What have dendritic cells ever done for adjuvant design? Cellular and molecular methods for the rational development of vaccine adjuvants

Our new molecular understanding of immune priming states that dendritic cell activation is absolutely pivotal for expansion and differentiation of naïve T lymphocytes, and it follows that understanding DC activation is essential to understand and design vaccine adjuvants. This chapter describes how dendritic cells can be used as a core tool to provide detailed quantitative and predictive immunomics information about how adjuvants function. The role of distinct antigen, costimulation, and differentiation signals from activated DC in priming is explained. Four categories of input signals which control DC activation – direct pathogen detection, sensing of injury or cell death, indirect activation via endogenous proinflammatory mediators, and feedback from activated T cells – are compared and contrasted. Practical methods for studying adjuvants using DC are summarised and the importance of DC subset choice, simulating T cell feedback, and use of knockout cells is highlighted. Finally, five case studies are examined that illustrate the benefit of DC activation analysis for understanding vaccine adjuvant function.

Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen

Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals.

Africa and Asia need a rational debate on GM crops

Policy-makers in developing countries should not be swayed by the politicized arguments dominant in Europe

Software-based study of a non-sorting method for median calculation on a set of integer numbers

This paper presents a software-based study of a hardware-based non-sorting median calculation method on a set of integer numbers. The method divides the binary representation of each integer element in the set into bit slices in order to find the element located in the middle position. The method exhibits a linear complexity order and our analysis shows that the best performance in execution time is obtained when slices of 4-bit in size are used for 8-bit and 16-bit integers, in mostly any data set size. Results suggest that software implementation of bit slice method for median calculation outperforms sorting-based methods with increasing improvement for larger data set size. For data set sizes of N > 5, our simulations show an improvement of at least 40%.

Organisational politics: reconciling leadership's rational-emotional paradox

Purpose – Effective leadership action requires managers to harness power that is intrinsically political. This paper aims to study and characterise the political nature of a manager's behaviour when taking leadership action. Design/methodology/approach – The methodological approach is qualitative and examines three organisations over a three-year period when these entities experienced a major product failure. The paper analyses the actual managerial behaviour of managers and provides insight into the factors that most strongly influence the effectiveness of managers when taking leadership action. Findings – Political behaviour when taking leadership action can be conceptualised in terms of rationality and emotionality. In so doing, it can be clarified how behaviour must be modified to ensure that leadership action is consistently effective. Research limitations/implications – A case study of three multinational engineering companies engaged in the design, development and manufacturing of turbomachinery provides the platform for the research. The concepts presented in the paper will require validating in other organisations of different demographic profiles. Practical implications – The concepts presented and the implications discussed provide insight into the political nature of managerial behaviour when taking leadership action. The paper highlights the practical steps individual managers can embrace to ensure that their behaviour is appropriate to context, even under the most traumatic situations. Thus, the paper provides managers with a model that facilitates effective leadership action. Originality/value – This paper provides insight into how managers behaved in circumstances that mattered to them. Through immersion in events at the time they took place, the authors captured situations in which managers were under real pressure and, in so doing, avoided the bias inherent when interviewing a manager about past events. As such, the paper concludes that the political behaviour in which managers engage when taking leadership action is rooted in the reality of the adversity that the most capable managers have both experienced and overcome. This detailed study reports behaviour in a situation where managers' business and future prospects were in jeopardy. This paper identifies why some managers were able to use the experience positively, helping them to adopt politically intrinsic behaviour to facilitate effective leadership action.

Construction of the transcomplex numbers from the complex numbers

A geometrical construction of the transcomplex numbers was given elsewhere. Here we simplify the transcomplex plane and construct the set of transcomplex numbers from the set of complex numbers. Thus transcomplex numbers and their arithmetic arise as consequences of their construction, not by an axiomatic development. This simplifes transcom- plex arithmetic, compared to the previous treatment, but retains totality so that every arithmetical operation can be applied to any transcomplex number(s) such that the result is a transcomplex number. Our proof establishes the consistency of transcomplex and transreal arithmetic and establishes the expected containment relationships amongst transcomplex, complex, transreal and real numbers. We discuss some of the advantages the transarithmetics have over their partial counterparts.

