Is the current EU climate instrument mix adequate?

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Investigations of Pyrrole-Imidazole Polyamide Effects on DNA Replication

Pyrrole–Imidazole polyamides are programmable, cell-permeable small molecules that bind in the minor groove of double-stranded DNA sequence-specifically. Polyamide binding has been shown to alter the local helical structure of DNA, disrupt protein-DNA interactions, and modulate endogenous gene expression. Py–Im polyamides targeted to the androgen receptor-DNA interface have been observed to decrease expression of androgen-regulated genes, upregulate p53, and induce apoptosis in a hormone-sensitive prostate cancer cell line. Here we report that androgen response element (ARE)-targeted polyamides induced DNA replication stress in a hormone-insensitive prostate cancer cell line. The ATR checkpoint kinase was activated in response to this stress, causing phosphorylation of MCM2, and FANCD2 was monoubiquitinated. Surprisingly, little single-stranded DNA was exhibited, and the ATR targets RPA2 and Chk1 were not phosphorylated. We conclude that polyamide induces relatively low level replication stress, and suggest inhibition of the replicative helicase as a putative mechanism based on in vitro assays. We also demonstrate polyamide-induced inhibition of DNA replication in cell free extracts from X. laevis oocytes. In this system, inhibition of chromatin decondensation is observed, preventing DNA replication initiation. Finally, we show that Py-Im polyamides targeted to the ARE and ETS binding sequence downregulate AR- and ERG-driven signaling in a prostate cancer cell line harboring the TMPRSS2-ERG fusion. In a mouse xenograft model, ARE-targeted polyamide treatment reduced growth of the tumor.

Redução de carga orgânica recalcitrante de efluente de indústria gráfica por reação de fenton

A Casa da Moeda do Brasil (CMB) é uma empresa nacional, com mais de 300 anos de experiência na produção de valores e impressos de segurança. A produção de cédulas, realizada pelo Departamento de Cédulas (DECED), consiste de três etapas de impressão, off-set, calografia e tipografia, seguida de acabamento e embalagem semi-automatizado. A impressão calcográfica consome solução de limpeza, composta de soda cáustica e óleo sulfonado, para limpeza do cilindro de impressão, gerando um efluente líquido saturado de tinta. Este efluente apresenta baixa biodegradabilidade, apresentando uma relação DBO / DQO de aproximadamente 1:4. Em termos de tratabilidade, as estações de tratamento de efluentes (ETE) apresentam uma configuração convencional, por via biológica, demonstram pouca eficiência na degradação da matéria orgânica deste efluente. Com compostos recalcitrantes, torna-se necessária a inclusão de uma etapa terciária que permita sua degradação por via química, permitindo o descarte do efluente com características menos danosas ao ambiente. Neste trabalho, aplicou-se a reação de Fenton no efluente do DECED por sua capacidade de converter a matéria orgânica em gás carbônico e água ou, caso seja utilizado em pré-tratamentos, torna-os biodegradáveis. Foram estudadas diferentes condições para medir a influência de diferentes parâmetros na eficiência da reação. A reação de Fenton consiste na geração de radicais hidroxil (HO), por diferentes rotas, em quantidades suficientes para a degradação de matéria orgânica. Esses radicais são gerados a partir de peróxido de hidrogênio (H2O2) em reações com diferentes precursores como ozônio (O3), luz UV (ultravioleta), ultra-som e sais de ferro. No presente trabalho restringiu-se às reações com sais de ferro. Dentre os resultados obtidos, verificou-se o tempo mínimo para reação em 10 minutos. A relação entre íons ferro e peróxido de hidrogênio é menor do que a literatura normalmente sugere, 1:2, contra 1:3. Como a solução de sulfato ferroso é muito instável, passando os íons ferrosos a férricos, utilizou-se a adição direta do sal. Em escala industrial, a solução de sulfato ferroso deve ser preparada em poucas quantidades para que tenha baixo tempo de estocagem, a fim de não ser degradada. A temperatura, na faixa estudada (de 20C à 45C), é um parâmetro que tem pouca influência, pois a redução da eficiência da reação foi pequena (de 99,0% para 94,9%). O ferro utilizado na reação não se demonstrou uma nova fonte de transtornos para o ambiente. Nas condições utilizadas, a concentração de ferro residual esteve próxima ao limite permitido pela legislação no efluente tratado, necessitando apenas de alguns ajustes para a correção do problema

Heterogeneous catalysts for biodiesel production

The production of biodiesel is greatly increasing due to its enviromental benefits. However, production costs are still rather high, compared to petroleum-based diesel fuel. The introduction of a solid heterogeneous catalyst in biodiesel production could reduce its price, becoming competitive with diesel also from a financial point of view. Therefore, great research efforts have been underway recently to find the right catalysts. This paper will be concerned with reviewing acid and basic heterogeneous catalyst performances for biodiesel production, examining both scientific and patent literature.

