Leishmania tarentolae and Phytomonas serpens (Kinetoplastida) is strongly influenced by pre-ATG triplet and its 5´ sequence context

Czech Academy of Sciences Publication Activity Database

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

2006-01-01

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

, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation.......58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1......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...
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 recent years, user interfaces enabled us to record user events such as eye-movements or keystrokes. Although there have been insightful descriptive analysis of the translation process, there are multiple advantages in enabling quantitative inference. We present methods to classify sequences of fixations...... 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....
The mechanism of translation initiation on Aichivirus RNA mediated by a novel type of picornavirus IRES.

Science.gov (United States)

Yu, Yingpu; Sweeney, Trevor R; Kafasla, Panagiota; Jackson, Richard J; Pestova, Tatyana V; Hellen, Christopher Ut

2011-08-26

Picornavirus mRNAs contain IRESs that sustain their translation during infection, when host protein synthesis is shut off. The major classes of picornavirus IRESs (Types 1 and 2) have distinct structures and sequences, but initiation on both is determined by their specific interaction with eIF4G. We report here that Aichivirus (AV), a member of the Kobuvirus genus of Picornaviridae, contains an IRES that differs structurally from Type 1 and Type 2 IRESs. Its function similarly involves interaction with eIF4G, but its eIF4G-interacting domain is structurally distinct, although it contains an apical eIF4G-interacting motif similar to that in Type 2 IRESs. Like Type 1 and Type 2 IRESs, AV IRES function is enhanced by pyrimidine tract-binding protein (PTB), but the pattern of PTB's interaction with each of these IRESs is distinct. Unlike all known IRESs, the AV IRES is absolutely dependent on DHX29, a requirement imposed by sequestration of its initiation codon in a stable hairpin.
Interaction in vitro between the proteinase of Tomato ringspot virus (genus Nepovirus) and the eukaryotic translation initiation factor iso4E from Arabidopsis thaliana.

Science.gov (United States)

Léonard, Simon; Chisholm, Joan; Laliberté, Jean-François; Sanfaçon, Hélène

2002-08-01

Eukaryotic initiation factor eIF(iso)4E binds to the cap structure of mRNAs leading to assembly of the translation complex. This factor also interacts with the potyvirus VPg and this interaction has been correlated with virus infectivity. In this study, we show an interaction between eIF(iso)4E and the proteinase (Pro) of a nepovirus (Tomato ringspot virus; ToRSV) in vitro. The ToRSV VPg did not interact with eIF(iso)4E although its presence on the VPg-Pro precursor increased the binding affinity of Pro for the initiation factor. A major determinant of the interaction was mapped to the first 93 residues of Pro. Formation of the complex was inhibited by addition of m(7)GTP (a cap analogue), suggesting that Pro-containing molecules compete with cellular mRNAs for eIF(iso)4E binding. The possible implications of this interaction for translation and/or replication of the virus genome are discussed.
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.
The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling.

Science.gov (United States)

Lin, Chen-Ju; Robert, Francis; Sukarieh, Rami; Michnick, Stephen; Pelletier, Jerry

2010-04-15

Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2alpha phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Emu-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. (c) 2010 AACR.
Optimum design of 6-DOF parallel manipulator with translational/rotational workspaces for haptic device application

Energy Technology Data Exchange (ETDEWEB)

Yoon, Jung Won; Hwang, Yoon Kwon [Gyeongsang National University, Jinju (Korea, Republic of); Ryu, Je Ha [Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of)

2010-05-15

This paper proposes an optimum design method that satisfies the desired orientation workspace at the boundary of the translation workspace while maximizing the mechanism isotropy for parallel manipulators. A simple genetic algorithm is used to obtain the optimal linkage parameters of a six-degree-of-freedom parallel manipulator that can be used as a haptic device. The objective function is composed of a desired spherical shape translation workspace and a desired orientation workspace located on the boundaries of the desired translation workspace, along with a global conditioning index based on a homogeneous Jacobian matrix. The objective function was optimized to satisfy the desired orientation workspace at the boundary positions as translated from a neutral position of the increased entropy mechanism. An optimization result with desired translation and orientation workspaces for a haptic device was obtained to show the effectiveness of the suggested scheme, and the kinematic performances of the proposed model were compared with those of a preexisting base model
Optimum design of 6-DOF parallel manipulator with translational/rotational workspaces for haptic device application

International Nuclear Information System (INIS)

Yoon, Jung Won; Hwang, Yoon Kwon; Ryu, Je Ha

2010-01-01

This paper proposes an optimum design method that satisfies the desired orientation workspace at the boundary of the translation workspace while maximizing the mechanism isotropy for parallel manipulators. A simple genetic algorithm is used to obtain the optimal linkage parameters of a six-degree-of-freedom parallel manipulator that can be used as a haptic device. The objective function is composed of a desired spherical shape translation workspace and a desired orientation workspace located on the boundaries of the desired translation workspace, along with a global conditioning index based on a homogeneous Jacobian matrix. The objective function was optimized to satisfy the desired orientation workspace at the boundary positions as translated from a neutral position of the increased entropy mechanism. An optimization result with desired translation and orientation workspaces for a haptic device was obtained to show the effectiveness of the suggested scheme, and the kinematic performances of the proposed model were compared with those of a preexisting base model
Initiating stochastic maintenance optimization at Candu Power Plants

International Nuclear Information System (INIS)

Doyle, E.K.

2003-01-01

As previously reported at ICONE 6 in New Orleans (1996), the use of various innovative maintenance optimization techniques at Bruce has lead to cost effective preventive maintenance applications for complex systems. Further cost refinement of the station maintenance strategy is being evaluated via the applicability of statistical analysis of historical failure data. Since the statistical evaluation was initiated in 1999 significant progress has been made in demonstrating the viability of stochastic methods in Candu maintenance. Some of the relevant results were presented at ICONE 10 in Washington DC (2002). Success with the graphical displays and the relatively easy to implement stochastic computer programs was sufficient to move the program along to the next significant phase. This next phase consists of investigating the validity of using subjective elicitation techniques to obtain component lifetime distributions. This technique provides access to the elusive failure statistics, the lack of which is often referred to in the literature as the principle impediment preventing the use of stochastic methods in large industry. At the same time the technique allows very valuable information to be captured from the fast retiring 'baby boom generation'. Initial indications have been quite positive. (author)
Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

Science.gov (United States)

Hainfellner, J A; Heinzl, H

2010-01-01

Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.
Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma

Science.gov (United States)

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

2015-01-01

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

International Nuclear Information System (INIS)

Savitski, D.W.

2001-01-01

This paper examines state initiation of public service (or utility) commission regulation of investor-owned utilities (IOUs) using an economic theory of regulation. The decision to regulate IOUs is assumed to have depended on the strength of competing interest groups, e.g. consumers and producers, and on institutional factors, e.g. whether commissioners were appointed or elected. Regulators, which then had jurisdiction over IOU rates, are assumed to have been optimizing agents. The potential benefits of regulation, in turn, translated into pressure to initiate regulation. To test this, a hazard model is applied to state-level data. On the demand side of the regulation market, the distribution of federal power and population density were unrelated, while a set of time dummies was positively related to the probability that a state initiated regulation. On the supply side, the fraction of the population that was urban and whether the governor was Republican or not were positively and negatively related to this probability
FRC translation into a compression coil

International Nuclear Information System (INIS)

Chrien, R.E.

1985-01-01

Several features of the problem of FRC translation into a compression coil are considered. First, the magnitude of the guide field is calculated and found to exceed that which would be applied to a flux conserver. Second, energy conservation is applied to FRC translation from a flux conserver into a compression coil. It is found that a significant temperature decrease is required for translation to be energetically possible. The temperature change depends on the external inductance in the compression circuit. An analogous case is that of a compression region composed of a compound magnet; in this case the temperature change depends on the ratio of inner and outer coil radii. Finally, the kinematics of intermediate translation states are calculated using an ''abrupt transition'' model. It is found, in this model, that the FRC must overcome a potential hill during translation, which requires a small initial velocity
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 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......, 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....
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.

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

Science.gov (United States)

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

2016-01-01

Background and Objective: 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. Design: 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. Results: 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. Conclusions: 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. PMID:26755459
The 5'-poly(A leader of poxvirus mRNA confers a translational advantage that can be achieved in cells with impaired cap-dependent translation.

Directory of Open Access Journals (Sweden)

Pragyesh Dhungel

2017-08-01

Full Text Available The poly(A leader at the 5'-untranslated region (5'-UTR is an unusually striking feature of all poxvirus mRNAs transcribed after viral DNA replication (post-replicative mRNAs. These poly(A leaders are non-templated and of heterogeneous lengths; and their function during poxvirus infection remains a long-standing question. Here, we discovered that a 5'-poly(A leader conferred a selective translational advantage to mRNA in poxvirus-infected cells. A constitutive and uninterrupted 5'-poly(A leader with 12 residues was optimal. Because the most frequent lengths of the 5'-poly(A leaders are 8-12 residues, the result suggests that the poly(A leader has been evolutionarily optimized to boost poxvirus protein production. A 5'-poly(A leader also could increase protein production in the bacteriophage T7 promoter-based expression system of vaccinia virus, the prototypic member of poxviruses. Interestingly, although vaccinia virus post-replicative mRNAs do have 5'- methylated guanosine caps and can use cap-dependent translation, in vaccinia virus-infected cells, mRNA with a 5'-poly(A leader could also be efficiently translated in cells with impaired cap-dependent translation. However, the translation was not mediated through an internal ribosome entry site (IRES. These results point to a fundamental mechanism poxvirus uses to efficiently translate its post-replicative mRNAs.
Optimizing Quality of Care and Patient Safety in Malaysia: The Current Global Initiatives, Gaps and Suggested Solutions

OpenAIRE

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

2015-01-01

Background and Objective: 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. Design: 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 patie...
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.
Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

International Nuclear Information System (INIS)

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

2007-01-01

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

Energy Technology Data Exchange (ETDEWEB)

Ventrucci, Gislaine [Laboratório de Nutrição e Câncer, Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-970, São Paulo (Brazil); Mello, Maria Alice R [Departamento de Fisiologia e Biofísica, Instituto Biociências, Universidade Estadual de São Paulo, UNESP, Rio Claro, 13506-900, São Paulo (Brazil); Gomes-Marcondes, Maria Cristina C [Laboratório de Nutrição e Câncer, Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-970, São Paulo (Brazil)

2007-03-06

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

Science.gov (United States)

Batman, Angela M; Miles, Michael F

2015-01-01

Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of stream-lining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD.
FRC translation into a compression coil

International Nuclear Information System (INIS)

Chrien, R.E.

1986-01-01

The equilibrium and translational kinematics of Field-Reversed Configurations (FRCs) in a cylindrical coil which does not conserve flux are problems that arise in connection with adiabatic compressional heating. In this paper, they consider several features of the problem of FRC translation into a compression coil. First, the magnitude of the guide field is calculated and found to exceed that which would be applied to a flux conserver. Second, energy conservation is applied to FRC translation from a flux conserver into a compression coil. It is found that a significant temperature decrease is required for translation to be energetically possible. The temperature change depends on the external inductance in the compression circuit. An analogous case is that of a compression region composed of a compound magnet; in this case the temperature change depends on the ratio of inner and outer coil radii. Finally, the kinematics of intermediate translation states are calculated using an abrupt transition model. It is found, in this model, that the FRC must overcome a potential hill during translation, which requires a small initial velocity
Variational data assimilation for the optimized ozone initial state and the short-time forecasting

Directory of Open Access Journals (Sweden)

S.-Y. Park

2016-03-01

Full Text Available 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 are 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 h assimilation periods and the 120 observatory sites show a 49.4 % decrease in the root mean squared 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 (root mean squared error with assimilation versus that without assimilation are 8 and 13 % for the +24 and +12 h, respectively. Such a significant improvement in the forecast accuracy is obtained solely by using the optimized initial state. The potential
The N-terminal region of eukaryotic translation initiation factor 5A signals to nuclear localization of the protein

International Nuclear Information System (INIS)

Parreiras-e-Silva, Lucas T.; Gomes, Marcelo D.; Oliveira, Eduardo B.; Costa-Neto, Claudio M.

2007-01-01

The eukaryotic translation initiation factor 5A (eIF5A) is a ubiquitous protein of eukaryotic and archaeal organisms which undergoes hypusination, a unique post-translational modification. We have generated a polyclonal antibody against murine eIF5A, which in immunocytochemical assays in B16-F10 cells revealed that the endogenous protein is preferentially localized to the nuclear region. We therefore analyzed possible structural features present in eIF5A proteins that could be responsible for that characteristic. Multiple sequence alignment analysis of eIF5A proteins from different eukaryotic and archaeal organisms showed that the former sequences have an extended N-terminal segment. We have then performed in silico prediction analyses and constructed different truncated forms of murine eIF5A to verify any possible role that the N-terminal extension might have in determining the subcellular localization of the eIF5A in eukaryotic organisms. Our results indicate that the N-terminal extension of the eukaryotic eIF5A contributes in signaling this protein to nuclear localization, despite of bearing no structural similarity with classical nuclear localization signals
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…
Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid.

Science.gov (United States)

Aragonès, Lluís; Guix, Susana; Ribes, Enric; Bosch, Albert; Pintó, Rosa M

2010-03-05

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.
Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid.

Directory of Open Access Journals (Sweden)

Lluís Aragonès

2010-03-01

Full Text Available Hepatitis A virus (HAV, the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.
PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer.

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Hsu, Jessie Hao-Ru; Hubbell-Engler, Benjamin; Adelmant, Guillaume; Huang, Jialiang; Joyce, Cailin E; Vazquez, Francisca; Weir, Barbara A; Montgomery, Philip; Tsherniak, Aviad; Giacomelli, Andrew O; Perry, Jennifer A; Trowbridge, Jennifer; Fujiwara, Yuko; Cowley, Glenn S; Xie, Huafeng; Kim, Woojin; Novina, Carl D; Hahn, William C; Marto, Jarrod A; Orkin, Stuart H

2017-09-01

Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. p53/Rb-null cells were sensitive to p53-induced translation stress, and analysis of human cancer cell line data from Project Achilles further revealed that Prmt1 and translation-associated pathways converged on the same functional networks. We propose that targeted therapy against Prmt1 and its associated translation-related pathways offer a mechanistic rationale for treatment of osteosarcomas and other cancers that exhibit dependencies on translation stress response. Cancer Res; 77(17); 4613-25. ©2017 AACR . ©2017 American Association for Cancer Research.
Translation of the shallot virus X TGB3 gene depends on non-AUG initiation and leaky scanning.

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Lezzhov, Alexander A; Gushchin, Vladimir A; Lazareva, Ekaterina A; Vishnichenko, Valery K; Morozov, Sergey Y; Solovyev, Andrey G

2015-10-01

Triple gene block (TGB), a conserved gene module found in the genomes of many filamentous and rod-shaped plant viruses, encodes three proteins, TGB1, TGB2 and TGB3, required for viral cell-to-cell movement through plasmodesmata and systemic transport via the phloem. The genome of Shallot virus X, the type species of the genus Allexivirus, includes TGB1 and TGB2 genes, but contains no canonical ORF for TGB3 protein. However, a TGB3-like protein-encoding sequence lacking an AUG initiator codon has been found in the shallot virus X (ShVX) genome in a position typical for TGB3 genes. This putative TGB3 gene is conserved in all allexiviruses. Here, we carried out sequence analysis to predict possible non-AUG initiator codons in the ShVX TGB3-encoding sequence. We further used an agroinfiltration assay in Nicotiana benthamiana to confirm this prediction. Site-directed mutagenesis was used to demonstrate that the ShVX TGB3 could be translated on a bicistronic mRNA template via a leaky scanning mechanism.
Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape.

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Scarlet S Shell

2015-11-01

Full Text Available RNA-seq technologies have provided significant insight into the transcription networks of mycobacteria. However, such studies provide no definitive information on the translational landscape. Here, we use a combination of high-throughput transcriptome and proteome-profiling approaches to more rigorously understand protein expression in two mycobacterial species. RNA-seq and ribosome profiling in Mycobacterium smegmatis, and transcription start site (TSS mapping and N-terminal peptide mass spectrometry in Mycobacterium tuberculosis, provide complementary, empirical datasets to examine the congruence of transcription and translation in the Mycobacterium genus. We find that nearly one-quarter of mycobacterial transcripts are leaderless, lacking a 5' untranslated region (UTR and Shine-Dalgarno ribosome-binding site. Our data indicate that leaderless translation is a major feature of mycobacterial genomes and is comparably robust to leadered initiation. Using translational reporters to systematically probe the cis-sequence requirements of leaderless translation initiation in mycobacteria, we find that an ATG or GTG at the mRNA 5' end is both necessary and sufficient. This criterion, together with our ribosome occupancy data, suggests that mycobacteria encode hundreds of small, unannotated proteins at the 5' ends of transcripts. The conservation of small proteins in both mycobacterial species tested suggests that some play important roles in mycobacterial physiology. Our translational-reporter system further indicates that mycobacterial leadered translation initiation requires a Shine Dalgarno site in the 5' UTR and that ATG, GTG, TTG, and ATT codons can robustly initiate translation. Our combined approaches provide the first comprehensive view of mycobacterial gene structures and their non-canonical mechanisms of protein expression.
Diffusion-accomodated rigid-body translations along grain boundaries in nanostructured materials

International Nuclear Information System (INIS)

Bachurin, D.V.; Nazarov, A.A.; Shenderova, O.A.; Brenner, D.W.

2003-01-01

A model for the structural relaxation of grain boundaries (GBs) in nanostructured materials (NSMs) by diffusion-accommodated rigid body translations along GBs is proposed. The model is based on the results of recent computer simulations that have demonstrated that the GBs in NSMs retain a high-energy structure with random translational states due to severe geometrical constraints applied from neighboring grains (J. Appl. Phys. 78 (1995) 847; Scripta Metall. Mater. 33 (1995) 1245). The shear stresses within a GB caused by non-optimized rigid-body translations (RBTs) can be accommodated by diffusive flow of atoms along a GB. This mechanism is particularly important for low-angle and vicinal GBs, the energy of which noticeably depends on the rigid body translations. At moderate and high temperatures the model yields relaxation times that are very short and therefore GBs in NSMs can attain an equilibrium structure with optimized rigid body translations. In contrast, at room temperature the model predicts that in some metals non-equilibrium structures can be preserved for a long time, which may result in the observation of grain boundary structures different from those in coarse grained polycrystals
Translational control in plant antiviral immunity

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João Paulo B. Machado

Full Text Available Abstract Due to the limited coding capacity of viral genomes, plant viruses depend extensively on the host cell machinery to support the viral life cycle and, thereby, interact with a large number of host proteins during infection. Within this context, as plant viruses do not harbor translation-required components, they have developed several strategies to subvert the host protein synthesis machinery to produce rapidly and efficiently the viral proteins. As a countermeasure against infection, plants have evolved defense mechanisms that impair viral infections. Among them, the host-mediated translational suppression has been characterized as an efficient mean to restrict infection. To specifically suppress translation of viral mRNAs, plants can deploy susceptible recessive resistance genes, which encode translation initiation factors from the eIF4E and eIF4G family and are required for viral mRNA translation and multiplication. Additionally, recent evidence has demonstrated that, alternatively to the cleavage of viral RNA targets, host cells can suppress viral protein translation to silence viral RNA. Finally, a novel strategy of plant antiviral defense based on suppression of host global translation, which is mediated by the transmembrane immune receptor NIK1 (nuclear shuttle protein (NSP-Interacting Kinase1, is discussed in this review.
The Sydney West Knowledge Portal: Evaluating the Growth of a Knowledge Portal to Support Translational Research.

Science.gov (United States)

Janssen, Anna; Robinson, Tracy Elizabeth; Provan, Pamela; Shaw, Tim

2016-06-29

The Sydney West Translational Cancer Research Centre is an organization funded to build capacity for translational research in cancer. Translational research is essential for ensuring the integration of best available evidence into practice and for improving patient outcomes. However, there is a low level of awareness regarding what it is and how to conduct it optimally. One solution to addressing this gap is the design and deployment of web-based knowledge portals to disseminate new knowledge and engage with and connect dispersed networks of researchers. A knowledge portal is an web-based platform for increasing knowledge dissemination and management in a specialized area. To measure the design and growth of an web-based knowledge portal for increasing individual awareness of translational research and to build organizational capacity for the delivery of translational research projects in cancer. An adaptive methodology was used to capture the design and growth of an web-based knowledge portal in cancer. This involved stakeholder consultations to inform initial design of the portal. Once the portal was live, site analytics were reviewed to evaluate member usage of the portal and to measure growth in membership. Knowledge portal membership grew consistently for the first 18 months after deployment, before leveling out. Analysis of site metrics revealed members were most likely to visit portal pages with community-generated content, particularly pages with a focus on translational research. This was closely followed by pages that disseminated educational material about translational research. Preliminary data from this study suggest that knowledge portals may be beneficial tools for translating new evidence and fostering an environment of communication and collaboration.

Knowledge translation of research findings

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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
Knowledge translation of research findings.

Science.gov (United States)

Grimshaw, Jeremy M; Eccles, Martin P; Lavis, John N; Hill, Sophie J; Squires, Janet E

2012-05-31

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? 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 translation strategy is informed by an assessment of the
An Ad-Hoc Initial Solution Heuristic for Metaheuristic Optimization of Energy Market Participation Portfolios

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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.
Translation in cell-free systems

International Nuclear Information System (INIS)

Jagus, R.

1987-01-01

The simplest, unambiguous identification of a particular mRNA is the identification of its protein product. This can be established by translation of the mRNA of interest in a cell-free protein-synthesizing system. Messenger RNA protein product identification is important in the isolation of a particular mRNA species for cDNA cloning and in the identification of positive cDNA clones. The two high-activity translation systems in common use are those prepared from rabbit reticulocytes and from wheat germ. Both systems are easy to prepare, and both are available commercially. Each has advantages and disadvantages over the other and a choice between the two will depend on the type of mRNAs to be translated, the prejudices of experience, and availability. The main disadvantage of the reticulocyte system is that it requires removal of endogenous mRNA. However, this is a relatively simple procedure. The wheat germ system does not require removal of endogenous mRNA and may translate weakly initiating mRNAs more efficiently. However, ionic optima for translation in the wheat germ system are more sensitive to the nature and concentration of mRNA and may need to be determined for each template. The biggest problem with the use of the wheat germ system is its tendency to produce incomplete translation products due to premature termination
AtLa1 protein initiates IRES-dependent translation of WUSCHEL mRNA and regulates the stem cell homeostasis of Arabidopsis in response to environmental hazards.

Science.gov (United States)

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

2015-10-01

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

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Marygold, Steven J; Attrill, Helen; Lasko, Paul

2017-01-02

Synthesis of polypeptides from mRNA (translation) is a fundamental cellular process that is coordinated and catalyzed by a set of canonical 'translation factors'. Surprisingly, the translation factors of Drosophila melanogaster have not yet been systematically identified, leading to inconsistencies in their nomenclature and shortcomings in functional (Gene Ontology, GO) annotations. Here, we describe the complete set of translation factors in D. melanogaster, applying nomenclature already in widespread use in other species, and revising their functional annotation. The collection comprises 43 initiation factors, 12 elongation factors, 3 release factors and 6 recycling factors, totaling 64 of which 55 are cytoplasmic and 9 are mitochondrial. We also provide an overview of notable findings and particular insights derived from Drosophila about these factors. This catalog, together with the incorporation of the improved nomenclature and GO annotation into FlyBase, will greatly facilitate access to information about the functional roles of these important proteins.
Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

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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.
Regulation of mRNA translation influences hypoxia tolerance

International Nuclear Information System (INIS)

Koritzinsky, M.; Wouters, B.G.; Koumenis, C.

2003-01-01

Hypoxia is a heterogenous but common characteristic of human tumours and poor oxygenation is associated with poor prognosis. We believe that the presence of viable hypoxic tumor cells reflects in part an adaptation and tolerance of these cells to oxygen deficiency. Since oxidative phosphorylation is compromized during hypoxia, adaptation may involve both the upregulation of glycolysis as well as downregulation of energy consumption. mRNA translation is one of the most energy costly cellular processes, and we and others have shown that global mRNA translation is rapidly inhibited during hypoxia. However, some mRNAs, including those coding for HIF-1 α and VEGF, remain efficiently translated during hypoxia. Clearly, the mechanisms responsible for the overall inhibition of translation during hypoxia does not compromize the translation of certain hypoxia-induced mRNA species. We therefore hypothesize that the inhibition of mRNA translation serves to promote hypoxia tolerance in two ways: i) through conservation of energy and ii) through differential gene expression involved in hypoxia adaptation. We have recently identified two pathways that are responsible for the global inhibition of translation during hypoxia. The phosphorylation of the eukaryotic initiation factor eIF2 α by the ER resident kinase PERK results in down-regulation of protein synthesis shortly after the onset of hypoxia. In addition, the initiation complex eIF4F is disrupted during long lasting hypoxic conditions. The identification of the molecular pathways responsible for the inhibition of overall translation during hypoxia has rendered it possible to investigate their importance for hypoxia tolerance. We have found that mouse embryo fibroblasts that are knockout for PERK and therefore not able to inhibit protein synthesis efficiently during oxygen deficiency are significantly less tolerant to hypoxia than their wildtype counterparts. We are currently also investigating the functional significance
Mapping Translation Technology Research in Translation Studies

DEFF Research Database (Denmark)

Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

2017-01-01

section aims to improve this situation by presenting new and innovative research papers that reflect on recent technological advances and their impact on the translation profession and translators from a diversity of perspectives and using a variety of methods. In Section 2, we present translation......Due to the growing uptake of translation technology in the language industry and its documented impact on the translation profession, translation students and scholars need in-depth and empirically founded knowledge of the nature and influences of translation technology (e.g. Christensen....../Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...
Translation of SNOMED CT - strategies and description of a pilot project.

Science.gov (United States)

Klein, Gunnar O; Chen, Rong

2009-01-01

The translation and localization of SNOMED CT (Systematized Nomenclature of Medicine - Clinical Terms) have been initiated in a few countries. In Sweden, we conducted the first evaluation of this terminology in a project called REFTERM in which we also developed a software tool which could handle a large scale translation with a number of translators and reviewers in a web-based environment. The system makes use of existing authorized English-Swedish translations of medical terminologies such as ICD-10. The paper discusses possible strategies for a national project to translate and adapt this terminology.
Trans-acting translational regulatory RNA binding proteins.

Science.gov (United States)

Harvey, Robert F; Smith, Tom S; Mulroney, Thomas; Queiroz, Rayner M L; Pizzinga, Mariavittoria; Dezi, Veronica; Villenueva, Eneko; Ramakrishna, Manasa; Lilley, Kathryn S; Willis, Anne E

2018-05-01

The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans-acting regulatory RNA-binding proteins (RBPs) are necessary to provide mRNA-specific translation, and these interact with 5' and 3' untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans-acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans-acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans-acting ribosomal proteins in directing the translation of specific mRNAs. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Translation Regulation Translation > Translation Mechanisms. © 2018 Medical Research Council and University of Cambridge. WIREs RNA published by Wiley Periodicals, Inc.
Cause for concern? Attitudes towards translation crowdsourcing in professional translators’ blogs

DEFF Research Database (Denmark)

Flanagan, Marian

2016-01-01

This paper seeks to identify professional translators’ attitudes towards the practice of translation crowdsourcing. The data consist of 48 professional translator blogs. A thematic analysis of their blog posts highlights three main findings: translation crowdsourcing can enhance visibility...... do not openly discuss their motives for differentiating between the various non-profit initiatives, and while there is much discussion on translation crowdsourcing for humanitarian causes, little or no attention is paid to free and open source software projects....
Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation.

Science.gov (United States)

Allavena, Giulia; Cuomo, Francesca; Baumgartner, Georg; Bele, Tadeja; Sellgren, Alexander Yarar; Oo, Kyaw Soe; Johnson, Kaylee; Gogvadze, Vladimir; Zhivotovsky, Boris; Kaminskyy, Vitaliy O

2018-01-01

Macroautophagy/autophagy inhibition under stress conditions is often associated with increased cell death. We found that under nutrient limitation, activation of CASP8/caspase-8 was significantly increased in autophagy-deficient lung cancer cells, which precedes mitochondria outer membrane permeabilization (MOMP), CYCS/cytochrome c release, and activation of CASP9/caspase-9, indicating that under such conditions the activation of CASP8 is a primary event in the initiation of apoptosis as well as essential to reduce clonogenic survival of autophagy-deficient cells. Starvation leads to suppression of CFLAR proteosynthesis and accumulation of CASP8 in SQSTM1 puncta. Overexpression of CFLARs reduces CASP8 activation and apoptosis during starvation, while its silencing promotes efficient activation of CASP8 and apoptosis in autophagy-deficient U1810 lung cancer cells even under nutrient-rich conditions. Similar to starvation, inhibition of protein translation leads to efficient activation of CASP8 and cell death in autophagy-deficient lung cancer cells. Thus, here for the first time we report that suppressed translation leads to activation of CASP8-dependent apoptosis in autophagy-deficient NSCLC cells under conditions of nutrient limitation. Our data suggest that targeting translational machinery can be beneficial for elimination of autophagy-deficient cells via the CASP8-dependent apoptotic pathway.
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
From Translational Research to Translational Effectiveness: The “Patient-Centered Dental Home” Model

Directory of Open Access Journals (Sweden)

Francesco Chiappelli

2011-06-01

Full Text Available Toward revitalizing the Nation’s primary medical care system, the Agency for Health Research & Quality (AHRQ stated that new foundational measures must be crafted for achieving high-quality, accessible, efficient health care for all Americans. The efficiency of medical care is viewed along two dimensions: first, we must continue to pursue translational research; and second, we must translate research to optimize effectiveness in specific clinical settings. It is increasingly evident that the efficiency of both translational processes is critical to the revitalization of health care, and that it rests on the practical functionality of the nexus among three cardinal entities: the researcher, the clinician, and the patient. A novel model has evolved that encapsulates this notion, and that proposes the advanced pri-mary care “medical home”, more commonly referred to as the “patient-centered medical home” (PCMH. It is a promising model for transforming the organization and delivery of primary medical care, because it is not simply a place per se, but it is a function-ing unit that delivers medical care along the fundamental principles of being patient-centered, comprehensive, coordinated, and accessible. It is energized by translational research, and its principal aim and ultimate goal is translational effectiveness. The PCMH is a model that works well within the priorities set by the American Recovery and Reinvestment Act of 2009, and the Health Care Reform Act of 2010. However, while dentistry has a clearly defined place in both Acts, the PCMH is designed for medical and nursing care. A parallel model of the “patient-centered dental home” (PCDH must be realized.
Lack of anomalous diffusion in linear translationally-invariant systems determined by only one initial condition

International Nuclear Information System (INIS)

Khorrami, Mohammad; Shariati, Ahmad; Aghamohammadi, Amir; Fatollahi, Amir H.

2012-01-01

It is shown that as far as the linear diffusion equation meets both time- and space-translational invariance, the time dependence of a moment of degree α is a polynomial of degree at most equal to α, while all connected moments are at most linear functions of time. As a special case, the variance is an at most linear function of time. -- Highlights: ► The sufficient conditions for having the non-anomalous diffusion are given. ► Conditions are linearity, space-time translation invariance, solution uniqueness. ► Some versions of the fractional derivatives lack the translational invariance. ► It is shown the encoded inhomogeneity in derivatives causes anomalous behavior.
Lack of anomalous diffusion in linear translationally-invariant systems determined by only one initial condition

Energy Technology Data Exchange (ETDEWEB)

Khorrami, Mohammad, E-mail: mamwad@mailaps.org [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of); Shariati, Ahmad, E-mail: shariati@mailaps.org [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of); Aghamohammadi, Amir, E-mail: mohamadi@alzahra.ac.ir [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of); Fatollahi, Amir H., E-mail: ahfatol@gmail.com [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of)

2012-01-16

It is shown that as far as the linear diffusion equation meets both time- and space-translational invariance, the time dependence of a moment of degree α is a polynomial of degree at most equal to α, while all connected moments are at most linear functions of time. As a special case, the variance is an at most linear function of time. -- Highlights: ► The sufficient conditions for having the non-anomalous diffusion are given. ► Conditions are linearity, space-time translation invariance, solution uniqueness. ► Some versions of the fractional derivatives lack the translational invariance. ► It is shown the encoded inhomogeneity in derivatives causes anomalous behavior.
Translational behavioral medicine for population and individual health: gaps, opportunities, and vision for practice-based translational behavior change research.