Fish oil supplementation alters numbers of circulating endothelial progenitor cells and micro particles independent of eNOS genotype

Background Emerging cellular markers of endothelial damage and repair include endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) respectively. Effects of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and influence of genetic background on these markers are not known. Objective This study investigated the effects of fish oil supplementation on both classical and novel markers of endothelial function in subjects prospectively genotyped for the Asp298 eNOS polymorphism and at moderate risk of CVD. Design 84 subjects with moderate risk of CVD (n=40 GG and n=44 GT/TT) completed a randomized, double-blind, placebo-controlled, 8-week cross-over trial of fish oil supplementation providing 1.5 g/d LC n-3 PUFA. Effects of genotype and fish oil supplementation on the blood lipid profile, inflammatory markers, vascular function (EndoPAT) and numbers of circulating EPCs and EMP (flow cytometry) were assessed. Results There was no significant effect of fish oil supplementation on blood pressure, plasma lipids or plasma glucose, although there was a trend (P = 0.069) towards a decrease in plasma TG concentration after FO supplementation compared to placebo. GT/TT subjects tended to have higher levels of total cholesterol and LDL-cholesterol, but vascular function was not affected by either treatment or eNOS genotype. Biochemical markers of endothelial function were also unaffected by treatment and eNOS genotype. In contrast, there was a significant effect of fish oil supplementation on cellular markers of endothelial function. Fish oil supplementation increased numbers of EPCs and reduced numbers of EMPs relative to the placebo, potentially favouring maintenance of endothelial integrity. There was no influence of genotype for any of the cellular markers of endothelial function, indicating that the effects of fish oil supplementation were independent of eNOS genotype. Conclusions Emerging cellular markers of endothelial damage, integrity and repair appear to be sensitive to potentially beneficial modification by dietary n-3 PUFA.

Accounting as interpretive framing

The study furthers our understanding of the persuasive and constructive aspects of accounting information. We consider it as a process of ‘interpretive framing’ in the quest for legitimacy - an attempt to justify decisions and excuse mistakes. We base our theoretical discussion on the premise that the picture reported by accounting information is an example of institutional reality and thus mediated by the social contexts in which it is constructed and interpreted. Accounting information is a matter of ‘the interpretation of interpretations’ - the provision of accounting information, which is already a result of a competitive interplay among prior interpretations of certain aspects of our economic phenomena, undergoes further interpretation by the recipients of that information. This notion applies equally to narratives and numbers. We challenge notions of rigor, accuracy and objectivity assigned to quantification in accounting and posit that numbers can be an even more powerful rhetorical device due to their image of being rational and ‘rhetoric free’. We illustrate our theoretical propositions presenting explicit references to the constructive and rhetorical aspects of financial reporting from Pacioli and his times (late 15th century) to the recent regulatory developments of FASB/IASB in 2013, i.e. from the rhetoric of double entry book-keeping to the rhetoric of 'fair value’. We acknowledge, building on these theoretical foundations, the inherent subjectivity of accounting information (influenced by perceptions and interests) without entirely denying however its informative functions. We illustrate the practical implications of this, in a situation where “shared and socially accepted” perceptions may be the nearest we can get to anything resembling a faithful representation of economic reality. The paper contributes to a broader understanding of how accounting information can be viewed as a social and humanistic construction, and challenges taken-for-granted assumptions about impartiality, neutrality and rationality in regard to the process.

The multidimensional character of accounting numbers

This paper takes as its motivation debates surrounding the multiplicity of functions of accounting information. We are in particular interested in the existential function of accounting numbers and argue that numerical signs having discursive possibilities may acquire new meanings through reframing. Drawing on Goffman’s (1974) frame analysis and Vollmer’s (2007) work on three-dimensional character of numerical signs, we explore the ways in which numbers can go through instantaneous transformations and tell a new kind of story. In our analysis, we look at the main historical developments and current controversies surrounding accounting practice with a specific focus on scandals involving numerical signs as moments where our understandings and the discursive function of previously inoffensive signs shifts through a collective involvement. We map the purpose and usefulness of Vollmer’s three-dimensional framework in the analysis of selected financial accounting practices and scandals as examples of instances where numbers are reframed to suddenly perform a different existential function in context of their calculative and symptomatic dimensions.

Numbers in motion

We explore the debates surrounding the constructive and discursive capabilities of accounting information focusing in particular on the reception volatility of numbers once they are produced and ‘exposed’ to various communities of minds. Drawing on Goffman’s (1974) frame analysis and Vollmer’s (2007) work on the three-dimensional character of numerical signs, we explore how numbers can go through gradual or instantaneous transformations, get caught up in public debates and become ‘agents’ or ‘captives’ in creating social order and in some cases social drama. In our analysis we also relate to the work of Durkheim (1993, 2002) on the sociology of morality to illustrate how numbers can become indicators of moral transgression. The study explores both historical and contemporary examples of controversies and recent accounting scandals to demonstrate how preparers (of financial information) can lose control over numbers which then acquire new meanings through social context and collective (re)framing. The main contribution of the study is to illustrate how the narratives attached to numbers are malleable and fluid across both time and space.

The proportion of failures of the Hasse norm principle

For any number field we calculate the exact proportion of rational numbers which are everywhere locally a norm but not globally a norm from the number field.