Structure and properties of microporous titanosilicate determined by first-principles calculations

The structure of EST-10, a member of synthetic microporous titanosilicates, was recently determined by an ingenious combination of experimental and simulational techniques. However, the locations of the alkali atoms in the framework remain elusive and its electronic structure is totally unknown. Based on first-principles local density calculations, the possible locations of the alkali atoms are identified and its electronic structure and bonding fully elucidated. ETS-10 is a semiconductor with a direct band gap of 2.33 eV. The Na atoms are likely to locate inside the seven-member ring pore adjacent to the one-dimensional Ti-O-Ti-O- chain.

Cloning, characterization, and expression analysis of extracellular copper/zinc superoxide dismutase gene from bay scallop Argopecten irradians

Extracellular superoxide dismutase (ECSOD) is a major extracellular antioxidant enzyme that protects organs from damage by reactive oxygen species (ROS). We cloned a novel ECSOD from the bay scallop Argopecten irradians (AiECSOD) by 3' and 5' RACE. The full-length cDNA of AiECSOD was 893 bp with a 657 bp open reading frame encoding 218 amino acids. The deduced amino acid sequence contained a putative signal peptide of 20 amino acids, and sequence comparison showed that AiECSOD had low degree of homology to ECSODs of other organisms. The genomic length of the AiECSOD gene was about 5276 bp containing five exons and six introns. The promoter region contained many putative transcription factor binding sites such as c-Myb, Oct-1, Sp1, Kruppel-like, c-ETS, NF kappa B, GATA-1, AP-1, and Ubx binding sites. Furthermore, tissue-specific expressions of AiECSOD and temporal expressions of AiECSOD in haemocytes of bay scallops challenged with bacteria Vibrio anguillarum were quantified using qRT-PCR. High levels of expression were detected in haemocytes, but not in gonad and mantle. The expression of AiECSOD reached the highest level at 12 h post-injection with V. anguillarum and then returned to normal between 24 h and 48 h post-injection. These results indicated that AiECSOD was an inducible protein and that it may play an important role in the immune responses against V anguillarum. Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.

Tecnologias CAC e Inquéritos de Percepção da Opinião Pública sobre “O papel da Captação e do Armazenamento/Sequestração de Dióxido de Carbono no Futuro da Energia na Europa”:O caso-de-estudo da Comunidade Fernando Pessoa