Science.gov (United States)

Ma, Jun; Lewis, Megan A; Smyth, Joshua M

2018-04-12

In this commentary, we propose a vision for "practice-based translational behavior change research," which we define as clinical and public health practice-embedded research on the implementation, optimization, and fundamental mechanisms of behavioral interventions. This vision intends to be inclusive of important research elements for behavioral intervention development, testing, and implementation. We discuss important research gaps and conceptual and methodological advances in three key areas along the discovery (development) to delivery (implementation) continuum of evidence-based interventions to improve behavior and health that could help achieve our vision of practice-based translational behavior change research. We expect our proposed vision to be refined and evolve over time. Through highlighting critical gaps that can be addressed by integrating modern theoretical and methodological approaches across disciplines in behavioral medicine, we hope to inspire the development and funding of innovative research on more potent and implementable behavior change interventions for optimal population and individual health.
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.
On Interactive Teaching Model of Translation Course Based on Wechat

Science.gov (United States)

Lin, Wang

2017-01-01

Constructivism is a theory related to knowledge and learning, focusing on learners' subjective initiative, based on which the interactive approach has been proved to play a crucial role in language learning. Accordingly, the interactive approach can also be applied to translation teaching since translation itself is a bilingual transformational…

Relationship among Translational Medicine, Evidence-Based Medicine and Precision Medicine

OpenAIRE

Xin-en HUANG

2016-01-01

Translational medicine is a new concept in international medical field. It integrates experimental research results and clinical guidance into the optimal implementation criteria for promoting the prediction, prevention and treatment of diseases. Based on people’s higher demand for medicine and health, appearance of translational medicine changes the mode of medical research.Evidence-based medicine (EBM) refers to cautious and accurate application of the current best research evidence and com...
Translation of field-reversed configurations in the FRX C/T experiment

Energy Technology Data Exchange (ETDEWEB)

Rej, D.J.; Armstrong, W.T.; Chrien, R.E.; Klingner, P.L.; Linford, R.K.; McKenna, K.F.; Milroy, R.D.; Sherwood, E.G.; Siemon, R.E.; Tuszewski, M.

1984-01-01

One of the unique features inherent to compact toroids is the potential ability to translate the plasma along its geometric axis. CT translation has proven useful in reactor design studies, and has been the focus of several experimental investigations. In this paper, we report on the initial results from translation experiments performed with the field-reversed configuration (FRC) plasmas generated in the FRX-C/T device.
Translation of field-reversed configurations in the FRX C/T experiment

International Nuclear Information System (INIS)

Rej, D.J.; Armstrong, W.T.; Chrien, R.E.

1984-01-01

One of the unique features inherent to compact toroids is the potential ability to translate the plasma along its geometric axis. CT translation has proven useful in reactor design studies, and has been the focus of several experimental investigations. In this paper, we report on the initial results from translation experiments performed with the field-reversed configuration (FRC) plasmas generated in the FRX-C/T device
NATIONAL FRAMEWORK FOR THE SUSTAINABILITY OF HEALTH KNOWLEDGE TRANSLATION INITIATIVES IN UGANDA.

Science.gov (United States)

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

2018-01-01

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

Science.gov (United States)

Shapiro, Robyn S.; Layde, Peter M.

2008-01-01

Abstract Recent initiatives to improve human health emphasize the need to effectively and appropriately translate new knowledge gleaned from basic biomedical and behavioral research to clinical and community application. To maximize the beneficial impact of scientific advances in clinical practice and community health, and to guard against potential deleterious medical and societal consequences of such advances, incorporation of bioethics at each stage of clinical and translational science research is essential. At the earliest stage, bioethics input is critical to address issues such as whether to limit certain areas of scientific inquiry. Subsequently, bioethics input is important to assure not only that human subjects trials are conducted and reported responsibly, but also that results are incorporated into clinical and community practices in a way that promotes and protects bioethical principles. At the final stage of clinical and translational science research, bioethics helps to identify the need and approach for refining clinical practices when safety or other concerns arise. The framework we present depicts how bioethics interfaces with each stage of clinical and translational science research, and suggests an important research agenda for systematically and comprehensively assuring bioethics input into clinical and translational science initiatives. PMID:20443821
Measurement of the translation and rotation of a sphere in fluid flow

Science.gov (United States)

Barros, Diogo; Hiltbrand, Ben; Longmire, Ellen K.

2018-06-01

The problem of determining the translation and rotation of a spherical particle moving in fluid flow is considered. Lagrangian tracking of markers printed over the surface of a sphere is employed to compute the center motion and the angular velocity of the solid body. The method initially calculates the sphere center from the 3D coordinates of the reconstructed markers, then finds the optimal rotation matrix that aligns a set of markers tracked at sequential time steps. The parameters involved in the experimental implementation of this procedure are discussed, and the associated uncertainty is estimated from numerical analysis. Finally, the proposed methodology is applied to characterize the motion of a large spherical particle released in a turbulent boundary layer developing in a water channel.
Understanding Translation

DEFF Research Database (Denmark)

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

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

Science.gov (United States)

Ectors, N

2011-01-01

Translational research and biobanking are "in", also in Flanders and in Belgium. In Flanders the Advice report 120 from the Flemish Council for Science and innovation, entitled "Extension of translational research in Flanders" paved the way for the Center for Medical Innovation. The Center for Medical Innovation aims at promoting collaboration between Flemish Universities, university hospitals, pharma and biotech industry and the Flemish Government specifically in the domain of translational research. The Initiative # 27 of the Cancer plan from the Federal Government aims at financing a virtual interuniversity tumor bank in order to promote "cancer" translational research in a collaborative network between academic structures, general hospitals en different industrial partners (pharmacy, biotechnology, diagnostics, ...) active in research in Belgium. However, the scientific interest in the human tissues is not new, at all. This text aims at giving an overview of the development and evolutions of "biobanking" initiatives.
NASA-IGES Translator and Viewer

Science.gov (United States)

Chou, Jin J.; Logan, Michael A.

1995-01-01

NASA-IGES Translator (NIGEStranslator) is a batch program that translates a general IGES (Initial Graphics Exchange Specification) file to a NASA-IGES-Nurbs-Only (NINO) file. IGES is the most popular geometry exchange standard among Computer Aided Geometric Design (CAD) systems. NINO format is a subset of IGES, implementing the simple and yet the most popular NURBS (Non-Uniform Rational B-Splines) representation. NIGEStranslator converts a complex IGES file to the simpler NINO file to simplify the tasks of CFD grid generation for models in CAD format. The NASA-IGES Viewer (NIGESview) is an Open-Inventor-based, highly interactive viewer/ editor for NINO files. Geometry in the IGES files can be viewed, copied, transformed, deleted, and inquired. Users can use NIGEStranslator to translate IGES files from CAD systems to NINO files. The geometry then can be examined with NIGESview. Extraneous geometries can be interactively removed, and the cleaned model can be written to an IGES file, ready to be used in grid generation.
Plant Translation Factors and Virus Resistance

Directory of Open Access Journals (Sweden)

Hélène Sanfaçon

2015-06-01

Full Text Available Plant viruses recruit cellular translation factors not only to translate their viral RNAs but also to regulate their replication and potentiate their local and systemic movement. Because of the virus dependence on cellular translation factors, it is perhaps not surprising that many natural plant recessive resistance genes have been mapped to mutations of translation initiation factors eIF4E and eIF4G or their isoforms, eIFiso4E and eIFiso4G. The partial functional redundancy of these isoforms allows specific mutation or knock-down of one isoform to provide virus resistance without hindering the general health of the plant. New possible targets for antiviral strategies have also been identified following the characterization of other plant translation factors (eIF4A-like helicases, eIF3, eEF1A and eEF1B that specifically interact with viral RNAs and proteins and regulate various aspects of the infection cycle. Emerging evidence that translation repression operates as an alternative antiviral RNA silencing mechanism is also discussed. Understanding the mechanisms that control the development of natural viral resistance and the emergence of virulent isolates in response to these plant defense responses will provide the basis for the selection of new sources of resistance and for the intelligent design of engineered resistance that is broad-spectrum and durable.
Splicing of goose parvovirus pre-mRNA influences cytoplasmic translation of the processed mRNA

Energy Technology Data Exchange (ETDEWEB)

Li, Long; Pintel, David J., E-mail: pinteld@missouri.edu

2012-04-25

Translation of goose parvovirus (GPV) 72 kDa Rep 1 is initiated from unspliced P9-generated mRNAs in ORF1 from the first in-frame AUG (537 AUG); however, this AUG is bypassed in spliced P9-generated RNA: translation of the 52 kDa Rep 2 protein from spliced RNA is initiated in ORF2 at the next AUG downstream (650 AUG). Usage of the 537 AUG was restored in spliced RNA when the GPV intron was replaced with a chimeric SV40 intron, or following specific mutations of the GPV intron which did not appear in the final spliced mRNA. Additionally, 650 AUG usage was gained in unspliced RNA when the GPV intron splice sites were debilitated. Splicing-dependent regulation of translation initiation was mediated in cis by GPV RNA surrounding the target AUGs. Thus, nuclear RNA processing of GPV P9-generated pre-mRNAs has a complex, but significant, effect on alternative translation initiation of the GPV Rep proteins.
Splicing of goose parvovirus pre-mRNA influences cytoplasmic translation of the processed mRNA

International Nuclear Information System (INIS)

Li, Long; Pintel, David J.

2012-01-01

Translation of goose parvovirus (GPV) 72 kDa Rep 1 is initiated from unspliced P9-generated mRNAs in ORF1 from the first in-frame AUG (537 AUG); however, this AUG is bypassed in spliced P9-generated RNA: translation of the 52 kDa Rep 2 protein from spliced RNA is initiated in ORF2 at the next AUG downstream (650 AUG). Usage of the 537 AUG was restored in spliced RNA when the GPV intron was replaced with a chimeric SV40 intron, or following specific mutations of the GPV intron which did not appear in the final spliced mRNA. Additionally, 650 AUG usage was gained in unspliced RNA when the GPV intron splice sites were debilitated. Splicing-dependent regulation of translation initiation was mediated in cis by GPV RNA surrounding the target AUGs. Thus, nuclear RNA processing of GPV P9-generated pre-mRNAs has a complex, but significant, effect on alternative translation initiation of the GPV Rep proteins.
m-AAA Complexes Are Not Crucial for the Survival of Arabidopsis Under Optimal Growth Conditions Despite Their Importance for Mitochondrial Translation.

Science.gov (United States)

Kolodziejczak, Marta; Skibior-Blaszczyk, Renata; Janska, Hanna

2018-05-01

For optimal mitochondrial activity, the mitochondrial proteome must be properly maintained or altered in response to developmental and environmental stimuli. Based on studies of yeast and humans, one of the key players in this control are m-AAA proteases, mitochondrial inner membrane-bound ATP-dependent metalloenzymes. This study focuses on the importance of m-AAA proteases in plant mitochondria, providing their first experimentally proven physiological substrate. We found that the Arabidopsis m- AAA complexes composed of AtFTSH3 and/or AtFTSH10 are involved in the proteolytic maturation of ribosomal subunit L32. Consequently, in the double Arabidopsis ftsh3/10 mutant, mitoribosome biogenesis, mitochondrial translation and functionality of OXPHOS (oxidative phosphorylation) complexes are impaired. However, in contrast to their mammalian or yeast counterparts, plant m-AAA complexes are not critical for the survival of Arabidopsis under optimal conditions; ftsh3/10 plants are only slightly smaller in size at the early developmental stage compared with plants containing m-AAA complexes. Our data suggest that a lack of significant visible morphological alterations under optimal growth conditions involves mechanisms which rely on existing functional redundancy and induced functional compensation in Arabidopsis mitochondria.
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.
ERK 1/2 kinase metabolic pathway is responsible for phosphorylation of translation initiation factor eIF4E during in vitro maturation of pig oocytes

Czech Academy of Sciences Publication Activity Database

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

2008-01-01

Roč. 75, č. 2 (2008), s. 309-317 ISSN 1040-452X R&D Projects: GA ČR GA524/04/0104 Grant - others:Deutsche Forschungsgemeinschaft(DE) 463 TSE 113/28 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50110509 Keywords : meiosis * translation initiation * eIF4E Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.287, year: 2008
Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated.

Science.gov (United States)

Suryawan, Agus; Orellana, Renan A; Nguyen, Hanh V; Jeyapalan, Asumthia S; Fleming, Jillian R; Davis, Teresa A

2007-12-01

Insulin and amino acids act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the separate effects of fed levels of INS and AA on the activation of signaling components leading to translation initiation and how these responses change with development. Overnight-fasted 6- (n = 4/group) and 26-day-old (n = 6/ group) pigs were studied during 1) euinsulinemic-euglycemiceuaminoacidemic conditions (controls), 2) euinsulinemic-euglycemichyperaminoacidemic clamps (AA), and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps (INS). INS, but not AA, increased the phosphorylation of protein kinase B (PKB) and tuberous sclerosis 2 (TSC2). Both INS and AA increased protein synthesis and the phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1), and these responses were higher in 6-day-old compared with 26-day-old pigs. Both INS and AA decreased the binding of 4E-BP1 to eIF4E and increased eIF4E binding to eIF4G; these effects were greater in 6-day-old than in 26-day-old pigs. Neither INS nor AA altered the composition of mTORC1 (raptor, mTOR, and GbetaL) or mTORC2 (rictor, mTOR, and GbetaL) complexes. Furthermore, neither INS, AA, nor age had any effect on the abundance of Rheb and the phosphorylation of AMP-activated protein kinase and eukaryotic elongation factor 2. Our results suggest that the activation by insulin and amino acids of signaling components leading to translation initiation is developmentally regulated and parallels the developmental decline in protein synthesis in skeletal muscle of neonatal pigs.
Mapping Translation Technology Research in Translation Studies

DEFF Research Database (Denmark)

Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

2017-01-01

/Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...... section aims to improve this situation by presenting new and innovative research papers that reflect on recent technological advances and their impact on the translation profession and translators from a diversity of perspectives and using a variety of methods. In Section 2, we present translation...... technology research as a subdiscipline of TS, and we define and discuss some basic concepts and models of the field that we use in the rest of the paper. Based on a small-scale study of papers published in TS journals between 2006 and 2016, Section 3 attempts to map relevant developments of translation...
Translational Control in Plasmodium and Toxoplasma Parasites

Science.gov (United States)

Joyce, Bradley R.; Sullivan, William J.; Nussenzweig, Victor

2013-01-01

The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α∼P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α∼P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis. PMID:23243065
Translational control in Plasmodium and toxoplasma parasites.

Science.gov (United States)

Zhang, Min; Joyce, Bradley R; Sullivan, William J; Nussenzweig, Victor

2013-02-01

The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α∼P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α∼P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis.

A community translational research pilot grants program to facilitate community--academic partnerships: lessons from Colorado's clinical translational science awards.

Science.gov (United States)

Main, Deborah S; Felzien, Maret C; Magid, David J; Calonge, B Ned; O'Brien, Ruth A; Kempe, Allison; Nearing, Kathryn

2012-01-01

National growth in translational research has increased the need for practical tools to improve how academic institutions engage communities in research. One used by the Colorado Clinical and Translational Sciences Institute (CCTSI) to target investments in community-based translational research on health disparities is a Community Engagement (CE) Pilot Grants program. Innovative in design, the program accepts proposals from either community or academic applicants, requires that at least half of requested grant funds go to the community partner, and offers two funding tracks: One to develop new community-academic partnerships (up to $10,000), the other to strengthen existing partnerships through community translational research projects (up to $30,000). We have seen early success in both traditional and capacity building metrics: the initial investment of $272,742 in our first cycle led to over $2.8 million dollars in additional grant funding, with grantees reporting strengthening capacity of their community- academic partnerships and the rigor and relevance of their research.
Audiovisual English-Arabic Translation: De Beaugrande's Perspective

Directory of Open Access Journals (Sweden)

Alaa Eddin Hussain

2016-05-01

Full Text Available This paper attempts to demonstrate the significance of the seven standards of textuality with special application to audiovisual English Arabic translation. Ample and thoroughly analysed examples have been provided to help in audiovisual English-Arabic translation decision-making. A text is meaningful if and only if it carries meaning and knowledge to its audience, and is optimally activatable, recoverable and accessible. The same is equally applicable to audiovisual translation (AVT. The latter should also carry knowledge which can be easily accessed by the TL audience, and be processed with least energy and time, i.e. achieving the utmost level of efficiency. Communication occurs only when that text is coherent, with continuity of senses and concepts that are appropriately linked. Coherence of a text will be achieved when all aspects of cohesive devices are well accounted for pragmatically. This combined with a good amount of psycholinguistic element will provide a text with optimal communicative value. Non-text is certainly devoid of such components and ultimately non-communicative. Communicative knowledge can be classified into three categories: determinate knowledge, typical knowledge and accidental knowledge. To create dramatic suspense and the element of surprise, the text in AV environment, as in any dialogue, often carries accidental knowledge. This unusual knowledge aims to make AV material interesting in the eyes of its audience. That cognitive environment is enhanced by an adequate employment of material (picture and sound, and helps to recover sense in the text. Hence, the premise of this paper is the application of certain aspects of these standards to AV texts taken from various recent feature films and documentaries, in order to facilitate the translating process and produce a final appropriate product.
Africa Centre for Systematic Reviews and Knowledge Translation ...

International Development Research Centre (IDRC) Digital Library (Canada)

Several initiatives focused on bridging the "know-do" gap emphasize ... and knowledge translation to bridge the gaps between research and health policy. ... International Water Resources Association, in close collaboration with IDRC, ...
Creativity in Translator Training: Between the Possible, the Improbable and the (Apparently Impossible

Directory of Open Access Journals (Sweden)

Hewson Lance

2016-12-01

Full Text Available The first part of this paper looks at how creativity has been explored in writings in the field of translation studies. It examines the stages in creative translation and investigates the creative process. The second part of the paper looks at how creativity can be exploited in the translation class by concentrating in particular on the liberating role of intralingual and interlingual paraphrase, while considering the various constraints operating on the selection of the optimal target text.
Effective knowledge management in translational medicine.

Science.gov (United States)

Szalma, Sándor; Koka, Venkata; Khasanova, Tatiana; Perakslis, Eric D

2010-07-19

The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA) in the US and the Seventh Framework Programme (FP7) of EU with emphasis on translating research for human health. The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern. The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface. The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.
Internal field probing of translating FRCs

International Nuclear Information System (INIS)

Armstrong, W.T.; Chrien, R.E.; Milroy, R.D.

1984-11-01

Magnetic field probes have been employed to study the internal field structure of Field-Reversed Configurations (FRCs) translating past the probes in the FRX-C/T device. Internal closed flux surfaces can be studied in this manner with minimal perturbation because of the rapid transit of the plasma (translation velocity v/sub z/ approx. 10 cm/μs). Data have been taken using a 5-mtorr-D 2 gas-puff mode of operation in the FRC source coil which yields an initial plasma density of approx. 1 x 10 15 cm -3 and x/sub s/ approx. 0.40. FRCs translate from the approx. 25 cm radius source coil into a 20 cm radius metal translation vessel. Of many translation conditions studied, the condition considered here is translation into a weak guide field resulting in expansion of the FRC to conditions of density approx. 3 x 10 14 and x/sub s/ approx. 0.7. The expected reversed B/sub z/ structure is observed. Evidence of island structure is also observed. Fluctuating levels of B/sub THETA/ are observed with amplitudes less than or equal to B 0 /3 and values of flux approx. 4 x the poloidal flux. Values of β on the separatrix of β/sub s/ approx. = 0.3 (indexed to the external field) are implied from the field measurements. This decrease of β/sub s/ with increased x/sub s/ is expected, and desirable for improved plasma confinement
Effective knowledge management in translational medicine

Directory of Open Access Journals (Sweden)

Khasanova Tatiana

2010-07-01

Full Text Available Abstract Background The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA in the US and the Seventh Framework Programme (FP7 of EU with emphasis on translating research for human health. Methods The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern. Results The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface. Conclusions The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.
T box riboswitches in Actinobacteria: Translational regulation via novel tRNA interactions

Science.gov (United States)

Sherwood, Anna V.; Grundy, Frank J.; Henkin, Tina M.

2015-01-01

The T box riboswitch regulates many amino acid-related genes in Gram-positive bacteria. T box riboswitch-mediated gene regulation was shown previously to occur at the level of transcription attenuation via structural rearrangements in the 5′ untranslated (leader) region of the mRNA in response to binding of a specific uncharged tRNA. In this study, a novel group of isoleucyl-tRNA synthetase gene (ileS) T box leader sequences found in organisms of the phylum Actinobacteria was investigated. The Stem I domains of these RNAs lack several highly conserved elements that are essential for interaction with the tRNA ligand in other T box RNAs. Many of these RNAs were predicted to regulate gene expression at the level of translation initiation through tRNA-dependent stabilization of a helix that sequesters a sequence complementary to the Shine–Dalgarno (SD) sequence, thus freeing the SD sequence for ribosome binding and translation initiation. We demonstrated specific binding to the cognate tRNAIle and tRNAIle-dependent structural rearrangements consistent with regulation at the level of translation initiation, providing the first biochemical demonstration, to our knowledge, of translational regulation in a T box riboswitch. PMID:25583497
Health Narratives in the Greek Translated Press

Directory of Open Access Journals (Sweden)

Themis Panagiotis Kaniklidou

2016-08-01

Full Text Available This paper looks see how meaning is constructed in translated news texts about health and science and awards a narrative potential to unforced translation shifts, moving along the theoretical lines of Baker's Narrative Theory (2006. The thematic thread of health zooms in on “emotional frames” (Nabi, 2003 of risk and fear of human health that is narrated as being 'under attack’ by potentially dangerous diseases. Themes also orbit around schemas that promote hope and optimism about science represented as coming to the rescue of man from fear of the disease. The data consists of 21 pairs of English-Greek health news articles culled from the Greek newspapers I Kathimerini, To Vima and Ta Nea. Findings point towards translation as a process that employs lexicogrammatical and intrasentential configurations to a give emphasis to the risk or hope dimensions underlying a heath or science story, b enable the reflection or emergence of a cascade of public, conceptual and master narratives.
Report of Committee for JAEA Internationalization Initiative (Translated document)

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-07-15

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

International Nuclear Information System (INIS)

2013-07-01

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

International Nuclear Information System (INIS)

Torres, J.L.

1989-01-01

It is assumed that Darwin's principle translates into optimal regimes of operation along metabolical pathways in an ecological system. Fitness is then defined in terms of the distance of a given individual's thermodynamic parameters from their optimal values. The method is illustrated testing maximum power as a criterion of merit satisfied in ATP synthesis. (author). 26 refs, 2 figs
Optimal initiation of electronic excited state mediated intramolecular H-transfer in malonaldehyde by UV-laser pulses

Science.gov (United States)

Nandipati, K. R.; Singh, H.; Nagaprasad Reddy, S.; Kumar, K. A.; Mahapatra, S.

2014-12-01

Optimally controlled initiation of intramolecular H-transfer in malonaldehyde is accomplished by designing a sequence of ultrashort (~80 fs) down-chirped pump-dump ultra violet (UV)-laser pulses through an optically bright electronic excited [ S 2 ( π π ∗)] state as a mediator. The sequence of such laser pulses is theoretically synthesized within the framework of optimal control theory (OCT) and employing the well-known pump-dump scheme of Tannor and Rice [D.J. Tannor, S.A. Rice, J. Chem. Phys. 83, 5013 (1985)]. In the OCT, the control task is framed as the maximization of cost functional defined in terms of an objective function along with the constraints on the field intensity and system dynamics. The latter is monitored by solving the time-dependent Schrödinger equation. The initial guess, laser driven dynamics and the optimized pulse structure (i.e., the spectral content and temporal profile) followed by associated mechanism involved in fulfilling the control task are examined in detail and discussed. A comparative account of the dynamical outcomes within the Condon approximation for the transition dipole moment versus its more realistic value calculated ab initio is also presented.
Spanish translation Questionnaire of the Developmental Coordination Disorder

Directory of Open Access Journals (Sweden)

Salamanca LM

2012-05-01

Full Text Available The developmental coordination disorder can be recognized by motor difficulties that affect the performance in daily and school activities; therefore, it is necessary to get its early diagnosis in order to initiate early intervention. A tool for diagnosis is the Developmental coordination disorder questionnaire’07, DCDQ’07. Objective: the translation and cultural adaptation of the DCDQ’07 into Spanish. Materials and methods: three independent translators translated the questionnaire into Spanish. Its items were classified according to their equivalent or non-equivalent problems in some words, and also according to their experiential, semantic, conceptual or idioms equivalence. Results: 8 items out of 15 questionnaire items were classified as equivalent 8, 6 of them presented problems in a few words and only one was classified as non-equivalent, 10 items correspond to experiential equivalence translation, 4 items were classified as semantic equivalent and only one got two equivalents. The author agreed the Spanish version. Also, the parent´s opinions about the questionnaire were positive. Conclusions: most of the items of the questionnaire did not have translation difficulties. It allowed its translation and cultural adaptation into Spanish as well as its validation continuity and reliability process
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...
“De interpretatione recta...”: Early Modern Theories of Translation

Directory of Open Access Journals (Sweden)

Zaharia Oana-Alis

2014-12-01

Full Text Available Translation has been essential to the development of languages and cultures throughout the centuries, particularly in the early modern period when it became a cornerstone of the process of transition from Latin to vernacular productions, in such countries as France, Italy, England and Spain. This process was accompanied by a growing interest in defining the rules and features of the practice of translation. The present article aims to examine the principles that underlay the highly intertextual early modern translation theory by considering its classical sources and development. It focuses on subjects that were constantly reiterated in any discussion about translation: the debate concerning the best methods of translation, the sense-for-sense/ word-for-word dichotomy - a topos that can be traced to the discourse on translation initiated by Cicero and Horace and was further developed by the Church fathers, notably St. Jerome, and eventually inherited by both medieval and Renaissance translators. Furthermore, it looks at the differences and continuities that characterise the medieval and Renaissance discourses on translation with a focus on the transition from the medieval, free manner of translation to the humanist, philological one.
Topical Review: Translating Translational Research in Behavioral Science.

Science.gov (United States)

Hommel, Kevin A; Modi, Avani C; Piazza-Waggoner, Carrie; Myers, James D

2015-01-01

To present a model of translational research for behavioral science that communicates the role of behavioral research at each phase of translation. A task force identified gaps in knowledge regarding behavioral translational research processes and made recommendations regarding advancement of knowledge. A comprehensive model of translational behavioral research was developed. This model represents T1, T2, and T3 research activities, as well as Phase 1, 2, 3, and 4 clinical trials. Clinical illustrations of translational processes are also offered as support for the model. Behavioral science has struggled with defining a translational research model that effectively articulates each stage of translation and complements biomedical research. Our model defines key activities at each phase of translation from basic discovery to dissemination/implementation. This should be a starting point for communicating the role of behavioral science in translational research and a catalyst for better integration of biomedical and behavioral research. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Molecular modeling of the human eukaryotic translation initiation factor 5A (eIF5A) based on spectroscopic and computational analyses

International Nuclear Information System (INIS)

Costa-Neto, Claudio M.; Parreiras-e-Silva, Lucas T.; Ruller, Roberto; Oliveira, Eduardo B.; Miranda, Antonio; Oliveira, Laerte; Ward, Richard J.

2006-01-01

The eukaryotic translation initiation factor 5A (eIF5A) is a protein ubiquitously present in archaea and eukarya, which undergoes a unique two-step post-translational modification called hypusination. Several studies have shown that hypusination is essential for a variety of functional roles for eIF5A, including cell proliferation and synthesis of proteins involved in cell cycle control. Up to now neither a totally selective inhibitor of hypusination nor an inhibitor capable of directly binding to eIF5A has been reported in the literature. The discovery of such an inhibitor might be achieved by computer-aided drug design based on the 3D structure of the human eIF5A. In this study, we present a molecular model for the human eIF5A protein based on the crystal structure of the eIF5A from Leishmania brasiliensis, and compare the modeled conformation of the loop bearing the hypusination site with circular dichroism data obtained with a synthetic peptide of this loop. Furthermore, analysis of amino acid variability between different human eIF5A isoforms revealed peculiar structural characteristics that are of functional relevance
Finite translation surfaces with maximal number of translations

OpenAIRE

Schlage-Puchta, Jan-Christoph; Weitze-Schmithuesen, Gabriela

2013-01-01

The natural automorphism group of a translation surface is its group of translations. For finite translation surfaces of genus g > 1 the order of this group is naturally bounded in terms of g due to a Riemann-Hurwitz formula argument. In analogy with classical Hurwitz surfaces, we call surfaces which achieve the maximal bound Hurwitz translation surfaces. We study for which g there exist Hurwitz translation surfaces of genus g.
Machine Translation Tools - Tools of The Translator's Trade

DEFF Research Database (Denmark)

Kastberg, Peter

2012-01-01

In this article three of the more common types of translation tools are presented, discussed and critically evaluated. The types of translation tools dealt with in this article are: Fully Automated Machine Translation (or FAMT), Human Aided Machine Translation (or HAMT) and Machine Aided Human...... Translation (or MAHT). The strengths and weaknesses of the different types of tools are discussed and evaluated by means of a number of examples. The article aims at two things: at presenting a sort of state of the art of what is commonly referred to as “machine translation” as well as at providing the reader...... with a sound basis for considering what translation tool (if any) is the most appropriate in order to meet his or her specific translation needs....

Sapovirus translation requires an interaction between VPg and the cap binding protein eIF4E.

