Nonlinearity in genetic decoding: Homologous DNA replicase genes use alternatives of transcriptional slippage or translational frameshifting

The τ and γ subunits of DNA polymerase III are both encoded by a single gene in Escherichia coli and Thermus thermophilus. γ is two-thirds the size of τ and shares virtually all its amino acid sequence with τ. E. coli and T. thermophilus have evolved very different mechanisms for setting the approximate 1:1 ratio between τ and γ. Both mechanisms put ribosomes into alternate reading frames so that stop codons in the new frame serve to make the smaller γ protein. In E. coli, ≈50% of initiating ribosomes translate the dnaX mRNA conventionally to give τ, but the other 50% shift into the −1 reading frame at a specific site (A AAA AAG) in the mRNA to produce γ. In T. thermophilus ribosomal frameshifting is not required: the dnaX mRNA is a heterogeneous population of molecules with different numbers of A residues arising from transcriptional slippage on a run of nine T residues in the DNA template. Translation of the subpopulation containing nine As (or +/− multiples of three As) yields τ. The rest of the population of mRNAs (containing nine +/− nonmultiples of three As) puts ribosomes into the alternate reading frames to produce the γ protein(s). It is surprising that two rather similar dnaX sequences in E. coli and T. thermophilus lead to very different mechanisms of expression.

Physical reasons for the unusual α-helix stabilization afforded by charged or neutral polar residues in alanine-rich peptides

We have carried out conformational energy calculations on alanine-based copolymers with the sequence Ac-AAAAAXAAAA-NH2 in water, where X stands for lysine or glutamine, to identify the underlying source of stability of alanine-based polypeptides containing charged or highly soluble polar residues in the absence of charge–charge interactions. The results indicate that ionizable or neutral polar residues introduced into the sequence to make them soluble sequester the water away from the CO and NH groups of the backbone, thereby enabling them to form internal hydrogen bonds. This solvation effect dictates the conformational preference and, hence, modifies the conformational propensity of alanine residues. Even though we carried out simulations for specific amino acid sequences, our results provide an understanding of some of the basic principles that govern the process of folding of these short sequences independently of the kind of residues introduced to make them soluble. In addition, we have investigated through simulations the effect of the bulk dielectric constant on the conformational preferences of these peptides. Extensive conformational Monte Carlo searches on terminally blocked 10-mer and 16-mer homopolymers of alanine in the absence of salt were carried out assuming values for the dielectric constant of the solvent ɛ of 80, 40, and 2. Our simulations show a clear tendency of these oligopeptides to augment the α-helix content as the bulk dielectric constant of the solvent is lowered. This behavior is due mainly to a loss of exposure of the CO and NH groups to the aqueous solvent. Experimental evidence indicates that the helical propensity of the amino acids in water shows a dramatic increase on addition of certain alcohols, such us trifluoroethanol. Our results provide a possible explanation of the mechanism by which alcohol/water mixtures affect the free energy of helical alanine oligopeptides relative to nonhelical ones.

