Mapping of domains on HIV envelope protein mediating association with calnexin and protein-disulfide isomerase.

The cell catalysts calnexin (CNX) and protein-disulfide isomerase (PDI) cooperate in establishing the disulfide bonding of the HIV envelope (Env) glycoprotein. Following HIV binding to lymphocytes, cell-surface PDI also reduces Env to induce the fusogenic conformation. We sought to define the contact points between Env and these catalysts to illustrate their potential as therapeutic targets. In lysates of Env-expressing cells, 15% of the gp160 precursor, but not gp120, coprecipitated with CNX, whereas only 0.25% of gp160 and gp120 coprecipitated with PDI. Under in vitro conditions, which mimic the Env/PDI interaction during virus/cell contact, PDI readily associated with Env. The domains of Env interacting in cellulo with CNX or in vitro with PDI were then determined using anti-Env antibodies whose binding site was occluded by CNX or PDI. Antibodies against domains V1/V2, C2, and the C terminus of V3 did not bind CNX-associated Env, whereas those against C1, V1/V2, and the CD4-binding domain did not react with PDI-associated Env. In addition, a mixture of the latter antibodies interfered with PDI-mediated Env reduction. Thus, Env interacts with intracellular CNX and extracellular PDI via discrete, largely nonoverlapping, regions. The sites of interaction explain the mode of action of compounds that target these two catalysts and may enable the design of further new competitive agents.

Social consensus, moral intensity and willingness to pay to address a farm animal welfare issue

An experimental contingent valuation (CV) survey of university students was undertaken to explore the impact of social consensus information on people's stated willingness to pay (wtp) to address a farm animal welfare issue. The survey found that additional information presented to respondents on social consensus concerning the moral dimensions of the issue led to a greater perception of social consensus by respondents. This greater perception of social consensus appeared to result in a higher level of moral intensity associated with the issue and a higher stated wtp by respondents for policy to address the issue. However, as for many CV studies of public goods, a question remains as to whether the estimated wtp is a true measure of people's preferences and relative values or merely a measure of attitudes on an arbitrary monetary scale.

Moral intensity and willingness to pay concerning farm animal welfare issues and the implications for agricultural policy

An experimental survey was undertaken to explore the links between the characteristics of a moral issue, the degree of moral intensity/moral imperative associated with the issue (Jones, 1991), and people's stated willingness to pay (wtp) for policy to address the issue. Two farm animal welfare issues were chosen for comparison and the contingent valuation method was used to elicit people's wtp. The findings of the survey suggest that increases in moral characteristics do appear to result in an increase in moral intensity and the degree of moral imperative associated with an issue. Moreover, there was a positive link between moral intensity/moral imperative associated with an issue and people's stated wtp for policy to address the issue. The paper discusses the relevance of the findings of the survey in the context of the debate concerning the relationship between moral and economic values and the use of the contingent valuation method to estimate people's wtp of policy options with moral dimensions.

‘God’s Truth’: Kant, Mill and moral epistemology in Oliver Twist

This essay aims to demonstrate how Dickens’s search for ‘truth’ (and his understanding of what that abstraction consists of) entered into and emerged from one of the key philosophical discussions of the early nineteenth century: namely whether moral knowledge is the sum of one’s experiences or whether there are such things as a priori or ‘natural’ principles of ethics that transcend human practice.

Bibliographic analysis of persuasive systems: techniques, methods and domains of application

This paper presents findings of our study on peer-reviewed papers published in the International Conference on Persuasive Technology from 2006 to 2010. The study indicated that out of 44 systems reviewed, 23 were reported to be successful, 2 to be unsuccessful and 19 did not specify whether or not it was successful. 56 different techniques were mentioned and it was observed that most designers use ad hoc definitions for techniques or methods used in design. Hence we propose the need for research to establish unambiguous definitions of techniques and methods in the field.

Complexity theory and planning: examining 'fractals' for organising policy domains in planning practice

This article examines selected methodological insights that complexity theory might provide for planning. In particular, it focuses on the concept of fractals and, through this concept, how ways of organising policy domains across scales might have particular causal impacts. The aim of this article is therefore twofold: (a) to position complexity theory within social science through a ‘generalised discourse’, thereby orienting it to particular ontological and epistemological biases and (b) to reintroduce a comparatively new concept – fractals – from complexity theory in a way that is consistent with the ontological and epistemological biases argued for, and expand on the contribution that this might make to planning. Complexity theory is theoretically positioned as a neo-systems theory with reasons elaborated. Fractal systems from complexity theory are systems that exhibit self-similarity across scales. This concept (as previously introduced by the author in ‘Fractal spaces in planning and governance’) is further developed in this article to (a) illustrate the ontological and epistemological claims for complexity theory, and to (b) draw attention to ways of organising policy systems across scales to emphasise certain characteristics of the systems – certain distinctions. These distinctions when repeated across scales reinforce associated processes/values/end goals resulting in particular policy outcomes. Finally, empirical insights from two case studies in two different policy domains are presented and compared to illustrate the workings of fractals in planning practice.

A generalized collectively compact operator theory with an application to integral equations on unbounded domains

In this paper a generalization of collectively compact operator theory in Banach spaces is developed. A feature of the new theory is that the operators involved are no longer required to be compact in the norm topology. Instead it is required that the image of a bounded set under the operator family is sequentially compact in a weaker topology. As an application, the theory developed is used to establish solvability results for a class of systems of second kind integral equations on unbounded domains, this class including in particular systems of Wiener-Hopf integral equations with L1 convolutions kernels

On the solvability of a class of second kind integral equations on unbounded domains

We consider integral equations of the form ψ(x) = φ(x) + ∫Ωk(x, y)z(y)ψ(y) dy(in operator form ψ = φ + Kzψ), where Ω is some subset ofRn(n ≥ 1). The functionsk,z, and φ are assumed known, withz ∈ L∞(Ω) and φ ∈ Y, the space of bounded continuous functions on Ω. The function ψ ∈ Yis to be determined. The class of domains Ω and kernelskconsidered includes the case Ω = Rnandk(x, y) = κ(x − y) with κ ∈ L1(Rn), in which case, ifzis the characteristic function of some setG, the integral equation is one of Wiener–Hopf type. The main theorems, proved using arguments derived from collectively compact operator theory, are conditions on a setW ⊂ L∞(Ω) which ensure that ifI − Kzis injective for allz ∈ WthenI − Kzis also surjective and, moreover, the inverse operators (I − Kz)−1onYare bounded uniformly inz. These general theorems are used to recover classical results on Wiener–Hopf integral operators of21and19, and generalisations of these results, and are applied to analyse the Lippmann–Schwinger integral equation.