Science.gov (United States)

Hosmillo, Myra; Chaudhry, Yasmin; Kim, Deok-Song; Goodfellow, Ian; Cho, Kyoung-Oh

2014-11-01

Sapoviruses of the Caliciviridae family of small RNA viruses are emerging pathogens that cause gastroenteritis in humans and animals. Molecular studies on human sapovirus have been hampered due to the lack of a cell culture system. In contrast, porcine sapovirus (PSaV) can be grown in cell culture, making it a suitable model for understanding the infectious cycle of sapoviruses and the related enteric caliciviruses. Caliciviruses are known to use a novel mechanism of protein synthesis that relies on the interaction of cellular translation initiation factors with the virus genome-encoded viral protein genome (VPg) protein, which is covalently linked to the 5' end of the viral genome. Using PSaV as a representative member of the Sapovirus genus, we characterized the role of the viral VPg protein in sapovirus translation. As observed for other caliciviruses, the PSaV genome was found to be covalently linked to VPg, and this linkage was required for the translation and the infectivity of viral RNA. The PSaV VPg protein was associated with the 4F subunit of the eukaryotic translation initiation factor (eIF4F) complex in infected cells and bound directly to the eIF4E protein. As has been previously demonstrated for feline calicivirus, a member of the Vesivirus genus, PSaV translation required eIF4E and the interaction between eIF4E and eIF4G. Overall, our study provides new insights into the novel mechanism of sapovirus translation, suggesting that sapovirus VPg can hijack the cellular translation initiation mechanism by recruiting the eIF4F complex through a direct eIF4E interaction. Sapoviruses, which are members of the Caliciviridae family, are one of the causative agents of viral gastroenteritis in humans. However, human sapovirus remains noncultivable in cell culture, hampering the ability to characterize the virus infectious cycle. Here, we show that the VPg protein from porcine sapovirus, the only cultivatable sapovirus, is essential for viral translation and
Precise control of Si(001) initial oxidation by translational kinetic energy of O2 molecules

International Nuclear Information System (INIS)

Teraoka, Yuden; Yoshigoe, Akitaka

2002-01-01

The influence of translation kinetic energy of incident O 2 molecules on the passive oxidation of the clean Si(001) surface and the partially oxidized-Si(001) surface has been studied by high-resolution photoemission spectroscopy using synchrotron radiation. The incident energy of O 2 molecules was controlled up to 3 eV by a supersonic seeded molecular beam technique. Although two incident energy thresholds (1.0 eV and 2.6 eV) have been determined for the partially oxidized-surface oxidation in accordance with the first-principle calculation, the monotonic increase of oxygen saturation coverage was observed for the clean surface oxidation. The difference is caused by the initial dangling bond termination (Si-H and Si-OH) on the partially oxidized surface. Si-2p and O-1s photoemission spectra measured at representative incident energies showed the incident-energy-induced oxidation at the back bonds of Si dimers and the second-layer (subsurface) Si atoms. Moreover, the low-and high-binding-energy components in the O-1s photoemission spectra were assigned to bridge site oxygen and dangling bond site oxygen for the partially oxidized-surface oxidation. (author)
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....
Translational research in medicine

Directory of Open Access Journals (Sweden)

Bakir Mehić

2011-05-01

Full Text Available Translational medicine is a medical practice based on interventional epidemiology. It is regarded by its proponents as a natural progression from Evidence-Based Medicine. It integrates research from the basic sciences, social sciences and political sciences with the aim of optimizing patient care and preventive measures which may extend beyond healthcare services. In short, it is the process of turning appropriate biological discoveries into drugs and medical devices that can be used in the treatment of patients.[1]Scientific research and the development of modern powerful techniques are crucial for improving patient care in a society that is increasingly demanding the highest quality health services.[2] Indeed, effective patient care requires the continuous improvement of knowledge on the pathophysiology of the diseases, diagnostic procedures and therapeutic tools available. To this end, development of both clinical and basic research in health sciences is required. However, what is most effective in improving medical knowledge, and hence patient care, is the cross-fertilization between basic and clinical science. This has been specifically highlighted in recent years with the coining of the term “translational research”.[3] Translational research is of great importance in all medical specialties.Translational Research is the basis for Translational Medicine. It is the process which leads from evidence based medicine to sustainable solutions for public health problems.[4] It aims to improve the health and longevity of the world’s populations and depends on developing broad-based teams of scientists and scholars who are able to focus their efforts to link basic scientific discoveries with the arena of clinical investigation, and translating the results of clinical trials into changes in clinical practice, informed by evidence from the social and political sciences. Clinical science and ecological support from effective policies can�
Optimality conditions for the numerical solution of optimization problems with PDE constraints :

Energy Technology Data Exchange (ETDEWEB)

Aguilo Valentin, Miguel Alejandro; Ridzal, Denis

2014-03-01

A theoretical framework for the numerical solution of partial di erential equation (PDE) constrained optimization problems is presented in this report. This theoretical framework embodies the fundamental infrastructure required to e ciently implement and solve this class of problems. Detail derivations of the optimality conditions required to accurately solve several parameter identi cation and optimal control problems are also provided in this report. This will allow the reader to further understand how the theoretical abstraction presented in this report translates to the application.
Translation Techniques

OpenAIRE

Marcia Pinheiro

2015-01-01

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 a...
Identification and Evaluation of Medical Translator Mobile Applications Using an Adapted APPLICATIONS Scoring System.

Science.gov (United States)

Khander, Amrin; Farag, Sara; Chen, Katherine T

2017-12-22

With an increasing number of patients requiring translator services, many providers are turning to mobile applications (apps) for assistance. However, there have been no published reviews of medical translator apps. To identify and evaluate medical translator mobile apps using an adapted APPLICATIONS scoring system. A list of apps was identified from the Apple iTunes and Google Play stores, using the search term, "medical translator." Apps not found on two different searches, not in an English-based platform, not used for translation, or not functional after purchase, were excluded. The remaining apps were evaluated using an adapted APPLICATIONS scoring system, which included both objective and subjective criteria. App comprehensiveness was a weighted score defined by the number of non-English languages included in each app relative to the proportion of non-English speakers in the United States. The Apple iTunes and Google Play stores. Medical translator apps identified using the search term "medical translator." Main Outcomes and Measures: Compilation of medical translator apps for provider usage. A total of 524 apps were initially found. After applying the exclusion criteria, 20 (8.2%) apps from the Google Play store and 26 (9.2%) apps from the Apple iTunes store remained for evaluation. The highest scoring apps, Canopy Medical Translator, Universal Doctor Speaker, and Vocre Translate, scored 13.5 out of 18.7 possible points. A large proportion of apps initially found did not function as medical translator apps. Using the APPLICATIONS scoring system, we have identified and evaluated medical translator apps for providers who care for non-English speaking patients.
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…
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…
A GRAMMATICAL ADJUSTMENT ANALYSIS OF STATISTICAL MACHINE TRANSLATION METHOD USED BY GOOGLE TRANSLATE COMPARED TO HUMAN TRANSLATION IN TRANSLATING ENGLISH TEXT TO INDONESIAN

Directory of Open Access Journals (Sweden)

Eko Pujianto

2017-04-01

Full Text Available Google translate is a program which provides fast, free and effortless translating service. This service uses a unique method to translate. The system is called ―Statistical Machine Translation‖, the newest method in automatic translation. Machine translation (MT is an area of many kinds of different subjects of study and technique from linguistics, computers science, artificial intelligent (AI, translation theory, and statistics. SMT works by using statistical methods and mathematics to process the training data. The training data is corpus-based. It is a compilation of sentences and words of the languages (SL and TL from translation done by human. By using this method, Google let their machine discovers the rules for themselves. They do this by analyzing millions of documents that have already been translated by human translators and then generate the result based on the corpus/training data. However, questions arise when the results of the automatic translation prove to be unreliable in some extent. This paper questions the dependability of Google translate in comparison with grammatical adjustment that naturally characterizes human translators' specific advantage. The attempt is manifested through the analysis of the TL of some texts translated by the SMT. It is expected that by using the sample of TL produced by SMT we can learn the potential flaws of the translation. If such exists, the partial of more substantial undependability of SMT may open more windows to the debates of whether this service may suffice the users‘ need.
Non-AUG translation: a new start for protein synthesis in eukaryotes.

Science.gov (United States)

Kearse, Michael G; Wilusz, Jeremy E

2017-09-01

Although it was long thought that eukaryotic translation almost always initiates at an AUG start codon, recent advancements in ribosome footprint mapping have revealed that non-AUG start codons are used at an astonishing frequency. These non-AUG initiation events are not simply errors but instead are used to generate or regulate proteins with key cellular functions; for example, during development or stress. Misregulation of non-AUG initiation events contributes to multiple human diseases, including cancer and neurodegeneration, and modulation of non-AUG usage may represent a novel therapeutic strategy. It is thus becoming increasingly clear that start codon selection is regulated by many trans -acting initiation factors as well as sequence/structural elements within messenger RNAs and that non-AUG translation has a profound impact on cellular states. © 2017 Kearse and Wilusz; Published by Cold Spring Harbor Laboratory Press.
Development Of Translational Motion Of Unmanned Aerial Vehicle Using MATLAB

Directory of Open Access Journals (Sweden)

Thwe Thwe Htoo

2015-08-01

Full Text Available This research work describes the translational motion analysis of unmanned aerial vehicle UAV. Since the center of mass of the receiver is timevarying the equations are written in a reference frame that is geometrically fixed in the aircraft. Due to the fact that aerial vehicle simulation and control deal with the position and orientation of the UAV the equations of motion are derived in terms of the translational and rotational position and velocity with respect to the aircraft location. The formation relative motion control is a challenging problem due to the coupled translational and rotational dynamics. As the translational vector depends on the current attitude and its angular velocity and some of the attitude constraints also couple the position and attitude of the spacecraft it makes the formation control problem high dimensional. This work develops UAV stability conditions including translational vector maneuverability condition and included angle condition between the translational and the rotational motion of UAV system and then presents two methods to calculate the UAV attitude. Both of the two methods need first design the optimal trajectory of the translational vector and then use geometric and nonlinear programming methods to calculate the target trajectory. The validity of the proposed approach is demonstrated in a UAV by using MATLAB. The performance of the translational motion control is evaluated by the simulated results.
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.
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.
Translation and cultural adaptation of the Aguado Syntax Test (AST) into Brazilian Portuguese.

Science.gov (United States)

Baggio, Gustavo Inheta; Hage, Simone Rocha de Vasconcellos

2017-12-07

To perform the translation and cultural adaptation of the Aguado Syntax Test (AST) into Brazilian Portuguese considering the linguistic and cultural reality of the language. The AST assesses the early morphosyntactic development in children aged 3 to 7 in terms of understanding and expression of various types of structures such as sentences, pronouns, verbal voices, comparisons, prepositions and verbal desinence as to number, mode and tense. The process of translation and cultural adaptation followed four steps: 1) preparation of two translations; 2) synthesis of consensual translations; 3) backtranslation; and 4) verification of equivalence between the initial translations and backtranslations that resulted in the final translated version. The whole process of translation and cultural adaptation revealed the presence of equivalence and reconciliation of the translated items and an almost complete semantic equivalence between the two translations and the absence of consistent translation difficulties. The AST was translated and culturally adapted into Brazilian Portuguese, constituting the first step towards validation and standardization of the test.
[Correlation of codon biases and potential secondary structures with mRNA translation efficiency in unicellular organisms].

Science.gov (United States)

Vladimirov, N V; Likhoshvaĭ, V A; Matushkin, Iu G

2007-01-01

Gene expression is known to correlate with degree of codon bias in many unicellular organisms. However, such correlation is absent in some organisms. Recently we demonstrated that inverted complementary repeats within coding DNA sequence must be considered for proper estimation of translation efficiency, since they may form secondary structures that obstruct ribosome movement. We have developed a program for estimation of potential coding DNA sequence expression in defined unicellular organism using its genome sequence. The program computes elongation efficiency index. Computation is based on estimation of coding DNA sequence elongation efficiency, taking into account three key factors: codon bias, average number of inverted complementary repeats, and free energy of potential stem-loop structures formed by the repeats. The influence of these factors on translation is numerically estimated. An optimal proportion of these factors is computed for each organism individually. Quantitative translational characteristics of 384 unicellular organisms (351 bacteria, 28 archaea, 5 eukaryota) have been computed using their annotated genomes from NCBI GenBank. Five potential evolutionary strategies of translational optimization have been determined among studied organisms. A considerable difference of preferred translational strategies between Bacteria and Archaea has been revealed. Significant correlations between elongation efficiency index and gene expression levels have been shown for two organisms (S. cerevisiae and H. pylori) using available microarray data. The proposed method allows to estimate numerically the coding DNA sequence translation efficiency and to optimize nucleotide composition of heterologous genes in unicellular organisms. http://www.mgs.bionet.nsc.ru/mgs/programs/eei-calculator/.
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.
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.
French translation and cross-cultural adaptation of The Myotonic Dystrophy Health Index.

Science.gov (United States)

Gagnon, Cynthia; Tremblay, Marjolaine; CôTé, Isabelle; Heatwole, Chad

2018-04-01

Validation studies of disease-specific instruments for myotonic dystrophy type-1 (DM1) are required prior to their global use in clinical trials involving different cultures and countries. Here we translate and culturally adapt the Myotonic Dystrophy Health Index (MDHI), a disease-specific patient-reported outcome (PRO) measure, for a French DM1 population. Using the International Society for Pharmacoeconomics and Outcomes Research Task Force method for translation and adaptation of PRO questionnaires, we created a French translation of the MDHI. We subsequently tested this instrument in a cohort of French-speaking patients with DM1. The MDHI was forward and back translated and modified by consensus to create the most compatible translation. Cognitive interviews were conducted with 5 patients with DM1 to ensure the usability and understanding of the translation. The French version of the MDHI is an optimal translation of the original instrument that is acceptable to native patients and ready for clinical trial use. Muscle Nerve 57: 686-689, 2018. © 2017 Wiley Periodicals, Inc.
The Role of Semantics in Translation Recognition: Effects of Number of Translations, Dominance of Translations and Semantic Relatedness of Multiple Translations

Science.gov (United States)

Laxen, Jannika; Lavaur, Jean-Marc

2010-01-01

This study aims to examine the influence of multiple translations of a word on bilingual processing in three translation recognition experiments during which French-English bilinguals had to decide whether two words were translations of each other or not. In the first experiment, words with only one translation were recognized as translations…

The significance of translation regulation in the stress response

Science.gov (United States)

2013-01-01

Background The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation. To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although m
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
PERSONALITY TYPE AND TRANSLATION PERFORMANCE OF PERSIAN TRANSLATOR TRAINEES

Directory of Open Access Journals (Sweden)

Reza Shaki

2017-09-01

Full Text Available The study investigated the relationship between the personality typology of a sample of Iranian translation students and their translation quality in terms of expressive, appellative, and informative text types. The study also attempted to identify the personality types that can perform better in English to Persian translation of the three text types. For that purpose, the personality type and the translation quality of the participants was assessed using Myers-Briggs Type Indicator (MBTI personality test and translation quality assessment (TQA, respectively. The analysis of the data revealed that the personality type of the participants seemed relevant to the translation quality of all the text types. The translation quality of the participants with intuitive and thinking types was significantly better than the sensing type counterparts in translating expressive texts. The participants with intuitive and feeling types also performed better than their counterparts with sensing type in translation of the informative text. Moreover, the participants with intuitive, feeling, and thinking personality types performed more successfully than the participants with sensing type in translation of the appellative text. The findings of the study are discussed in light of the existing research literature.
Hybrid intelligent methodology to design translation invariant morphological operators for Brazilian stock market prediction.

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Araújo, Ricardo de A

2010-12-01

This paper presents a hybrid intelligent methodology to design increasing translation invariant morphological operators applied to Brazilian stock market prediction (overcoming the random walk dilemma). The proposed Translation Invariant Morphological Robust Automatic phase-Adjustment (TIMRAA) method consists of a hybrid intelligent model composed of a Modular Morphological Neural Network (MMNN) with a Quantum-Inspired Evolutionary Algorithm (QIEA), which searches for the best time lags to reconstruct the phase space of the time series generator phenomenon and determines the initial (sub-optimal) parameters of the MMNN. Each individual of the QIEA population is further trained by the Back Propagation (BP) algorithm to improve the MMNN parameters supplied by the QIEA. Also, for each prediction model generated, it uses a behavioral statistical test and a phase fix procedure to adjust time phase distortions observed in stock market time series. Furthermore, an experimental analysis is conducted with the proposed method through four Brazilian stock market time series, and the achieved results are discussed and compared to results found with random walk models and the previously introduced Time-delay Added Evolutionary Forecasting (TAEF) and Morphological-Rank-Linear Time-lag Added Evolutionary Forecasting (MRLTAEF) methods. Copyright © 2010 Elsevier Ltd. All rights reserved.
Tinkering with Translation: Protein Synthesis in Virus-Infected Cells

Science.gov (United States)

Walsh, Derek; Mathews, Michael B.; Mohr, Ian

2013-01-01

Viruses are obligate intracellular parasites, and their replication requires host cell functions. Although the size, composition, complexity, and functions encoded by their genomes are remarkably diverse, all viruses rely absolutely on the protein synthesis machinery of their host cells. Lacking their own translational apparatus, they must recruit cellular ribosomes in order to translate viral mRNAs and produce the protein products required for their replication. In addition, there are other constraints on viral protein production. Crucially, host innate defenses and stress responses capable of inactivating the translation machinery must be effectively neutralized. Furthermore, the limited coding capacity of the viral genome needs to be used optimally. These demands have resulted in complex interactions between virus and host that exploit ostensibly virus-specific mechanisms and, at the same time, illuminate the functioning of the cellular protein synthesis apparatus. PMID:23209131
Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

Energy Technology Data Exchange (ETDEWEB)

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

2016-02-05

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

International Nuclear Information System (INIS)

Tariq, Mohammad; Ito, Akihiro; Ishfaq, Muhammad; Bradshaw, Elliot; Yoshida, Minoru

2016-01-01

The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.
Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB

Science.gov (United States)

Fiume, Giuseppe; Rossi, Annalisa; de Laurentiis, Annamaria; Falcone, Cristina; Pisano, Antonio; Vecchio, Eleonora; Pontoriero, Marilena; Scala, Iris; Scialdone, Annarita; Masci, Francesca Fasanella; Mimmi, Selena; Palmieri, Camillo; Scala, Giuseppe; Quinto, Ileana

2013-01-01

Protein synthesis is mainly regulated at the initiation step, allowing the fast, reversible and spatial control of gene expression. Initiation of protein synthesis requires at least 13 translation initiation factors to assemble the 80S ribosomal initiation complex. Loss of translation control may result in cell malignant transformation. Here, we asked whether translational initiation factors could be regulated by NF-κB transcription factor, a major regulator of genes involved in cell proliferation, survival, and inflammatory response. We show that the p65 subunit of NF-κB activates the transcription of eIF4H gene, which is the regulatory subunit of eIF4A, the most relevant RNA helicase in translation initiation. The p65-dependent transcriptional activation of eIF4H increased the eIF4H protein content augmenting the rate of global protein synthesis. In this context, our results provide novel insights into protein synthesis regulation in response to NF-κB activation signalling, suggesting a transcription-translation coupled mechanism of control. PMID:23776612
Pareto optimality in infinite horizon linear quadratic differential games

NARCIS (Netherlands)

Reddy, P.V.; Engwerda, J.C.

2013-01-01

In this article we derive conditions for the existence of Pareto optimal solutions for linear quadratic infinite horizon cooperative differential games. First, we present a necessary and sufficient characterization for Pareto optimality which translates to solving a set of constrained optimal
Optimal Retention Level for Infinite Time Horizons under MADM

Directory of Open Access Journals (Sweden)

Başak Bulut Karageyik

2016-12-01

Full Text Available In this paper, we approximate the aggregate claims process by using the translated gamma process under the classical risk model assumptions, and we investigate the ultimate ruin probability. We consider optimal reinsurance under the minimum ultimate ruin probability, as well as the maximum benefit criteria: released capital, expected profit and exponential-fractional-logarithmic utility from the insurer’s point of view. Numerical examples are presented to explain how the optimal initial surplus and retention level are changed according to the individual claim amounts, loading factors and weights of the criteria. In the decision making process, we use The Analytical Hierarchy Process (AHP and The Technique for Order of Preference by Similarity to ideal Solution (TOPSIS methods as the Multi-Attribute Decision Making methods (MADM and compare our results considering different combinations of loading factors for both exponential and Pareto individual claims.
The Ezrin Metastatic Phenotype Is Associated with the Initiation of Protein Translation

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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.
Efficient Translation of LTL Formulae into Buchi Automata

Science.gov (United States)

Giannakopoulou, Dimitra; Lerda, Flavio

2001-01-01

Model checking is a fully automated technique for checking that a system satisfies a set of required properties. With explicit-state model checkers, properties are typically defined in linear-time temporal logic (LTL), and are translated into B chi automata in order to be checked. This report presents how we have combined and improved existing techniques to obtain an efficient LTL to B chi automata translator. In particular, we optimize the core of existing tableau-based approaches to generate significantly smaller automata. Our approach has been implemented and is being released as part of the Java PathFinder software (JPF), an explicit state model checker under development at the NASA Ames Research Center.
Translational selection is ubiquitous in prokaryotes.

Directory of Open Access Journals (Sweden)

Fran Supek

2010-06-01

Full Text Available Codon usage bias in prokaryotic genomes is largely a consequence of background substitution patterns in DNA, but highly expressed genes may show a preference towards codons that enable more efficient and/or accurate translation. We introduce a novel approach based on supervised machine learning that detects effects of translational selection on genes, while controlling for local variation in nucleotide substitution patterns represented as sequence composition of intergenic DNA. A cornerstone of our method is a Random Forest classifier that outperformed previous distance measure-based approaches, such as the codon adaptation index, in the task of discerning the (highly expressed ribosomal protein genes by their codon frequencies. Unlike previous reports, we show evidence that translational selection in prokaryotes is practically universal: in 460 of 461 examined microbial genomes, we find that a subset of genes shows a higher codon usage similarity to the ribosomal proteins than would be expected from the local sequence composition. These genes constitute a substantial part of the genome--between 5% and 33%, depending on genome size--while also exhibiting higher experimentally measured mRNA abundances and tending toward codons that match tRNA anticodons by canonical base pairing. Certain gene functional categories are generally enriched with, or depleted of codon-optimized genes, the trends of enrichment/depletion being conserved between Archaea and Bacteria. Prominent exceptions from these trends might indicate genes with alternative physiological roles; we speculate on specific examples related to detoxication of oxygen radicals and ammonia and to possible misannotations of asparaginyl-tRNA synthetases. Since the presence of codon optimizations on genes is a valid proxy for expression levels in fully sequenced genomes, we provide an example of an "adaptome" by highlighting gene functions with expression levels elevated specifically in
Applicability of initial optimal maternal and fetal electrocardiogram combination vectors to subsequent recordings

International Nuclear Information System (INIS)

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

2014-01-01

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. (interdisciplinary physics and related areas of science and technology)
Pauses by Student and Professional Translators in Translation Process

Directory of Open Access Journals (Sweden)

Rusdi Noor Rosa

2018-01-01

Full Text Available Translation as a process of meaning making activity requires a cognitive process one of which is realized in a pause, a temporary stop or a break indicating doing other than typing activities in a certain period of translation process. Scholars agree that pauses are an indicator of cognitive process without which there will never be any translation practices. Despite such agreement, pauses are debatable as well, either in terms of their length or in terms of the activities managed by a translator while taking pauses. This study, in particular, aims at finding out how student translators and professional translators managed the pauses in a translation process. This was a descriptive research taking two student translators and two professional translators as the participants who were asked to translate a text from English into bahasa Indonesia. The source text (ST was a historical recount text entitled ‘Early History of Yellowstone National Park’ downloaded from http://www.nezperce.com/yelpark9.html composed of 230-word long from English into bahasa Indonesia. The data were collected using Translog protocols, think aloud protocols (TAPs and screen recording. Based on the data analysis, it was found that student translators took the longest pauses in the drafting phase spent to solve the problems related to finding out the right equivalent for the ST words or terms and to solve the difficulties encountered in encoding their ST understanding in the TL; meanwhile, professional translators took the longest pauses in the pos-drafting phase spent to ensure whether their TT had been natural and whether their TT had corresponded to the prevailing grammatical rules of the TL.
Machine translation

Energy Technology Data Exchange (ETDEWEB)

Nagao, M

1982-04-01

Each language has its own structure. In translating one language into another one, language attributes and grammatical interpretation must be defined in an unambiguous form. In order to parse a sentence, it is necessary to recognize its structure. A so-called context-free grammar can help in this respect for machine translation and machine-aided translation. Problems to be solved in studying machine translation are taken up in the paper, which discusses subjects for semantics and for syntactic analysis and translation software. 14 references.
Personalized translational epilepsy research - Novel approaches and future perspectives: Part II: Experimental and translational approaches.

Science.gov (United States)

Bauer, Sebastian; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Rosenow, Felix

2017-11-01

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1]. Copyright © 2017
On the optimization of thorium bundle distribution in the initial core loading for a PHWR

International Nuclear Information System (INIS)

Mishra, S.; Ray, S.; Kumar, A.N.; Modak, R.S.; Ganesan, S.

2009-01-01

If the initial core of Indian 220 MWe PHWR is loaded with all fresh Natural Uranium fuel, only about 70% Full Power can be drawn in the initial operation due to large power peaking. It is possible to load few tens of Th bundles at selected locations to get nearly full power without violating any safety limits. Finding the best possible locations is, however, a fairly complex and massive combinatorial optimization problem. Here, optimum solutions are obtained by a latest evolutionary algorithm called EDA implemented on the EKA built at Computational Research Laboratories (CRL) in Pune. The effect of varying the number of Th bundles on results is discussed. (author)
Strain sensors optimal placement for vibration-based structural health monitoring. The effect of damage on the initially optimal configuration

Science.gov (United States)

Loutas, T. H.; Bourikas, A.

2017-12-01

We revisit the optimal sensor placement of engineering structures problem with an emphasis on in-plane dynamic strain measurements and to the direction of modal identification as well as vibration-based damage detection for structural health monitoring purposes. The approach utilized is based on the maximization of a norm of the Fisher Information Matrix built with numerically obtained mode shapes of the structure and at the same time prohibit the sensorization of neighbor degrees of freedom as well as those carrying similar information, in order to obtain a satisfactory coverage. A new convergence criterion of the Fisher Information Matrix (FIM) norm is proposed in order to deal with the issue of choosing an appropriate sensor redundancy threshold, a concept recently introduced but not further investigated concerning its choice. The sensor configurations obtained via a forward sequential placement algorithm are sub-optimal in terms of FIM norm values but the selected sensors are not allowed to be placed in neighbor degrees of freedom providing thus a better coverage of the structure and a subsequent better identification of the experimental mode shapes. The issue of how service induced damage affects the initially nominated as optimal sensor configuration is also investigated and reported. The numerical model of a composite sandwich panel serves as a representative aerospace structure upon which our investigations are based.
The same allele of translation initiation factor 4E mediates resistance against two Potyvirus spp. in Pisum sativum

DEFF Research Database (Denmark)

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

2007-01-01

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...... 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...

Translating gene transfer: a stalled effort.

Science.gov (United States)

Greenberg, Alexandra J; McCormick, Jennifer; Tapia, Carmen J; Windebank, Anthony J

2011-08-01

The journey of gene transfer from laboratory to clinic has been slow and fraught with many challenges and barriers. Despite the development of the initial technology in the early 1970s, a standard clinical treatment involving "gene therapy" remains to be seen. Furthermore, much was written about the technology in the early 1990s, but since then, not much has been written about the journey of gene transfer. The translational path of gene transfer thus far, both pitfalls and successes, can serve as a study not only in navigating ethical and safety concerns, but also in the importance of scientist-public interactions. Here, we examine the translational progress of gene transfer and what can be gleaned from its history. © 2011 Wiley Periodicals, Inc.
Optimizing Temporal Queries: Efficient Handling of Duplicates

DEFF Research Database (Denmark)

Toman, David; Bowman, Ivan Thomas

2001-01-01

, these query languages are implemented by translating temporal queries into standard relational queries. However, the compiled queries are often quite cumbersome and expensive to execute even using state-of-the- art relational products. This paper presents an optimization technique that produces more efficient...... translated SQL queries by taking into account the properties of the encoding used for temporal attributes. For concreteness, this translation technique is presented in the context of SQL/TP; however, these techniques are also applicable to other temporal query languages....
Translation elicits a growth rate-dependent, genome-wide, differential protein production in Bacillus subtilis.

Science.gov (United States)

Borkowski, Olivier; Goelzer, Anne; Schaffer, Marc; Calabre, Magali; Mäder, Ulrike; Aymerich, Stéphane; Jules, Matthieu; Fromion, Vincent

2016-05-17

Complex regulatory programs control cell adaptation to environmental changes by setting condition-specific proteomes. In balanced growth, bacterial protein abundances depend on the dilution rate, transcript abundances and transcript-specific translation efficiencies. We revisited the current theory claiming the invariance of bacterial translation efficiency. By integrating genome-wide transcriptome datasets and datasets from a library of synthetic gfp-reporter fusions, we demonstrated that translation efficiencies in Bacillus subtilis decreased up to fourfold from slow to fast growth. The translation initiation regions elicited a growth rate-dependent, differential production of proteins without regulators, hence revealing a unique, hard-coded, growth rate-dependent mode of regulation. We combined model-based data analyses of transcript and protein abundances genome-wide and revealed that this global regulation is extensively used in B. subtilis We eventually developed a knowledge-based, three-step translation initiation model, experimentally challenged the model predictions and proposed that a growth rate-dependent drop in free ribosome abundance accounted for the differential protein production. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.
Proposal for a telehealth concept in the translational research model.

Science.gov (United States)

Silva, Angélica Baptista; Morel, Carlos Médicis; Moraes, Ilara Hämmerli Sozzi de

2014-04-01

To review the conceptual relationship between telehealth and translational research. Bibliographical search on telehealth was conducted in the Scopus, Cochrane BVS, LILACS and MEDLINE databases to find experiences of telehealth in conjunction with discussion of translational research in health. The search retrieved eight studies based on analysis of models of the five stages of translational research and the multiple strands of public health policy in the context of telehealth in Brazil. The models were applied to telehealth activities concerning the Network of Human Milk Banks, in the Telemedicine University Network. The translational research cycle of human milk collected, stored and distributed presents several integrated telehealth initiatives, such as video conferencing, and software and portals for synthesizing knowledge, composing elements of an information ecosystem, mediated by information and communication technologies in the health system. Telehealth should be composed of a set of activities in a computer mediated network promoting the translation of knowledge between research and health services.
Helper component proteinase of the genus Potyvirus is an interaction partner of translation initiation factors eIF(iso)4E and eIF4E and contains a 4E binding motif.

Science.gov (United States)

Ala-Poikela, Marjo; Goytia, Elisa; Haikonen, Tuuli; Rajamäki, Minna-Liisa; Valkonen, Jari P T

2011-07-01

The multifunctional helper component proteinase (HCpro) of potyviruses (genus Potyvirus; Potyviridae) shows self-interaction and interacts with other potyviral and host plant proteins. Host proteins that are pivotal to potyvirus infection include the eukaryotic translation initiation factor eIF4E and the isoform eIF(iso)4E, which interact with viral genome-linked protein (VPg). Here we show that HCpro of Potato virus A (PVA) interacts with both eIF4E and eIF(iso)4E, with interactions with eIF(iso)4E being stronger, as judged by the data of a yeast two-hybrid system assay. A bimolecular fluorescence complementation assay on leaves of Nicotiana benthamiana showed that HCpro from three potyviruses (PVA, Potato virus Y, and Tobacco etch virus) interacted with the eIF(iso)4E and eIF4E of tobacco (Nicotiana tabacum); interactions with eIF(iso)4E and eIF4E of potato (Solanum tuberosum) were weaker. In PVA-infected cells, interactions between HCpro and tobacco eIF(iso)4E were confined to round structures that colocalized with 6K2-induced vesicles. Point mutations introduced to a 4E binding motif identified in the C-terminal region of HCpro debilitated interactions of HCpro with translation initiation factors and were detrimental to the virulence of PVA in plants. The 4E binding motif conserved in HCpro of potyviruses and HCpro-initiation factor interactions suggest new roles for HCpro and/or translation factors in the potyvirus infection cycle.
Heat shock protein 70 promotes coxsackievirus B3 translation initiation and elongation via Akt-mTORC1 pathway depending on activation of p70S6K and Cdc2.