O carvão e outros combustíveis fósseis, continuarão a ser, por décadas, a principal matéria-prima energética para as Centrais Térmicas, não obstante os esforços para, dentro do possível, substituir os combustíveis fósseis por fontes de energia renovável.Tal como está, hoje, bem documentado, a produção de gases com efeito estufa (GEE), designadamente CO2, resulta da combustão dos ditos combustíveis fósseis, sendo que se espera ser possível mitigar substancialmente a emissão de tais gases com a aplicação das chamadas Tecnologias Limpas do Carvão.Há, pois, necessidade de promover o abatimento do CO2 através de Tecnologias de Emissão Zero ou Tecnologias Livres de Carbono, incluindo designadamente a Captura, o Transporte e a Sequestração geológica de CO2 correspondentes ao que é costume designar por Tecnologias CAC (Captação e Armazenamento de Carbono). De facto, tais tecnologias e, designadamente, o armazenamento geológico de CO2 são as únicas que, no estado actual do conhecimento, são capazes de permitir que se cumpram as metas do ambicioso programa da EU para a energia e o ambiente conhecido por “20 20 para 2020” em conjugação com os aspectos económicos das directivas relativas ao Comércio Europeu de Licenças de Emissão – CELE (Directivas 2003/87/EC, 2004/101/EC e 2009/29/EC).A importância do tema está, aliás, bem demonstrada com o facto da Comissão Europeia ter formalmente admitido que as metas supracitadas serão impossíveis de atingir sem Sequestração Geológica de CO2. Esta é, pois, uma das razões de ter sido recentemente publicada a Directiva Europeia 2009/31/EC de 23 de Abril de 2009 expressamente dedicada ao tema do Armazenamento Geológico de CO2.Ora, a questão do armazenamento geológico de CO2 implica, para além das Tecnologias CAC acima mencionadas e da sua viabilização em termos tanto técnicos como económicos, ou seja, neste último aspecto, competitiva com o sistema CELE, também o conhecimento, da percepção pública sobre o assunto. Isto é, a praticabilidade das Tecnologias CAC implica que se conheça a opinião pública sobre o tema e, naturalmente, que face a esta realidade se prestem os esclarecimentos necessários como, aliás, é reconhecido na própria Directiva Europeia 2009/31/EC.Dado que a Fundação Fernando Pessoa / Universidade Fernando Pessoa através do seu Centro de Investigação em Alterações Globais, Energia, Ambiente e Bioengenharia – CIAGEB tem ultimado um Projecto de Engenharia relativo à Sequestração Geológica de CO2 nos Carvões (Metantracites) da Bacia Carbonífera do Douro – o Projecto COSEQ, preocupou-se naturalmente, desde o início, com o lançamento de inquéritos de percepção da opinião pública sobre o assunto.Tal implicou, nesta fase, a tradução para português e o lançamento do inquérito europeu ACCSEPT que não tinha sido ainda formalmente lançado de forma generalizada entre nós. Antes, porém, de lançar publicamente tal inquérito – o que está actualmente já em curso – resolveu-se testar o método de lançamento, a recolha de dados e o seu tratamento com uma amostra correspondente ao que se designou por Comunidade Fernando Pessoa, i.e. o conjunto de docentes, discentes, funcionários e outras pessoas relacionadas com a Universidade Fernando Pessoa (cerca de 5000 individualidades).Este trabalho diz, precisamente, respeito à preparação, lançamento e análise dos resultados do dito inquérito Europeu ACCSEPT a nível da Comunidade Fernando Pessoa. Foram recebidas 525 respostas representando 10,5% da amostra. A análise de resultados foi sistematicamente comparada com os obtidos nos outros países europeus, através do projecto ACCSEPT e, bem assim, com os resultados obtidos num inquérito homólogo lançado no Brasil. The use of coal, and other fossil fuels, will remain for decades as the main source of energy for power generation, despite the important efforts made to replace, as far as possible, fossil fuels with renewable power sources.As is well documented, the production of Greenhouse Gases (GHG), mainly CO2, arises primarily from the combustion of fossil fuels. The increasing application of Clean Coal Technologies-CCTs, is expected to mitigate substantially against the emission of such gases.There is consequently a need to promote the CO2 abatement through Zero Emission (Carbon Free) Technologies - ZETs, which includes CO2 capture, transport and geological storage, i.e. the so-called CCS (Carbon, Capture and Storage) technologies. In fact, these technologies are the only ones that are presently able to conform to the ambitious EU targets set out under the “20 20 by 2020” EU energy and environment programme, jointly with the economic aspects of the EU Directives 2003/87/EC, 2004/101/EC and 2009/29/EC concerned with the Greenhouse Gas Emissions Allowance Trading Scheme – ETS scheme. The European Commission formal admission that the referred targets will be impossible to reach without the implementation and contribution of geological storage clearly demonstrate the importance of this particular issue, and for this reason the EC Directive 2009/31/EC of April 23, 2009 on Geological Storage of CO2 was recently published.In considering the technical and economical viabilities of CCS technologies, the latter in competition with the ETS scheme, it is believed that public perception will dictate the success of the development and implementation of CO2 geological storage at a large industrial level. This means that, in order to successfully implement CCS technologies, not only must public opinion be taken into consideration but objective information must also be provided to the public in order to raise subject awareness, as recognized in the referred Directive 2009/31/EC.In this context, the Fernando Pessoa Foundation / University Fernando Pessoa, through its CIAGEB (Global Change, Energy, Environment and Bioengineering) RDID&D Unit, is the sponsor of an Engineering Project for the Geological Sequestration of CO2 in Douro Coalfield Meta-anthracites - the COSEQ Project, and is therefore also engaged in public perception surveys with regards to CCS technologies.At this stage, the original European ACCSEPT inquiry was translated to Portuguese and submitted only to the “Fernando Pessoa Community” - comprising university lecturers, students, other employees, as well as, former students and persons that have a professional or academic relationship with the university (c. 5000 individuals). The results obtained from this first inquiry will be used to improve the survey informatics system in terms of communication, database, and data treatment prior to resubmission of the inquiry to the Portuguese public at large.The present publication summarizes the process and the results obtained from the ACCSEPT survey distributed to the “Fernando Pessoa Community”. 525 replies, representing 10.5% of the sample, have been received and analysed. The assessment of the results was systematically compared with those obtained from other European Countries, as reported by the ACCSEPT inquiry, as well as with those from an identical inquiry launched in Brazil.

