Efficient HIV-1 inhibition by a 16 nt-long RNA aptamer designed by combining in vitro selection and in silico optimisation strategies

The human immunodeficiency virus type-1 (HIV-1) genome contains multiple, highly conserved structural RNA domains that play key roles in essential viral processes. Interference with the function of these RNA domains either by disrupting their structures or by blocking their interaction with viral or cellular factors may seriously compromise HIV-1 viability. RNA aptamers are amongst the most promising synthetic molecules able to interact with structural domains of viral genomes. However, aptamer shortening up to their minimal active domain is usually necessary for scaling up production, what requires very time-consuming, trial-and-error approaches. Here we report on the in vitro selection of 64 nt-long specific aptamers against the complete 5' -untranslated region of HIV-1 genome, which inhibit more than 75% of HIV-1 production in a human cell line. The analysis of the selected sequences and structures allowed for the identification of a highly conserved 16 nt-long stem-loop motif containing a common 8 nt-long apical loop. Based on this result, an in silico designed 16 nt-long RNA aptamer, termed RNApt16, was synthesized, with sequence 5'-CCCCGGCAAGGAGGGG-3-'. The HIV-1 inhibition efficiency of such an aptamer was close to 85%, thus constituting the shortest RNA molecule so far described that efficiently interferes with HIV-1 replication.

Single-cell analysis for bioprocessing

Cell population heterogeneity has attracted great interest for understanding the individual cellular performances in their response to external stimuli and in the production of targeted products. Physical characterization of single cells and analysis of dynamic gene expression, synthesized proteins, and cellular metabolites from one single cell are reviewed. Advanced techniques have been developed to achieve high-throughput and ultrahigh resolution or sensitivity. Single cell capture methods are discussed as well. How to make use of cellular heterogeneities for maximizing cellular productivity is still in the infant stage, and control strategies will be formulated after the causes for heterogeneity have been elucidated.

Large-volume metrology instrument selection and measurability analysis

A wide range of metrology processes are involved in the manufacture of large products. In addition to the traditional tool-setting and product-verification operations, increasingly flexible metrology-enabled automation is also being used. Faced with many possible measurement problems and a very large number of metrology instruments employing diverse technologies, the selection of the appropriate instrument for a given task can be highly complex. Also, as metrology has become a key manufacturing process, it should be considered in the early stages of design, and there is currently very little research to support this. This paper provides an overview of the important selection criteria for typical measurement processes and presents some novel selection strategies. Metrics that can be used to assess measurability are also discussed. A prototype instrument selection and measurability analysis application is also presented, with discussion of how this can be used as the basis for development of a more sophisticated measurement planning tool. © 2010 Authors.

Strategies to optimize the impact of nutritional surveys and epidemiological studies

The development of nutrition and health guidelines and policies requires reliable scientific information. Unfortunately, theoretical considerations and empirical evidence indicate that a large percentage of science-based claims rely on studies that fail to replicate. The session "Strategies to Optimize the Impact of Nutrition Surveys and Epidemiological Studies" focused on the elements of design, interpretation, and communication of nutritional surveys and epidemiological studies to enhance and encourage the production of reliable, objective evidence for use in developing dietary guidance for the public. The speakers called for more transparency of research, raw data, consistent data-staging techniques, and improved data analysis. New approaches to collecting data are urgently needed to increase the credibility and utility of findings from nutrition epidemiological studies. Such studies are critical for furthering our knowledge and understanding of the effects of diet on health.

Handbook of research on strategic performance management and measurement using data envelopment analysis

Organizations can use the valuable tool of data envelopment analysis (DEA) to make informed decisions on developing successful strategies, setting specific goals, and identifying underperforming activities to improve the output or outcome of performance measurement. The Handbook of Research on Strategic Performance Management and Measurement Using Data Envelopment Analysis highlights the advantages of using DEA as a tool to improve business performance and identify sources of inefficiency in public and private organizations. These recently developed theories and applications of DEA will be useful for policymakers, managers, and practitioners in the areas of sustainable development of our society including environment, agriculture, finance, and higher education sectors. All rights reserved.