Science.gov (United States)

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

2017-07-01

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

DEFF Research Database (Denmark)

Fallov, Mia Arp; Birk, Rasmus

2018-01-01

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

Science.gov (United States)

Zhou, Wu; Weldon, Patrick; Tang, Bingfeng; King, W. M.; Shelhamer, M. J. (Principal Investigator)

2003-01-01

Motor learning was induced in the translational vestibulo-ocular reflex (TVOR) when monkeys were repeatedly subjected to a brief (0.5 sec) head translation while they tried to maintain binocular fixation on a visual target for juice rewards. If the target was world-fixed, the initial eye speed of the TVOR gradually increased; if the target was head-fixed, the initial eye speed of the TVOR gradually decreased. The rate of learning acquisition was very rapid, with a time constant of approximately 100 trials, which was equivalent to or=1 d without any reinforcement, indicating induction of long-term synaptic plasticity. Although the learning generalized to targets with different viewing distances and to head translations with different accelerations, it was highly specific for the particular combination of head motion and evoked eye movement associated with the training. For example, it was specific to the modality of the stimulus (translation vs rotation) and the direction of the evoked eye movement in the training. Furthermore, when one eye was aligned with the heading direction so that it remained motionless during training, learning was not expressed in this eye, but only in the other nonaligned eye. These specificities show that the learning sites are neither in the sensory nor the motor limb of the reflex but in the sensory-motor transformation stage of the reflex. The dependence of the learning on both head motion and evoked eye movement suggests that Hebbian learning may be one of the underlying cellular mechanisms.
Selection of mRNA 5'-untranslated region sequence with high translation efficiency through ribosome display

International Nuclear Information System (INIS)

Mie, Masayasu; Shimizu, Shun; Takahashi, Fumio; Kobatake, Eiry

2008-01-01

The 5'-untranslated region (5'-UTR) of mRNAs functions as a translation enhancer, promoting translation efficiency. Many in vitro translation systems exhibit a reduced efficiency in protein translation due to decreased translation initiation. The use of a 5'-UTR sequence with high translation efficiency greatly enhances protein production in these systems. In this study, we have developed an in vitro selection system that favors 5'-UTRs with high translation efficiency using a ribosome display technique. A 5'-UTR random library, comprised of 5'-UTRs tagged with a His-tag and Renilla luciferase (R-luc) fusion, were in vitro translated in rabbit reticulocytes. By limiting the translation period, only mRNAs with high translation efficiency were translated. During translation, mRNA, ribosome and translated R-luc with His-tag formed ternary complexes. They were collected with translated His-tag using Ni-particles. Extracted mRNA from ternary complex was amplified using RT-PCR and sequenced. Finally, 5'-UTR with high translation efficiency was obtained from random 5'-UTR library
Optimal Computing Budget Allocation for Particle Swarm Optimization in Stochastic Optimization.

Science.gov (United States)

Zhang, Si; Xu, Jie; Lee, Loo Hay; Chew, Ek Peng; Wong, Wai Peng; Chen, Chun-Hung

2017-04-01

Particle Swarm Optimization (PSO) is a popular metaheuristic for deterministic optimization. Originated in the interpretations of the movement of individuals in a bird flock or fish school, PSO introduces the concept of personal best and global best to simulate the pattern of searching for food by flocking and successfully translate the natural phenomena to the optimization of complex functions. Many real-life applications of PSO cope with stochastic problems. To solve a stochastic problem using PSO, a straightforward approach is to equally allocate computational effort among all particles and obtain the same number of samples of fitness values. This is not an efficient use of computational budget and leaves considerable room for improvement. This paper proposes a seamless integration of the concept of optimal computing budget allocation (OCBA) into PSO to improve the computational efficiency of PSO for stochastic optimization problems. We derive an asymptotically optimal allocation rule to intelligently determine the number of samples for all particles such that the PSO algorithm can efficiently select the personal best and global best when there is stochastic estimation noise in fitness values. We also propose an easy-to-implement sequential procedure. Numerical tests show that our new approach can obtain much better results using the same amount of computational effort.
Translation and Culture:Translation as a Cross-cultural Mediation

Institute of Scientific and Technical Information of China (English)

叶谋锦

2013-01-01

Translation is a complex activity which involves language competence as well as proficiency in multiculturalism. From the perspective of multiculturalism, translation resembles recreation of source text by grasping essential meanings to produce a sub-tle target text which can be clearly perceived by target readers. Ignoring cultural issues can present serious mistranslations in the field of advertising translation. This paper aims to explore the significance of connotation confined by the framework of culture and point out that verbal translation is a dangerous inclination by illustrating three business examples. This paper argues that cross-cultural mediation plays an important role in translation.
Towards a classification of translation styles based on eye-tracking and keylogging data

Directory of Open Access Journals (Sweden)

Barbara Dragsted & Michael Carl

2013-06-01

Full Text Available This article seeks to formulate translator profiles based on process data from keylogging and eye-tracking, while at the same time identifying features which are shared by all translators in a sample consisting of both students and professionals. Data have been collected from 12 professional translators and 12 graduate students translating three texts of varying complexity. We found that individual behavioural characteristics with respect to initial orientation in the source text (ST, online ST reading, and online and end revision remained relatively constant across texts of varying complexity, supporting our hypothesis that translator profiles can be observed which are independent of the difficulty of the translation task. The analysis of the data also indicated that translators could be grouped into broad categories of locally-oriented and globally-oriented translation styles, which are partly, though not entirely, comparable to styles known from writing research. We also identified shared features with respect to reading and revision behaviour during drafting. Common to all translators was that they looked beyond the source text word they were about to translate, and that they made revisions while drafting the translation.
Making the most of a translator.

Science.gov (United States)

Dannenfeldt, D

1994-01-01

Anaheim Memorial Hospital in California is a trailblazer. It's one of the first hospitals in the nation to use translation software for both supply procurement and claims-related transactions. Initially, it acquired the software to streamline the ordering of supplies by shifting to standard electronic formats. Today, the hospital is using the software to receive electronic remittance advice, and it has plans for other labor-saving applications.
MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles

DEFF Research Database (Denmark)

Reinert, Line; Shi, B; Nandi, S

2006-01-01

MCT-1 is an oncogene that was initially identified in a human T cell lymphoma and has been shown to induce cell proliferation as well as activate survival-related pathways. MCT-1 contains the PUA domain, a recently described RNA-binding domain that is found in several tRNA and rRNA modification...... enzymes. Here, we established that MCT-1 protein interacts with the cap complex through its PUA domain and recruits the density-regulated protein (DENR/DRP), containing the SUI1 translation initiation domain. Through the use of microarray analysis on polysome-associated mRNAs, we showed that up......-regulation of MCT-1 was able to modulate the translation profiles of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs, despite equivalent levels of mRNAs in the cytoplasm. Our data establish a role for MCT-1 in translational regulation, and support a linkage between translational control and oncogenesis....
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.
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.
Ectopic expression of eIF4E-transporter triggers the movement of eIF4E into P-bodies, inhibiting steady-state translation but not the pioneer round of translation

International Nuclear Information System (INIS)

Lee, Hyung Chul; Cho, Hana; Kim, Yoon Ki

2008-01-01

Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism; this process removes faulty mRNAs harboring premature termination codons (PTCs). NMD targets newly synthesized mRNAs bound by nuclear cap-binding proteins 80/20 (CBP80/20) and exon junction complex (EJC), the former of which is thought to recruit the ribosome to initiate the pioneer round of translation. After completion of the pioneer round of translation, CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E, which mediates steady-state translation in the cytoplasm. Here, we show that overexpression of eIF4E-T preferentially inhibits cap-dependent steady-state translation, but not the pioneer round of translation. We also demonstrate that overexpression of eIF4E-T or Dcp1a triggers the movement of eIF4E into the processing bodies. These results suggest that the pioneer round of translation differs from steady-state translation in terms of ribosome recruitment
The Effect of Translators' Emotional Intelligence on Their Translation Quality

Science.gov (United States)

Varzande, Mohsen; Jadidi, Esmaeil

2015-01-01

Translators differ from each other in many ways in terms of their knowledge, professional and psychological conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' Emotional Intelligence on their translation quality. Following a "causal-comparative study," a sample of…
Translation of a nonpolyadenylated viral RNA is enhanced by binding of viral coat protein or polyadenylation of the RNA.

Science.gov (United States)

Neeleman, L; Olsthoorn, R C; Linthorst, H J; Bol, J F

2001-12-04

On entering a host cell, positive-strand RNA virus genomes have to serve as messenger for the translation of viral proteins. Efficient translation of cellular messengers requires interactions between initiation factors bound to the 5'-cap structure and the poly(A) binding protein bound to the 3'-poly(A) tail. Initiation of infection with the tripartite RNA genomes of alfalfa mosaic virus (AMV) and viruses from the genus Ilarvirus requires binding of a few molecules of coat protein (CP) to the 3' end of the nonpolyadenylated viral RNAs. Moreover, infection with the genomic RNAs can be initiated by addition of the subgenomic messenger for CP, RNA 4. We report here that extension of the AMV RNAs with a poly(A) tail of 40 to 80 A-residues permitted initiation of infection independently of CP or RNA 4 in the inoculum. Specifically, polyadenylation of RNA 1 relieved an apparent bottleneck in the translation of the viral RNAs. Translation of RNA 4 in plant protoplasts was autocatalytically stimulated by its encoded CP. Mutations that interfered with CP binding to the 3' end of viral RNAs reduced translation of RNA 4 to undetectable levels. Possibly, CP of AMV and ilarviruses stimulates translation of viral RNAs by acting as a functional analogue of poly(A) binding protein or other cellular proteins.

Translating India

CERN Document Server

Kothari, Rita

2014-01-01

The cultural universe of urban, English-speaking middle class in India shows signs of growing inclusiveness as far as English is concerned. This phenomenon manifests itself in increasing forms of bilingualism (combination of English and one Indian language) in everyday forms of speech - advertisement jingles, bilingual movies, signboards, and of course conversations. It is also evident in the startling prominence of Indian Writing in English and somewhat less visibly, but steadily rising, activity of English translation from Indian languages. Since the eighties this has led to a frenetic activity around English translation in India's academic and literary circles. Kothari makes this very current phenomenon her chief concern in Translating India. The study covers aspects such as the production, reception and marketability of English translation. Through an unusually multi-disciplinary approach, this study situates English translation in India amidst local and global debates on translation, representation an...
The Impact of Translators' Academic Experience on Their Translation Quality

Science.gov (United States)

Varzande, Mohsen; Jadidi, Esmaeil

2015-01-01

Translators differ from each other in many ways in terms of their knowledge and professional conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' academic experience on their translation quality. Following a "causal-comparative study", a sample of 100 male and…
Translating Legal Collocations in Contract Agreements by Iraqi EFL Students-Translators

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Muntaha A. Abdulwahid

2017-01-01

Full Text Available Legal translation of contract agreements is a challenge to translators as it involves combining the literary translation with the technical terminological precision. In translating legal contract agreements, a legal translator must utilize the lexical or syntactic precision and, more importantly, the pragmatic awareness of the context. This will guarantee an overall communicative process and avoid inconsistency in legal translation. However, the inability of the translator to meet these two functions in translating the contract item not only affects the contractors’ comprehension of the contract item but also affects the parties’ contractual obligations. In light of this, the purpose of this study was to find out how legal collocations used in contract agreements are translated from Arabic into English by student-translators in terms of (1 purely technical, (2 semi-technical, and (3 everyday vocabulary collocations. For the data collection, a multiple-choice collocation test was used to be answered by 35 EFL Iraqi undergraduate translator-students to decide on the aspects of weaknesses and strengths of their translation, thus decide on the aspects of correction. The findings showed that these students had serious problems in translating legal collocations as they lack the linguistic knowledge and pragmatic awareness needed to achieve the legal meaning and effect. They were also unable to make a difference among the three categories of legal collocations, purely technical, semi-technical, and everyday vocabulary collocations. These students should be exposed to more legal translation practices to obtain the required experience needed for their future career.
Alternative strategy for steady growth towards high quality translation networks

Energy Technology Data Exchange (ETDEWEB)

Witkam, A P.M.

1983-01-01

This paper points out a rather new and largely unexplored direction. In machine translation (MT), but also in data-base enquiry, advanced word processing and natural language programming systems, the analysis of the source text is the crucial process, responsible for parsing and disambiguation. For this purpose, conventional MT systems initially relied on only grammar and dictionary, the grammar being limited to morphology and syntax. The author points to artificial intelligence as an alternative strategy, leading to knowledge based translation. 12 references.
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...... level. We include a volume constraint and a compliance constraint. Topology optimized designs are compared to an intuitively-designed RF switch. The switches contain similar features. The compliance constraint is varied such that the topology optimized switch performance approaches the intuitively......-designed one. Finally, the importance of the compliance constraint and of the robust formulation are discussed....
Using corpora in scientific and technical translation training: resources to identify conventionality and promote creativity

OpenAIRE

Clara Inés López-Rodríguez

2016-01-01

http://dx.doi.org/10.5007/2175-7968.2016v36nesp1p88 Since the first Corpus Use and Learning to Translate (CULT) Conference in Bertinoro (Italy) in 1997, the usefulness of corpora for translators and trainee translators has been highlighted. From an initial approach where translators compiled ad hoc corpora in their hard drive for a subsequent study with lexical analysis software, there emerged a new trend towards the use of the Internet as corpus. In this second approach, the Web is perce...
Translation Analysis on Civil Engineering Text Produced by Machine Translator

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Sutopo Anam

2018-01-01

Full Text Available Translation is extremely needed in communication since people have serious problem in the language used. Translation activity is done by the person in charge for translating the material. Translation activity is also able to be done by machine. It is called machine translation, reflected in the programs developed by programmer. One of them is Transtool. Many people used Transtool for helping them in solving the problem related with translation activities. This paper wants to deliver how important is the Transtool program, how effective is Transtool program and how is the function of Transtool for human business. This study applies qualitative research. The sources of data were document and informant. This study used documentation and in dept-interviewing as the techniques for collecting data. The collected data were analyzed by using interactive analysis. The results of the study show that, first; Transtool program is helpful for people in translating the civil engineering text and it functions as the aid or helper, second; the working of Transtool software program is effective enough and third; the result of translation produced by Transtool is good for short and simple sentences and not readable, not understandable and not accurate for long sentences (compound, complex and compound complex thought the result is informative. The translated material must be edited by the professional translator.
Translation Analysis on Civil Engineering Text Produced by Machine Translator

Science.gov (United States)

Sutopo, Anam

2018-02-01

Translation is extremely needed in communication since people have serious problem in the language used. Translation activity is done by the person in charge for translating the material. Translation activity is also able to be done by machine. It is called machine translation, reflected in the programs developed by programmer. One of them is Transtool. Many people used Transtool for helping them in solving the problem related with translation activities. This paper wants to deliver how important is the Transtool program, how effective is Transtool program and how is the function of Transtool for human business. This study applies qualitative research. The sources of data were document and informant. This study used documentation and in dept-interviewing as the techniques for collecting data. The collected data were analyzed by using interactive analysis. The results of the study show that, first; Transtool program is helpful for people in translating the civil engineering text and it functions as the aid or helper, second; the working of Transtool software program is effective enough and third; the result of translation produced by Transtool is good for short and simple sentences and not readable, not understandable and not accurate for long sentences (compound, complex and compound complex) thought the result is informative. The translated material must be edited by the professional translator.
The Triticum Mosaic Virus 5' Leader Binds to Both eIF4G and eIFiso4G for Translation.

Directory of Open Access Journals (Sweden)

Robyn Roberts

Full Text Available We recently identified a remarkably strong (739 nt-long IRES-like element in the 5' untranslated region (UTR of Triticum mosaic virus (TriMV, Potyviridae. Here, we define the components of the cap-binding translation initiation complex that are required for TriMV translation. Using bio-layer interferometry and affinity capture of the native translation apparatus, we reveal that the viral translation element has a ten-fold greater affinity for the large subunit eIF4G/eIFiso4G than to the cap binding protein eIF4E/eIFiso4E. This data supports a translation mechanism that is largely dependent on eIF4G and its isoform. The binding of both scaffold isoforms requires an eight base-pair-long hairpin structure located 270 nucleotides upstream of the translation initiation site, which we have previously shown to be crucial for IRES activity. Despite a weak binding affinity to the mRNA, eIFiso4G alone or in combination with eIFiso4E supports TriMV translation in a cap-binding factor-depleted wheat germ extract. Notably, TriMV 5' UTR-mediated translation is dependent upon eIF4A helicase activity, as the addition of the eIF4A inhibitor hippuristanol inhibits 5' UTR-mediated translation. This inhibition is reversible with the addition of recombinant wheat eIF4A. These results and previous observations demonstrate a key role of eIF4G and eIF4A in this unique mechanism of cap-independent-translation. This work provides new insights into the lesser studied translation mechanisms of plant virus-mediated internal translation initiation.
Identifying translational science within the triangle of biomedicine.

Science.gov (United States)

Weber, Griffin M

2013-05-24

The National Institutes of Health (NIH) Roadmap places special emphasis on "bench-to-bedside" research, or the "translation" of basic science research into practical clinical applications. The Clinical and Translational Science Awards (CTSA) Consortium is one example of the large investments being made to develop a national infrastructure to support translational science, which involves reducing regulatory burdens, launching new educational initiatives, and forming partnerships between academia and industry. However, while numerous definitions have been suggested for translational science, including the qualitative T1-T4 classification, a consensus has not yet been reached. This makes it challenging to tract the impact of these major policy changes. In this study, we use a bibliometric approach to map PubMed articles onto a graph, called the Triangle of Biomedicine. The corners of the triangle represent research related to animals, cells and molecules, and humans; and, the position of a publication on the graph is based on its topics, as determined by its Medical Subject Headings (MeSH). We define translation as movement of a collection of articles, or the articles that cite those articles, towards the human corner. The Triangle of Biomedicine provides a quantitative way of determining if an individual scientist, research organization, funding agency, or scientific field is producing results that are relevant to clinical medicine. We validate our technique using examples that have been previously described in the literature and by comparing it to prior methods of measuring translational science. The Triangle of Biomedicine is a novel way to identify translational science and track changes over time. This is important to policy makers in evaluating the impact of the large investments being made to accelerate translation. The Triangle of Biomedicine also provides a simple visual way of depicting this impact, which can be far more powerful than numbers alone.
Translation: between what can be translated and what must be translated

Directory of Open Access Journals (Sweden)

Magda Jeanrenaud

2016-02-01

Full Text Available Starting from a disconcerting interpretation of Jacques Derrida, our analysis aims at investigating and also tries to explain the blockage which appears in the English, French and Romanian translations (signed by Maurice de Gandillac, Antoine Berman, Laurent Lamy, Alexis Nouss, Harry Zohn, Steven Rendall, Martine Broda, Catrinel Pleșu etc. of a well-known text of Walter Benjamin, Die Aufgabe des Übersetzers, when translators transpose in their target languages the two quotations given by Benjamin: one of Mallarmé, left untranslated in the source text, and another, signed by Pannwitz. The fact is that both quotations have something in common: a discoursive form which results from an unusual syntax, as if they were already, in a certain sense, „translations”. As if the translators feared—a feature of the translator’s psychology?—not to render their text sufficiently accessible, even when the source text is not intended to be accessible. Hence the painful dilemma of the intentional fallacy (not only of the text to be translated.
Integrating Automatic Speech Recognition and Machine Translation for Better Translation Outputs

DEFF Research Database (Denmark)

Liyanapathirana, Jeevanthi

translations, combining machine translation with computer assisted translation has drawn attention in current research. This combines two prospects: the opportunity of ensuring high quality translation along with a significant performance gain. Automatic Speech Recognition (ASR) is another important area......, which caters important functionalities in language processing and natural language understanding tasks. In this work we integrate automatic speech recognition and machine translation in parallel. We aim to avoid manual typing of possible translations as dictating the translation would take less time...... to the n-best list rescoring, we also use word graphs with the expectation of arriving at a tighter integration of ASR and MT models. Integration methods include constraining ASR models using language and translation models of MT, and vice versa. We currently develop and experiment different methods...
(Con)figuring gender in Bible translation: Cultural, translational and ...

African Journals Online (AJOL)

The gendered intersection of cultural studies and Bible translation is under acknowledged. Accounting for gender criticism in translation work requires, besides responsible theory and practice of translation, also attention to interwoven gender critical aspects. After a brief investigation of the intersections between biblical, ...
Translation and identity: Translation of the Freedom Charter into ...

African Journals Online (AJOL)

A comparative analysis of the Afrikaans translations reveals how the respective translators struggled sporadically through certain ideological constraints in order to provide a satisfactory narrative. Their inability to internalise the principles contained in the Freedom Charter resulted in them presenting a 'framed' translation ...
Russian translations for Cochrane.

Science.gov (United States)

Yudina, E V; Ziganshina, L E

2015-01-01

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

Science.gov (United States)

Murday, James S; Siegel, Richard W; Stein, Judith; Wright, J Fraser

2009-09-01

Nano-enabled technologies hold great promise for medicine and health. The rapid progress by the physical sciences/engineering communities in synthesizing nanostructures and characterizing their properties must be rapidly exploited in medicine and health toward reducing mortality rate, morbidity an illness imposes on a patient, disease prevalence, and general societal burden. A National Science Foundation-funded workshop, "Re-Engineering Basic and Clinical Research to Catalyze Translational Nanoscience," was held 16-19 March 2008 at the University of Southern California. Based on that workshop and literature review, this article briefly explores scientific, economic, and societal drivers for nanomedicine initiatives; examines the science, engineering, and medical research needs; succinctly reviews the US federal investment directly germane to medicine and health, with brief mention of the European Union (EU) effort; and presents recommendations to accelerate the translation of nano-enabled technologies from laboratory discovery into clinical practice. An excellent review paper based on the NSF funded workshop "Re-Engineering Basic and Clinical Research to Catalyze Translational Nanoscience" (16-19 March 2008) and extensive literature search, this paper briefly explores the current state and future perspectives of nanomedicine.
Temporo-spatial IMRT optimization: concepts, implementation and initial results

International Nuclear Information System (INIS)

Trofimov, Alexei; Rietzel, Eike; Lu Hsiaoming; Martin, Benjamin; Jiang, Steve; Chen, George T Y; Bortfeld, Thomas

2005-01-01

With the recent availability of 4D-CT, the accuracy of information on internal organ motion during respiration has improved significantly. We investigate the utility of organ motion information in IMRT treatment planning, using an in-house prototype optimization system. Four approaches are compared: (1) planning with optimized margins, based on motion information; (2) the 'motion kernel' approach, in which a more accurate description of the dose deposit from a pencil beam to a moving target is achieved either through time-weighted averaging of influence matrices, calculated for different instances of anatomy (subsets of 4D-CT data, corresponding to various phases of motion) or through convolution of the pencil beam kernel with the probability density function describing the target motion; (3) optimal gating, or tracking with beam intensity maps optimized independently for each instance of anatomy; and (4) optimal tracking with beam intensity maps optimized simultaneously for all instances of anatomy. The optimization is based on a gradient technique and can handle both physical (dose-volume) and equivalent uniform dose constraints. Optimization requires voxel mapping from phase to phase in order to score the dose in individual voxels as they move. The results show that, compared to the other approaches, margin expansion has a significant disadvantage by substantially increasing the integral dose to patient. While gating or tracking result in the best dose conformation to the target, the former elongates treatment time, and the latter significantly complicates the delivery procedure. The 'motion kernel' approach does not provide a dosimetric advantage, compared to optimal tracking or gating, but might lead to more efficient delivery. A combination of gating with the 'motion kernel' or margin expansion approach will increase the duty cycle and may provide one with the most efficient solution, in terms of complexity of the delivery procedure and dose conformality to
Word translation entropy in translation

DEFF Research Database (Denmark)

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

2016-01-01

This study reports on an investigation into the relationship between the number of translation alternatives for a single word and eye movements on the source text. In addition, the effect of word order differences between source and target text on eye movements on the source text is studied....... In particular, the current study investigates the effect of these variables on early and late eye movement measures. Early eye movement measures are indicative of processes that are more automatic while late measures are more indicative of conscious processing. Most studies that found evidence of target...... language activation during source text reading in translation, i.e. co-activation of the two linguistic systems, employed late eye movement measures or reaction times. The current study therefore aims to investigate if and to what extent earlier eye movement measures in reading for translation show...

New insights into the interplay between the translation machinery and nonsense-mediated mRNA decay factors.

Science.gov (United States)

Raimondeau, Etienne; Bufton, Joshua C; Schaffitzel, Christiane

2018-06-19

Faulty mRNAs with a premature stop codon (PTC) are recognized and degraded by nonsense-mediated mRNA decay (NMD). Recognition of a nonsense mRNA depends on translation and on the presence of NMD-enhancing or the absence of NMD-inhibiting factors in the 3'-untranslated region. Our review summarizes our current understanding of the molecular function of the conserved NMD factors UPF3B and UPF1, and of the anti-NMD factor Poly(A)-binding protein, and their interactions with ribosomes translating PTC-containing mRNAs. Our recent discovery that UPF3B interferes with human translation termination and enhances ribosome dissociation in vitro , whereas UPF1 is inactive in these assays, suggests a re-interpretation of previous experiments and modification of prevalent NMD models. Moreover, we discuss recent work suggesting new functions of the key NMD factor UPF1 in ribosome recycling, inhibition of translation re-initiation and nascent chain ubiquitylation. These new findings suggest that the interplay of UPF proteins with the translation machinery is more intricate than previously appreciated, and that this interplay quality-controls the efficiency of termination, ribosome recycling and translation re-initiation. © 2018 The Author(s).
(Configuring gender in Bible translation: Cultural, translational and gender critical intersections

Directory of Open Access Journals (Sweden)

Jeremy Punt

2014-06-01

Full Text Available The gendered intersection of cultural studies and Bible translation is under acknowledged. Accounting for gender criticism in translation work requires, besides responsible theory and practice of translation, also attention to interwoven gender critical aspects. After a brief investigation of the intersections between biblical, translation and gender studies, translation in a few Pauline texts with bearing on gender and sexuality are investigated.
Translation of vph mRNA in Streptomyces lividans and Escherichia coli after removal of the 5' untranslated leader.

Science.gov (United States)

Wu, C J; Janssen, G R

1996-10-01

The Streptomyces vinaceus viomycin phosphotransferase (vph) mRNA contains an untranslated leader with a conventional Shine-Dalgarno homology. The vph leader was removed by ligation of the vph coding sequence to the transcriptional start site of a Streptomyces or an Escherichia coli promoter, such that transcription would initiate at the first position of the vph start codon. Analysis of mRNA demonstrated that transcription initiated primarily at the A of the vph AUG translational start codon in both Streptomyces lividans and E. coli; cells expressing the unleadered vph mRNA were resistant to viomycin indicating that the Shine-Dalgarno sequence, or other features contained within the leader, was not necessary for vph translation. Addition of four nucleotides (5'-AUGC-3') onto the 5' end of the unleadered vph mRNA resulted in translation initiation from the vph start codon and the AUG triplet contained within the added sequence. Translational fusions of vph sequence to a Tn5 neo reporter gene indicated that the first 16 codons of vph coding sequence were sufficient to specify the translational start site and reading frame for expression of neomycin resistance in both E. coli and S. lividans.
Optimizing the prevention of venous thromboembolism: recent quality initiatives and strategies to drive improvement.

Science.gov (United States)

Amin, Alpesh N; Deitelzweig, Steven B

2009-11-01

Venous thromboembolism (VTE) is associated with a substantial health care and economic burden, yet many VTE events are preventable. Despite the availability of evidence-based guidelines derailing effective thromboprophylaxis strategies, the underuse and inappropriate prescribing of VTE prophylaxis are common. Current national quality initiatives were reviewed to identify strategies that may help hospitals and health care professionals optimize current VTE prophylaxis practices. A computerized literature search was performed using PubMed and MEDLINE, and this was complemented by hand searches of relevant journals and Web sites to identify additional literature related to VTE prevention and quality improvement. Many organizations, including the Centers for Medicare & Medicaid Services, the National Quality Forum, the Joint Commission, and the Agency for Healthcare Research and Quality have developed performance measures, quality indicators, public reporting initiatives, incentive programs, and "negative reimbursement" that are designed to help improve VTE prevention. It remains the responsibility of individual hospitals to identify specific areas in which they can improve their VTE prophylaxis rates to obtain positive results from the reporting initiatives and incentive programs. If performance measures are to be met, all hospital departments will need to implement effective VTE prevention policies, including early risk assessment, appropriate prophylaxis prescribing, monitoring, and follow-up. Multifaceted, integrated initiatives involving risk assessment tools, decision support, electronic alert systems, and hospitalwide education, with a mechanism for audit and feedback, may help ensure that all health care professionals comply with VTE-prevention policies and initiatives.
Literal Translation using Google Translate in Translating the Text from French to English in Digital Tourism Brochure “Bienvenue À Paris”

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Rila Hilma

2011-05-01

Full Text Available Translation is basically change of form. The form from which the translation is made will be called the source language and the form into which it is to be changed will be called the receptor language. Translation consists of transferring the meaning of the source language into the receptor language. Translating is not an easy job to do because many things to be considered to do this activity because translation means determining the meaning of a text, then reconstructing this same meaning using the appropriate structure and form in the receptor language. Translation is basically divided by two types of translation, one is literal and the other is idiomatic. Literal translation is really strict to the structure and form then often can not well express the true meaning of source language. Idiomatic translation makes every effort to communicate the meaning of the source language text in the natural forms of the receptor language. Then the most popular translation machine, Google Translate, in this study shows the results of translation which remain odd, unnatural, and nonsensical because the unsuccessful of message delivery, which is notably the typically error of literal translation.
The ICNP BaT - from translation tool to translation web service.

Science.gov (United States)

Schrader, Ulrich

2009-01-01

The ICNP BaT has been developed as a web application to support the collaborative translation of different versions of the ICNP into different languages. A prototype of a web service is described that could reuse the translations in the database of the ICNP BaT to provide automatic translations of nursing content based on the ICNP terminology globally. The translation web service is based on a service-oriented architecture making it easy to interoperate with different applications. Such a global translation server would free individual institutions from the maintenance costs of realizing their own translation services.
Post-translational regulation enables robust p53 regulation.

Science.gov (United States)

Shin, Yong-Jun; Chen, Kai-Yuan; Sayed, Ali H; Hencey, Brandon; Shen, Xiling

2013-08-30

The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism. We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise. Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.
Translation research: from accurate diagnosis to appropriate treatment

Directory of Open Access Journals (Sweden)

Pass Harvey I

2004-10-01

Full Text Available Abstract This review article focuses on the various aspects of translational research, where research on human subjects can ultimately enhance the diagnosis and treatment of future patients. While we will use specific examples relating to the asbestos related cancer mesothelioma, it should be stressed that the general approach outlined throughout this review is readily applicable to other diseases with an underlying molecular basis. Through the integration of molecular-based technologies, systematic tissue procurement and medical informatics, we now have the ability to identify clinically applicable "genotype"-"phenotype" associations across cohorts of patients that can rapidly be translated into useful diagnostic and treatment strategies. This review will touch on the various steps in the translational pipeline, and highlight some of the most essential elements as well as possible roadblocks that can impact success of the program. Critical issues with regard to Institutional Review Board (IRB and Health Insurance Portability and Accountability Act (HIPAA compliance, data standardization, sample procurement, quality control (QC, quality assurance (QA, data analysis, preclinical models and clinical trials are addressed. The various facets of the translational pipeline have been incorporated into a fully integrated computational system, appropriately named Dx2Tx. This system readily allows for the identification of new diagnostic tests, the discovery of biomarkers and drugable targets, and prediction of optimal treatments based upon the underlying molecular basis of the disease.
On Various Negative Translations

Directory of Open Access Journals (Sweden)

Gilda Ferreira

2011-01-01

Full Text Available Several proof translations of classical mathematics into intuitionistic mathematics have been proposed in the literature over the past century. These are normally referred to as negative translations or double-negation translations. Among those, the most commonly cited are translations due to Kolmogorov, Godel, Gentzen, Kuroda and Krivine (in chronological order. In this paper we propose a framework for explaining how these different translations are related to each other. More precisely, we define a notion of a (modular simplification starting from Kolmogorov translation, which leads to a partial order between different negative translations. In this derived ordering, Kuroda and Krivine are minimal elements. Two new minimal translations are introduced, with Godel and Gentzen translations sitting in between Kolmogorov and one of these new translations.
Bi-polarized translation of ascidian maternal mRNA determinant pem-1 associated with regulators of the translation machinery on cortical Endoplasmic Reticulum (cER).

