CDT, GGT, and AST as markers of alcohol use: The WHO/ISBRA Collaborative Project

Background: Estimates of the performance of carbohydrate deficient transferrin (CDT) and gamma glutamyltransferase (GGT) as markers of alcohol consumption have varied widely. Studies have differed in design and subject characteristics. The WHO/ISBRA Collaborative Study allows assessment and comparison of CDT, GGT, and aspartate aminotransferase (AST) as markers of drinking in a large, well-characterized, multicenter sample. Methods: A total of 1863 subjects were recruited from five countries (Australia, Brazil, Canada, Finland, and Japan). Recruitment was stratified by alcohol use, age, and sex. Demographic characteristics, alcohol consumption, and presence of ICD-10 dependence were recorded using an interview schedule based on the AUDADIS, CDT was assayed using CDTect(TM) and GGT and AST by standard methods. Statistical techniques included receiver operating characteristic (ROC) analysis. Multiple regression was used to measure the impact of factors other than alcohol on test performance. Results: CDT and GGT had comparable performance on ROC analysis, with AST performing slightly less well. CDT was a slightly but significantly better marker of high-risk consumption in men. All were more effective for detection of high-risk rather than intermediate-risk drinking. CDT and GGT levels were influenced by body mass index, sex, age, and smoking status. Conclusions: CDT was little better than GGT in detecting high- or intermediate-risk alcohol consumption in this large, multicenter, predominantly community-based sample. As the two tests are relatively independent of each other, their combination is likely to provide better performance than either test alone, Test interpretation should take account sex, age. and body mass index.

Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A

Chk1 kinase coordinates cell cycle progression and preserves genome integrity. Here, we show that chemical or genetic ablation of human Chk1 triggered supraphysiological accumulation of the S phase-promoting Cdc25A phosphatase, prevented ionizing radiation (IR)-induced degradation of Cdc25A, and caused radioresistant DNA synthesis (RDS). The basal turnover of Cdc25A operating in unperturbed S phase required Chk1-dependent phosphorylation of serines 123, 178, 278, and 292. IR-induced acceleration of Cdc25A proteolysis correlated with increased phosphate incorporation into these residues generated by a combined action of Chk1 and Chk2 kinases. Finally, phosphorylation of Chk1 by ATM was required to fully accelerate the IR-induced degradation of Cdc25A. Our results provide evidence that the mammalian S phase checkpoint functions via amplification of physiologically operating, Chk1-dependent mechanisms.

Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation

In mammals, the ATM (ataxia-telangiectasia-mutated) and ATR (ATM and Rad3-related) protein kinases function as critical regulators of the cellular DNA damage response. The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2. In mammalian cells, evidence has been presented that Chk1 is devoted to the ATR signaling pathway and is modified by ATR in response to replication inhibition and UV-induced damage, whereas Chk2 functions primarily through ATM in response to ionizing radiation (IR), suggesting that Chk2 and Chk1 might have evolved to channel the DNA damage signal from ATM and ATR, respectively. We demonstrate here that the ATR-Chk1 and ATM-Chk2 pathways are not parallel branches of the DNA damage response pathway but instead show a high degree of cross-talk and connectivity. ATM does in fact signal to Chk1 in response to IR. Phosphorylation of Chk1 on Ser-317 in response to IR is ATM-dependent. We also show that functional NBS1 is required for phosphorylation of Chk1, indicating that NES1 might facilitate the access of Chk1 to ATM at the sites of DNA damage. Abrogation of Chk1 expression by RNA interference resulted in defects in IR-induced S and G2/M phase checkpoints; however, the overexpression of phosphorylation site mutant (S317A, S345A or S317A/S345A double mutant) Chk1 failed to interfere with these checkpoints. Surprisingly, the kinase-dead Chk1 (D130A) also failed to abrogate the S and G2 checkpoint through any obvious dominant negative effect toward endogenous Chk1. Therefore, further studies will be required to assess the contribution made by phosphorylation events to Chk1 regulation. Overall, the data presented in the study challenge the model in which Chk1 only functions downstream from ATR and indicate that ATM does signal to Chk1. In addition, this study also demonstrates that Chk1 is essential for IR-induced inhibition of DNA synthesis and the G2/M checkpoint.

Expression analysis of four Pinus radiata male cone promoters in the heterologous host Arabidopsis

Four male cone-specific promoters were isolated from the genome of Pinus radiata D. Don, fused to the beta-glucuronidase (GUS) reporter gene and analysed in the heterologous host Arabidopsis thaliana (L.) Heynh. The temporal and spatial activities of the promoters PrCHS1, PrLTP2, PrMC2 and PrMALE1 during seven anther developmental stages are described in detail. The two promoters PrMC2 and PrMALE1 confer an identical GUS expression pattern on Arabidopsis anthers. DNA sequence analysis of the PrMC2 and PrMALE1 promoters revealed an 88% sequence identity over 276 bp and divergence further upstream (

Five generations of peace operations: from the "thin blue line" to "painting a country blue"

This article combines both international practice and analytical contributions into a systematic and synthetic presentation of the evolution of peace operations from their modern inception in 1948 to the present. It seeks to serve a didactic purpose in proposing a basic structure for Brazilian scholars' burgeoning debate on peace operations and intervention, rather than a definitive characterization of blue helmet practice. Peace operations' progression is traced through five analytical "generations," each adding a crucial factor distinguishing it from its predecessors. Each generation is placed in relation to changes in the nature of conflict and in the interpretation of the foundational principles of peace operations, and links to broader theoretical issues in International Relations are made explicit at each stage.