Avaliação da judicialização da saúde no município de Ribeirão Preto/SP

A Constituição Federal Brasileira institucionalizou o direito a saúde no Brasil, o artigo 196 que diz: A saúde é um direito de todos e um dever do Estado apresenta esse direito. Ao regulamentar a criação do Sistema Único de Saúde a lei 8.080 reafirma a obrigação do Estado com a Saúde da população. Dentro desse contexto a Assistência Farmacêutica (AF) tem importante papel de garantir medicamentos seguros, eficácias, em tempo e quantidade necessária para atender a demanda dos cidadãos, porém apesar das constantes atualizações em prol de promover maior eficiência dos processos da AF, ainda acontecem situações em que o paciente não tem o medicamento requerido, seja por falta nas unidades dispensadoras ou a não presença nas listas de medicamentos padronizados. Essa situação faz com que o cidadão recorra à via judicial na tentativa de garantir o acesso ao medicamento pleiteado, fenômeno conhecido como judicialização da saúde, que traz grandes implicações sobre a gestão da assistência farmacêutica. Diante disso o objetivo do trabalho foi descrever o panorama geral das ações judiciais pleiteando medicamentos e insumos para insulina que foram assumidos pela prefeitura de Ribeirão Preto. Para alcançar esses objetivos, foi realizado um estudo do tipo descritivo. Foram analisados ao todo 1861 processos judiciais sendo 1083 ainda ativos e 778 que já haviam sido encerrados. Na maioria dos processos o juiz dava como prazo máximo 30 dias (99%) para se cumprir a ação, o que é insuficiente para realizar uma licitação pública obrigando a gestão a utilizar via paralela de compra. O Ministério Público foi o principal representante legal (71,7%) utilizado e a maioria das prescrições foram advindas de hospitais e clínicas particulares (50,1%). Os principais diagnósticos referidos nas ações foram diabetes e o transtorno de déficit de atenção e hiperatividade (TDAH). Já os medicamentos mais prevalentes foram as insulinas e o metilfenidato. Dentre os médicos prescritores 3% somam aproximadamente 30% das prescrições. Diante dos resultados expostos, o presente estudo evidenciou o impacto da judicialização da saúde no município de Ribeirão Preto, demandando da gestão pública organização estrutural e financeira para lidar com as demandas judiciais.

Save the Planet - Buy Organic: The Role of Consumers in the Sustainable Agricultural Movement

The severity of the environmental situation in agriculture is described. Progress made so far is then listed and critiqued. Misconceptions that sustainable agriculture cannot produce as much food as industrial agriculture, as well as the false impression that sustainably-produced foods must cost more are discussed. In conclusion, the only force strong enough to convince farmers to switch to sustainable practices is the consumer. Advertisements and educational campaigns will inform consumers about industrial agriculture. The shift in demand for sustainable goods will eventually cause prices to fall, allowing more consumers to purchase these formally expensive goods. This process will make a sustainable agricultural revolution possible and profitable.

Outsourcing and strategy in Spanish town halls: a field study

Purpose – This study seeks to analyse the links between strategies, structures and processes in the case of the largest Spanish town halls, using the Miles and Snow's models about organisational strategies, and asking the following questions: “What is the situation of municipal services' outsourcing in the largest Spanish town halls?”; “Do Spanish town halls follow the strategies suggested in Miles and Snow's model?”; and “Is there a relationship between the strategic position adopted by town halls and their stance on outsourcing?”. Design/methodology/approach – In order to achieve these aims a questionnaire was administered to the human resource managers in the town halls of the largest Spanish cities. Findings – The paper finds that outsourcing is a complement, which seeks to improve the services delivered, and local institutions do not resort to it due to a lack of internal resources but as a way to complement their own capabilities. Originality/value – The paper has identified three distinct strategic profiles in the town halls interviewed which coincide with the profiles that Miles and Snow call prospective, defensive and reactive strategies. It reveals that town halls which outsource to a greater extent are the ones which identify more with the prospective or reactive strategy, whereas those which outsource less are closer to the defensive strategy.

Information systems offshore outsourcing: managerial conclusions from academic research

In the light of the growing interest raised by Information Systems Offshore Outsourcing both in the managerial world and in the academic arena, the present work carries out a revision of the research in this area. We have analysed 89 research articles on this topic published in 17 prestigious journals. The analysis deals with aspects such as research methodologies, level of analysis in the studies, data perspective, economic theories used or location of vendors and clients of these services; and it additionally identifies the most frequent topics in this field as well as the most prolific authors and countries. Although other reviews about the research in this area have been published, the present paper achieves a greater level of detail than previous works. The review of the literature in the area could have interesting implications not only for academics but also for business practice.