Science.gov (United States)

Paix, Alexandre; Le Nguyen, Phuong Ngan; Sardet, Christian

2011-09-01

Polarized cortical mRNA determinants such as maternal macho-1 and pem-1 in ascidians, like budding yeast mating factor ASH1 reside on the cER-mRNA domain a subdomain of cortical Endoplasmic Reticulum(ER) and are translated in its vicinity. Using high resolution imaging and isolated cortical fragments prepared from eggs and embryos we now find that macho-1 and pem-1 RNAs co-localize with phospho-protein regulators of translation initiation (MnK/4EBP/S6K). Translation of cortical pem-1 RNA follows its bi-polarized relocalization. About 10 min after fertilization or artificial activation with a calcium ionophore, PEM1 protein is detected in the vegetal cortex in the vicinity of pem-1 RNA. About 40 min after fertilization-when pem-1 RNA and P-MnK move to the posterior pole-PEM1 protein remains in place forming a network of cortical patches anchored at the level of the zygote plasma membrane before disappearing. Cortical PEM1 protein is detected again at the 4 cell stage in the posterior centrosome attracting body (CAB) region where the cER-mRNA domain harboring pem-1/P-MnK/P-4EBP/P-S6K is concentrated. Bi-polarized PEM1 protein signals are not detected when pem-1 morpholinos are injected into eggs or zygotes or when MnK is inhibited. We propose that localized translation of the pem-1 RNA determinant is triggered by the fertilization/calcium wave and that the process is controlled by phospho-protein regulators of translation initiation co-localized with the RNA determinant on a sub-domain of the cortical Endoplasmic Reticulum. Copyright © 2011 Elsevier Inc. All rights reserved.
Using Cognitive Interviews to Evaluate the Spanish-Language Translation of Dietary Questionnaire

Directory of Open Access Journals (Sweden)

Kerry Levin

2009-03-01

Full Text Available We present results from a qualitative evaluation of the Spanish-language version of a dietary intake questionnaire and characterize the types of findings which emerged from several rounds of cognitive testing. Cognitive interviews were used to test the Spanish translation of the National Health Interview Survey (NHIS Cancer Control Supplement dietary questions, with 36 Spanish-speaking and 9 English-speaking participants. Analyses of the results identified (a translation issues, (b culture-specific issues, and (c general design issues that affected both English and Spanish speakers. Results indicated that general design-oriented difficulties were particularly frequent. Our findings suggest that when appropriately structured, cognitive interviews that feature flexible probing can be useful for identifying a range of problems in survey translations, even after translations have been developed using currently accepted methods. We make several recommendations concerning practices that may be optimal in the conduct of empirical cross-cultural questionnaire evaluations.
ISN Nexus 2016 Symposia: Translational Immunology in Kidney Disease—The Berlin Roadmap

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Hans-Joachim Anders

2016-11-01

Full Text Available To date, the treatment of immune-mediated kidney diseases has only marginally benefited from highly specific biological drugs that have demonstrated remarkable effects in many other diseases. What accounts for this disparity? In April 2016, the International Society of Nephrology held a Nexus meeting on Translational Immunology in Nephrology in Berlin, Germany, to identify and discuss hurdles that block the translational flow of target identification, and preclinical and clinical target validation in the domain of immune-mediated kidney disease. A broad panel of experts including basic scientists, translational researchers, clinical trialists, pharmaceutical industry drug developers, and representatives of the American and European regulatory authorities made recommendations on how to overcome such hurdles at all levels of the translational research process. The results of these discussions are presented here, which may serve as a roadmap for how to optimize the process of developing more innovative and effective drugs for patients with immune-mediated kidney diseases.
Lost in translation?

DEFF Research Database (Denmark)

Granas, Anne Gerd; Nørgaard, Lotte Stig; Sporrong, Sofia Kälvemark

2014-01-01

OBJECTIVE: The "Beliefs about Medicines Questionnaire" (BMQ) assess balance of necessity and concern of medicines. The BMQ has been translated from English to many languages. However, the original meaning of statements, such as "My medicine is a mystery to me", may be lost in translation. The aim...... of this study is to compare three Scandinavian translations of the BMQ. (1) How reliable are the translations? (2) Are they still valid after translation? METHODS: Translated Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three native Scandinavian researchers. Linguistic differences...... and ambiguities in the 5-point Likert scale and the BMQ statements were compared. RESULTS: In the Scandinavian translations, the Likert scale expanded beyond the original version at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements, discrepancies ranged from smaller inaccuracies toward...
An Evergreen Challenge for Translators – The Translation of Idioms

Directory of Open Access Journals (Sweden)

Kovács Gabriella

2016-12-01

Full Text Available Translating idioms has always been a challenging decision-making process for translators mainly because not all idioms have direct equivalents in the target language. Translators usually and ideally have a solid knowledge of the target language and its cultural aspects, but even so they cannot match the ability of a native speaker in deciding when – i.e. in what context and text type – an idiom would or would not be appropriate. This study aims to explore the main characteristics of idioms and the difficulties which might occur when translating them. A needs analysis will also be presented, where the various solutions which a group of translator trainees chose while translating certain idioms from the novel “A Game of Thrones” by George R. R. Martin into Hungarian are examined. Their strategies and the appropriateness of their choices are analysed and compared with the options of the experienced literary translator (Tamás Pétersz. We consider this an important endeavour because, based on our experience, we believe that the topic of the translation of idioms should be included into the curriculum and appropriate materials and tasks should be designed to develop the translator trainees’ knowledge and skills in this domain. Therefore, the aim of this analysis is to obtain a clearer view of the difficulties they are dealing with and bear them in mind when designing teaching materials for them.
Structural modelling and phylogenetic analyses of PgeIF4A2 (Eukaryotic translation initiation factor) from Pennisetum glaucum reveal signature motifs with a role in stress tolerance and development.

Science.gov (United States)

Agarwal, Aakrati; Mudgil, Yashwanti; Pandey, Saurabh; Fartyal, Dhirendra; Reddy, Malireddy K

2016-01-01

Eukaryotic translation initiation factor 4A (eIF4A) is an indispensable component of the translation machinery and also play a role in developmental processes and stress alleviation in plants and animals. Different eIF4A isoforms are present in the cytosol of the cell, namely, eIF4A1, eIF4A2, and eIF4A3 and their expression is tightly regulated in cap-dependent translation. We revealed the structural model of PgeIF4A2 protein using the crystal structure of Homo sapiens eIF4A3 (PDB ID: 2J0S) as template by Modeller 9.12. The resultant PgeIF4A2 model structure was refined by PROCHECK, ProSA, Verify3D and RMSD that showed the model structure is reliable with 77 % amino acid sequence identity with template. Investigation revealed two conserved signatures for ATP-dependent RNA Helicase DEAD-box conserved site (VLDEADEML) and RNA helicase DEAD-box type, Q-motif in sheet-turn-helix and α-helical region respectively. All these conserved motifs are responsible for response during developmental stages and stress tolerance in plants.
CCL5 promotes proliferation of MCF-7 cells through mTOR-dependent mRNA translation

International Nuclear Information System (INIS)

Murooka, Thomas T.; Rahbar, Ramtin; Fish, Eleanor N.

2009-01-01

The proliferative capacity of cancer cells is regulated by factors intrinsic to cancer cells and by secreted factors in the microenvironment. Here, we investigated the proto-oncogenic potential of the chemokine receptor, CCR5, in MCF-7 breast cancer cell lines. At physiological levels, CCL5, a ligand for CCR5, enhanced MCF-7.CCR5 proliferation. Treatment with the mTOR inhibitor, rapamycin, inhibited this CCL5-inducible proliferation. Because mTOR directly modulates mRNA translation, we investigated whether CCL5 activation of CCR5 leads to increased translation. CCL5 induced the formation of the eIF4F translation initiation complex through an mTOR-dependent process. Indeed, CCL5 initiated mRNA translation, shown by an increase in high-molecular-weight polysomes. Specifically, we show that CCL5 mediated a rapid up-regulation of protein expression for cyclin D1, c-Myc and Dad-1, without affecting their mRNA levels. Taken together, we describe a mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs, thereby providing CCR5-positive breast cancer cells with a proliferative advantage.
Translation in Language Teaching: Insights from Professional Translator Training

Science.gov (United States)

Carreres, Angeles; Noriega-Sanchez, Maria

2011-01-01

The past three decades have seen vast changes in attitudes towards translation, both as an academic discipline and as a profession. The insights we have gained in recent years, in particular in the area of professional translator training, call for a reassessment of the role of translation in language teaching. Drawing on research and practices in…
Steady-state structural fluctuation is a predictor of the necessity of pausing-mediated co-translational folding for small proteins.

Science.gov (United States)

Huang, Wenxi; Liu, Wanting; Jin, Jingjie; Xiao, Qilan; Lu, Ruibin; Chen, Wei; Xiong, Sheng; Zhang, Gong

2018-03-25

Translational pausing coordinates protein synthesis and co-translational folding. It is a common factor that facilitates the correct folding of large, multi-domain proteins. For small proteins, pausing sites rarely occurs in the gene body, and the 3'-end pausing sites are only essential for the folding of a fraction of proteins. The determinant of the necessity of the pausings remains obscure. In this study, we demonstrated that the steady-state structural fluctuation is a predictor of the necessity of pausing-mediated co-translational folding for small proteins. Validated by experiments with 5 model proteins, we found that the rigid protein structures do not, while the flexible structures do need 3'-end pausings to fold correctly. Therefore, rational optimization of translational pausing can improve soluble expression of small proteins with flexible structures, but not the rigid ones. The rigidity of the structure can be quantitatively estimated in silico using molecular dynamic simulation. Nevertheless, we also found that the translational pausing optimization increases the fitness of the expression host, and thus benefits the recombinant protein production, independent from the soluble expression. These results shed light on the structural basis of the translational pausing and provided a practical tool for industrial protein fermentation. Copyright © 2017. Published by Elsevier Inc.
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....
Stimulation of translation by human Unr requires cold shock domains 2 and 4, and correlates with poly(A) binding protein interaction.

Science.gov (United States)

Ray, Swagat; Anderson, Emma C

2016-03-03

The RNA binding protein Unr, which contains five cold shock domains, has several specific roles in post-transcriptional control of gene expression. It can act as an activator or inhibitor of translation initiation, promote mRNA turnover, or stabilise mRNA. Its role depends on the mRNA and other proteins to which it binds, which includes cytoplasmic poly(A) binding protein 1 (PABP1). Since PABP1 binds to all polyadenylated mRNAs, and is involved in translation initiation by interaction with eukaryotic translation initiation factor 4G (eIF4G), we investigated whether Unr has a general role in translational control. We found that Unr strongly stimulates translation in vitro, and mutation of cold shock domains 2 or 4 inhibited its translation activity. The ability of Unr and its mutants to stimulate translation correlated with its ability to bind RNA, and to interact with PABP1. We found that Unr stimulated the binding of PABP1 to mRNA, and that Unr was required for the stable interaction of PABP1 and eIF4G in cells. siRNA-mediated knockdown of Unr reduced the overall level of cellular translation in cells, as well as that of cap-dependent and IRES-dependent reporters. These data describe a novel role for Unr in regulating cellular gene expression.

Structural and Functional Diversity of Plant Virus 3'-Cap-Independent Translation Enhancers (3'-CITEs).

Science.gov (United States)

Truniger, Verónica; Miras, Manuel; Aranda, Miguel A

2017-01-01

Most of the positive-strand RNA plant viruses lack the 5'-cap and/or the poly(A)-tail that act synergistically to stimulate canonical translation of cellular mRNAs. However, they have RNA elements in the 5'- or 3'-untranslated regions of their RNAs that are required for their cap-independent translation. Cap-independent translation enhancers (CITEs) have been identified in the genomic 3'-end of viruses belonging to the family Tombusviridae and the genus Luteovirus . Seven classes of 3'-CITEs have been described to date based on their different RNA structures. They generally control the efficient formation of the translation initiation complex by varying mechanisms. Some 3'-CITEs bind eukaryotic translation initiation factors, others ribosomal subunits, bridging these to the 5'-end by different mechanisms, often long-distance RNA-RNA interactions. As previously proposed and recently found in one case in nature, 3'-CITEs are functionally independent elements that are transferable through recombination between viral genomes, leading to potential advantages for virus multiplication. In this review, the knowledge on 3'-CITEs and their functioning is updated. We also suggest that there is local structural conservation in the regions interacting with eIF4E of 3'-CITEs belonging to different classes.
Skeletal muscle protein synthesis and the abundance of the mRNA translation initiation repressor PDCD4 are inversely regulated by fasting and refeeding in rats.

Science.gov (United States)

Zargar, Sana; Moreira, Tracy S; Samimi-Seisan, Helena; Jeganathan, Senthure; Kakade, Dhanshri; Islam, Nushaba; Campbell, Jonathan; Adegoke, Olasunkanmi A J

2011-06-01

Optimal skeletal muscle mass is vital to human health, because defects in muscle protein metabolism underlie or exacerbate human diseases. The mammalian target of rapamycin complex 1 is critical in the regulation of mRNA translation and protein synthesis. These functions are mediated in part by the ribosomal protein S6 kinase 1 (S6K1) through mechanisms that are poorly understood. The tumor suppressor programmed cell death 4 (PDCD4) has been identified as a novel substrate of S6K1. Here, we examined 1) the expression of PDCD4 in skeletal muscle and 2) its regulation by feed deprivation (FD) and refeeding. Male rats (~100 g; n = 6) were subjected to FD for 48 h; some rats were refed for 2 h. FD suppressed muscle fractional rates of protein synthesis and Ser(67) phosphorylation of PDCD4 (-50%) but increased PDCD4 abundance (P muscle fractional rates of protein synthesis and reduced PDCD4 abundance relative to FD. Finally, when myoblasts were grown in amino acid- and serum-free medium, phenylalanine incorporation into proteins in cells depleted of PDCD4 more than doubled the values in cells with a normal level of PDCD4 (P skeletal muscle in parallel with the reduction of the abundance of this mRNA translation inhibitor.
Untranslated regions of diverse plant viral RNAs vary greatly in translation enhancement efficiency

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Fan Qiuling

2012-05-01

Full Text Available Abstract Background Whole plants or plant cell cultures can serve as low cost bioreactors to produce massive amounts of a specific protein for pharmacological or industrial use. To maximize protein expression, translation of mRNA must be optimized. Many plant viral RNAs harbor extremely efficient translation enhancers. However, few of these different translation elements have been compared side-by-side. Thus, it is unclear which are the most efficient translation enhancers. Here, we compare the effects of untranslated regions (UTRs containing translation elements from six plant viruses on translation in wheat germ extract and in monocotyledenous and dicotyledenous plant cells. Results The highest expressing uncapped mRNAs contained viral UTRs harboring Barley yellow dwarf virus (BYDV-like cap-independent translation elements (BTEs. The BYDV BTE conferred the most efficient translation of a luciferase reporter in wheat germ extract and oat protoplasts, while uncapped mRNA containing the BTE from Tobacco necrosis virus-D translated most efficiently in tobacco cells. Capped mRNA containing the Tobacco mosaic virus omega sequence was the most efficient mRNA in tobacco cells. UTRs from Satellite tobacco necrosis virus, Tomato bushy stunt virus, and Crucifer-infecting tobamovirus (crTMV did not stimulate translation efficiently. mRNA with the crTMV 5′ UTR was unstable in tobacco protoplasts. Conclusions BTEs confer the highest levels of translation of uncapped mRNAs in vitro and in vivo, while the capped omega sequence is most efficient in tobacco cells. These results provide a basis for understanding mechanisms of translation enhancement, and for maximizing protein synthesis in cell-free systems, transgenic plants, or in viral expression vectors.
An in vitro system from Plasmodium falciparum active in endogenous mRNA translation

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Ferreras Ana

2000-01-01

Full Text Available An in vitro translation system has been prepared from Plasmodium falciparum by saponin lysis of infected-erythrocytes to free parasites which were homogeneized with glass beads, centrifuged to obtain a S-30 fraction followed by Sephadex G-25 gel filtration. This treatment produced a system with very low contamination of host proteins (<1%. The system, optimized for Mg2+ and K+, translates endogenous mRNA and is active for 80 min which suggests that their protein factors and mRNA are quite stable.
Writing Through: Practising Translation

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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
Speaking your Translation

DEFF Research Database (Denmark)

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

2011-01-01

In this article we discuss the translation processes and products of 14 MA students who produced translations from Danish (L1) into English (L2) under different working conditions: (1) written translation, (2) sight translation, and (3) sight translation with a speech recognition (SR) tool. Audio......, since students were dictating in their L2, we looked into the number and types of error that occurred when using the SR software. Items that were misrecognised by the program could be divided into three categories: homophones, hesitations, and incorrectly pronounced words. Well over fifty per cent...
Functional 5' UTR mRNA structures in eukaryotic translation regulation and how to find them.

Science.gov (United States)

Leppek, Kathrin; Das, Rhiju; Barna, Maria

2018-03-01

RNA molecules can fold into intricate shapes that can provide an additional layer of control of gene expression beyond that of their sequence. In this Review, we discuss the current mechanistic understanding of structures in 5' untranslated regions (UTRs) of eukaryotic mRNAs and the emerging methodologies used to explore them. These structures may regulate cap-dependent translation initiation through helicase-mediated remodelling of RNA structures and higher-order RNA interactions, as well as cap-independent translation initiation through internal ribosome entry sites (IRESs), mRNA modifications and other specialized translation pathways. We discuss known 5' UTR RNA structures and how new structure probing technologies coupled with prospective validation, particularly compensatory mutagenesis, are likely to identify classes of structured RNA elements that shape post-transcriptional control of gene expression and the development of multicellular organisms.
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....
Development of a mentorship strategy: a knowledge translation case study.

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Straus, Sharon E; Graham, Ian D; Taylor, Mark; Lockyer, Jocelyn

2008-01-01

There are many theories and frameworks for achieving knowledge translation, and the assortment can be confusing to those responsible for planning, evaluation, or policymaking in knowledge translation. A conceptual framework developed by Graham and colleagues provides an approach that builds on the commonalities found in an assessment of planned-action theories. This article describes the application of this knowledge to action framework to a mentorship initiative in academic medicine. Mentorship influences career success but is threatened in academia by increased clinical, research, and administrative demands. A case study review was undertaken of the role of mentors, the experiences of mentors and mentees, and mentorship initiatives in developing and retaining clinician scientists at two universities in Alberta, Canada. This project involved relevant stakeholders including researchers, university administrators, and research funders. The knowledge to action framework was used to develop a strategy for mentorship for clinician researchers. The framework highlights the need to identify and engage stakeholders in the process of knowledge implementation. A series of initiatives were selected and tailored to barriers and facilitators to implementation of the mentorship initiative; strategies for evaluating the knowledge use and its impact on outcomes were developed. The knowledge to action framework can be used to develop a mentorship initiative for clinician researchers. Future work to evaluate the impact of this intervention on recruitment and retention is planned.
Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA Translation.

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Jeeva, Subbiah; Cheng, Erdong; Ganaie, Safder S; Mir, Mohammad A

2017-08-01

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus. IMPORTANCE Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5' UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease. Copyright © 2017 American Society for Microbiology.
Double-diffusive translation of Earth's inner core

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Deguen, R.; Alboussiére, T.; Labrosse, S.

2018-03-01

The hemispherical asymmetry of the inner core has been interpreted as resulting form a high-viscosity mode of inner core convection, consisting in a translation of the inner core. A thermally driven translation, as originally proposed, is unlikely if the currently favoured high values of the thermal conductivity of iron at core conditions are correct. We consider here the possibility that inner core translation results from an unstable compositional gradient, which would develop either because the light elements present in the core become increasingly incompatible as the inner core grows, or because of a possibly positive feedback of the development of the F-layer on inner core convection. Though the magnitude of the destabilising effect of the compositional field is predicted to be similar to or smaller than the stabilising effect of the thermal field, the huge difference between thermal and chemical diffusivities implies that double-diffusive instabilities can still arise even if the net buoyancy increases upward. Using linear stability analysis and numerical simulations, we demonstrate that a translation mode can indeed exist if the compositional field is destabilising, even if the temperature profile is subadiabatic, and irrespectively of the relative magnitudes of the composition and potential temperature gradients. The existence of this double diffusive mode of translation requires that the following conditions are met: (i) the compositional profile within the inner core is destabilising, and remains so for a duration longer than the destabilisation timescale (on the order of 200 My, but strongly dependent on the magnitude of the initial perturbation); and (ii) the inner core viscosity is sufficiently large, the required value being a strongly increasing function of the inner core size (e.g. 1017 Pa.s when the inner core was 200 km in radius, and ≃ 3 × 1021 Pa.s at the current inner core size). If these conditions are met, the predicted inner core
A Comparative Study of "Google Translate" Translations: An Error Analysis of English-to-Persian and Persian-to-English Translations

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Ghasemi, Hadis; Hashemian, Mahmood

2016-01-01

Both lack of time and the need to translate texts for numerous reasons brought about an increase in studying machine translation with a history spanning over 65 years. During the last decades, Google Translate, as a statistical machine translation (SMT), was in the center of attention for supporting 90 languages. Although there are many studies on…
5'-Terminal AUGs in Escherichia coli mRNAs with Shine-Dalgarno Sequences: Identification and Analysis of Their Roles in Non-Canonical Translation Initiation.

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Heather J Beck

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

International Nuclear Information System (INIS)

Auclair, K. D.

2002-01-01

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
Bean Soup Translation: Flexible, Linguistically-Motivated Syntax for Machine Translation

Science.gov (United States)

Mehay, Dennis Nolan

2012-01-01

Machine translation (MT) systems attempt to translate texts from one language into another by translating words from a "source language" and rearranging them into fluent utterances in a "target language." When the two languages organize concepts in very different ways, knowledge of their general sentence structure, or…
FRC [field-reversed configuration] translation studies on FRX-C/LSM

International Nuclear Information System (INIS)

Rej, D.; Barnes, G.; Baron, M.

1989-01-01

In preparation for upcoming compression-heating experiments, field-reversed configurations (FRCs) have been translated out of the FRX-C/LSM θ-pinch source, and into the 0.4-m-id, 6.7-m-long translation region formerly used on FRX-C/T. Unlike earlier experiments FRCs are generated without magnetic tearing in the larger FRX-C/LSM source (nominal coil id = 0.70 m, length = 2 m); larger, lower-energy-density FRCs are formed: r/sub s/ ≅ 0.17 m, B/sub ext/ ≅ 0.35 T, ≅ 7 /times/ 10 20 m/sup /minus/3/ and T/sub e/ + T/sub i/ ≅ 400 eV. An initial 3-mtorr D 2 pressure is introduced by either static or puff fill. Asymmetric fields from auxiliary end coils (used for non-tearing formation) provide the accelerating force on the FRC, thereby eliminating the need for a conical θ-pinch coil. An important feature is the abrupt 44% decrease in the flux-conserving wall radius at the transition between the θ-pinch and translation region, similar to that in the compressor. In this paper we review a variety of issues addressed by the recent translation experiments: translation dynamics; translation through a modulated magnetic field; stabilization of the n = 2 rotational instability by weak helical quadrupole fields; and confinement properties. Results from internal magnetic field measurements in translating FRCs may be found in a companion paper. 10 refs., 5 figs
Recommendations for translation and reliability testing of International Spinal Cord Injury Data Sets.

Science.gov (United States)

Biering-Sørensen, F; Alexander, M S; Burns, S; Charlifue, S; DeVivo, M; Dietz, V; Krassioukov, A; Marino, R; Noonan, V; Post, M W M; Stripling, T; Vogel, L; Wing, P

2011-03-01

To provide recommendations regarding translation and reliability testing of International Spinal Cord Injury (SCI) Data Sets. The Executive Committee for the International SCI Standards and Data Sets. Translations of any specific International SCI Data Set can be accomplished by translation from the English version into the target language, and be followed by a back-translation into English, to confirm that the original meaning has been preserved. Another approach is to have the initial translation performed by translators who have knowledge of SCI, and afterwards controlled by other person(s) with the same kind of knowledge. The translation process includes both language translation and cultural adaptation, and therefore shall not be made word for word, but will strive to include conceptual equivalence. At a minimum, the inter-rater reliability should be tested by no less than two independent observers, and preferably in multiple countries. Translations must include information on the name, role and background of everyone involved in the translation process, and shall be dated and noted with a version number. By following the proposed guidelines, translated data sets should assure comparability of data acquisition across countries and cultures. If the translation process identifies irregularities or misrepresentation in either the original English version or the target language, the working group for the particular International SCI Data Set shall revise the data set accordingly, which may include re-wording of the original English version in order to accomplish a compromise in the content of the data set.
Molecular mechanism and structure of Trigger Factor bound to the translating ribosome

Science.gov (United States)

Merz, Frieder; Boehringer, Daniel; Schaffitzel, Christiane; Preissler, Steffen; Hoffmann, Anja; Maier, Timm; Rutkowska, Anna; Lozza, Jasmin; Ban, Nenad; Bukau, Bernd; Deuerling, Elke

2008-01-01

Ribosome-associated chaperone Trigger Factor (TF) initiates folding of newly synthesized proteins in bacteria. Here, we pinpoint by site-specific crosslinking the sequence of molecular interactions of Escherichia coli TF and nascent chains during translation. Furthermore, we provide the first full-length structure of TF associated with ribosome–nascent chain complexes by using cryo-electron microscopy. In its active state, TF arches over the ribosomal exit tunnel accepting nascent chains in a protective void. The growing nascent chain initially follows a predefined path through the entire interior of TF in an unfolded conformation, and even after folding into a domain it remains accommodated inside the protective cavity of ribosome-bound TF. The adaptability to accept nascent chains of different length and folding states may explain how TF is able to assist co-translational folding of all kinds of nascent polypeptides during ongoing synthesis. Moreover, we suggest a model of how TF's chaperoning function can be coordinated with the co-translational processing and membrane targeting of nascent polypeptides by other ribosome-associated factors. PMID:18497744
tRNA-like structure regulates translation of Brome mosaic virus RNA.

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Barends, Sharief; Rudinger-Thirion, Joëlle; Florentz, Catherine; Giegé, Richard; Pleij, Cornelis W A; Kraal, Barend

2004-04-01

For various groups of plant viruses, the genomic RNAs end with a tRNA-like structure (TLS) instead of the 3' poly(A) tail of common mRNAs. The actual function of these TLSs has long been enigmatic. Recently, however, it became clear that for turnip yellow mosaic virus, a tymovirus, the valylated TLS(TYMV) of the single genomic RNA functions as a bait for host ribosomes and directs them to the internal initiation site of translation (with N-terminal valine) of the second open reading frame for the polyprotein. This discovery prompted us to investigate whether the much larger TLSs of a different genus of viruses have a comparable function in translation. Brome mosaic virus (BMV), a bromovirus, has a tripartite RNA genome with a subgenomic RNA4 for coat protein expression. All four RNAs carry a highly conserved and bulky 3' TLS(BMV) (about 200 nucleotides) with determinants for tyrosylation. We discovered TLS(BMV)-catalyzed self-tyrosylation of the tyrosyl-tRNA synthetase but could not clearly detect tyrosine incorporation into any virus-encoded protein. We established that BMV proteins do not need TLS(BMV) tyrosylation for their initiation. However, disruption of the TLSs strongly reduced the translation of genomic RNA1, RNA2, and less strongly, RNA3, whereas coat protein expression from RNA4 remained unaffected. This aberrant translation could be partially restored by providing the TLS(BMV) in trans. Intriguingly, a subdomain of the TLS(BMV) could even almost fully restore translation to the original pattern. We discuss here a model with a central and dominant role for the TLS(BMV) during the BMV infection cycle.
Promised Land No More: Dynamic Shifts in Slovene Translation Market and Translator Education

Directory of Open Access Journals (Sweden)

Nike K. Pokorn

2016-12-01

Full Text Available The article outlines the changes of the translation market, the development of Higher Education (HE translator training and of the profession of translator in Slovenia. First, three HE translator-training programmes in Slovenia are briefly described. Second, through an analysis of the public database containing information on all business entities in Slovenia, a description of the translation market in 2014 is made and the findings are compared to those of a similar study carried out in 2007. Then two surveys of translation graduates of University of Ljubljana are presented, focusing in particular on graduate employment statistics and average earnings of junior translators. The results show that despite the fact that the Slovene translation market is thriving, this growth is not reflected in the average earnings of individual translators. Finally, in view of the fact that translation rates are constantly falling, it is argued that the role of professional associations becomes vital.

MD-CTS: An integrated terminology reference of clinical and translational medicine

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Will Ray

2016-01-01

Full Text Available New vocabularies are rapidly evolving in the literature relative to the practice of clinical medicine and translational research. To provide integrated access to new terms, we developed a mobile and desktop online reference—Marshfield Dictionary of Clinical and Translational Science (MD-CTS. It is the first public resource that comprehensively integrates Wiktionary (word definition, BioPortal (ontology, Wiki (image reference, and Medline abstract (word usage information. MD-CTS is accessible at http://spellchecker.mfldclin.edu/. The website provides a broadened capacity for the wider clinical and translational science community to keep pace with newly emerging scientific vocabulary. An initial evaluation using 63 randomly selected biomedical words suggests that online references generally provided better coverage (73%-95% than paper-based dictionaries (57–71%.
Translation in ESL Classes

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Nagy Imola Katalin

2015-12-01

Full Text Available The problem of translation in foreign language classes cannot be dealt with unless we attempt to make an overview of what translation meant for language teaching in different periods of language pedagogy. From the translation-oriented grammar-translation method through the complete ban on translation and mother tongue during the times of the audio-lingual approaches, we have come today to reconsider the role and status of translation in ESL classes. This article attempts to advocate for translation as a useful ESL class activity, which can completely fulfil the requirements of communicativeness. We also attempt to identify some activities and games, which rely on translation in some books published in the 1990s and the 2000s.
Analysis and prediction of translation rate based on sequence and functional features of the mRNA.

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Tao Huang

Full Text Available Protein concentrations depend not only on the mRNA level, but also on the translation rate and the degradation rate. Prediction of mRNA's translation rate would provide valuable information for in-depth understanding of the translation mechanism and dynamic proteome. In this study, we developed a new computational model to predict the translation rate, featured by (1 integrating various sequence-derived and functional features, (2 applying the maximum relevance & minimum redundancy method and incremental feature selection to select features to optimize the prediction model, and (3 being able to predict the translation rate of RNA into high or low translation rate category. The prediction accuracies under rich and starvation condition were 68.8% and 70.0%, respectively, evaluated by jackknife cross-validation. It was found that the following features were correlated with translation rate: codon usage frequency, some gene ontology enrichment scores, number of RNA binding proteins known to bind its mRNA product, coding sequence length, protein abundance and 5'UTR free energy. These findings might provide useful information for understanding the mechanisms of translation and dynamic proteome. Our translation rate prediction model might become a high throughput tool for annotating the translation rate of mRNAs in large-scale.
Numerical optimization of alignment reproducibility for customizable surgical guides.

Science.gov (United States)

Kroes, Thomas; Valstar, Edward; Eisemann, Elmar

2015-10-01

Computer-assisted orthopedic surgery aims at minimizing invasiveness, postoperative pain, and morbidity with computer-assisted preoperative planning and intra-operative guidance techniques, of which camera-based navigation and patient-specific templates (PST) are the most common. PSTs are one-time templates that guide the surgeon initially in cutting slits or drilling holes. This method can be extended to reusable and customizable surgical guides (CSG), which can be adapted to the patients' bone. Determining the right set of CSG input parameters by hand is a challenging task, given the vast amount of input parameter combinations and the complex physical interaction between the PST/CSG and the bone. This paper introduces a novel algorithm to solve the problem of choosing the right set of input parameters. Our approach predicts how well a CSG instance is able to reproduce the planned alignment based on a physical simulation and uses a genetic optimization algorithm to determine optimal configurations. We validate our technique with a prototype of a pin-based CSG and nine rapid prototyped distal femora. The proposed optimization technique has been compared to manual optimization by experts, as well as participants with domain experience. Using the optimization technique, the alignment errors remained within practical boundaries of 1.2 mm translation and [Formula: see text] rotation error. In all cases, the proposed method outperformed manual optimization. Manually optimizing CSG parameters turns out to be a counterintuitive task. Even after training, subjects with and without anatomical background fail in choosing appropriate CSG configurations. Our optimization algorithm ensures that the CSG is configured correctly, and we could demonstrate that the intended alignment of the CSG is accurately reproduced on all tested bone geometries.
Breaking the language barrier: machine assisted diagnosis using the medical speech translator.

