Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence

An estimated 3% of the global population are infected with hepatitis C virus (HCV), and the majority of these individuals will develop chronic liver disease. As with other chronic viruses, establishment of persistent infection requires that HCV-infected cells must be refractory to a range of pro-apoptotic stimuli. In response to oxidative stress, amplification of an outward K(+) current mediated by the Kv2.1 channel, precedes the onset of apoptosis. We show here that in human hepatoma cells either infected with HCV or harboring an HCV subgenomic replicon, oxidative stress failed to initiate apoptosis via Kv2.1. The HCV NS5A protein mediated this effect by inhibiting oxidative stress-induced p38 MAPK phosphorylation of Kv2.1. The inhibition of a host cell K(+) channel by a viral protein is a hitherto undescribed viral anti-apoptotic mechanism and represents a potential target for antiviral therapy.

Transatlantic Relations: Sharing Ideals and Costs

A study of European relations with the USA and Canada after the end of the Cold War

Brill Greek, Adobe Arno Pro, Adobe Text/Brevier Greek typefaces

Typeface design: a series of collaborative projects commissioned by Adobe, Inc. and Brill to develop extensive polytonic Greek typefaces. The two Adobe typefaces can be seen as extension of previous research for the Garamond Premier Pro family (2005), and concludes a research theme started in 1998 with work for Adobe’s Minion Pro Greek. These typefaces together define the state of the art for text-intensive Greek typesetting for wide character set texts (from classical texts, to poetry, to essays, to prose). They serve both as exemplar for other developers, and as vehicles for developing the potential of Greek text typography, for example with the parallel inclusion of monotonic and polytonic characters, detailed localised punctuation options, fluid handling of case-conversion issues, and innovative options such as accented small caps (originally requested by bibliographers, and subsequently rolled out to a general user base). The Brill typeface (for the established academic publisher) has an exceptionally wide character set to cover several academic disciplines, and is intended to differentiate sufficiently from its partner Latin typeface, while maintaining a clear texture in both offset and low-resolution print-on-demand reproduction. This work involved substantial amounts of testing and modifying the design, especially of diacritics, to maintain clarity the readability of unfamiliar words. All together these typefaces form a study in how Greek typesetting meets contemporary typographic requirements, while resonating with historically accurate styles, where these are present. Significant research in printing archives helped to identify appropriate styles, as well as originate variants that are coherent stylistically, even when historical equivalents were absent.

Cartels and rent sharing at the farmer–trader interface: evidence from Ghana’s tomato sector

Itinerant traders provide an important route for West Africa’s farmers’ to get their perishable produce rapidly to the distant urban markets. But these farmers often accuse the traders of offering “unfairly” low prices while preventing direct access to these markets. Using Ghana’s tomato sector as a case study, we provide the first detailed exploration of the interface between Ghana’s farmers and traders, combining a theoretical model with novel empirical data on daily sales prices and tomato quality. We find that although the prices traders pay farmers are lower than prices in the urban markets, taking into account transport costs, these prices are higher than farmers receive from the local rural market. Our article suggests that policymakers would do better to focus on opening up access to the urban markets rather than on strengthening farmers’ bargaining power with the traders, which restricts market volumes further and harms farmers unable to sell to traders.