Differentiated effect of advertising: Joint vs. separate consumption

In a context of intense competition, cooperative advertising between firms is critical. Accordingly, the objective of this article is to analyze the potential differentiated effect of advertising on two basic consumption patterns: individual products (i.e. hotel, restaurant) vs. bundle (i.e. hotel + restaurant). This research adds to the extant literature in that, for the first time, this potential differentiated effect is examined through a hierarchical modelling framework that reflects the way people make their decisions: first, they decide whether to visit or not a region; second, whether to purchase an advertised product in that region; and third, whether to buy products together or separately at the region. The empirical analysis, applied to a sample of 11,288 individuals, shows that the influence of advertising is positive for the decisions to visit and to purchase; however, when it comes to the joint or separate consumption, advertising has a differentiated effect: its impact is much greater on the joint alternative (“hotel + restaurant”) than the separate options (“hotel” and “restaurant”). Also, the variable distance moderates the advertising effect.

Africa, 1611 or 1612 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Nova Africae tabula, auctore Jodoco Hondio. It was published by Excusum in aedibus auctoris ca. between 1611 and 1612. Scale [ca. 1:24,000,000]. Covers Africa and small portions of Europe and the Middle East. Map in Latin.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Africa Sinusoidal projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown pictorially. Includes notes.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Tunis, Tunisia, 1910 or 1911 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de Tunis et ses environs, [dessiné par J. Vanney]. It was published by C. Saliba aîné between 1910-1911. Scale 1:8,000. Map in French.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM Zone 32N, meters, WGS 1984) projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, roads, railroads and stations, selected buildings and built-up areas, shoreline features, parks, fortification, and more.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Making or Breaking the Republic of Moldova? The Autonomy of Gagauzia. EDAP 02/2013

This article describes the process of self-determination and the creation of a territorial autonomy of the Gagauz people in the Republic of Moldova. It also analyses the situation in the autonomy after the change of government in Chisinau in 2009 and evaluates the current status of accommodation of the Gagauz’ interests in the country. Aspects of state-building and the influence of external actors are explored as well. Gagauzia (Gagauz Yeri) is one of the first post-Soviet autonomies. Since its establishment in 1994, no violent conflict has taken place there. However, the Gagauz language and culture remain relatively unprotected, and incentives as well as support for the integration of the Gagauz are low. The article outlines the potential for future disputes between the central government and local authorities, due to continuous attempts to limit Gagauzia’s self-governance and conflicting interpretations of how the autonomy should work. Furthermore, struggles between Gagauz political leaders and other local realities hamper the successful realization of Gagauz Yeri. With respect to Moldova’s efforts to resolve the Transnistrian conflict and to integrate with the European Union, compromises and cooperation through an ongoing dialogue between the centre and autonomy are clearly due. Resolving the remaining stumbling blocks could make Gagauzia a living, rather than symbolic autonomy.

Programming EU External Action Post-Lisbon: New Opportunities or Business as Usual?

Over 90% of the external relations budget of the EU is processed through its external financial instruments. With the Lisbon Treaty and the creation of the new European External Action Service (EEAS), the institutional architecture of these instruments was significantly reformed. This contribution analyses strategic programming both pre- and post-Lisbon, identifies ‘winners’ and ‘losers’, and examines the potential of the new provisions to increase the coherence of EU external action. The examination shows that the instruments can be categorised into three groupings: ‘the big three’ comprising the bulk of funding characterised by joint programming and responsibilities; the ‘Commission-only’ instruments where all powers remain with the Commission; and the ‘EEAS-led rest’ in which the High Representative and the EEAS play a strong role but only have limited financial resources available. The new system calls for strong coordination of all involved actors in order to make it work. Findings of a case study on the Instrument for Stability reveal, however, that so far the establishment of the EEAS has not made a substantial impact on strategic programming in its first two years.