Science.gov (United States)

Starlander, Marianne; Bouillon, Pierrette; Rayner, Manny; Chatzichrisafis, Nikos; Hockey, Beth Ann; Isahara, Hitoshi; Kanzaki, Kyoko; Nakao, Yukie; Santaholma, Marianne

2005-01-01

In this paper, we describe and evaluate an Open Source medical speech translation system (MedSLT) intended for safety-critical applications. The aim of this system is to eliminate the language barriers in emergency situation. It translates spoken questions from English into French, Japanese and Finnish in three medical subdomains (headache, chest pain and abdominal pain), using a vocabulary of about 250-400 words per sub-domain. The architecture is a compromise between fixed-phrase translation on one hand and complex linguistically-based systems on the other. Recognition is guided by a Context Free Grammar Language Model compiled from a general unification grammar, automatically specialised for the domain. We present an evaluation of this initial prototype that shows the advantages of this grammar-based approach for this particular translation task in term of both reliability and use.
Google Translate as a Supplementary Tool for Learning Malay: A Case Study at Universiti Sains Malaysia

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Hossein Bahri

2016-06-01

Full Text Available The present paper examines the use of Google Translate as a supplementary tool for helping international students at Universiti Sains Malaysia (USM to learn and develop their knowledge and skills in learning Bahasa Malaysia (Malay Language. The participants of the study were 16 international students at the School of Languages, Literacies, and Translation, USM who had registered for the LKM 100 Bahasa Malaysia (I course. Based on the literature review, analysis of the collected data, and an assessment of the course content and activities inside and outside the language classroom, the findings suggest that most international students at USM recognize Google Translate as an effective supplementary tool for learning vocabulary, writing, and reading in Bahasa Malaysia. In fact, some students reported that they could optimally benefit from their self-learning if they were assisted to use Google Translate effectively. Moreover, using Google Translate for doing classroom tasks and activities can encourage students to study independently, and to shape their own strategies for solving language learning problems. Keywords: Google Translate, supplementary tool, translation, language learning, Bahasa Malaysia
Characterization of Phospholipid Mixed Micelles by Translational Diffusion

International Nuclear Information System (INIS)

Chou, James J.; Baber, James L.; Bax, Ad

2004-01-01

The concentration dependence of the translational self diffusion rate, D s , has been measured for a range of micelle and mixed micelle systems. Use of bipolar gradient pulse pairs in the longitudinal eddy current delay experiment minimizes NOE attenuation and is found critical for optimizing sensitivity of the translational diffusion measurement of macromolecules and aggregates. For low volume fractions Φ (Φ ≤ 15% v/v) of the micelles, experimental measurement of the concentration dependence, combined with use of the D s =D o (1-3.2λΦ) relationship, yields the hydrodynamic volume. For proteins, the hydrodynamic volume, derived from D s at infinitely dilute concentration, is found to be about 2.6 times the unhydrated molecular volume. Using the data collected for hen egg white lysozyme as a reference, diffusion data for dihexanoyl phosphatidylcholine (DHPC) micelles indicate approximately 27 molecules per micelle, and a critical micelle concentration of 14 mM. Differences in translational diffusion rates for detergent and long chain phospholipids in mixed micelles are attributed to rapid exchange between free and micelle-bound detergent. This difference permits determination of the free detergent concentration, which, for a high detergent to long chain phospholipid molar ratio, is found to depend strongly on this ratio. The hydrodynamic volume of DHPC/POPC bicelles, loaded with an M2 channel peptide homolog, derived from translational diffusion, predicts a rotational correlation time that slightly exceeds the value obtained from peptide 15 N relaxation data
A Writer's Thoughts on Translation and Always Living in Translation.

Science.gov (United States)

Agosin, Marjorie; Jones, Robin

2000-01-01

Discusses how it feels to be a poet who writes in Spanish and has her work translated, examining the author's immigration experiences and noting the translator's contributions in making her work accessible across languages, borders, and cultures. Explains that writing in Spanish is a gesture of survival, and translation allows her memories to…
Innovative teaching methods for capacity building in knowledge translation

OpenAIRE

Wahabi, Hayfaa A; Al-Ansary, Lubna A

2011-01-01

Abstract Background In some current healthcare settings, there is a noticeable absence of national institutions committed to the synthesis and use of evidence in healthcare decision- and policy-making. This absence creates a need to broaden the responsibilities of healthcare providers to include knowledge brokering and advocacy in order to optimize knowledge translation to other stakeholders, especially policy-makers. However, this process requires practitioners and researchers to acquire cer...
Translation, cultural adaptation and validation of the Diabetes Attitudes Scale - third version into Brazilian Portuguese 1

Science.gov (United States)

Vieira, Gisele de Lacerda Chaves; Pagano, Adriana Silvino; Reis, Ilka Afonso; Rodrigues, Júlia Santos Nunes; Torres, Heloísa de Carvalho

2018-01-01

ABSTRACT Objective: to perform the translation, adaptation and validation of the Diabetes Attitudes Scale - third version instrument into Brazilian Portuguese. Methods: methodological study carried out in six stages: initial translation, synthesis of the initial translation, back-translation, evaluation of the translated version by the Committee of Judges (27 Linguists and 29 health professionals), pre-test and validation. The pre-test and validation (test-retest) steps included 22 and 120 health professionals, respectively. The Content Validity Index, the analyses of internal consistency and reproducibility were performed using the R statistical program. Results: in the content validation, the instrument presented good acceptance among the Judges with a mean Content Validity Index of 0.94. The scale presented acceptable internal consistency (Cronbach’s alpha = 0.60), while the correlation of the total score at the test and retest moments was considered high (Polychoric Correlation Coefficient = 0.86). The Intra-class Correlation Coefficient, for the total score, presented a value of 0.65. Conclusion: the Brazilian version of the instrument (Escala de Atitudes dos Profissionais em relação ao Diabetes Mellitus) was considered valid and reliable for application by health professionals in Brazil. PMID:29319739
Lost in translation?: Comparing three Scandinavian translations of the Beliefs about Medicines Questionnaire.

Science.gov (United States)

Granas, Anne Gerd; Nørgaard, Lotte Stig; Sporrong, Sofia Kälvemark

2014-08-01

The "Beliefs about Medicines Questionnaire" (BMQ) assess balance of necessity and concern of medicines. The BMQ has been translated from English to many languages. However, the original meaning of statements, such as "My medicine is a mystery to me", may be lost in translation. The aim of this study is to compare three Scandinavian translations of the BMQ. (1) How reliable are the translations? (2) Are they still valid after translation? Translated Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three native Scandinavian researchers. Linguistic differences and ambiguities in the 5-point Likert scale and the BMQ statements were compared. In the Scandinavian translations, the Likert scale expanded beyond the original version at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements, discrepancies ranged from smaller inaccuracies toward completely different meaning. Some dissimilarities reflect different cultural beliefs about medicines. When translating questionnaires, bilingual researchers should scrutinize translations across similar languages to address content validity across different countries and languages. Our findings are of relevance to other BMQ translations in non-English countries, as direct comparisons between different translations might not be reliable or valid. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Identification of Plasmodium falciparum translation initiation eIF2β subunit: direct interaction with Protein Phosphatase type 1

Directory of Open Access Journals (Sweden)

Géraldine eTellier

2016-05-01

Full Text Available Protein phosphatase 1 (PP1c is one of the main phosphatases whose function is shaped by many regulators to confer a specific location and a selective function for this enzyme. Here, we report that eukaryotic initiation factor 2 of P. falciparum (PfeIF2β is an interactor of PfPP1c. Sequence analysis of PfeIF2 revealed a deletion of 111 amino acids when compared to its human counterpart and the presence of two potential binding motifs to PfPP1 (29FGEKKK34, 103KVAW106. As expected, we showed that PfeIF2 binds PfeIF2 and PfeIF5, confirming its canonical interaction with partners of the translation complex. Studies of the PfeIF2-PfPP1 interaction using wild-type, single and double mutated versions of PfeIF2β revealed that both binding motifs are critical. We next showed that PfeIF2 is able to induce Germinal Vesicle BreakDown (GVBD when expressed in Xenopus oocytes, an indicator of its capacity to regulate PP1. Only combined mutations of both binding motifs abolished the interaction with PP1 and the induction of GVBD. In P. falciparum, although the locus is accessible for genetic manipulation, PfeIF2 seems to play an essential role in intraerythrocytic cycle as no viable knockout parasites were detectable. Interestingly, as for PfPP1, the subcellular fractionation of P. falciparum localized PfeIF2β in cytoplasm and nuclear extracts, suggesting a potential effect on PfPP1 in both compartments and raising the question of a non-canonical function of PfeIf2 in the nucleus. Hence, the role played by PfeIF2 in blood stage parasites could occur at multiple levels involving the binding to proteins of the translational complex and to PfPP1.
Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells

International Nuclear Information System (INIS)

Nakai, Yuji; Shiratsuchi, Akiko; Manaka, Junko; Nakayama, Hiroshi; Takio, Koji; Zhang Jianting; Suganuma, Tatsuo; Nakanishi, Yoshinobu

2005-01-01

We previously isolated a monoclonal antibody named PH2 that inhibits phosphatidylserine-mediated phagocytosis of apoptotic cells by macrophages [C. Fujii, A. Shiratsuchi, J. Manaka, S. Yonehara, Y. Nakanishi. Cell Death Differ. 8 (2001) 1113-1122]. We report here the identification of the cognate antigen. A protein bound by PH2 in Western blotting was identified as the 170-kDa subunit of eukaryotic translation initiation factor 3 (eIF3 p170/eIF3a). When eIF3a was expressed in a culture cell line as a protein fused to green fluorescence protein, the fusion protein was detected at the cell surface only after the induction of apoptosis. The same phenomenon was seen when the localization of endogenous eIF3a was determined using anti-eIF3a antibody, and eIF3a seemed to be partially degraded during apoptosis. Furthermore, bacterially expressed N-terminal half of eIF3a fused to glutathione S-transferase bound to the surface of macrophages and inhibited phagocytosis of apoptotic cells by macrophages when it was added to phagocytosis reactions. These results collectively suggest that eIF3a translocates to the cell surface upon apoptosis, probably after partial degradation, and bridges apoptotic cells and macrophages to enhance phagocytosis
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.
Ribosome Profiling Reveals Pervasive Translation Outside of Annotated Protein-Coding Genes

Directory of Open Access Journals (Sweden)

Nicholas T. Ingolia

2014-09-01

Full Text Available Ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be noncoding, including 5′ UTRs and long noncoding RNAs (lncRNAs. Apparent ribosome footprints outside of protein-coding regions raise the possibility of artifacts unrelated to translation, particularly when they occupy multiple, overlapping open reading frames (ORFs. Here, we show hallmarks of translation in these footprints: copurification with the large ribosomal subunit, response to drugs targeting elongation, trinucleotide periodicity, and initiation at early AUGs. We develop a metric for distinguishing between 80S footprints and nonribosomal sources using footprint size distributions, which validates the vast majority of footprints outside of coding regions. We present evidence for polypeptide production beyond annotated genes, including the induction of immune responses following human cytomegalovirus (HCMV infection. Translation is pervasive on cytosolic transcripts outside of conserved reading frames, and direct detection of this expanded universe of translated products enables efforts at understanding how cells manage and exploit its consequences.
Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress.

Science.gov (United States)

Sonobe, Yoshifumi; Ghadge, Ghanashyam; Masaki, Katsuhisa; Sendoel, Ataman; Fuchs, Elaine; Roos, Raymond P

2018-08-01

Expansion of a hexanucleotide repeat (HRE), GGGGCC, in the C9ORF72 gene is recognized as the most common cause of familial amyotrophic lateral sclerosis (FALS), frontotemporal dementia (FTD) and ALS-FTD, as well as 5-10% of sporadic ALS. Despite the location of the HRE in the non-coding region (with respect to the main C9ORF72 gene product), dipeptide repeat proteins (DPRs) that are thought to be toxic are translated from the HRE in all three reading frames from both the sense and antisense transcript. Here, we identified a CUG that has a good Kozak consensus sequence as the translation initiation codon. Mutation of this CTG significantly suppressed polyglycine-alanine (GA) translation. GA was translated when the G 4 C 2 construct was placed as the second cistron in a bicistronic construct. CRISPR/Cas9-induced knockout of a non-canonical translation initiation factor, eIF2A, impaired GA translation. Transfection of G 4 C 2 constructs induced an integrated stress response (ISR), while triggering the ISR led to a continuation of translation of GA with a decline in conventional cap-dependent translation. These in vitro observations were confirmed in chick embryo neural cells. The findings suggest that DPRs translated from an HRE in C9ORF72 aggregate and lead to an ISR that then leads to continuing DPR production and aggregation, thereby creating a continuing pathogenic cycle. Copyright © 2018 Elsevier Inc. All rights reserved.
Combat Wound Initiative program.

Science.gov (United States)

Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

2010-07-01

The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.
Using corpora in scientific and technical translation training: resources to identify conventionality and promote creativity

Directory of Open Access Journals (Sweden)

Clara Inés López-Rodríguez

2016-06-01

Full Text Available Since the first Corpus Use and Learning to Translate (CULT Conference in Bertinoro (Italy in 1997, the usefulness of corpora for translators and trainee translators has been highlighted. From an initial approach where translators compiled ad hoc corpora in their hard drive for a subsequent study with lexical analysis software, there emerged a new trend towards the use of the Internet as corpus. In this second approach, the Web is perceived as a huge corpus which is accessed by means of online tools which produce monolingual wordlists and concordances from texts available from the Internet or pre-existing corpora, or by means of bilingual or multilingual concordancers displaying aligned texts from international institutions' parallel corpora. Bilingual concordancers and translation memories are widely used by translators and trainee translators because of the immediate translation solutions they offer, but these tools can restrain creativity by offering conventional solutions and eliminating layout and multimodal elements in texts. The aim of this article is to describe the exploitation of quality corpora in a scientific and technical translation course, focusing on texts on health translated from English into Spanish, and on terminological variation as a reflection of creativity in language.
When Visions for City Planning and Development are Translated into Practice

DEFF Research Database (Denmark)

Zapata Campos, Maria José; Zapata, Patrik

The ‘knowing-doing’ gaps between policy goals and their outcome when implemented is of increasing concern both in practice and in research. This paper explores how the visions of a sustainable development and the corresponding planning are translated into practice; what aspects of visions and plans...... of the waste-pickers now are formally employed, and new housing for the informal settlement’s residents. The analysis is based on interviews, observations, workshop participations and document analysis; gathered from 2009 until 2012. It combines action net theory with the sociology of translation...... as theoretical framework. Despite the initial compliance to the program (funded and initially led by international aid organizations), local actors enacted a myriad of small acts of defiance and resistance that, without abruptly contesting the project, shaped it to better fit local needs; a) first by municipal...
From Translation to Organization to International Business: an Academic No Man’s Land

Directory of Open Access Journals (Sweden)

José Lambert

2016-08-01

Full Text Available Universities claim to represent a crucial component in the contemporary world of knowledge, which involves a given degree of self-criticism and the redefinition of a few priorities. The recognition of new departments, such as Translation Studies (TS is obviously part of this historical movement of self-criticism, and TS itself reflects similar processes in its own history, or rather prehistory. Although TS claims to have integrated Globalization and the new international world into its academic program, exactly how it will combine its initial self-definitions (built around translator training with academic definitions (What is translation? How can past and present translation phenomena be accounted for? How do language policies, multilingualism, media discourse or communities, not to mention ranking, fit into all this? is its challenge for the coming years. Without excluding topics from the initial moments of the new discipline (such as training or nation-state interaction, we propose to explore and exploit what can be learned from organization by making use of the contemporary business world (in this case the international car industry, which is a No Man’s Land within the coalescing traditions of the new discipline. And in this little-known world, fundamental new insights are waiting to be gathered.

From Translation to Organization to International Business: an Academic No Man’s Land

Directory of Open Access Journals (Sweden)

José Lambert

2016-05-01

Full Text Available Universities claim to represent a crucial component in the contemporary world of knowledge, which involves a given degree of self-criticism and the redefinition of a few priorities. The recognition of new departments, such as Translation Studies (TS is obviously part of this historical movement of self-criticism, and TS itself reflects similar processes in its own history, or rather prehistory. Although TS claims to have integrated Globalization and the new international world into its academic program, exactly how it will combine its initial self-definitions (built around translator training with academic definitions (What is translation? How can past and present translation phenomena be accounted for? How do language policies, multilingualism, media discourse or communities, not to mention ranking, fit into all this? is its challenge for the coming years. Without excluding topics from the initial moments of the new discipline (such as training or nation-state interaction, we propose to explore and exploit what can be learned from organization by making use of the contemporary business world (in this case the international car industry, which is a No Man’s Land within the coalescing traditions of the new discipline. And in this little-known world, fundamental new insights are waiting to be gathered.
Translating Gene Transfer: A Stalled Effort

OpenAIRE

Greenberg, Alexandra J.; McCormick, Jennifer; Tapia, Carmen J.; Windebank, Anthony J.

2011-01-01

The journey of gene transfer from laboratory to clinic has been slow and fraught with many challenges and barriers. Despite the development of the initial technology in the early 1970s, a standard clinical treatment involving “gene therapy” remains to be seen. Furthermore, much was written about the technology in the early 1990s, but since then, not much has been written about the journey of gene transfer. The translational path of gene transfer thus far, both pitfalls and successes, can serv...
Programmed cell death in the leaves of the Arabidopsis spontaneous necrotic spots (sns-D mutant correlates with increased expression of the eukaryotic translation initiation factor eIF4B2

Directory of Open Access Journals (Sweden)

Gwenael M.D.J.-M. Gaussand

2011-04-01

Full Text Available From a pool of transgenic Arabidopsis (Arabidopsis thaliana plants harboring an activator T-DNA construct, one mutant was identified that developed spontaneous necrotic spots (sns-D on the rosette leaves under aseptic conditions. The sns-D mutation is dominant and homozygous plants are embryo lethal. The mutant produced smaller rosettes with a different number of stomata than the wild-type. DNA fragmentation in the nuclei of cells in the necrotic spots and a significant increase of caspase-3 and caspase-6 like activities in sns-D leaf extracts indicated that the sns-D mutation caused programmed cell death (PCD. The integration of the activator T-DNA caused an increase of the expression level of At1g13020, which encodes the eukaryotic translation initiation factor eIF4B2. The expression level of eIF4B2 was positively correlated with the severity of sns-D mutant phenotype. Overexpression of the eIF4B2 cDNA mimicked phenotypic traits of the sns-D mutant indicating that the sns-D mutant phenotype is indeed caused by activation tagging of eIF4B2. Thus, incorrect regulation of translation initiation may result in PCD.
Translation Methods Applied in Translating Quotations in “the Secret” by Rhonda

OpenAIRE

FEBRIANTI, VICKY

2014-01-01

Keywords: Translation Methods, The Secret, Quotations.Translation helps human to get information written in any language evenwhen it is written in foreign languages. Therefore translation happens in printed media. Books have been popular printed media. The Secret written by Rhonda Byrne is a popular self-help book which has been translated into 50 languages including Indonesian (“The Secret”, n.d., para.5-6).This study is meant to find out the translation methods applied in The Secret. The wr...
Translational control of auditory imprinting and structural plasticity by eIF2α

Science.gov (United States)

Batista, Gervasio; Johnson, Jennifer Leigh; Dominguez, Elena; Costa-Mattioli, Mauro; Pena, Jose L

2016-01-01

The formation of imprinted memories during a critical period is crucial for vital behaviors, including filial attachment. Yet, little is known about the underlying molecular mechanisms. Using a combination of behavior, pharmacology, in vivo surface sensing of translation (SUnSET) and DiOlistic labeling we found that, translational control by the eukaryotic translation initiation factor 2 alpha (eIF2α) bidirectionally regulates auditory but not visual imprinting and related changes in structural plasticity in chickens. Increasing phosphorylation of eIF2α (p-eIF2α) reduces translation rates and spine plasticity, and selectively impairs auditory imprinting. By contrast, inhibition of an eIF2α kinase or blocking the translational program controlled by p-eIF2α enhances auditory imprinting. Importantly, these manipulations are able to reopen the critical period. Thus, we have identified a translational control mechanism that selectively underlies auditory imprinting. Restoring translational control of eIF2α holds the promise to rejuvenate adult brain plasticity and restore learning and memory in a variety of cognitive disorders. DOI: http://dx.doi.org/10.7554/eLife.17197.001 PMID:28009255
Inhibition of tumor cell growth by Sigma1 ligand mediated translational repression

International Nuclear Information System (INIS)

Kim, Felix J.; Schrock, Joel M.; Spino, Christina M.; Marino, Jacqueline C.; Pasternak, Gavril W.

2012-01-01

Highlights: ► Sigma1 ligand treatment mediates decrease in tumor cell mass. ► Identification of a Sigma1 ligand with reversible translational repressor actions. ► Demonstration of a role for Sigma1 in cellular protein synthesis. -- Abstract: Treatment with sigma1 receptor (Sigma1) ligands can inhibit cell proliferation in vitro and tumor growth in vivo. However, the cellular pathways engaged in response to Sigma1 ligand treatment that contribute to these outcomes remain largely undefined. Here, we show that treatment with putative antagonists of Sigma1 decreases cell mass. This effect corresponds with repressed cap-dependent translation initiation in multiple breast and prostate cancer cell lines. Sigma1 antagonist treatment suppresses phosphorylation of translational regulator proteins p70S6K, S6, and 4E-BP1. RNAi-mediated knockdown of Sigma1 also results in translational repression, consistent with the effects of antagonist treatment. Sigma1 antagonist mediated translational repression and decreased cell size are both reversible. Together, these data reveal a role for Sigma1 in tumor cell protein synthesis, and demonstrate that small molecule Sigma1 ligands can be used as modulators of protein translation.
Why Translation Is Difficult

DEFF Research Database (Denmark)

Carl, Michael; Schaeffer, Moritz Jonas

2017-01-01

The paper develops a definition of translation literality that is based on the syntactic and semantic similarity of the source and the target texts. We provide theoretical and empirical evidence that absolute literal translations are easy to produce. Based on a multilingual corpus of alternative...... translations we investigate the effects of cross-lingual syntactic and semantic distance on translation production times and find that non-literality makes from-scratch translation and post-editing difficult. We show that statistical machine translation systems encounter even more difficulties with non-literality....
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.
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.
Gender issues in translation

OpenAIRE

ERGASHEVA G.I.

2015-01-01

The following research is done regarding gender in translation dealing specifically with the issue of the translators’ gender identity and its effect on their translations, as well as on how gender itself is translated and produced. We will try to clarify what gender is, how gender manifests itself in the system of language, and what problems translators encounter when translating or producing gender-related materials
Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells

DEFF Research Database (Denmark)

Guzzi, Nicola; Cieśla, Maciej; Ngoc, Phuong Cao Thi

2018-01-01

early embryogenesis. Mechanistically, the Ψ "writer" PUS7 modifies and activates a novel network of tRNA-derived small fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translation regulation, leading to increased protein...... biosynthesis and defective germ layer specification. Remarkably, dysregulation of this posttranscriptional regulatory circuitry impairs hematopoietic stem cell commitment and is common to aggressive subtypes of human myelodysplastic syndromes. Our findings unveil a critical function of Ψ in directing...
Machine Translation

Indian Academy of Sciences (India)

Research Mt System Example: The 'Janus' Translating Phone Project. The Janus ... based on laptops, and simultaneous translation of two speakers in a dialogue. For more ..... The current focus in MT research is on using machine learning.
Opposite responses of rabbit and human globin mRNAs to translational inhibition by cap analogues

International Nuclear Information System (INIS)

Shakin, S.H.; Liebhaber, S.A.

1987-01-01

The translational efficiency of an mRNA may be determined at the step of translational initiation by the efficiency of its interaction with the cap binding protein complex. To further investigate the role of these interactions in translational control, the authors compare in vitro the relative sensitivities of rabbit and human α- and β-globin mRNAs to translational inhibition by cap analogues. They find that rabbit β-globin mRNA is more resistant to translational inhibition by cap analogues than rabbit α-globin mRNA, while in contrast, human β-globin mRNA is more sensitive to cap analogue inhibition than human α- and β-globin mRNAs is unexpected as direct in vivo and in vitro comparisons of polysome profiles reveal parallel translational handling of the α- and β-globin mRNAs from these two species. This discordance between the relative translational sensitivities of these mRNAs to cap analogues and their relative ribosome loading activities suggests that cap-dependent events may not be rate limiting in steady-state globin translation
Translating Proper Nouns: A Case Study on English Translation of Hafez's Lyrics

Science.gov (United States)

Shirinzadeh, Seyed Alireza; Mahadi, Tengku Sepora Tengku

2014-01-01

Proper nouns are regarded so simple that they might be taken for granted in translation explorations. Some may believe that they should not be translated in transmitting source texts to target texts. But, it is not the case; if one looks at present translations, he will notice that different strategies might be applied for translating proper…
Conversational Implicatures in English Plays and Their Persian Translations: A Norm-governed Study

Directory of Open Access Journals (Sweden)

Zahra Hassani Laharomi

2013-09-01

Full Text Available The present study attempted to describe in full detail the status of implicature translation in two 20-year time periods before and after Iran Islamic Revolution to provide a clear picture of the strategies applied by translators in the two eras and, as its main objective, to shed light on the translational norms of this linguistic element. To this end, it first sought to elaborate on the reasons and the ways they emerge in conversations. Accordingly, identifying the implicatures arose due to the violation of Grice’s (1975 four maxims of conversation, the researcher separately categorized the translations of the implicatures based on Desilla’s (2009 classification. As the last phase of the study, the strategies for implicature translation were thoroughly scrutinized with the hope to determine the dominant norms of implicature translation in light of Toury’s (1995 notion of initial norm. Based on the results obtained from both pre- and post-revolution data, preservation was revealed to be the most frequent strategy in both eras, attesting to the significance of the adequacy of implicature translation; modification and explicitation were the second and the third most frequent strategies respectively. However, the frequency of modification and explicitation increased in the post-revolution translations. It seems that the trend of the norm of implicature translation moves toward acceptability.
Translation and Quality Management

DEFF Research Database (Denmark)

Petersen, Margrethe

1996-01-01

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......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...
Translation-Memory (TM) Research

DEFF Research Database (Denmark)

Schjoldager, Anne Gram; Christensen, Tina Paulsen

2010-01-01

to be representative of the research field as a whole. Our analysis suggests that, while considerable knowledge is available about the technical side of TMs, more research is needed to understand how translators interact with TM technology and how TMs influence translators' cognitive translation processes....... It is no exaggeration to say that the advent of translation-memory (TM) systems in the translation profession has led to drastic changes in translators' processes and workflow, and yet, though many professional translators nowadays depend on some form of TM system, this has not been the object...... of much research. Our paper attempts to find out what we know about the nature, applications and influences of TM technology, including translators' interaction with TMs, and also how we know it. An essential part of the analysis is based on a selection of empirical TM studies, which we assume...
Translation modalities: an investigation of the translated short story “Dez de dezembro”

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Clara Peron da Silva Guedes

2017-05-01

Full Text Available During the translation process translators adopt linguistic strategies in order to make decisions that help to render a translated text suitable to the target language and culture. The translation modalities proposed by Aubert (105-10 constitute a tool that enables one to identify some of these strategies. In addition, they permit to measure the level of linguistic differentiation between a source text and a target text verifying the distance or the proximity of the target text to the linguistic and cultural issues of the source text. Thus, this paper aims to investigate the translation modalities in the short story “Dez de dezembro” (Saunders 204-38, a translation of the short story “Tenth of December” (Saunders 215-51. For quantifying the translation modalities in the translated text the noun phrases from the source text were selected and their counterparts in the target text were classified and annotated within Notepad++ software. The most recurrent translation modalities in the corpus were Literal Translation and Transposition, categories considered intermediate ones in the rank proposed by Aubert (105-10. Therefore, a relation of equivalence can be established between the target and the source texts.
Discourse Analysis in Translator Training

OpenAIRE

Gülfidan Ayvaz

2015-01-01

Translator training enables students to gain experience in both linguistic parameters and translation practice. Discourse Analysis is one of the strategies that lead to a better translation process and quality in translation. In that regard, this study aims to present DA as a translation strategy for translation practice and a useful tool for translator training. The relationship between DA and Translator Training is not widely studied. Therefore this study aims to define DA and how it can be...
Translation Competence and Translation Performance: Lexical, Syntactic and Textual Patterns in Student Translations of a Specialized EU Genre

Science.gov (United States)

Karoly, Adrienn

2012-01-01

This paper reports the findings of a study aiming to reveal the recurring patterns of lexical, syntactic and textual errors in student translations of a specialized EU genre from English into Hungarian. By comparing the student translations to the official translation of the text, this article uncovers the most frequent errors that students made…

How Italian dialect poets translate themselves and how they translate other poets

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Edoardo Zuccato

2017-07-01

Full Text Available Part one of this essay discusses the way most contemporary Italian dialect poets translate themselves into Italian. Part two of the essay examines examples of poetry translation into dialect made by some of the same contemporary authors. A comparison between the style of the self-translations, which is mainly lyrical, and the variety of styles of the translations from other poets, shows that each choice is an intentional strategy rather than a missed opportunity for a more creative self-translation, as some scholars have argued.
Translation Memory and Computer Assisted Translation Tool for Medieval Texts

Directory of Open Access Journals (Sweden)

Törcsvári Attila

2013-05-01

Full Text Available Translation memories (TMs, as part of Computer Assisted Translation (CAT tools, support translators reusing portions of formerly translated text. Fencing books are good candidates for using TMs due to the high number of repeated terms. Medieval texts suffer a number of drawbacks that make hard even “simple” rewording to the modern version of the same language. The analyzed difficulties are: lack of systematic spelling, unusual word orders and typos in the original. A hypothesis is made and verified that even simple modernization increases legibility and it is feasible, also it is worthwhile to apply translation memories due to the numerous and even extremely long repeated terms. Therefore, methods and algorithms are presented 1. for automated transcription of medieval texts (when a limited training set is available, and 2. collection of repeated patterns. The efficiency of the algorithms is analyzed for recall and precision.
Who translates the translation? (Retraduire les héros marginaux d'Alan Moore

Directory of Open Access Journals (Sweden)

Alice RAY

2016-11-01

Full Text Available The retranslation phenomenon is essential to the translation process. It is considered as the logical progression of this process which allows the translated literary work to regenerate in a restless cultural and language space. To a lesser extent, we can observe the same phenomenon in the translation of comics. However, this specific translation requires other competencies and a translating approach somehow different from the ones required to translate fiction literature, especially because of the presence of the visual system of drawings which is strongly bound to its own culture and the endless mutations it goes through. The comic book Watchmen (Les Gardiens, in the first French translation by Alan Moore and Dave Gibbons, is known in the whole world as the comic which had not only remodeled the vision we had of super-heroes, but had also given the comic books another voice. Watchmen was published between 1986 and 1987 in the United States and translated in French from 1987 to 1988. Fifteen years after this first translation by Jean-Patrick Manchette, Panini publishing decided to retranslate this famous comic in 2007. However, if the reviews of the first translation were laudatory, the retranslation did not enjoy a great reception from the readers or from the reviewers. This paper proposes a comparative analysis of both these translations and of their original version as well as an experiment on the readers, comic books readers or not, in order to establish why the first translation was a success and the retranslation a failure. Thus, we could withdraw the elements which allow us to understand the reception of comic translation.
Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA

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Eva Schrom

2017-06-01

Full Text Available Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis. Promising results have been reported for recombinant angiotensin-converting enzyme 2 (ACE2 protein administration in experimental liver and lung fibrosis. However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form. For this purpose, we advanced the latest RNA technology for liver- and lung-targeted ACE2 translation. We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA leads to robust translation of fully matured, membrane-anchored ACE2 protein. In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application. Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver- and lung-targeted translation of significant amounts of ACE2 protein, respectively. In summary, we provide evidence that RNA transcript therapy (RTT is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models.
Determinants of translation ambiguity

Science.gov (United States)

Degani, Tamar; Prior, Anat; Eddington, Chelsea M.; Arêas da Luz Fontes, Ana B.; Tokowicz, Natasha

2016-01-01

Ambiguity in translation is highly prevalent, and has consequences for second-language learning and for bilingual lexical processing. To better understand this phenomenon, the current study compared the determinants of translation ambiguity across four sets of translation norms from English to Spanish, Dutch, German and Hebrew. The number of translations an English word received was correlated across these different languages, and was also correlated with the number of senses the word has in English, demonstrating that translation ambiguity is partially determined by within-language semantic ambiguity. For semantically-ambiguous English words, the probability of the different translations in Spanish and Hebrew was predicted by the meaning-dominance structure in English, beyond the influence of other lexical and semantic factors, for bilinguals translating from their L1, and translating from their L2. These findings are consistent with models postulating direct access to meaning from L2 words for moderately-proficient bilinguals. PMID:27882188
Linguistic Levels of Translation: A Generic Exploration of Translation Difficulties in Literary Textual Corpus

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Magda Madkour

2016-11-01

Full Text Available This case study research was based on a generic exploration of the translation problems that graduate students face in literary translation. Literary translation is fundamental to translation programs at higher education due to the upsurge that has occurred in publishing classical and modern literary works from various cultures. However, literary texts have special characteristics that make the process of transferring them from one language into another a daunting task. Translating literary texts is difficult even for professional translators because misinterpreting the messages of the source texts can lead to distorting the aesthetic aspects of the literary work. Students need to learn various linguistic levels of literary translation as well as strategies and methods of translation. Learning the linguistics levels of translation necessitates providing adequate training that is based on enhancing students’ cognitive abilities. Cognitive-based translation training helps students learn the procedures of solving the problems of translating sound and literary devices. Cognitive approaches are relevant to the translation process since cognition implies mental activities that students can use to understand and synthesize the literary text, and reconstruct it creatively. Therefore, the current study aimed at examining the relationship between cognitive teaching methodologies and students’ performance in literary translation. To examine this relationship, qualitative and quantitative data was collected from graduate students at the College of Languages and Translation at Imam Mohammed bin Saud Islamic University (IMAMU University, Riyadh, Saudi Arabia. In addition, corpus data was gathered from authentic literary texts including, novels, short stories, and poetry, to investigate the effect of linguistic analysis and cognitive strategies on the quality of literary translation. Quantitative data was analyzed using the Statistical Package for the
Improving Utility of GPU in Accelerating Industrial Applications with User-centred Automatic Code Translation

DEFF Research Database (Denmark)

Yang, Po; Dong, Feng; Codreanu, Valeriu

2018-01-01

design and hard-to-use. Little attentions have been paid to the applicability, usability and learnability of these tools for normal users. In this paper, we present an online automated CPU-to-GPU source translation system, (GPSME) for inexperienced users to utilize GPU capability in accelerating general...... SME applications. This system designs and implements a directive programming model with new kernel generation scheme and memory management hierarchy to optimize its performance. A web service interface is designed for inexperienced users to easily and flexibly invoke the automatic resource translator...
An analysis of machine translation and speech synthesis in speech-to-speech translation system

OpenAIRE

Hashimoto, K.; Yamagishi, J.; Byrne, W.; King, S.; Tokuda, K.