Strategies for sustaining manufacturing competitiveness:comparative case studies in Australia and Sweden

Purpose - The purpose of this paper is to report an investigation of local sustainable production in Australia and Sweden aimed at exploring the factors contributing to survival and competitiveness of manufacturing companies. Design/methodology/approach - In Australia, six companies were studied in 2010, with comparisons being made with three of them from earlier projects. In Sweden, eight manufacturing companies were studied on two occasions 30 years apart, in 1980 and 2010. To provide a valid comparative perspective a common format for data collection and analysis was used. Findings - There has been a shift in the nature of competition in both Sweden and Australia due to an increasing complexity of the global business environment as well as changes in technology and customer expectations. Despite the differences in country context, the findings suggest that all the manufacturing companies have a good awareness of the elements of the market environment and the relationships with their competitive strategy. However, in general, the Swedish companies have more experience of managing the risks and benefits from operating in the international environment. Research limitations/implications - The results of the research are based on a relatively small sample of case companies in a limited number of industrial sectors. There are methodology implications for future research in the area. Practical implications - The research results have practical implications for the manufacturing industry, especially for companies operating in a competitive international environment. Originality/value - The paper is based on original case research and comparative analysis of data from different geographical contexts. It contributes to both theory and management practice about the strategic resources, decision choices, competitive environments and firm values needed to address external market demands as well as in building internal capabilities.

Giants and dwarfs:the multilevel lobbying strategies of national interest organizations

The article addresses the bias in interest representation within the EU by examining the lobbying strategies of national interest organisations within the EU’s multilevel political system. Both our theoretical framework, which includes the determinants of a national interest organisation's decision to act at the EU level, and the data analysis from the INTEREURO Multi-Level Governance Module (MLG) (www.intereuro.eu) reveal three main findings. Firstly, the greatest differentiation among interest organisations (IOs) appears to be between those IOs from the older member states (Germany, the UK and the Netherlands), which exhibit above-average levels of activity, and those from the newer EU member states (Sweden, Slovenia), which exhibit below-average levels of activity. Secondly, the variations in IO activity levels are much greater from country to country than from one policy field to another. Thirdly, although the IOs from all five countries in our study are more likely to employ media and publishing strategies (information politics) than to mobilise their members and supporters (protest politics), we can still observe national patterns in their selection of strategies and in the intensity of their instrumentalisation.

Online grooming: moves and strategies

Using transcripts of chatroom grooming interactions, this paper explores and evaluates the usefulness of Swales’ (1981) move analysis framework in contributing to the current understanding of online grooming processes. The framework is applied to seven transcripts of grooming interactions taken from perverted-justice.com. The paper presents 14 identified rhetorical moves used in chatroom grooming and explores the broad structures that grooming conversations take by presenting these structures as colour-coded visualisations which we have termed “move maps”. It also examines how some individual linguistic features are used to realise a single move termed “Assessing and Managing Risk”. The findings suggest that move analysis can usefully contribute in two key ways: determining communicative functions associated with 'grooming language' and the visualisation of variation between grooming interactions.

Large volume metrology instrument selection and measurability analysis

Metrology processes used in the manufacture of large products include tool setting, product verification and flexible metrology enabled automation. The range of applications and instruments available makes the selection of the appropriate instrument for a given task highly complex. Since metrology is a key manufacturing process it should be considered in the early stages of design. This paper provides an overview of the important selection criteria for typical measurement processes and presents some novel selection strategies. Metrics which can be used to assess measurability are also discussed. A prototype instrument selection and measurability analysis application is presented with discussion of how this can be used as the basis for development of a more sophisticated measurement planning tool. © Springer-Verlag Berlin Heidelberg 2010.

The Policy Dystopia Model:an interpretive analysis of tobacco industry political activity

BACKGROUND: Tobacco industry interference has been identified as the greatest obstacle to the implementation of evidence-based measures to reduce tobacco use. Understanding and addressing industry interference in public health policy-making is therefore crucial. Existing conceptualisations of corporate political activity (CPA) are embedded in a business perspective and do not attend to CPA's social and public health costs; most have not drawn on the unique resource represented by internal tobacco industry documents. Building on this literature, including systematic reviews, we develop a critically informed conceptual model of tobacco industry political activity. METHODS AND FINDINGS: We thematically analysed published papers included in two systematic reviews examining tobacco industry influence on taxation and marketing of tobacco; we included 45 of 46 papers in the former category and 20 of 48 papers in the latter (n = 65). We used a grounded theory approach to build taxonomies of "discursive" (argument-based) and "instrumental" (action-based) industry strategies and from these devised the Policy Dystopia Model, which shows that the industry, working through different constituencies, constructs a metanarrative to argue that proposed policies will lead to a dysfunctional future of policy failure and widely dispersed adverse social and economic consequences. Simultaneously, it uses diverse, interlocking insider and outsider instrumental strategies to disseminate this narrative and enhance its persuasiveness in order to secure its preferred policy outcomes. Limitations are that many papers were historical (some dating back to the 1970s) and focused on high-income regions. CONCLUSIONS: The model provides an evidence-based, accessible way of understanding diverse corporate political strategies. It should enable public health actors and officials to preempt these strategies and develop realistic assessments of the industry's claims.