Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration

Serrano-Nascimento C, Calil-Silveira J, Nunes MT. Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration. Am J Physiol Cell Physiol 298: C893-C899, 2010. First published January 27, 2010; doi:10.1152/ajpcell.00224.2009.-Iodide is an important regulator of thyroid activity. Its excess elicits the Wolff-Chaikoff effect, characterized by an acute suppression of thyroid hormone synthesis, which has been ascribed to serum TSH reduction or TGF-beta increase and production of iodolipids in the thyroid. These alterations take hours/days to occur, contrasting with the promptness of Wolff-Chaikoff effect. We investigated whether acute iodide administration could trigger events that precede those changes, such as reduction of sodium-iodide symporter (NIS) mRNA abundance and adenylation, and if perchlorate treatment could counteract them. Rats subjected or not to methylmercaptoimidazole treatment (0.03%) received NaI (2,000 mu g/0.5 ml saline) or saline intraperitoneally and were killed 30 min up to 24 h later. Another set of animals was treated with iodide and perchlorate, in equimolar doses. NIS mRNA content was evaluated by Northern blotting and real-time PCR, and NIS mRNA poly(A) tail length by rapid amplification of cDNA ends-poly(A) test (RACE-PAT). We observed that NIS mRNA abundance and poly(A) tail length were significantly reduced in all periods of iodide treatment. Perchlorate reversed these effects, indicating that iodide was the agent that triggered the modifications observed. Since the poly(A) tail length of mRNAs is directly associated with their stability and translation efficiency, we can assume that the rapid decay of NIS mRNA abundance observed was due to a reduction of its stability, a condition in which its translation could be impaired. Our data show for the first time that iodide regulates NIS mRNA expression at posttranscriptional level, providing a new mechanism by which iodide exerts its autoregulatory effect on thyroid.

Involvement of Eukaryotic Translation Initiation Factor 5A (eIF5A) in Skeletal Muscle Stem Cell Differentiation

The eukaryotic translation initiation factor 5A (eIF5A) contains a special amino acid residue named hypusine that is required for its activity, being produced by a post-translational modification using spermidine as substrate. Stem cells from rat skeletal muscles (satellite cells) were submitted to differentiation and an increase of eIF5A gene expression was observed. Higher content of eIF5A protein was found in satellite cells on differentiation in comparison to non-differentiated satellite cells and skeletal muscle. The treatment with NI-guanyl- 1,7-diaminoheptane (GC7), a hypusination inhibitor, reversibly abolished the differentiation process. In association with the differentiation blockage, an increase of glucose consumption and lactate production and a decrease of glucose and palmitic acid oxidation were observed. A reduction in cell proliferation and protein synthesis was also observed. L-Arginine, a spermidine precursor and partial suppressor of muscle dystrophic phenotype, partially abolished the GC7 inhibitory effect on satellite cell differentiation. These results reveal a new physiological role for eIF5A and contribute to elucidate the molecular mechanisms involved in muscle regeneration.

Using metrics from complex networks to evaluate machine translation

Establishing metrics to assess machine translation (MT) systems automatically is now crucial owing to the widespread use of MT over the web. In this study we show that such evaluation can be done by modeling text as complex networks. Specifically, we extend our previous work by employing additional metrics of complex networks, whose results were used as input for machine learning methods and allowed MT texts of distinct qualities to be distinguished. Also shown is that the node-to-node mapping between source and target texts (English-Portuguese and Spanish-Portuguese pairs) can be improved by adding further hierarchical levels for the metrics out-degree, in-degree, hierarchical common degree, cluster coefficient, inter-ring degree, intra-ring degree and convergence ratio. The results presented here amount to a proof-of-principle that the possible capturing of a wider context with the hierarchical levels may be combined with machine learning methods to yield an approach for assessing the quality of MT systems. (C) 2010 Elsevier B.V. All rights reserved.