2011-01-01

This paper provides an analysis of the impacts of machine translation and speech synthesis on speech-to-speech translation systems. The speech-to-speech translation system consists of three components: speech recognition, machine translation and speech synthesis. Many techniques for integration of speech recognition and machine translation have been proposed. However, speech synthesis has not yet been considered. Therefore, in this paper, we focus on machine translation and speech synthesis, ...
Advancing tuberculosis drug regimen development through innovative quantitative translational pharmacology methods and approaches.

Science.gov (United States)

Hanna, Debra; Romero, Klaus; Schito, Marco

2017-03-01

The development of novel tuberculosis (TB) multi-drug regimens that are more efficacious and of shorter duration requires a robust drug development pipeline. Advances in quantitative modeling and simulation can be used to maximize the utility of patient-level data from prior and contemporary clinical trials, thus optimizing study design for anti-TB regimens. This perspective article highlights the work of seven project teams developing first-in-class translational and quantitative methodologies that aim to inform drug development decision-making, dose selection, trial design, and safety assessments, in order to achieve shorter and safer therapies for patients in need. These tools offer the opportunity to evaluate multiple hypotheses and provide a means to identify, quantify, and understand relevant sources of variability, to optimize translation and clinical trial design. When incorporated into the broader regulatory sciences framework, these efforts have the potential to transform the development paradigm for TB combination development, as well as other areas of global health. Copyright © 2016. Published by Elsevier Ltd.
Plan of Action for Real-World Translation of LGBTQ Health and Aging Research.

Science.gov (United States)

Fredriksen-Goldsen, Karen I; Kim, Hyun-Jun; McKenzie, Glenise L; Krinsky, Lisa; Emlet, Charles A

2017-12-01

Despite accumulating evidence of health disparities, there exists limited translational research to enhance optimal health and aging of lesbian, gay, bisexual, transgender, and queer-identified * (LGBTQ) older adults. Based on the Health Equity Promotion Model that addresses the distinct needs and strengths of LGBTQ older adults, we underscore the important role of collaborations among researchers, practitioners, and communities to build community capacity. Given the rapidly shifting context, we advance principles to guide future work that will enhance translational research and the development of evidence-based practice so that LGBTQ older adults can reach their full health potential.
A sensitive mass spectrometric method for hypothesis-driven detection of peptide post-translational modifications: multiple reaction monitoring-initiated detection and sequencing (MIDAS).

Science.gov (United States)

Unwin, Richard D; Griffiths, John R; Whetton, Anthony D

2009-01-01

The application of a targeted mass spectrometric workflow to the sensitive identification of post-translational modifications is described. This protocol employs multiple reaction monitoring (MRM) to search for all putative peptides specifically modified in a target protein. Positive MRMs trigger an MS/MS experiment to confirm the nature and site of the modification. This approach, termed MIDAS (MRM-initiated detection and sequencing), is more sensitive than approaches using neutral loss scanning or precursor ion scanning methodologies, due to a more efficient use of duty cycle along with a decreased background signal associated with MRM. We describe the use of MIDAS for the identification of phosphorylation, with a typical experiment taking just a couple of hours from obtaining a peptide sample. With minor modifications, the MIDAS method can be applied to other protein modifications or unmodified peptides can be used as a MIDAS target.
Alternative translation initiation of Caveolin-2 desensitizes insulin signaling through dephosphorylation of insulin receptor by PTP1B and causes insulin resistance.

Science.gov (United States)

Kwon, Hayeong; Jang, Donghwan; Choi, Moonjeong; Lee, Jaewoong; Jeong, Kyuho; Pak, Yunbae

2018-06-01

Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2β isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2β-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2β is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI. Copyright © 2018 Elsevier B.V. All rights reserved.
Fast and frugal trees: translating population-based pharmacogenomics to medication prioritization

NARCIS (Netherlands)

Rooij, T. van; Roederer, M.; Wareham, H.T.; Rooij, I.J.E.I. van; McLeod, H.L.; Marsh, S.

2015-01-01

Aim: Fast and frugal decision trees (FFTs) can simplify clinical decision making by providing a heuristic approach to contextual guidance. We wanted to use FFTs for pharmacogenomic knowledge translation at point-of-care. Materials & Methods: The Pharmacogenomics for Every Nation Initiative (PGENI),
Translation Meets Cognitive Science: The Imprint of Translation on Cognitive Processing

Science.gov (United States)

Rojo, Ana

2015-01-01

Translation has long played a role in linguistic and literary studies research. More recently, the theoretical and methodological concerns of process research have given translation an additional role in cognitive science. The interest in the cognitive aspects of translation has led scholars to turn to disciplines such as cognitive linguistics,…
Audiovisual Translation:A Critical Review on Sino-western Perspectives of Film Subtitle Translation

OpenAIRE

Junchen Zhang

2018-01-01

The paper argues the development of audiovisual translation (mainly focuses on the strand of film subtitle translation) in the West and China. Firstly, the paper discusses film translation from the perspective of the West and critically reviews the achievements produced by western researchers. Secondly, the paper analyzes film translation from Chinese perspective and outlines its change and development in Mainland China. Thirdly, some major issues exited in film translation such as cultural p...
Hepatitis C virus translation preferentially depends on active RNA replication.

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Helene Minyi Liu

Full Text Available Hepatitis C virus (HCV RNA initiates its replication on a detergent-resistant membrane structure derived from the endoplasmic reticulum (ER in the HCV replicon cells. By performing a pulse-chase study of BrU-labeled HCV RNA, we found that the newly-synthesized HCV RNA traveled along the anterograde-membrane traffic and moved away from the ER. Presumably, the RNA moved to the site of translation or virion assembly in the later steps of viral life cycle. In this study, we further addressed how HCV RNA translation was regulated by HCV RNA trafficking. When the movement of HCV RNA from the site of RNA synthesis to the Golgi complex was blocked by nocodazole, an inhibitor of ER-Golgi transport, HCV protein translation was surprisingly enhanced, suggesting that the translation of viral proteins occurred near the site of RNA synthesis. We also found that the translation of HCV proteins was dependent on active RNA synthesis: inhibition of viral RNA synthesis by an NS5B inhibitor resulted in decreased HCV viral protein synthesis even when the total amount of intracellular HCV RNA remained unchanged. Furthermore, the translation activity of the replication-defective HCV replicons or viral RNA with an NS5B mutation was greatly reduced as compared to that of the corresponding wildtype RNA. By performing live cell labeling of newly synthesized HCV RNA and proteins, we further showed that the newly synthesized HCV proteins colocalized with the newly synthesized viral RNA, suggesting that HCV RNA replication and protein translation take place at or near the same site. Our findings together indicate that the translation of HCV RNA is coupled to RNA replication and that the both processes may occur at the same subcellular membrane compartments, which we term the replicasome.
Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them

Science.gov (United States)

Leppek, Kathrin; Das, Rhiju; Barna, Maria

2017-01-01

RNA molecules can fold into intricate shapes that can provide an additional layer of control of gene expression beyond that of their sequence. In this Review, we discuss the current mechanistic understanding of structures in 5′ untranslated regions (UTRs) of eukaryotic mRNAs and the emerging methodologies used to explore them. These structures may regulate cap-dependent translation initiation through helicase-mediated remodelling of RNA structures and higher-order RNA interactions, as well as cap-independent translation initiation through internal ribosome entry sites (IRESs), mRNA modifications and other specialized translation pathways. We discuss known 5′ UTR RNA structures and how new structure probing technologies coupled with prospective validation, particularly compensatory mutagenesis, are likely to identify classes of structured RNA elements that shape post-transcriptional control of gene expression and the development of multicellular organisms. PMID:29165424
TRANSLATING BLACKNESS: A CHALLENGE TO TRANSLATION STUDIES IN CONTEMPORANEITY

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Maria Aparecida Andrade Salgueiro

2014-07-01

Full Text Available The present article presents aspects of a work in progress about both African-American and Afro-Brazilian Literatures as well as Translation Studies. As it makes observations about how blackness has been translated in different contexts and geographical spaces, it calls the reader’s attention to power relations, processes of colonial and post-colonial identity construction, the rising of literary canons, cultural hegemony and globalization, demystifying spaces and showing translation as an activity that does not take place in a neutral space, but, for sure, inside social and political concrete situations.
Word reading and translation in bilinguals: The impact of formal and informal translation expertise

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Adolfo M. García

2014-11-01

Full Text Available Studies on bilingual word reading and translation have examined the effects of lexical variables (e.g., concreteness, cognate status by comparing groups of non-translators with varying levels of L2 proficiency. However, little attention has been paid to another relevant factor: translation expertise (TI. To explore this issue, we administered word reading and translation tasks to two groups of non-translators possessing different levels of informal TI (Experiment 1, and to three groups of bilinguals possessing different levels of translation training (Experiment 2. Reaction-time recordings showed that in all groups reading was faster than translation and unaffected by concreteness and cognate effects. Conversely, in both experiments, all groups translated concrete and cognate words faster than abstract and non-cognate words, respectively. Notably, an advantage of backward over forward translation was observed only for low-proficiency non-translators (in Experiment 1. Also, in Experiment 2, the modifications induced by translation expertise were more marked in the early than in the late stages of training and practice. The results suggest that TI contributes to modulating inter-equivalent connections in bilingual memory.
What is a translator?

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Martha Pulido

2016-08-01

Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.

What is a translator?

Directory of Open Access Journals (Sweden)

Martha Martha Pulido

2016-05-01

Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.
Using corpora in scientific and technical translation training: resources to identify conventionality and promote creativity

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Clara Inés López-Rodríguez

2016-04-01

Full Text Available http://dx.doi.org/10.5007/2175-7968.2016v36nesp1p88 Since the first Corpus Use and Learning to Translate (CULT Conference in Bertinoro (Italy in 1997, the usefulness of corpora for translators and trainee translators has been highlighted. From an initial approach where translators compiled ad hoc corpora in their hard drive for a subsequent study with lexical analysis software, there emerged a new trend towards the use of the Internet as corpus. In this second approach, the Web is perceived as a huge corpus which is accessed by means of online tools which produce monolingual wordlists and concordances from texts available from the Internet or pre-existing corpora, or by means of bilingual or multilingual concordancers displaying aligned texts from international institutions' parallel corpora. Bilingual concordancers and translation memories are widely used by translators and trainee translators because of the immediate translation solutions they offer, but these tools can restrain creativity by offering conventional solutions and eliminating layout and multimodal elements in texts. The aim of this article is to describe the exploitation of quality corpora in a scientific and technical translation course, focusing on texts on health translated from English into Spanish, and on terminological variation as a reflection of creativity in language.
Learning by Translating: A Contrastive Methodology for ESP Learning and Translation

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Sara Laviosa

2015-11-01

Full Text Available Over the last few years applied linguists have explored the possibility of integrating the insights of second language acquisition theories, contrastive analysis, foreign language teaching methodologies, and translation studies with a view to enhancing current communicative models and techniques for L2 teaching and translator training (see for example Sewell and Higgins 1996; Laviosa-Braithwaite 1997; Campbell 1998; Malmkjær 1998; Laviosa 2000; Colina 2002. We intend to make a contribution to this interdisciplinary orientation by putting forward a translation-based methodology for learning ESP vocabulary and grammar through real life mediating communicative activities. With particular reference to the translation task itself, we endeavour to provide teachers of English for special purposes and translator trainers with a methodology for guiding their students in producing, to the best of their abilities, a target text which meets the quality criteria of terminological accuracy and stylistic fluency, and is also effective in terms of the communicative situation it is intended for. After outlining the rationale and main theoretical approaches underpinning our work, we will illustrate our methodology for learning ESP vocabulary and translation skills from a contrastive perspective, as in our book Learning by Translating (Laviosa and Cleverton 2003.
Structural and Functional Diversity of Plant Virus 3′-Cap-Independent Translation Enhancers (3′-CITEs

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Verónica Truniger

2017-11-01

Full Text Available Most of the positive-strand RNA plant viruses lack the 5′-cap and/or the poly(A-tail that act synergistically to stimulate canonical translation of cellular mRNAs. However, they have RNA elements in the 5′- or 3′-untranslated regions of their RNAs that are required for their cap-independent translation. Cap-independent translation enhancers (CITEs have been identified in the genomic 3′-end of viruses belonging to the family Tombusviridae and the genus Luteovirus. Seven classes of 3′-CITEs have been described to date based on their different RNA structures. They generally control the efficient formation of the translation initiation complex by varying mechanisms. Some 3′-CITEs bind eukaryotic translation initiation factors, others ribosomal subunits, bridging these to the 5′-end by different mechanisms, often long-distance RNA–RNA interactions. As previously proposed and recently found in one case in nature, 3′-CITEs are functionally independent elements that are transferable through recombination between viral genomes, leading to potential advantages for virus multiplication. In this review, the knowledge on 3′-CITEs and their functioning is updated. We also suggest that there is local structural conservation in the regions interacting with eIF4E of 3′-CITEs belonging to different classes.
Structural and Functional Diversity of Plant Virus 3′-Cap-Independent Translation Enhancers (3′-CITEs)

Science.gov (United States)

Truniger, Verónica; Miras, Manuel; Aranda, Miguel A.

2017-01-01

Most of the positive-strand RNA plant viruses lack the 5′-cap and/or the poly(A)-tail that act synergistically to stimulate canonical translation of cellular mRNAs. However, they have RNA elements in the 5′- or 3′-untranslated regions of their RNAs that are required for their cap-independent translation. Cap-independent translation enhancers (CITEs) have been identified in the genomic 3′-end of viruses belonging to the family Tombusviridae and the genus Luteovirus. Seven classes of 3′-CITEs have been described to date based on their different RNA structures. They generally control the efficient formation of the translation initiation complex by varying mechanisms. Some 3′-CITEs bind eukaryotic translation initiation factors, others ribosomal subunits, bridging these to the 5′-end by different mechanisms, often long-distance RNA–RNA interactions. As previously proposed and recently found in one case in nature, 3′-CITEs are functionally independent elements that are transferable through recombination between viral genomes, leading to potential advantages for virus multiplication. In this review, the knowledge on 3′-CITEs and their functioning is updated. We also suggest that there is local structural conservation in the regions interacting with eIF4E of 3′-CITEs belonging to different classes. PMID:29238357
Translation and Intertextuality

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Mohammad Rahimi

2015-09-01

Full Text Available This study is intends to describe and Presents a new theory of translation based on the "Intertextuality" unlike the Translation theories that presented to date, what all are based on the principle of "Equivalence". Our theory is based on the examples of Arabic poetry translated into Persian poetry. The major findings of this study show that the Intertextuality can serve as a link between the original text and the target. it can also interact with other texts is the translation result in the target language, Whtich is the book of poetic eloquence is addressed and was mentioned Literary robbery.
Compositional translation

NARCIS (Netherlands)

Appelo, Lisette; Janssen, Theo; Jong, de F.M.G.; Landsbergen, S.P.J.

1994-01-01

This book provides an in-depth review of machine translation by discussing in detail a particular method, called compositional translation, and a particular system, Rosetta, which is based on this method. The Rosetta project is a unique combination of fundamental research and large-scale
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......), 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...
Translation Training in the Jordanian Context: Curriculum Evaluation in Translator Education

Science.gov (United States)

Mahasneh, Anjad

2013-01-01

This study aims at drawing a clear picture of translator training in Jordan through the evaluation of translation programs at the Master's level. The framework of the Context, Input, Process, and Product components of the CIPP evaluation model developed by Daniel Stufflebeam in 1971 was used to evaluate the three translation Master's programs at…
Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α Phosphorylation

Science.gov (United States)

Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J.; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed

2006-01-01

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2α phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2α phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2α to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2α phosphorylation-dependent and -independent pathways that target translation initiation. PMID:16870703
Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation.

Science.gov (United States)

Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed; Pelletier, Jerry

2006-10-01

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation.
Advancing the management of Obstructive Airways Diseases through Translational Research

DEFF Research Database (Denmark)

Porsbjerg, Celeste; Sverrild, Asger; Baines, Katherine J

2018-01-01

Obstructive airways diseases (OAD) represent a huge burden of illness worldwide, and in spite of the development of effective therapies, significant morbidity and mortality related to asthma and COPD still remains. Over the past decade, our understanding of OAD has improved vastly, and novel...... treatments have evolved. This evolution is the result of successful translational research, which has connected clinical presentations of OAD and underlying disease mechanisms, thereby enabling the development of targeted treatments. The next challenge of translational research will be to position...... these novel treatments for OAD for optimal clinical use. At the same time, there is great potential in these treatments providing even better insights into disease mechanisms in OAD, by studying the effects of blocking individual immunological pathways. To optimise this potential, there is a need to ensure...
Measuring Difficulty in English-Chinese Translation: Towards a General Model of Translation Difficulty

Science.gov (United States)

Sun, Sanjun

2012-01-01

Accurate assessment of a text's level of translation difficulty is critical for translator training and accreditation, translation research, and the language industry as well. Traditionally, people rely on their general impression to gauge a text's translation difficulty level. If the evaluation process is to be more effective and the…
Translator-computer interaction in action

DEFF Research Database (Denmark)

Bundgaard, Kristine; Christensen, Tina Paulsen; Schjoldager, Anne

2016-01-01

perspective, this paper investigates the relationship between machines and humans in the field of translation, analysing a CAT process in which machine-translation (MT) technology was integrated into a translation-memory (TM) suite. After a review of empirical research into the impact of CAT tools......Though we lack empirically-based knowledge of the impact of computer-aided translation (CAT) tools on translation processes, it is generally agreed that all professional translators are now involved in some kind of translator-computer interaction (TCI), using O’Brien’s (2012) term. Taking a TCI......, the study indicates that the tool helps the translator conform to project and customer requirements....
Computer-aided translation tools

DEFF Research Database (Denmark)

Christensen, Tina Paulsen; Schjoldager, Anne

2016-01-01

in Denmark is rather high in general, but limited in the case of machine translation (MT) tools: While most TSPs use translation-memory (TM) software, often in combination with a terminology management system (TMS), only very few have implemented MT, which is criticised for its low quality output, especially......The paper reports on a questionnaire survey from 2013 of the uptake and use of computer-aided translation (CAT) tools by Danish translation service providers (TSPs) and discusses how these tools appear to have impacted on the Danish translation industry. According to our results, the uptake...
Modeling timelines for translational science in cancer; the impact of technological maturation.

Directory of Open Access Journals (Sweden)

Laura M McNamee

Full Text Available This work examines translational science in cancer based on theories of innovation that posit a relationship between the maturation of technologies and their capacity to generate successful products. We examined the growth of technologies associated with 138 anticancer drugs using an analytical model that identifies the point of initiation of exponential growth and the point at which growth slows as the technology becomes established. Approval of targeted and biological products corresponded with technological maturation, with first approval averaging 14 years after the established point and 44 years after initiation of associated technologies. The lag in cancer drug approvals after the increases in cancer funding and dramatic scientific advances of the 1970s thus reflects predictable timelines of technology maturation. Analytical models of technological maturation may be used for technological forecasting to guide more efficient translation of scientific discoveries into cures.
Dual Nature of Translational Control by Regulatory BC RNAs ▿

Science.gov (United States)

Eom, Taesun; Berardi, Valerio; Zhong, Jun; Risuleo, Gianfranco; Tiedge, Henri

2011-01-01

In higher eukaryotes, increasing evidence suggests, gene expression is to a large degree controlled by RNA. Regulatory RNAs have been implicated in the management of neuronal function and plasticity in mammalian brains. However, much of the molecular-mechanistic framework that enables neuronal regulatory RNAs to control gene expression remains poorly understood. Here, we establish molecular mechanisms that underlie the regulatory capacity of neuronal BC RNAs in the translational control of gene expression. We report that regulatory BC RNAs employ a two-pronged approach in translational control. One of two distinct repression mechanisms is mediated by C-loop motifs in BC RNA 3′ stem-loop domains. These C-loops bind to eIF4B and prevent the factor's interaction with 18S rRNA of the small ribosomal subunit. In the second mechanism, the central A-rich domains of BC RNAs target eIF4A, specifically inhibiting its RNA helicase activity. Thus, BC RNAs repress translation initiation in a bimodal mechanistic approach. As BC RNA functionality has evolved independently in rodent and primate lineages, our data suggest that BC RNA translational control was necessitated and implemented during mammalian phylogenetic development of complex neural systems. PMID:21930783
Quantitative analysis of ribosome–mRNA complexes at different translation stages

Science.gov (United States)

Shirokikh, Nikolay E.; Alkalaeva, Elena Z.; Vassilenko, Konstantin S.; Afonina, Zhanna A.; Alekhina, Olga M.; Kisselev, Lev L.; Spirin, Alexander S.

2010-01-01

Inhibition of primer extension by ribosome–mRNA complexes (toeprinting) is a proven and powerful technique for studying mechanisms of mRNA translation. Here we have assayed an advanced toeprinting approach that employs fluorescently labeled DNA primers, followed by capillary electrophoresis utilizing standard instruments for sequencing and fragment analysis. We demonstrate that this improved technique is not merely fast and cost-effective, but also brings the primer extension inhibition method up to the next level. The electrophoretic pattern of the primer extension reaction can be characterized with a precision unattainable by the common toeprint analysis utilizing radioactive isotopes. This method allows us to detect and quantify stable ribosomal complexes at all stages of translation, including initiation, elongation and termination, generated during the complete translation process in both the in vitro reconstituted translation system and the cell lysate. We also point out the unique advantages of this new methodology, including the ability to assay sites of the ribosomal complex assembly on several mRNA species in the same reaction mixture. PMID:19910372
The role of PKA in the translational response to heat stress in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Carla E Barraza

Full Text Available Cellular responses to stress stem from a variety of different mechanisms, including translation arrest and relocation of the translationally repressed mRNAs to ribonucleoprotein particles like stress granules (SGs and processing bodies (PBs. Here, we examine the role of PKA in the S. cerevisiae heat shock response. Under mild heat stress Tpk3 aggregates and promotes aggregation of eIF4G, Pab1 and eIF4E, whereas severe heat stress leads to the formation of PBs and SGs that contain both Tpk2 and Tpk3 and a larger 48S translation initiation complex. Deletion of TPK2 or TPK3 impacts upon the translational response to heat stress of several mRNAs including CYC1, HSP42, HSP30 and ENO2. TPK2 deletion leads to a robust translational arrest, an increase in SGs/PBs aggregation and translational hypersensitivity to heat stress, whereas TPK3 deletion represses SGs/PBs formation, translational arrest and response for the analyzed mRNAs. Therefore, this work provides evidence indicating that Tpk2 and Tpk3 have opposing roles in translational adaptation during heat stress, and highlight how the same signaling pathway can be regulated to generate strikingly distinct physiological outputs.
STRAPIR, an European initiative for optimizing radiation protection in interventional radiology

International Nuclear Information System (INIS)

Vano, E.; Gonzalez, L.; Loon, R. van; Padovani, R.; Maccia, C.; Eggermont, G.

1997-01-01

In 1995, a European initiative for optimizing radiation protection in interventional radiology was proposed by 8 research groups. The project acronym was STPAPIR (Staff Radiation Protection in Interventional Radiology). Interventional Radiology involves an important number of specialists and their risk level is not well known, since dosimetric records exhibit important discrepancies. Many professionals using these techniques are not radiologists and the basic rules of radiation protection, known by radiologists, are not always correctly and completely followed, hence the use of protection devices is not as regular as desirable. Additionally, x-ray systems not specifically designed for interventional procedures are still used in many hospitals, what entails a significant occupational risk increase to the specialists. Some relevant questions for regulatory bodies are presented, namely, reliability of the actual data banks for occupational dosimetry, use of two personal dosimeters for assessing effective dose, actions to strengthen the systematic use of personal dosimeters and protection tools, proposals for specific training in radiation protection and use of x-ray systems specifically designed for interventional procedures, publication of reports about accidents and incidents, are also discussed. (author)

Translation goes to the movies

CERN Document Server

Cronin, Michael

2008-01-01

This highly accessible introduction to translation theory, written by a leading author in the field, uses the genre of film to bring the main themes in translation to life. Through analyzing films as diverse as the Marx Brothers' A Night at the Opera, The Star Wars Trilogies and Lost in Translation, the reader is encouraged to think about both issues and problems of translation as they are played out on the screen and issues of filmic representation through examining the translation dimension of specific films. In highlighting how translation has featured in both mainstream commercial and arthouse films over the years, Cronin shows how translation has been a concern of filmmakers dealing with questions of culture, identity, conflict and representation. This book is a lively and accessible text for translation theory courses and offers a new and largely unexplored approach to topics of identity and representation on screen. Translation Goes to the Movies will be of interest to those on translation studies...
Mutation of a Nicotiana tabacum L. eukaryotic translation-initiation factor gene reduces susceptibility to a resistance-breaking strain of Potato Virus Y.

Science.gov (United States)

Takakura, Yoshimitsu; Udagawa, Hisashi; Shinjo, Akira; Koga, Kazuharu

2018-04-06

Eukaryotic translation-initiation factors eIF4E and eIF(iso)4E in plants play key roles in infection by potyviruses and other plant RNA viruses. Mutations in the genes encoding these factors reduce susceptibility to the viruses, and are the basis of several recessive virus-resistance genes widely used in plant breeding. Because virus variants occasionally break such resistance, the molecular basis for this process must be elucidated. Although deletion mutants of eIF4E1-S of tobacco (Nicotiana tabacum L.) resist Potato virus Y (PVY; the type member of the genus Potyvirus), resistance-breaking strains of PVY threaten tobacco production worldwide. Here, we used RNA interference technology to knock down tobacco eIF4E2-S and eIF4E2-T genes or eIF(iso)4E-S and eIF(iso)4E-T genes. Transgenic plants with reduced transcript levels of both eIF(iso)4E-S and eIF(iso)4E-T showed reduced susceptibility to a resistance-breaking PVY strain with a K105E mutation in the viral genome-associated protein (VPg). By screening a population of chemically-induced mutants of eIF(iso)4E-S and eIF(iso)4E-T, we showed that plants with a nonsense mutation in eIF(iso)4E-T, but not eIF(iso)4E-S, showed reduced susceptibility to the resistance-breaking PVY strain. In a yeast two-hybrid assay, VPg of the resistance-breaking strain, but not wild-type PVY, physically interacted with the eIF(iso)4E-T protein. Thus, eIF4E1-S is required for infection by PVY, but eIF(iso)4E-T is required for infection by the resistance-breaking strain. Our study provides the first evidence for the involvement of a host eukaryotic translation-initiation factor in the infection cycle of a resistance-breaking virus strain. The eIF(iso)4E-T mutants will be useful in tobacco breeding to introduce resistance against resistance-breaking PVY strains. This article is protected by copyright. All rights reserved. © 2018 BSPP and John Wiley & Sons Ltd.
Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication

Directory of Open Access Journals (Sweden)

Michael Niepmann

2018-03-01

Full Text Available Hepatitis C virus (HCV preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES in the 5′ untranslated region (5′ UTR, while also downstream elements like the cis-replication element (CRE in the coding region and the 3′ UTR are involved in translation regulation. The cis-elements controlling replication of the viral RNA genome are located mainly in the 5′- and 3′-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA–RNA interactions (LRIs are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis-elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122 binds to two target sites at the 5′ end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3′ UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis-elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis-element in
Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication.

Science.gov (United States)

Niepmann, Michael; Shalamova, Lyudmila A; Gerresheim, Gesche K; Rossbach, Oliver

2018-01-01

Hepatitis C virus (HCV) preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES) in the 5' untranslated region (5' UTR), while also downstream elements like the cis -replication element (CRE) in the coding region and the 3' UTR are involved in translation regulation. The cis -elements controlling replication of the viral RNA genome are located mainly in the 5'- and 3'-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA-RNA interactions (LRIs) are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis -elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122) binds to two target sites at the 5' end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3' UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis -elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis -element in question acts on HCV
Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells.