A study of the regulation of Trib family members expression in normal and malignant haematopoiesis

The Tribbles family of genes consist of three members; TRIB1, TRIB2 and TRIB3. Trib1 and Trib2 have been identified as oncogenes that can induce AML in mice. However little is known about how the expressions of the Tribbles family genes are controlled in the cell during haematopoiesis or leukaemogenesis. To investigate the Tribbles genes in leukaemia a bioinformatics approach was used. TRIB2 expression was found to be elevated in T-ALL and ALL with t(1;19). TRIB1 was found not to be significantly elevated in any leukaemic subtypes. Analyses of the TRIB1 and TRIB2 gene signatures in both leukaemic and normal haematopoietic cells identified pathways and transcription factors associated with these signatures. Pathways enriched for the TRIB1 signature included TLR signalling pathways and NF-κB pathways. Transcription factors enriched for this signature include C/EBP and SRF. Enriched for the TRIB2 signature includes T cell signalling pathways and Notch signalling pathways. Transcription factors enriched for this signature include E2F and ETS. Further investigation in vitro confirmed the finding that E2F1 was as a potential regulator of TRIB2 expression. E2F1 is able to directly bind to the TRIB2 promoter region and induce TRIB2 expression. C/EBPα p42 was found to inhibit E2F1 and the p30 isoform was found to cooperate with E2F1 induced activation of the TRIB2 promoter. Indicating the potential presence of a regulatory loop involved in the regulation of the TRIB2 gene. In conclusion we have investigated the Tribbles gene signatures in both normal haematopoietic and leukaemic cells. This has led to the identification of a number of pathways and transcription factors associated with these genes. We have also identified a family of transcription factors directly responsible for the regulation of TRIB2 expression. This regulatory pathway has the potential to be targeted in the treatment of leukaemia with a high TRIB2 signature.

Characterization of the human and mouse ETV1/ER81 transcription factor genes: Role of the two alternatively spliced isoforms in the human

The Ets transcription factors of the PEA3 group - E1AF/PEA3, ETV1/ER81 and ERM - are almost identical in the ETS DNA-binding and the transcriptional acidic domains. To accelerate our understanding of the molecular basis of putative diseases linked to ETV1 such as Ewing's sarcoma we characterized the human ETV1 and the mouse ER81 genes. We showed that these genes are both encoded by 13 exons in more than 90 kbp genomic DNA, and that the classical acceptor and donor splicing sites are present in each junction except for the 5' donor site of intron 9 where GT is replaced by TT. The genomic organization of the ETS and acidic domains in the human ETV1 and mouse ER81 (localized to chromosome 12) genes is similar to that observed in human ERM and human E1AF/PEA3 genes. Moreover, as in human ERM and human E1AF/PEA3 genes, a first untranslated exon is upstream from the first methionine, and the mouse ER81 gene transcription is regulated by a 1.8 kbp of genomic DNA upstream from this exon. In human, the alternative splicing of the ETV1 gene leads to the presence (ETV1α) or the absence (ETV1β) of exon 5 encoding the C-terminal part of the transcriptional acidic domain, but without affecting the alpha helix previously described as crucial for transactivation. We demonstrated here that the truncated isoform (human ETV1β) and the full-length isoform (human ETV1α) bind similarly specific DNA Ets binding sites. Moreover, they both activate transcription similarly through the PKA-transduction pathway, so suggesting that this alternative splicing is not crucial for the function of this protein as a transcription factor. The comparison of human ETV1α and human ETV1β expression in the same tissues, such as the adrenal gland or the bladder, showed no clear-cut differences. Altogether, these data open a new avenue of investigation leading to a better understanding of the functional role of this transcription factor.

Les facteurs de transcription du groupe PEA3: Régulateurs transcriptionnels dans le processus de cancérisation

Erm, Er81, and Pea3 are the three members of the PEA3 group which belong to the Ets transcription factors family. These proteins regulate transcription of multiple target genes, such as those encoding several matrix metalloproteinases (MMP), which are enzymes degrading the extracellular matrix during cancer metastasis. In fact, PEA3-group genes are often overexpressed in different types of human cancers that also over-express these MMP and display a disseminating phenotype. In experimental models, regulation of PEA3 group member expression has been shown to influence the metastatic process, thus suggesting that these factors play a key role in metastasis. © John Libbey Eurotext.