ENO adaptive method for solving one-dimensional conservation laws

In this work an efficient third order non-linear finite difference scheme for solving adaptively hyperbolic systems of one-dimensional conservation laws is developed. The method is based oil applying to the solution of the differential equation an interpolating wavelet transform at each time step, generating a multilevel representation for the solution, which is thresholded and a sparse point representation is generated. The numerical fluxes obtained by a Lax-Friedrichs flux splitting are evaluated oil the sparse grid by an essentially non-oscillatory (ENO) approximation, which chooses the locally smoothest stencil among all the possibilities for each point of the sparse grid. The time evolution of the differential operator is done on this sparse representation by a total variation diminishing (TVD) Runge-Kutta method. Four classical examples of initial value problems for the Euler equations of gas dynamics are accurately solved and their sparse solutions are analyzed with respect to the threshold parameters, confirming the efficiency of the wavelet transform as an adaptive grid generation technique. (C) 2008 IMACS. Published by Elsevier B.V. All rights reserved.

Translation, Communication and 'Learning' : Experiences from teaching a master program in Viet Nam

In Vietnam, as in other Asian countries, co-operation with foreign universities plays an important role for the development of higher education. This paper is based on personal experiences from teaching a Swedish Master Programme in Education Science at Vietnam National University in Hanoi. Using theories developed by Lev Vygotsky and Donald Schon, the programme is explored as an inter-cultural learning process. Three aspects are focused upon. Firstly, the fact that communication between students and teachers is conducted with the help of translators who support both teachers and students in their attempt to understand and make themselves understood. Secondly, the expressed need to connect the ideas and techniques which are studied in the programme to the students´ professional worlds. Thirdly, the need to construct a framework wherein the students can inquire into their own situations and to encourage them to try new and more productive ways to deal with problems they are confronted with.

Machine Translation and the Disruption of Foreign Language Learning Activities

This study examines the question of how language teachers in a highly technologyfriendly university environment view machine translation and the implications that this has for the personal learning environments of students. It brings an activity-theory perspective to the question, examining the ways that the introduction of new tools can disrupt the relationship between different elements in an activity system. This perspective opens up for an investigation of the ways that new tools have the potential to fundamentally alter traditional learning activities. In questionnaires and group discussions, respondents showed general agreement that although use of machine translation by students could be considered cheating, students are bound to use it anyway, and suggested that teachers focus on the kinds of skills students would need when using machine translation and design assignments and exams to practice and assess these skills. The results of the empirical study are used to reflect upon questions of what the roles of teachers and students are in a context where many of the skills that a person needs to be able to interact in a foreign language increasingly can be outsourced to laptops and smartphones.

Knowledge translation in Uganda : a qualitative study of Ugandan midwives' and managers' perceived relevance of the sub-elements of the context cornerstone in the PARIHS framework

BACKGROUND: A large proportion of the annual 3.3 million neonatal deaths could be averted if there was a high uptake of basic evidence-based practices. In order to overcome this 'know-do' gap, there is an urgent need for in-depth understanding of knowledge translation (KT). A major factor to consider in the successful translation of knowledge into practice is the influence of organizational context. A theoretical framework highlighting this process is Promoting Action on Research Implementation in Health Services (PARIHS). However, research linked to this framework has almost exclusively been conducted in high-income countries. Therefore, the objective of this study was to examine the perceived relevance of the subelements of the organizational context cornerstone of the PARIHS framework, and also whether other factors in the organizational context were perceived to influence KT in a specific low-income setting. METHODS: This qualitative study was conducted in a district of Uganda, where focus group discussions and semi-structured interviews were conducted with midwives (n = 18) and managers (n = 5) within the catchment area of the general hospital. The interview guide was developed based on the context sub-elements in the PARIHS framework (receptive context, culture, leadership, and evaluation). Interviews were transcribed verbatim, followed by directed content analysis of the data. RESULTS: The sub-elements of organizational context in the PARIHS framework--i.e., receptive context, culture, leadership, and evaluation--also appear to be relevant in a low-income setting like Uganda, but there are additional factors to consider. Access to resources, commitment and informal payment, and community involvement were all perceived to play important roles for successful KT. CONCLUSIONS: In further development of the context assessment tool, assessing factors for successful implementation of evidence in low-income settings--resources, community involvement, and commitment and informal payment--should be considered for inclusion. For low-income settings, resources are of significant importance, and might be considered as a separate subelement of the PARIHS framework as a whole.