Discourses of cyberspace securitization in Brazil and in the United States

Abstract This paper uses the framework of the Copenhagen School to understand the process of securitization of cyberspace, exploring how something in such sphere becomes a threat. Seeking to contribute to the debate, this study analyses the securitization discourses of Brazil and of the United States from Hansen and Nissenbaum's (2009) theorization about the existence of a specific sector for cybersecurity. To comprehend the securitization of cyberspace in these terms allows not only to identify distinct levels of securitization, but also to capture the dynamics of cyber threats, distinguishing them from those existent in other sectors, as well as to trace distinctions between tendencies of securitization and militarization.

Linguística funcional e tradução

No âmbito da tradução nas suas múltiplas vertentes e face às diferentes abordagens que nem sempre se articulam de maneira inequívoca, é conveniente termos referências bem definidas. A linguística na linha de André Martinet1, que elabora sobre o funcionamento de um sistema linguístico de forma simples e nãonormativa, parece-nos fornecer uma excelente base para quem estuda e trabalha em tradução e, em geral, na área das Línguas. A abordagem em questão é aplicável aos fenómenos linguísticos, nomeadamente aos níveis fonológico e morfo-sintáctico. A ponte para abordagens de carácter semântico-pragmático pode estabelecer-se através do plano da axiologia - área intermédia entre sintaxe e semântica - em que conseguimos operar com elementos discretos, intimamente ligados aos processos da significação. Veremos, no esboço que se segue, como se pode, num primeiro momento, analisar um determinado fenómeno gramatical existente em dois sistemas linguísticos. Vamos concentrar-nos no conjuntivo em alemão e em português, tendo em linha de conta os princípios da linguística martinetiana.

Em vez dos elementos

O artigo pode ser lido como uma pequena introdução à linguística funcionalista martinetiana. Consiste numa breve apresentação comentada de alguns dos conceitos fundamentais (monema, dupla articulação, relação funcional, valor axiológico) da obra ―Elementos de Linguística Geral―1 aplicada, nas suas exemplificações, à língua alemã. Consideramos a abordagem de André Martinet digna de ser conhecida por todos os estudantes e interessados da linguística. Descreve e explica, de forma não-dogmática e simples, o funcionamento de um sistema linguístico, isto é, de uma língua humana (no original, da língua francesa), facilita o entendimento da dinâmica desse mesmo sistema e abre caminho para abordagens científicas (operação com elementos discretos, segmentação, comutação), também ao nível da significação.

Transtextualidade na tradução de "Der mann im fahrstuhl / The mann in the elevator"

In an age where Babel has turned into transcultural communication, an interlingual approach – i.e. in English and in French – to the translating process from German to Portuguese appeared pertinent. Aiming at a refinement of the translating competence, this process consists in contrasting different linguistic and literary strategies through an intercultural and multi-etymological perspective. Thus, we settled upon Heiner Müller‘s play Der Auftrag. Erinnerung an eine Revolution (1980), on which the composer Heiner Goebbels has based himself to textually and musically dramatize an excerpt, Der Mann im Farhstuhl / The Man in the Elevator. A transcription of such excerpt in its source language, German, as well as its translation into English (Carl Weber, 1984, Performing Arts Publications, New York) and French (Jean Jourdheuil, Heinz Schwarzinger, Editions Minuit, Paris) can be found in the booklet that accompanies the CD – edited in 1988 by ECD (München: Records GmbH). It should be emphasized that such a creation allows a framing of Müller‘s text into a musical scenography and, therefore, encourages an intersemiotic contrast. This experience enabled us to come up with a unique imagery of Müller‘s piece of writing, by means of its dramatic and musical conversion and, simultaneously, lead us to stretch our textual consciousness to a multitude of intra-, extra- and interlinguistic elements.

Melhoria energética do sector de soda leve conforme a nova metodologia manufacturing excellence solvay Portugal

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

[Editorial] Current challenges in modeling cellular metabolism

The authors would like to thank the financial support from the NovoNordiskFoundation.

A narrativa da liderança escolar: os alunos como agentes de revelação

Publicado em "Educação, territórios e desenvolvimento humano: atas do I Seminário Internacional, Vol. I – conferências e intervenções". ISBN 978-989-96186-9-5

Current Challenges in Modeling Cellular Metabolism

Mathematical and computational models play an essential role in understanding the cellular metabolism. They are used as platforms to integrate current knowledge on a biological system and to systematically test and predict the effect of manipulations to such systems. The recent advances in genome sequencing techniques have facilitated the reconstruction of genome-scale metabolic networks for a wide variety of organisms from microbes to human cells. These models have been successfully used in multiple biotechnological applications. Despite these advancements, modeling cellular metabolism still presents many challenges. The aim of this Research Topic is not only to expose and consolidate the state-of-the-art in metabolic modeling approaches, but also to push this frontier beyond the current edge through the introduction of innovative solutions. The articles presented in this e-book address some of the main challenges in the field, including the integration of different modeling formalisms, the integration of heterogeneous data sources into metabolic models, explicit representation of other biological processes during phenotype simulation, and standardization efforts in the representation of metabolic models and simulation results.

Anfragetechniken für heterogene Datenbanksysteme

Magdeburg, Univ., Fak. für Informatik, Habil.-Schr., 2003

Beitrag zur verteilten und adaptiven Materialflusssteuerung für Stückguttransport

Magdeburg, Univ., Fak. für Maschinenbau, Diss., 2003