The PG500 series : novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy

Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellular carcinoma. Advances in the chemistry of the PG500 series provide numerous advantages over PI-88. These new compounds are fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development. The rational design of these compounds has led to vast improvements in potency compared to PI-88, based on in vitro angiogenesis assays and in vivo tumor models. Based on these and other data, PG545 has been selected as the lead clinical candidate for oncology and is currently undergoing formal preclinical development as a novel treatment for advanced cancer.

Thomas Young's contribution to visual optics : the Bakerian lecture "On the mechanism of the eye"

Thomas Young (1773-1829) carried out major pioneering work in many different subjects. In 1800 he gave the Bakerian Lecture of the Royal Society on the topic of the “mechanism of the eye”: this was published in the following year (Young, 1801). Young used his own design of optometer to measure refraction and accommodation, and discovered his own astigmatism. He considered the different possible origins of accommodation and confirmed that it was due to change in shape of the lens rather than to change in shape of the cornea or an increase in axial length. However, the paper also dealt with many other aspects of visual and ophthalmic optics, such as biometric parameters, peripheral refraction, longitudinal chromatic aberration, depth-of-focus and instrument myopia. These aspects of the paper have previously received little attention. We now give detailed consideration to these and other less-familiar features of Young’s work and conclude that his studies remain relevant to many of the topics which currently engage visual scientists.

Beware of geeks bearing gifts? Online latent and untapped outlets for farmers' markets in South East Wales

This chapter sets out to identify related issues surrounding the use of Information and Computer Technology (ICT) in developing relationships between local food producers and consumers (both individuals and businesses). Three surveys were conducted in South- East Wales to consider the overlapping issues. The first concerned the role of ICT in relationships between farmers’ market (FMs) vendors and their traditional customers. The second survey examined potential new markets for farmers in the propensity of restaurants and hotels to buy locally, the types and sources of purchases made and the modes of advertising of these businesses. The final survey focused on the potential to expand local web- based selling of farmers’ produce in the future, by examining the potential market of high ICT- use small hotels. Despite the development of tailored ICT facilities, farmers’ market vendors and current individual customers are antipathetic to them. In addition, whilst there is a desire for more local produce particularly amongst independent local restaurants and hotels, this has not been capitalised upon and there is much work to be done even amongst high ICT-use small hotels, to expand the range and scope of farmers’ markets. This raises the need for creation and utilisation of enhanced logistics, payment and marketing management capacity available through a web- based presence, linked to promotion of FMs in business- to- business (B2B) links with local restaurants and hotels. This linked quantitative research highlights the potential value in substantial development of both web portals and supporting logistics to exploit this potential in the future.

Equity in the twenty-first century

Issues of equity and inequity have always been part of employment relations and are a fundamental part of the industrial landscape. For example, in most countries in the nineteenth century and a large part of the twentieth century women and members of ethnic groups (often a minority in the workforce) were barred from certain occupations, industries or work locations, and received less pay than the dominant male ethnic group for the same work. In recent decades attention has been focused on issues of equity between groups, predominantly women and different ethnic groups in the workforce. This has been embodied in industrial legislation, for example in equal pay for women and men, and frequently in specific equity legislation. In this way a whole new area of law and associated workplace practice has developed in many countries. Historically, employment relations and industrial relations research has not examined employment issues disaggregated by gender or ethnic group. Born out of concern with conflict and regulation at the workplace, studies tended to concentrate on white, male, unionized workers in manufacturing and heavy industry (Ackers, 2002, p. 4). The influential systems model crafted by Dunlop (1958) gave rise to The discipline’s preoccupation with the ‘problem of order’ [which] ensures the invisibility of women, not only because women have generally been less successful in mobilizing around their own needs and discontents, but more profoundly because this approach identifies the employment relationship as the ultimate source of power and conflict at work (Forrest, 1993, p. 410). While ‘the system approach does not deliberately exclude gender . . . by reproducing a very narrow research approach and understanding of issues of relevance for the research, gender is in general excluded or looked on as something of peripheral interest’ (Hansen, 2002, p. 198). However, long-lived patterns of gender segregation in occupations and industries, together with discriminatory access to work and social views about women and ethnic groups in the paid workforce, mean that the employment experience of women and ethnic groups is frequently quite different to that of men in the dominant ethnic group. Since the 1980s, research into women and employment has figured in the employment relations literature, but it is often relegated to a separate category in specific articles or book chapters, with women implicitly or explicitly seen as the atypical or exceptional worker (Hansen, 2002; Wajcman, 2000). The same conclusion can be reached for other groups with different labour force patterns and employment outcomes. This chapter proposes that awareness of equity issues is central to employment relations. Like industrial relations legislation and approaches, each country will have a unique set of equity policies and legislation, reflecting their history and culture. Yet while most books on employment and industrial relations deal with issues of equity in a separate chapter (most commonly on equity for women or more recently on ‘diversity’), the reality in the workplace is that all types of legislation and policies which impact on the wages and working conditions interact, and their impact cannot be disentangled one from another. When discussing equity in workplaces in the twenty-first century we are now faced with a plethora of different terms in English. Terms used include discrimination, equity, equal opportunity, affirmative action and diversity with all its variants (workplace diversity, managing diversity, and so on). There is a lack of agreed definitions, particularly when the terms are used outside of a legislative context. This ‘shifting linguistic terrain’ (Kennedy-Dubourdieu, 2006b, p. 3) varies from country to country and changes over time even within the one country. There is frequently a division made between equity and its related concepts and the range of expressions using the term ‘diversity’ (Wilson and Iles, 1999; Thomas and Ely, 1996). These present dilemmas for practitioners and researchers due to the amount and range of ideas prevalent – and the breadth of issues that are covered when we say ‘equity and diversity in employment’. To add to these dilemmas, the literature on equity and diversity has become bifurcated: the literature on workplace diversity/management diversity appears largely in the business literature while that on equity in employment appears frequently in legal and industrial relations journals. Workplaces of the twenty-first century differ from those of the nineteenth and twentieth century not only in the way they deal with individual and group differences but also in the way they interpret what are fair and equitable outcomes for different individuals and groups. These variations are the result of a range of social conditions, legislation and workplace constraints that have influenced the development of employment equity and the management of diversity. Attempts to achieve employment equity have primarily been dealt with through legislative means, and in the last fifty years this legislation has included elements of anti-discrimination, affirmative action, and equal employment opportunity in virtually all OECD countries (Mor Barak, 2005, pp. 17–52). Established on human rights and social justice principles, this legislation is based on the premise that systemic discrimination has and/or continues to exist in the labour force and particular groups of citizens have less advantageous employment outcomes. It is based on group identity, and employment equity programmes in general apply across all workplaces and are mandatory. The more recent notions of diversity in the workplace are based on ideas coming principally from the USA in the 1980s which have spread widely in the Western world since the 1990s. Broadly speaking, diversity ideas focus on individual differences either on their own or in concert with the idea of group differences. The diversity literature is based on a business case: that is diversity is profitable in a variety of ways for business, and generally lacks a social justice or human rights justification (Burgess et al., 2009, pp. 81–2). Managing diversity is represented at the organizational level as a voluntary and local programme. This chapter discusses some major models and theories for equity and diversity. It begins by charting the history of ideas about equity in employment and then briefly discusses what is meant by equality and equity. The chapter then analyses the major debates about the ways in which equity can be achieved. The more recent ideas about diversity are then discussed, including the history of these ideas and the principles which guide this concept. The following section discusses both major frameworks of equity and diversity. The chapter then raises some ways in which insights from the equity and diversity literature can inform employment relations. Finally, the future of equity and diversity ideas is discussed.