The 26S proteasome system degrades the ERM transcription factor and regulates its transcription-enhancing activity

ERM is a member of the ETS transcription factor family. High levels of the corresponding mRNA are detected in a variety of human breast cancer cell lines, as well as in aggressive human breast tumors. As ERM protein is almost undetectable in these cells, high degradation of this transcription factor has been postulated. Here we have investigated whether ERM degradation might depend on the proteasome pathway. We show that endogenous and ectopically expressed ERM protein is short-lived protein and undergoes proteasome-dependent degradation. Deletion mutagenesis studies indicate that the 61 C-terminal amino acids of ERM are critical for its proteolysis and serve as a degradation signal. Although ERM conjugates with ubiquitin, this post-translational modification does not depend on the C-terminal domain. We have used an Ets-responsive ICAM-1 reporter plasmid to show that the ubiquitin-proteasome pathway can affect transcriptional function of ERM. Thus, ERM is subject to degradation via the 26S proteasome pathway, and this pathway probably plays an important role in regulating ERM transcriptional activity. © 2007 Nature Publishing Group. All rights reserved.

Solution structure of the N-terminal transactivation domain of ERM modified by SUMO-1.

ERM is a member of the PEA3 group of the Ets transcription factor family that plays important roles in development and tumorigenesis. The PEA3s share an N-terminal transactivation domain (TADn) whose activity is inhibited by small ubiquitin-like modifier (SUMO). However, the consequences of sumoylation and its underlying molecular mechanism remain unclear. The domain structure of ERM TADn alone or modified by SUMO-1 was analyzed using small-angle X-ray scattering (SAXS). Low resolution shapes determined ab initio from the scattering data indicated an elongated shape and an unstructured conformation of TADn in solution. Covalent attachment of SUMO-1 does not perturb the structure of TADn as indicated by the linear arrangement of the SUMO moiety with respect to TADn. Thus, ERM belongs to the growing family of proteins that contain intrinsically unstructured regions. The flexible nature of TADn may be instrumental for ERM recognition and binding to diverse molecular partners.

Two steps forward, one step back: developing the curriculum for training teachers for technical and further education England 1945-1956

This paper discusses the development of provision for the training of teachers in English further and technical education from 1945 to 1956. While these years saw little growth in this provision, they were formative in that the institutional and curricular patterns of teacher training for the diverse fields of technical and further education were developed at this time. The work of the three national centres in Bolton, London and Huddersfield, during the period of the Emergency Training Scheme (ETS) is summarised with particular reference to the influence of the Ministry of Education‟s conditions for ETS colleges and courses. With the ending of the ETS in 1951 the three centres were given permanent status as teacher training colleges which in turn brought them into association with their local universities as constituent colleges of their Area Training Organisations. The consequences of this transfer to the universities for the curriculum and assessment of technical teacher training and the 'policy dichotomy' of teacher training for secondary and technical education are examined.

Questions of 'h' in Northern Ireland: Breathing New Life on the Aspiration Theory

This paper considers existing ideas concerning pronunciation of the letter name for (LNH) in Northern Irish English (NIE). Traditionally, the status of LNH realisation as an ethnic marker has gone unquestioned: Catholics are thought to say [het&Mac186;] while the Protestant norm is assumed to be [etS]. The phonetic difference between these realisations is consistently described as word-initial aspiration versus non-aspiration, with aspiration attributed exclusively to Irish language influence. Here, we show that an explanation based on aspiration alone is phonologically unsatisfying and question whether aspiration is, in fact, an Irish language or ethnically dictated phenomenon. It is further suggested here that the overwhelming stigmatisation of LNH realisation may be responsible for blocking a potential sound change in NIE. While this paper is not intended as a detailed account of ethnolinguistic differences in NI phonology, it engages critically with the over-simplistic and widespread notion that LNH realisation is a result of transfer from the Irish language to the English used by Catholics in Northern Ireland.

Adaptation to the Environment: Changes in Initial Projects in Ottoman Shephardic Press

The origins of Sephardic press date back to the mid-20th century, when the influence of the Western world spread across the Sephardim communities of the East. The content of these newspapers was diverse: pieces of general interest, but also scientific, literary and humorous works, with various political orientations. These papers were published in different languages, writing styles and alphabets. Those to be analysed here, however, were published in aljamiado Judeo-Spanish: three papers from Smyrna and one from Salonica. Throughout this work we will focus on the different obstacles and difficulties the editors and publishers of this Ottoman Sephardic press had to face to bring their publications to light.