Sharing power? Prospects for a U.S. concert-balance strategy

The Pax Americana and the grand strategy of hegemony (or “Primacy”) that underpins it may be becoming unsustainable. Particularly in the wake of exhausting wars, the Global Financial Crisis, and the shift of wealth from West to East, it may no longer be possible or prudent for the United States to act as the unipolar sheriff or guardian of a world order. But how viable are the alternatives, and what difficulties will these alternatives entail in their design and execution? This analysis offers a sympathetic but critical analysis of alternative U.S. National Security Strategies of “retrenchment” that critics of American diplomacy offer. In these strategies, the United States would anticipate the coming of a more multipolar world and organize its behavior around the dual principles of “concert” and “balance,” seeking a collaborative relationship with other great powers, while being prepared to counterbalance any hostile aggressor that threatens world order. The proponents of such strategies argue that by scaling back its global military presence and its commitments, the United States can trade prestige for security, shift burdens, and attain a more free hand. To support this theory, they often look to the 19th-century concert of Europe as a model of a successful security regime and to general theories about the natural balancing behavior of states. This monograph examines this precedent and measures its usefulness for contemporary statecraft to identify how great power concerts are sustained and how they break down. The project also applies competing theories to how states might behave if world politics are in transition: Will they balance, bandwagon, or hedge? This demonstrates the multiple possible futures that could shape and be shaped by a new strategy. viii A new strategy based on an acceptance of multipolarity and the limits of power is prudent. There is scope for such a shift. The convergence of several trends—including transnational problems needing collaborative efforts, the military advantages of defenders, the reluctance of states to engage in unbridled competition, and hegemony fatigue among the American people—means that an opportunity exists internationally and at home for a shift to a new strategy. But a Concert-Balance strategy will still need to deal with several potential dilemmas. These include the difficulty of reconciling competitive balancing with cooperative concerts, the limits of balancing without a forward-reaching onshore military capability, possible unanticipated consequences such as a rise in regional power competition or the emergence of blocs (such as a Chinese East Asia or an Iranian Gulf), and the challenge of sustaining domestic political support for a strategy that voluntarily abdicates world leadership. These difficulties can be mitigated, but they must be met with pragmatic and gradual implementation as well as elegant theorizing and the need to avoid swapping one ironclad, doctrinaire grand strategy for another.

The role of undisclosed reserves in English open outcry auctions

This study considers the role that reserve prices may play in residential property auctions. In comparison to much of the previous empirical work, this study has access to undisclosed reserve prices from English auctions. Consistent with theoretical arguments in the auction literature, the results obtained illustrate that whilst higher reserve prices increase the revenue obtained for the seller, they also reduce the probability of sale. The findings also highlight the importance of auction participation, with the number of individual bidders and the number of bids significant in most specifications.

Pro-competitive price beating guarantees: experimental evidence

We report experimental results on duopoly pricing with and without price beating guarantees (PBG). In two control treatments, price beating is either imposed as an industry-wide rule or offered as a business strategy. Our major finding is that when price beating guarantees are imposed as a rule or offered as an option, effective prices are equal to or lower than those in a baseline treatment in which price beating is forbidden. Also, when price beating is treated as a business strategy, less than 50% of subjects adopted the guarantee, suggesting that, subjects realize the pro-competitive effects of the guarantee.

Promoting mother–infant book sharing and infant attention and language development in an impoverished South African population: a pilot study

The low rates of child literacy in South Africa are cause for considerable concern. Research from the developed world shows that parental sharing of picture books with infants and young children is beneficial for child language and cognitive development, as well as literacy skills. We conducted a pilot study to examine whether such benefits might extend to an impoverished community in South Africa, by evaluating the impact of training mothers in book sharing with their 14–18 month old infants. Seventeen mothers received book sharing training; and 13 mothers did not, but instead received a comparison training in toy play. We assessed the mothers’ behavior during both book sharing and toy play before and after training, and we also assessed infant attention and language. Mothers receiving book sharing training engaged well with it, and they also benefited from it; thus, compared to the comparison group mothers, they became more sensitive, more facilitating, and more elaborative with their infants during book sharing, and they also became more sensitive to their infants during toy play. In addition, infants whose mothers received the book sharing training showed greater benefits than the comparison group infants in both their attention and language. Training in book sharing for families living in conditions of marked socio-economic adversity in South Africa has the potential to be of considerable benefit to child developmental progress. A large scale controlled trial is required to confirm this.

Enabling sharing and reuse of scientific data

The purpose of this study was to develop an understanding of the current state of scientific data sharing that stakeholders could use to develop and implement effective data sharing strategies and policies. The study developed a conceptual model to describe the process of data sharing, and the drivers, barriers, and enablers that determine stakeholder engagement. The conceptual model was used as a framework to structure discussions and interviews with key members of all stakeholder groups. Analysis of data obtained from interviewees identified a number of themes that highlight key requirements for the development of a mature data sharing culture.