Swedish translation and psychometric testing of the safety attitudes questionnaire (operating room version)

Background: Tens of millions of patients worldwide suffer from avoidable disabling injuries and death every year. Measuring the safety climate in health care is an important step in improving patient safety. The most commonly used instrument to measure safety climate is the Safety Attitudes Questionnaire (SAQ). The aim of the present study was to establish the validity and reliability of the translated version of the SAQ. Methods: The SAQ was translated and adapted to the Swedish context. The survey was then carried out with 374 respondents in the operating room (OR) setting. Data was received from three hospitals, a total of 237 responses. Cronbach's alpha and confirmatory factor analysis (CFA) was used to evaluate the reliability and validity of the instrument. Results: The Cronbach's alpha values for each of the factors of the SAQ ranged between 0.59 and 0.83. The CFA and its goodness-of-fit indices (SRMR 0.055, RMSEA 0.043, CFI 0.98) showed good model fit. Intercorrelations between the factors safety climate, teamwork climate, job satisfaction, perceptions of management, and working conditions showed moderate to high correlation with each other. The factor stress recognition had no significant correlation with teamwork climate, perception of management, or job satisfaction. Conclusions: Therefore, the Swedish translation and psychometric testing of the SAQ (OR version) has good construct validity. However, the reliability analysis suggested that some of the items need further refinement to establish sound internal consistency. As suggested by previous research, the SAQ is potentially a useful tool for evaluating safety climate. However, further psychometric testing is required with larger samples to establish the psychometric properties of the instrument for use in Sweden.

Process evaluation of a knowledge translation intervention using facilitation of local stakeholder groups to improve neonatal survival in the Quang Ninh province, Vietnam

BACKGROUND: Annually, 2.8 million neonatal deaths occur worldwide, despite the fact that three-quarters of them could be prevented if available evidence-based interventions were used. Facilitation of community groups has been recognized as a promising method to translate knowledge into practice. In northern Vietnam, the Neonatal Health - Knowledge Into Practice trial evaluated facilitation of community groups (2008-2011) and succeeded in reducing the neonatal mortality rate (adjusted odds ratio, 0.51; 95 % confidence interval 0.30-0.89). The aim of this paper is to report on the process (implementation and mechanism of impact) of this intervention. METHODS: Process data were excerpted from diary information from meetings with facilitators and intervention groups, and from supervisor records of monthly meetings with facilitators. Data were analyzed using descriptive statistics. An evaluation including attributes and skills of facilitators (e.g., group management, communication, and commitment) was performed at the end of the intervention using a six-item instrument. Odds ratios were analyzed, adjusted for cluster randomization using general linear mixed models. RESULTS: To ensure eight active facilitators over 3 years, 11 Women's Union representatives were recruited and trained. Of the 44 intervention groups, composed of health staff and commune stakeholders, 43 completed their activities until the end of the study. In total, 95 % (n = 1508) of the intended monthly meetings with an intervention group and a facilitator were conducted. The overall attendance of intervention group members was 86 %. The groups identified 32 unique problems and implemented 39 unique actions. The identified problems targeted health issues concerning both women and neonates. Actions implemented were mainly communication activities. Communes supported by a group with a facilitator who was rated high on attributes and skills (n = 27) had lower odds of neonatal mortality (odds ratio, 0.37; 95 % confidence interval, 0.19-0.73) than control communes (n = 46). CONCLUSIONS: This evaluation identified several factors that might have influenced the outcomes of the trial: continuity of intervention groups' work, adequate attributes and skills of facilitators, and targeting problems along a continuum of care. Such factors are important to consider in scaling-up efforts.

Laws of large numbers for non-additive probabilities

We apply the concept of exchangeable random variables to the case of non-additive robability distributions exhibiting ncertainty aversion, and in the lass generated bya convex core convex non-additive probabilities, ith a convex core). We are able to rove two versions of the law of arge numbers (de Finetti's heorems). By making use of two efinitions. of independence we rove two versions of the strong law f large numbers. It turns out that e cannot assure the convergence of he sample averages to a constant. e then modal the case there is a true" probability distribution ehind the successive realizations of the uncertain random variable. In this case convergence occurs. This result is important because it renders true the intuition that it is possible "to learn" the "true" additive distribution behind an uncertain event if one repeatedly observes it (a sufficiently large number of times). We also provide a conjecture regarding the "Iearning" (or updating) process above, and prove a partia I result for the case of Dempster-Shafer updating rule and binomial trials.

