Hepatitis C Virus Antigenic Convergence

Vaccine development against hepatitis C virus (HCV) is hindered by poor understanding of factors defining cross-immunoreactivity among heterogeneous epitopes. Using synthetic peptides and mouse immunization as a model, we conducted a quantitative analysis of cross-immunoreactivity among variants of the HCV hypervariable region 1 (HVR1). Analysis of 26,883 immunological reactions among pairs of peptides showed that the distribution of cross-immunoreactivity among HVR1 variants was skewed, with antibodies against a few variants reacting with all tested peptides. The HVR1 cross-immunoreactivity was accurately modeled based on amino acid sequence alone. The tested peptides were mapped in the HVR1 sequence space, which was visualized as a network of 11,319 sequences. The HVR1 variants with a greater network centrality showed a broader cross-immunoreactivity. The entire sequence space is explored by each HCV genotype and subtype. These findings indicate that HVR1 antigenic diversity is extensively convergent and effectively limited, suggesting significant implications for vaccine development

Catholic Interests and the Politics of English Overseas Expansion 1660–1689

AbstractThroughout the reign of Charles II, a growing number of Catholics entered into the civil and military infrastructure of the overseas colonies. While Maryland was consolidated as a center of settlement, a new crop of English and Irish officeholders shaped the political development of Tangier, New York and the Leeward Islands. Their careers highlighted the opportunities of overseas expansion as a route into the public domain: a chance for Catholics to sidestep the penal restrictions of the three kingdoms and construct an alternative relationship with the crown. This article examines the emergence of Catholic authority within the plantations, and situates the experiment within larger shifts in strategic and ideological debate over English colonization. I suggest that experiences in the colonies invigorated economic and political strategies that became central to the advancement of Catholic interests in the domestic realm. While colonial trade bolstered Catholic estates against penal pressures, the new settlements provided the training ground for attempts to demonstrate the compatibility of confessional pluralism with commercial flourishing and civil allegiance. The effect, however, was to raise conflict in colonial politics and heighten anxieties in the domestic realm over the effects of overseas plantation. I argue that by uncovering a neglected sphere of “recusant history” we gain new insights into the ideological fragilities that disrupted the pursuit of territories overseas. Catholic promotions exposed a growing tension between the “Protestant interest” and the principles and practices that informed the expansion of the Stuart realm.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Cambridge University Press

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Access to research and technical information in Denmark

A knowledge economy has been described as one in which the generation and exploitation of knowledge has come to play the predominant part in the creation of wealth. It is not simply about pushing back the frontiers of knowledge; it is also about the more effective use and exploitation of all types of knowledge in all manner of economic activities (Department of Trade and Industry 1998). Small and medium sized enterprises (SMEs) form a major part of many econo- mies and they play a key role in innovation. Consequently, SME access to and use of research findings is important, not only for firm-level performance but also for the overall performance of national economies. The aim of this study is to examine levels of access to and use of research and technical information by knowledge-based SMEs in Denmark. We explore current levels of access and use, whether there are any barriers to access, access difficulties or gaps, and the costs and benefits involved in accessing research findings

Restarting and recentering genetic algorithm variations for DNA fragment assembly: The necessity of a multi-strategy approach

DNA Fragment assembly – an NP-Hard problem – is one of the major steps in of DNA sequencing. Multiple strategies have been used for this problem, including greedy graph-based algorithms, deBruijn graphs, and the overlap-layout-consensus approach. This study focuses on the overlap-layout-consensus approach. Heuristics and computational intelligence methods are combined to exploit their respective benefits. These algorithm combinations were able to produce high quality results surpassing the best results obtained by a number of competitive algorithms specially designed and tuned for this problem on thirteen of sixteen popular benchmarks. This work also reinforces the necessity of using multiple search strategies as it is clearly observed that algorithm performance is dependent on problem instance; without a deeper look into many searches, top solutions could be missed entirely