To Be or Not to Be a Normative Power: The EU’s Promotion of Human Rights and Democracy in Russia. Bruges Regional Integration & Global Governance Papers 2/2013

The ‘Normative Power Europe’ debate has been a leitmotif in the academic discourse for over a decade. Far from being obsolete, the topic is as relevant as when the term was first coined by Ian Manners in 2002.1 ‘To be or not to be a normative power’ is certainly one of the existential dilemmas in the foreign policy of the European Union. This paper, however, intends to move beyond the black-and-white debate on whether the European Union is a normative power and to make it more nuanced by examining the factors that make it such. Contrary to the conventional perception that the European Union is a necessarily ‘benign’ force in the world, it assumes that it has aspirations to be a viable international actor. Consequently, it pursues different types of foreign policy behaviour with a varying degree of normativity in them. The paper addresses the question of under what conditions the European Union is a ‘normative power’. The findings of the study demonstrate that the ‘normative power’ of the European Union is conditioned upon internal and external elements, engaged in a complex interaction with a decisive role played by the often neglected external elements.

The Treaty of Lisbon or intergovernmental temptation?

From the Introduction. This question goes to the very heart of the European project: it is fundamental for the future of the European Union and its role in the world. The Treaty of Lisbon emerged from the ashes of the European Constitution. Driven forward by Angela Merkel, as President of the European Council, Nicolas Sarkozy and José Manuel Barroso, the main advances made in the Constitution were preserved at the expense of a few concessions and symbolic sacrifices in order to make the Union more effective and more democratic.

Brexit or not? Time for the EU to move. EPC Commentary, 8 September 2014

The deteriorating relationship between the United Kingdom (UK) and the rest of the EU, including the prospect of a referendum on EU membership, would have dominated the Union’s agenda had it not been for the economic/financial crisis, followed by the external crisis which we are now facing in the East. Precisely because of these crises, it is now time for the incoming European Commission to take the bull by the horns and ensure that the EU can move on from a potential referendum and its possible outcomes. The June European Council noted that “the UK raised some concerns related to the future development of the EU. These concerns will need to be addressed. In this context, the European Council noted that the concept of ever closer union allows for different paths of integration for different countries, allowing those that want to deepen integration to move ahead, while respecting the wish of those who do not want to deepen any further.” While the EU has, arguably, successfully developed at different speeds for decades, to address the UK’s (fundamental) concerns, it is now time to work out whether and how the UK can be accommodated, and what this would mean in practice. UK membership is desirable but not at any price, so the aim should be to keep the UK in, while also ensuring that the principles on which the EU is built are protected. There will need to be a modus operandi which enables the EU and in particular, the Eurozone, to continue to make progress in addressing the shortcomings of European integration and European Monetary Union (EMU) in particular, while at the same time offering a reform package that can satisfy the UK. This does not necessarily mean that all EMU reforms have to be within the EU framework: additional intergovernmental arrangements could also be a possibility. However, this could add to the complexity and inefficiency of the system, as well as sidelining the supranational element of EU governance which will be needed to make EMU function.

Humanitarian Visas: Option or obligation?. CEPS Liberty and Security in Europe No. 68, 27 October 2014

Third-country nationals seeking protection have no EU-wide legal channels at present for entering EU territory and triggering protection mechanisms under the Common European Asylum System. As a result, many embark on hazardous journeys, with concomitant risks and loss of human life. The absence of ‘protection-sensitive’ mechanisms for accessing EU territory, along with EU external and extraterritorial border and migration management and control, undermine Member States' refugee and human rights obligations. Humanitarian visas may offer a remedy in this regard by enabling third-country nationals to apply in situ for entry to EU territory on humanitarian grounds or because of international obligations. This study asks whether the existing Visa Code actually obliges Member States to issue humanitarian visas. It also examines past implementation of humanitarian visa schemes by Member States and considers whether more could be done to encourage them to make use of existing provisions in EU law. Finally, with a Commission proposal for Visa Code reform on the table, it asks whether there is now an opportunity to lay down clear rules for humanitarian visa schemes.