Disputing the application of laws: the constitutionality of the Brazilian Statute against domestic violence in the courts

This study aimed to map the key positions regarding the constitutionality of the Maria da Penha Law (Law 11.340/2006) in the Brazilian judicial system. The law, the result of political struggles by the Brazilian feminist movement, has been the subject of discussions in the public sphere and actions aimed at consolidating its constitutionality before the Federal Supreme Court. We examined and discussed the arguments used in the Courts, intending to show that the creation of law is not limited to the legislative moment, but rather that its social meaning is also constituted through disputes within the Judiciary.

Production of active recombinant eIF5A: reconstitution in E.coli of eukaryotic hypusine modification of eIF5A by its coexpression with modifying enzymes

Eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein that contains the polyamine-modified lysine, hypusine [N(epsilon)-(4-amino-2-hydroxybutyl)lysine]. Hypusine occurs only in eukaryotes and certain archaea, but not in eubacteria. It is formed post-translationally by two consecutive enzymatic reactions catalyzed by deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). Hypusine modification is essential for the activity of eIF5A and for eukaryotic cell proliferation. eIF5A binds to the ribosome and stimulates translation in a hypusine-dependent manner, but its mode of action in translation is not well understood. Since quantities of highly pure hypusine-modified eIF5A is desired for structural studies as well as for determination of its binding sites on the ribosome, we have used a polycistronic vector, pST39, to express eIF5A alone, or to co-express human eIF5A-1 with DHS or with both DHS and DOHH in Escherichia coli cells, to engineer recombinant proteins, unmodified eIF5A, deoxyhypusine- or hypusine-modified eIF5A. We have accomplished production of three different forms of recombinant eIF5A in high quantity and purity. The recombinant hypusine-modified eIF5A was as active in methionyl-puromycin synthesis as the native, eIF5A (hypusine form) purified from mammalian tissue. The recombinant eIF5A proteins will be useful tools in future structure/function and the mechanism studies in translation.

Is there a role for eIF5A in translation?

The putative translation factor eIF5A is essential for cell viability and is highly conserved from archaebacteria to mammals. This factor is the only cellular protein that undergoes an essential posttranslational modification dependent on the polyamine spermidine, called hypusination. This review focuses on the functional characterization of eIF5A. Although this protein was originally identified as a translation initiation factor, subsequent studies did not support a role for eIF5A in general translation initiation. eIF5A has also been implicated in nuclear export of HIV-1 Rev and mRNA decay, but these findings are controversial in the literature and may reflect secondary effects of eIF-5A function. Next, the involvement of eIF5A and hypusination in the control of the cell cycle and proliferation in various organisms is reviewed. Finally, recent evidence in favor of reconsidering the role of eIF5A as a translation factor is discussed. Future studies may reveal the specific mechanism by which eIF5A affects protein synthesis.

Sensitivity analysis by neural networks applied to power systems transient stability

This work presents a procedure for transient stability analysis and preventive control of electric power systems, which is formulated by a multilayer feedforward neural network. The neural network training is realized by using the back-propagation algorithm with fuzzy controller and adaptation of the inclination and translation parameters of the nonlinear function. These procedures provide a faster convergence and more precise results, if compared to the traditional back-propagation algorithm. The adaptation of the training rate is effectuated by using the information of the global error and global error variation. After finishing the training, the neural network is capable of estimating the security margin and the sensitivity analysis. Considering this information, it is possible to develop a method for the realization of the security correction (preventive control) for levels considered appropriate to the system, based on generation reallocation and load shedding. An application for a multimachine power system is presented to illustrate the proposed methodology. (c) 2006 Elsevier B.V. All rights reserved.

New laws for author's rights: adequate for digital preservation?

Introduction. Besides technical and economic-organisational problems, digital preservation also faces legal issues, especially regarding copyright legislation, since all digital preservation strategies involve copying materials and/or using software which is typically copyrighted. The purpose of this paper is to ascertain the extent to which current copyright laws meet the preservation requirements of library materials..Methodology. A cross-sectional analysis of recently updated national copyright laws as well as the impact of the other two protection methods: contractual and technological.Results. Even after the latest updates current copyright legislation is almost useless for digital preservation activities since the opportunities provided by WIPO Copyright Treaty to adapt and extend copyright exceptions and limitations have been used to the full.Conclusion. We need a legislation reform that will make it possible to carry out all required copying and communication activities and software use, even if circumventing technological protection is needed. But that is not enough for licensed works. The best solution for this kind of work is to include specific clauses in the licences that facilitate preservation activities. Thus, cooperation between both parties, libraries and rights' holders, is essential.