Innovative approaches For enhancing the flow of funds into the Benefit Sharing Fund of the International Treaty on Plant Genetic Resources for Food and Agriculture: an evaluation of options

This report assesses the implications and revenue-generating potential of options for reform of the International Treaty on Plant Genetic Resources for Food and Agriculture in the context of the structure of the global seed industry and the emerging landscape of plant variety innovation for different crops. The implementation of these options would require modifications of Treaty and provisions of the Standard Material Transfer Agreements to alter the nature of payment obligations related to different categories of products, the payment rates under different options and the coverage of crops in Annex-I to the Treaty.

The role of undisclosed reserves in English open outcry auctions

This study considers the role that reserve prices may play in residential property auctions. In comparison to much of the previous empirical work, this study has access to undisclosed reserve prices from English auctions. Consistent with theoretical arguments in the auction literature, the results obtained illustrate that whilst higher reserve prices increase the revenue obtained for the seller, they also reduce the probability of sale. The findings also highlight the importance of auction participation, with the number of individual bidders and the number of bids significant in most specifications.

Proteomic analysis of Artemisia annua – towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin

Background: MS-based proteomics was applied to the analysis of the medicinal plant Artemisia annua, exploiting a recently published contig sequence database (Graham et al. (2010) Science 327, 328–331) and other genomic and proteomic sequence databases for comparison. A. annua is the predominant natural source of artemisinin, the precursor for artemisinin-based combination therapies (ACTs), which are the WHO-recommended treatment for P. falciparum malaria. Results: The comparison of various databases containing A. annua sequences (NCBInr/viridiplantae, UniProt/ viridiplantae, UniProt/A. annua, an A. annua trichome Trinity contig database, the above contig database and another A. annua EST database) revealed significant differences in respect of their suitability for proteomic analysis, showing that an organism-specific database that has undergone extensive curation, leading to longer contig sequences, can greatly increase the number of true positive protein identifications, while reducing the number of false positives. Compared to previously published data an order-of-magnitude more proteins have been identified from trichome-enriched A. annua samples, including proteins which are known to be involved in the biosynthesis of artemisinin, as well as other highly abundant proteins, which suggest additional enzymatic processes occurring within the trichomes that are important for the biosynthesis of artemisinin. Conclusions: The newly gained information allows for the possibility of an enzymatic pathway, utilizing peroxidases, for the less well understood final stages of artemisinin’s biosynthesis, as an alternative to the known non-enzymatic in vitro conversion of dihydroartemisinic acid to artemisinin. Data are available via ProteomeXchange with identifier PXD000703.

Research data management and openness: the role of data sharing in developing institutional policies and practices

Purpose: To investigate the relationship between research data management (RDM) and data sharing in the formulation of RDM policies and development of practices in higher education institutions (HEIs). Design/methodology/approach: Two strands of work were undertaken sequentially: firstly, content analysis of 37 RDM policies from UK HEIs; secondly, two detailed case studies of institutions with different approaches to RDM based on semi-structured interviews with staff involved in the development of RDM policy and services. The data are interpreted using insights from Actor Network Theory. Findings: RDM policy formation and service development has created a complex set of networks within and beyond institutions involving different professional groups with widely varying priorities shaping activities. Data sharing is considered an important activity in the policies and services of HEIs studied, but its prominence can in most cases be attributed to the positions adopted by large research funders. Research limitations/implications: The case studies, as research based on qualitative data, cannot be assumed to be universally applicable but do illustrate a variety of issues and challenges experienced more generally, particularly in the UK. Practical implications: The research may help to inform development of policy and practice in RDM in HEIs and funder organisations. Originality/value: This paper makes an early contribution to the RDM literature on the specific topic of the relationship between RDM policy and services, and openness – a topic which to date has received limited attention.