Science.gov (United States)

Sugiyama, Hayami; Takahashi, Kazutoshi; Yamamoto, Takuya; Iwasaki, Mio; Narita, Megumi; Nakamura, Masahiro; Rand, Tim A; Nakagawa, Masato; Watanabe, Akira; Yamanaka, Shinya

2017-01-10

Novel APOBEC1 target 1 (Nat1) (also known as "p97," "Dap5," and "Eif4g2") is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors eIF3 and eIF4A and ribosomal proteins. However, NAT1 did not bind to eIF4E or poly(A)-binding proteins, which are critical for cap-dependent translation initiation. In contrast, compared with eIF4G1, NAT1 preferentially interacted with eIF2, fragile X mental retardation proteins (FMR), and related proteins and especially with members of the proline-rich and coiled-coil-containing protein 2 (PRRC2) family. We also found that Nat1-null mES cells possess a transcriptional profile similar, although not identical, to the ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and glycogen synthase kinase 3 (GSK3) signaling pathways. In Nat1-null mES cells, the ERK pathway is suppressed even without inhibitors. Ribosome profiling revealed that translation of mitogen-activated protein kinase kinase kinase 3 (Map3k3) and son of sevenless homolog 1 (Sos1) is suppressed in the absence of Nat1 Forced expression of Map3k3 induced differentiation of Nat1-null mES cells. These data collectively show that Nat1 is involved in the translation of proteins that are required for cell differentiation.
Translation and adaptation of the Competencias Esenciales en Salud Pública para los recursos humanos en salud 1

Science.gov (United States)

de Almeida, Maria de Lourdes; Peres, Aida Maris; Ferreira, Maria Manuela Frederico; Mantovani, Maria de Fátima

2017-01-01

ABSTRACT Objective: to perform the translation and cultural adaptation of the document named Marco Regional de Competencias Esenciales en Salud Pública para los Recursos Humanos en Salud de la Región de las Américas (Regional Framework of Core Competencies in Public Health for Health Human Resources in the Region of Americas) from Spanish to Brazilian Portuguese. Method: a methodological study comprising the following phases: authorization for translation; initial translation; synthesis of translations and consensus; back-translation and formation of an expert committee. Result: in the translation of domain names, there was no difference in 66.7% (N = 4); in the translation of domain description and competencies there were divergences in 100% of them (N = 6, N = 56). A consensus of more than 80% was obtained in the translation and improvement in the expert committee by the change of words and expressions for approximation of meanings to the Brazilian context. Conclusion: the translated and adapted document has the potential of application in research, and use in the practice of collective/public health care in Brazil. PMID:28591302
Jungmann's translation of Paradise Lost

OpenAIRE

Janů, Karel

2014-01-01

This thesis examines Josef Jungmann's translation of John Milton's Paradise Lost. Josef Jungmann was one of the leading figures of the Czech National Revival and translated Milton 's poem between the years 1800 and 1804. The thesis covers Jungmann's theoretical model of translation and presents Jungmann's motives for translation of Milton's epic poem. The paper also describes the aims Jungmann had with his translation and whether he has achieved them. The reception Jungmann's translation rece...
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.
40 Years of Research Put p53 in Translation

Science.gov (United States)

Marcel, Virginie; Nguyen Van Long, Flora; Diaz, Jean-Jacques

2018-01-01

Since its discovery in 1979, p53 has shown multiple facets. Initially the tumor suppressor p53 protein was considered as a stress sensor able to maintain the genome integrity by regulating transcription of genes involved in cell cycle arrest, apoptosis and DNA repair. However, it rapidly came into light that p53 regulates gene expression to control a wider range of biological processes allowing rapid cell adaptation to environmental context. Among them, those related to cancer have been extensively documented. In addition to its role as transcription factor, scattered studies reported that p53 regulates miRNA processing, modulates protein activity by direct interaction or exhibits RNA-binding activity, thus suggesting a role of p53 in regulating several layers of gene expression not restricted to transcription. After 40 years of research, it appears more and more clearly that p53 is strongly implicated in translational regulation as well as in the control of the production and activity of the translational machinery. Translation control of specific mRNAs could provide yet unsuspected capabilities to this well-known guardian of the genome.
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...... and from related species were aligned and revealed an interspecies conserved central and C-terminal part, and an N-terminal part that is highly variable in length and amino acid sequence. The diversity and relationships in a collection of 58 genetically distinct strains of S. agalactiae were evaluated...... by comparing a partial sequence of infB. A total of six alleles were detected for the region of infB analysed. The alleles correlated with the separation of the same strains of S. agalactiae into major evolutionary lineages, as shown in previous work. The partial sequences of infB were furthermore used...
Theory of Test Translation Error

Science.gov (United States)

Solano-Flores, Guillermo; Backhoff, Eduardo; Contreras-Nino, Luis Angel

2009-01-01

In this article, we present a theory of test translation whose intent is to provide the conceptual foundation for effective, systematic work in the process of test translation and test translation review. According to the theory, translation error is multidimensional; it is not simply the consequence of defective translation but an inevitable fact…
JavaScript DNA translator: DNA-aligned protein translations.

Science.gov (United States)

Perry, William L

2002-12-01

There are many instances in molecular biology when it is necessary to identify ORFs in a DNA sequence. While programs exist for displaying protein translations in multiple ORFs in alignment with a DNA sequence, they are often expensive, exist as add-ons to software that must be purchased, or are only compatible with a particular operating system. JavaScript DNA Translator is a shareware application written in JavaScript, a scripting language interpreted by the Netscape Communicator and Internet Explorer Web browsers, which makes it compatible with several different operating systems. While the program uses a familiar Web page interface, it requires no connection to the Internet since calculations are performed on the user's own computer. The program analyzes one or multiple DNA sequences and generates translations in up to six reading frames aligned to a DNA sequence, in addition to displaying translations as separate sequences in FASTA format. ORFs within a reading frame can also be displayed as separate sequences. Flexible formatting options are provided, including the ability to hide ORFs below a minimum size specified by the user. The program is available free of charge at the BioTechniques Software Library (www.Biotechniques.com).
Lost in Translation

Science.gov (United States)

Lass, Wiebke; Reusswig, Fritz

2014-05-01

Lost in Translation? Introducing Planetary Boundaries into Social Systems. Fritz Reusswig, Wiebke Lass Potsdam Institute for Climate Impact Research, Potsdam, Germany Identifying and quantifying planetary boundaries by interdisciplinary science efforts is a challenging task—and a risky one, as the 1972 Limits to Growth publication has shown. Even if we may be assured that scientific understanding of underlying processes of the Earth system has significantly improved since then, the challenge of translating these findings into the social systems of the planet remains crucial for any kind of action, and in many respects far more challenging. We would like to conceptualize what could also be termed a problem of coupling social and natural systems as a nested set of social translation processes, well aware of the limited applicability of the language-related translation metaphor. Societies must, first, perceive these boundaries, and they have to understand their relevance. This includes, among many other things, the organization of transdisciplinary scientific cooperation. They will then have to translate this understood perception into possible actions, i.e. strategies for different local bodies, actors, and institutional settings. This implies a lot of 'internal' translation processes, e.g. from the scientific subsystem to the mass media, the political and the economic subsystem. And it implies to develop subsystem-specific schemes of evaluation for these alternatives, e.g. convincing narratives, cost-benefit analyses, or ethical legitimacy considerations. And, finally, societies do have to translate chosen action alternatives into monitoring and evaluation schemes, e.g. for agricultural production or renewable energies. This process includes the continuation of observing and re-analyzing the planetary boundary concept itself, as a re-adjustment of these boundaries in the light of new scientific insights cannot be excluded. Taken all together, societies may well
The spatial biology of transcription and translation in rapidly growing Escherichia coli

Directory of Open Access Journals (Sweden)

Somenath eBakshi

2015-07-01

Full Text Available Single-molecule fluorescence provides high resolution spatial distributions of ribosomes and RNA polymerase (RNAP in live, rapidly growing E. coli. Ribosomes are more strongly segregated from the nucleoids (chromosomal DNA than previous widefield fluorescence studies suggested. While most transcription may be co-translational, the evidence indicates that most translation occurs on free mRNA copies that have diffused from the nucleoids to a ribosome-rich region. Analysis of time-resolved images of the nucleoid spatial distribution after treatment with the transcription-halting drug rifampicin and the translation-halting drug chloramphenicol shows that both drugs cause nucleoid contraction on the 0-3 min timescale. This is consistent with the transertion hypothesis. We suggest that the longer-term (20-30 min nucleoid expansion after Rif treatment arises from conversion of 70S-polysomes to 30S and 50S subunits, which readily penetrate the nucleoids. Monte Carlo simulations of a polymer bead model built to mimic the chromosomal DNA and ribosomes (either 70S-polysomes or 30S and 50S subunits explain spatial segregation or mixing of ribosomes and nucleoids in terms of excluded volume and entropic effects alone. A comprehensive model of the transcription-translation-transertion system incorporates this new information about the spatial organization of the E. coli cytoplasm. We propose that transertion, which radially expands the nucleoids, is essential for recycling of 30S and 50S subunits from ribosome-rich regions back into the nucleoids. There they initiate co-transcriptional translation, which is an important mechanism for maintaining RNAP forward progress and protecting the nascent mRNA chain. Segregation of 70S-polysomes from the nucleoid may facilitate rapid growth by shortening the search time for ribosomes to find free mRNA concentrated outside the nucleoid and the search time for RNAP concentrated within the nucleoid to find transcription
AC-600 reactor reloading pattern optimization by using genetic algorithms

International Nuclear Information System (INIS)

Wu Hongchun; Xie Zhongsheng; Yao Dong; Li Dongsheng; Zhang Zongyao

2000-01-01

The use of genetic algorithms to optimize reloading pattern of the nuclear power plant reactor is proposed. And a new encoding and translating method is given. Optimization results of minimizing core power peak and maximizing cycle length for both low-leakage and out-in loading pattern of AC-600 reactor are obtained
Translation and Creation

Directory of Open Access Journals (Sweden)

Paulo Bezerra

2012-12-01

Full Text Available The article begins with the differences betweenscientific and fictional translations, and focus on the second.The fictional translation works with meanings, opens itselfto the plurissignification in the purpose to create a similarity of the dissimilarity; in this process, the translator does nottranslate a language, but what a creative individuality makeswith a language. At last there is an approach to the knowledgeand skills necessaries to a translator of literature: theknowledge of the theories of the literature and of thetranslation, the capacity to preserve the national color ofthe original text and at the same time to respect the arrivallanguage, and the sensibility to his national languagevariations present in the daily and in the literary spheres.
On Literal Translation of English Idioms

Science.gov (United States)

Chen, Linli

2009-01-01

There are six translation tactics in translating English idioms into Chinese: literal translation, compensatory translation, free translation, explanational translation, borrowing, integrated approach. Each tactic should be reasonably employed in the process of translating, so as to keep the flavor of the original English idioms as well as to…
Optimal Initial Public O¤ering design with aftermarket trading.

OpenAIRE

Fabrice Rousseau; Sarah Parlane

2009-01-01

We characterize the optimal pricing and allocation of shares in the presence of distinct adverse selection problems. Some investors have private information at the time of the IPO and sell their shares in the after-market upon facing liquidity needs. Others learn their private interest in the after-market, and sell their shares strategically. The optimal mechanism trades-o¤ informational rents and rents to strategic traders. Flipping facilitates truthful information revelation. When liquidity...
Advancing System Flexibility for High Penetration Renewable Integration (Chinese Translation)

Energy Technology Data Exchange (ETDEWEB)

Milligan, Michael [National Renewable Energy Lab. (NREL), Golden, CO (United States); Frew, Bethany [National Renewable Energy Lab. (NREL), Golden, CO (United States); Zhou, Ella [National Renewable Energy Lab. (NREL), Golden, CO (United States); Arent, Douglas J. [Joint Inst. for Strategic Energy Analysis, Golden, CO (United States)

2015-10-01

This is a Chinese translation of NREL/TP-6A20-64864. This report summarizes some of the issues discussed during the engagement on power system flexibility. By design, the focus is on flexibility options used in the United States. Exploration of whether and how U.S. experiences can inform Chinese energy planning will be part of the continuing project, and will benefit from the knowledge base provided by this report. We believe the initial stage of collaboration represented in this report has successfully started a process of mutual understanding, helping Chinese researchers to begin evaluating how lessons learned in other countries might translate to China's unique geographic, economic, social, and political contexts.
A Study of Translation Institutional Ethics

Institute of Scientific and Technical Information of China (English)

LuoXianfeng; ZhouJin

2017-01-01

Traditional translation ethics characterized by translators' ethics cannot provide a strong moral support to the translation practice,or guarantee the moral requirement towards translation activities in the social transformation caused by the market economy,because it does not have the power of punishment.Translation institutional ethics,however,a new form of translation ethics,integrates the translation ethic norm,translation regulations and relative laws together.As an inevitable outcome in the new era,it can escort the orderly and healthy translation activities.Its purpose is to strengthen the translators' moral consciousness,to sublimate their moral notions and to transfer from heteronomy to autonomy.

The translational regulator Cup controls NMJ presynaptic terminal morphology.

Science.gov (United States)

Menon, Kaushiki P; Carrillo, Robert A; Zinn, Kai

2015-07-01

During oogenesis and early embryonic development in Drosophila, translation of proteins from maternally deposited mRNAs is tightly controlled. We and others have previously shown that translational regulatory proteins that function during oogenesis also have essential roles in the nervous system. Here we examine the role of Cup in neuromuscular system development. Maternal Cup controls translation of localized mRNAs encoding the Oskar and Nanos proteins and binds to the general translation initiation factor eIF4E. In this paper, we show that zygotic Cup protein is localized to presynaptic terminals at larval neuromuscular junctions (NMJs). cup mutant NMJs have strong phenotypes characterized by the presence of small clustered boutons called satellite boutons. They also exhibit an increase in the frequency of spontaneous glutamate release events (mEPSPs). Reduction of eIF4E expression synergizes with partial loss of Cup expression to produce satellite bouton phenotypes. The presence of satellite boutons is often associated with increases in retrograde bone morphogenetic protein (BMP) signaling, and we show that synaptic BMP signaling is elevated in cup mutants. cup genetically interacts with two genes, EndoA and Dap160, that encode proteins involved in endocytosis that are also neuronal modulators of the BMP pathway. Endophilin protein, encoded by the EndoA gene, is downregulated in a cup mutant. Our results are consistent with a model in which Cup and eIF4E work together to ensure efficient localization and translation of endocytosis proteins in motor neurons and control the strength of the retrograde BMP signal. Copyright © 2015 Elsevier Inc. All rights reserved.
Efficient use of a translation start codon in BDNF exon I.

Science.gov (United States)

Koppel, Indrek; Tuvikene, Jürgen; Lekk, Ingrid; Timmusk, Tõnis

2015-09-01

The brain-derived neurotrophic factor (BDNF) gene contains a number of 5' exons alternatively spliced with a common 3' exon. BDNF protein is synthesized from alternative transcripts as a prepro-precursor encoded by the common 3' exon IX, which has a translation start site 21 bp downstream of the splicing site. BDNF mRNAs containing exon I are an exception to this arrangement as the last three nucleotides of this exon constitute an in-frame AUG. Here, we show that this AUG is efficiently used for translation initiation in PC12 cells and cultured cortical neurons. Use of exon I-specific AUG produces higher levels of BDNF protein than use of the common translation start site, resulting from a higher translation rate. No differences in protein degradation, constitutive or regulated secretion were detected between BDNF isoforms with alternative 5' termini. As the BDNF promoter preceding exon I is known to be highly regulated by neuronal activity, our results suggest that the function of this translation start site may be efficient stimulus-dependent synthesis of BDNF protein. The brain-derived neurotrophic factor (BDNF) gene contains multiple untranslated 5' exons alternatively spliced to one common protein-coding 3' exon. However, exon I contains an in-frame ATG in a favorable translation context. Here, we show that use of this ATG is associated with more efficient protein synthesis than the commonly used ATG in exon IX. © 2015 International Society for Neurochemistry.
Dynamic expression of the translational machinery during Bacillus subtilis life cycle at a single cell level.

Directory of Open Access Journals (Sweden)

Alex Rosenberg

Full Text Available The ability of bacteria to responsively regulate the expression of translation components is crucial for rapid adaptation to fluctuating environments. Utilizing Bacillus subtilis (B. subtilis as a model organism, we followed the dynamics of the translational machinery at a single cell resolution during growth and differentiation. By comprehensive monitoring the activity of the major rrn promoters and ribosomal protein production, we revealed diverse dynamics between cells grown in rich and poor medium, with the most prominent dissimilarities exhibited during deep stationary phase. Further, the variability pattern of translational activity varied among the cells, being affected by nutrient availability. We have monitored for the first time translational dynamics during the developmental process of sporulation within the two distinct cellular compartments of forespore and mother-cell. Our study uncovers a transient forespore specific increase in expression of translational components. Finally, the contribution of each rrn promoter throughout the bacterium life cycle was found to be relatively constant, implying that differential expression is not the main purpose for the existence of multiple rrn genes. Instead, we propose that coordination of the rrn operons serves as a strategy to rapidly fine tune translational activities in a synchronized fashion to achieve an optimal translation level for a given condition.
The Impact of Translators' Epistemological Beliefs and Gender on Their Translation Quality

Science.gov (United States)

Araghizade, Elmira; Jadidi, Esmaeil

2016-01-01

This study aimed to determine the relationship between translators' epistemological beliefs and gender on their Persian-to-English translation quality. To do so, a group of 53 MA translation students both male and female were selected, through convenient sampling to participate in this study. For data collection two instruments were employed: 1…
Onomastics and Translation: The Case of Igbo→English Translation ...

African Journals Online (AJOL)

The qualitative research method will be used to translate, analyze and explain the data from the anthroponomical, semiotic and linguistic perspectives to show that contrary to the view held in some Western circles that names are obscure and may consist of words that can hardly be interpreted or translated, they, as symbols ...
The eukaryotic translation initiation factor 3 subunit L protein interacts with Flavivirus NS5 and may modulate yellow fever virus replication.

Science.gov (United States)

Morais, Ana Ts; Terzian, Ana Cb; Duarte, Danilo Vb; Bronzoni, Roberta Vm; Madrid, Maria Cfs; Gavioli, Arieli F; Gil, Laura Hvg; Oliveira, Amanda G; Zanelli, Cleslei F; Valentini, Sandro R; Rahal, Paula; Nogueira, Mauricio L

2013-06-22

Yellow fever virus (YFV) belongs to the Flavivirus genus and causes an important disease. An alarming resurgence of viral circulation and the expansion of YFV-endemic zones have been detected in Africa and South America in recent years. NS5 is a viral protein that contains methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, which are essential for viral replication, and the interactions between NS5 and cellular proteins have been studied to better understand viral replication. The aim of this study was to characterize the interaction of the NS5 protein with eukaryotic translation initiation factor 3 subunit L (eIF3L) and to evaluate the role of eIF3L in yellow fever replication. To identify interactions of YFV NS5 with cellular proteins, we performed a two-hybrid screen using the YFV NS5 RdRp domain as bait with a human cDNA library, and RNApol deletion mutants were generated and analyzed using the two-hybrid system for mapping the interactions. The RNApol region involved was segmented into three fragments and analyzed using an eIF3L-expressing yeast strain. To map the NS5 residues that are critical for the interactions, we performed site-direct mutagenesis in segment 3 of the interaction domain (ID) and confirmed the interaction using in vitro assays and in vivo coimmunoprecipitation. The significance of eIF3L for YFV replication was investigated using eIF3L overexpression and RNA interference. In this work, we describe and characterize the interaction of NS5 with the translation factor eIF3L. The interaction between NS5 and eIF3L was confirmed using in vitro binding and in vivo coimmunoprecipitation assays. This interaction occurs at a region (the interaction domain of the RNApol domain) that is conserved in several flaviviruses and that is, therefore, likely to be relevant to the genus. eIF3L overexpression and plaque reduction assays showed a slight effect on YFV replication, indicating that the interaction of eIF3L with YFV NS5 may play a role
TRANSAUTOPHAGY: European network for multidisciplinary research and translation of autophagy knowledge

Science.gov (United States)

Casas, Caty; Codogno, Patrice; Pinti, Marcello; Batoko, Henri; Morán, María; Proikas-Cezanne, Tassula; Reggiori, Fulvio; Sirko, Agnieszka; Soengas, María S; Velasco, Guillermo; Lafont, Frank; Lane, Jon; Faure, Mathias; Cossarizza, Andrea

2016-01-01

abstract A collaborative consortium, named “TRANSAUTOPHAGY,” has been created among European research groups, comprising more than 150 scientists from 21 countries studying diverse branches of basic and translational autophagy. The consortium was approved in the framework of the Horizon 2020 Program in November 2015 as a COST Action of the European Union (COST means: CO-operation in Science and Technology), and will be sponsored for 4 years. TRANSAUTOPHAGY will form an interdisciplinary platform for basic and translational researchers, enterprises and stakeholders of diverse disciplines (including nanotechnology, bioinformatics, physics, chemistry, biology and various medical disciplines). TRANSAUTOPHAGY will establish 5 different thematic working groups, formulated to cooperate in research projects, share ideas, and results through workshops, meetings and short term exchanges of personnel (among other initiatives). TRANSAUTOPHAGY aims to generate breakthrough multidisciplinary knowledge about autophagy regulation, and to boost translation of this knowledge into biomedical and biotechnological applications. PMID:27046256
A Transcription and Translation Protocol for Sensitive Cross-Cultural Team Research.

Science.gov (United States)

Clark, Lauren; Birkhead, Ana Sanchez; Fernandez, Cecilia; Egger, Marlene J

2017-10-01

Assurance of transcript accuracy and quality in interview-based qualitative research is foundational for data accuracy and study validity. Based on our experience in a cross-cultural ethnographic study of women's pelvic organ prolapse, we provide practical guidance to set up step-by-step interview transcription and translation protocols for team-based research on sensitive topics. Beginning with team decisions about level of detail in transcription, completeness, and accuracy, we operationalize the process of securing vendors to deliver the required quality of transcription and translation. We also share rubrics for assessing transcript quality and the team protocol for managing transcripts (assuring consistency of format, insertion of metadata, anonymization, and file labeling conventions) and procuring an acceptable initial translation of Spanish-language interviews. Accurate, complete, and systematically constructed transcripts in both source and target languages respond to the call for more transparency and reproducibility of scientific methods.
TRANSAUTOPHAGY: European network for multidisciplinary research and translation of autophagy knowledge.

Science.gov (United States)

Casas, Caty; Codogno, Patrice; Pinti, Marcello; Batoko, Henri; Morán, María; Proikas-Cezanne, Tassula; Reggiori, Fulvio; Sirko, Agnieszka; Soengas, María S; Velasco, Guillermo; Lafont, Frank; Lane, Jon; Faure, Mathias; Cossarizza, Andrea

2016-01-01

A collaborative consortium, named "TRANSAUTOPHAGY," has been created among European research groups, comprising more than 150 scientists from 21 countries studying diverse branches of basic and translational autophagy. The consortium was approved in the framework of the Horizon 2020 Program in November 2015 as a COST Action of the European Union (COST means: CO-operation in Science and Technology), and will be sponsored for 4 years. TRANSAUTOPHAGY will form an interdisciplinary platform for basic and translational researchers, enterprises and stakeholders of diverse disciplines (including nanotechnology, bioinformatics, physics, chemistry, biology and various medical disciplines). TRANSAUTOPHAGY will establish 5 different thematic working groups, formulated to cooperate in research projects, share ideas, and results through workshops, meetings and short term exchanges of personnel (among other initiatives). TRANSAUTOPHAGY aims to generate breakthrough multidisciplinary knowledge about autophagy regulation, and to boost translation of this knowledge into biomedical and biotechnological applications.
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.
Dynamics of Chloroplast Translation during Chloroplast Differentiation in Maize.

Directory of Open Access Journals (Sweden)

Prakitchai Chotewutmontri

2016-07-01

does not generally discriminate between edited and unedited RNAs. However, editing of ACG to AUG at the rpl2 start codon is essential for translation initiation, demonstrating that ACG does not serve as a start codon in maize chloroplasts.
Language policies and sign language translation and interpreting: connections between Brazil and Mozambique

Directory of Open Access Journals (Sweden)

Silvana Aguiar dos Santos

2015-12-01

Full Text Available http://dx.doi.org/10.5007/1984-8420.2015v16n2p101 This paper is the result of an initial attempt to establish a connection between Brazil and Mozambique regarding sign language translation and interpreting. It reviews some important landmarks in language policies aimed at sign languages in these countries and discusses how certain actions directly impact political decisions related to sign language translation and interpreting. In this context, two lines of argument are developed. The first one addresses the role of sign language translation and interpreting in the Portuguese-speaking context, since Portuguese is the official language in both countries; the other offers some reflections about the Deaf movements and the movements of sign language translators and interpreters, the legal recognition of sign languages, the development of undergraduate courses and the contemporary challenges in the work of translation professionals. Finally, it is suggested that sign language translators and interpreters in both Brazil and Mozambique undertake efforts to press government bodies to invest in: (i area-specific training for translators and interpreters, (ii qualification of the services provided by such professionals, and (iii development of human resources at master’s and doctoral levels in order to strengthen research on sign language translation and interpreting in the Community of Portuguese-Speaking Countries.
Sound Effects in Translation

DEFF Research Database (Denmark)

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

2015-01-01

), 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...
Simultaneous optimization of sequential IMRT plans

International Nuclear Information System (INIS)

Popple, Richard A.; Prellop, Perri B.; Spencer, Sharon A.; Santos, Jennifer F. de los; Duan, Jun; Fiveash, John B.; Brezovich, Ivan A.

2005-01-01

Radiotherapy often comprises two phases, in which irradiation of a volume at risk for microscopic disease is followed by a sequential dose escalation to a smaller volume either at a higher risk for microscopic disease or containing only gross disease. This technique is difficult to implement with intensity modulated radiotherapy, as the tolerance doses of critical structures must be respected over the sum of the two plans. Techniques that include an integrated boost have been proposed to address this problem. However, clinical experience with such techniques is limited, and many clinicians are uncomfortable prescribing nonconventional fractionation schemes. To solve this problem, we developed an optimization technique that simultaneously generates sequential initial and boost IMRT plans. We have developed an optimization tool that uses a commercial treatment planning system (TPS) and a high level programming language for technical computing. The tool uses the TPS to calculate the dose deposition coefficients (DDCs) for optimization. The DDCs were imported into external software and the treatment ports duplicated to create the boost plan. The initial, boost, and tolerance doses were specified and used to construct cost functions. The initial and boost plans were optimized simultaneously using a gradient search technique. Following optimization, the fluence maps were exported to the TPS for dose calculation. Seven patients treated using sequential techniques were selected from our clinical database. The initial and boost plans used to treat these patients were developed independently of each other by dividing the tolerance doses proportionally between the initial and boost plans and then iteratively optimizing the plans until a summation that met the treatment goals was obtained. We used the simultaneous optimization technique to generate plans that met the original planning goals. The coverage of the initial and boost target volumes in the simultaneously optimized
A network of hydrophobic residues impeding helix alphaC rotation maintains latency of kinase Gcn2, which phosphorylates the alpha subunit of translation initiation factor 2.

Science.gov (United States)

Gárriz, Andrés; Qiu, Hongfang; Dey, Madhusudan; Seo, Eun-Joo; Dever, Thomas E; Hinnebusch, Alan G

2009-03-01

Kinase Gcn2 is activated by amino acid starvation and downregulates translation initiation by phosphorylating the alpha subunit of translation initiation factor 2 (eIF2alpha). The Gcn2 kinase domain (KD) is inert and must be activated by tRNA binding to the adjacent regulatory domain. Previous work indicated that Saccharomyces cerevisiae Gcn2 latency results from inflexibility of the hinge connecting the N and C lobes and a partially obstructed ATP-binding site in the KD. Here, we provide strong evidence that a network of hydrophobic interactions centered on Leu-856 also promotes latency by constraining helix alphaC rotation in the KD in a manner relieved during amino acid starvation by tRNA binding and autophosphorylation of Thr-882 in the activation loop. Thus, we show that mutationally disrupting the hydrophobic network in various ways constitutively activates eIF2alpha phosphorylation in vivo and bypasses the requirement for a key tRNA binding motif (m2) and Thr-882 in Gcn2. In particular, replacing Leu-856 with any nonhydrophobic residue activates Gcn2, while substitutions with various hydrophobic residues maintain kinase latency. We further provide strong evidence that parallel, back-to-back dimerization of the KD is a step on the Gcn2 activation pathway promoted by tRNA binding and autophosphorylation. Remarkably, mutations that disrupt the L856 hydrophobic network or enhance hinge flexibility eliminate the need for the conserved salt bridge at the parallel dimer interface, implying that KD dimerization facilitates the reorientation of alphaC and remodeling of the active site for enhanced ATP binding and catalysis. We propose that hinge remodeling, parallel dimerization, and reorientation of alphaC are mutually reinforcing conformational transitions stimulated by tRNA binding and secured by the ensuing autophosphorylation of T882 for stable kinase activation.
Optimization the initial weights of artificial neural networks via genetic algorithm applied to hip bone fracture prediction

OpenAIRE

Chang, Y-T; Lin, J; Shieh, J-S; Abbod, MF

2012-01-01

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 expirat...
Automatic treatment plan re-optimization for adaptive radiotherapy guided with the initial plan DVHs

International Nuclear Information System (INIS)

Li, Nan; Zarepisheh, Masoud; Uribe-Sanchez, Andres; Moore, Kevin; Tian, Zhen; Zhen, Xin; Graves, Yan Jiang; Gautier, Quentin; Mell, Loren; Jia, Xun; Jiang, Steve; Zhou, Linghong

2013-01-01

Adaptive radiation therapy (ART) can reduce normal tissue toxicity and/or improve tumor control through treatment adaptations based on the current patient anatomy. Developing an efficient and effective re-planning algorithm is an important step toward the clinical realization of ART. For the re-planning process, manual trial-and-error approach to fine-tune planning parameters is time-consuming and is usually considered unpractical, especially for online ART. It is desirable to automate this step to yield a plan of acceptable quality with minimal interventions. In ART, prior information in the original plan is available, such as dose–volume histogram (DVH), which can be employed to facilitate the automatic re-planning process. The goal of this work is to develop an automatic re-planning algorithm to generate a plan with similar, or possibly better, DVH curves compared with the clinically delivered original plan. Specifically, our algorithm iterates the following two loops. An inner loop is the traditional fluence map optimization, in which we optimize a quadratic objective function penalizing the deviation of the dose received by each voxel from its prescribed or threshold dose with a set of fixed voxel weighting factors. In outer loop, the voxel weighting factors in the objective function are adjusted according to the deviation of the current DVH curves from those in the original plan. The process is repeated until the DVH curves are acceptable or maximum iteration step is reached. The whole algorithm is implemented on GPU for high efficiency. The feasibility of our algorithm has been demonstrated with three head-and-neck cancer IMRT cases, each having an initial planning CT scan and another treatment CT scan acquired in the middle of treatment course. Compared with the DVH curves in the original plan, the DVH curves in the resulting plan using our algorithm with 30 iterations are better for almost all structures. The re-optimization process takes about 30�
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
A Novel Quality Measure and Correction Procedure for the Annotation of Microbial Translation Initiation Sites.

Directory of Open Access Journals (Sweden)

Lex Overmars

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

Science.gov (United States)

Wooten, Kevin C; Dann, Sara M; Finnerty, Celeste C; Kotarba, Joseph A

2014-07-01

The development of leadership and project management skills is increasingly important to the evolution of translational science and team-based endeavors. Team science is dependent upon individuals at various stages in their careers, inclusive of postdocs. Data from case histories, as well as from interviews with current and former postdocs, and those supervising postdocs, indicate six essential tasks required of project managers in multidisciplinary translational teams, along with eight skill-related themes critical to their success. To optimize the opportunities available and to ensure sequential development of team project management skills, a life cycle model for the development of translational team skills is proposed, ranging from graduate trainees, postdocs, assistant professors, and finally to mature scientists. Specific goals, challenges and project management roles and tasks are recommended for each stage for the life cycle.

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