Thomas Young’s contributions to geometrical optics

In addition to his work on physical optics, Thomas Young (1773-1829) made several contributions to geometrical optics, most of which received little recognition in his time or since. We describe and assess some of these contributions: Young’s construction (the basis for much of his geometric work), paraxial refraction equations, oblique astigmatism and field curvature, and gradient-index optics.

Thomas Young’s investigations in gradient-index optics

Purpose: James Clerk Maxwell is usually recognized as being the first, in 1854, to consider using inhomogeneous media in optical systems. However, some fifty years earlier Thomas Young, stimulated by his interest in the optics of the eye and accommodation, had already modeled some applications of gradient-index optics. These applications included using an axial gradient to provide spherical aberration-free optics and a spherical gradient to describe the optics of the atmosphere and the eye lens. We evaluated Young’s contributions. Method: We attempted to derive Young’s equations for axial and spherical refractive index gradients. Raytracing was used to confirm accuracy of formula. Results: We did not confirm Young’s equation for the axial gradient to provide aberration-free optics, but derived a slightly different equation. We confirmed the correctness of his equations for deviation of rays in a spherical gradient index and for the focal length of a lens with a nucleus of fixed index surrounded by a cortex of reducing index towards the edge. Young claimed that the equation for focal length applied to a lens with part of the constant index nucleus of the sphere removed, such that the loss of focal length was a quarter of the thickness removed, but this is not strictly correct. Conclusion: Young’s theoretical work in gradient-index optics received no acknowledgement from either his contemporaries or later authors. While his model of the eye lens is not an accurate physiological description of the human lens, with the index reducing least quickly at the edge, it represented a bold attempt to approximate the characteristics of the lens. Thomas Young’s work deserves wider recognition.

Expression of HPV-11 L1 protein in transgenic Arabidopsis thaliana and Nicotiana tabacum

Background We have investigated the possibility and feasibility of producing the HPV-11 L1 major capsid protein in transgenic Arabidopsis thaliana ecotype Columbia and Nicotiana tabacum cv. Xanthi as potential sources for an inexpensive subunit vaccine. Results Transformation of plants was only achieved with the HPV-11 L1 gene with the C-terminal nuclear localization signal (NLS-) encoding region removed, and not with the full-length gene. The HPV-11 L1 NLS- gene was stably integrated and inherited through several generations of transgenic plants. Plant-derived HPV-11 L1 protein was capable of assembling into virus-like particles (VLPs), although resulting particles displayed a pleomorphic phenotype. Neutralising monoclonal antibodies binding both surface-linear and conformation-specific epitopes bound the A. thaliana-derived particles and - to a lesser degree - the N. tabacum-derived particles, suggesting that plant-derived and insect cell-derived VLPs displayed similar antigenic properties. Yields of up to 12 μg/g of HPV-11 L1 NLS- protein were harvested from transgenic A. thaliana plants, and 2 μg/g from N. tabacum plants - a significant increase over previous efforts. Immunization of New Zealand white rabbits with ∼50 μg of plant-derived HPV-11 L1 NLS- protein induced an antibody response that predominantly recognized insect cell-produced HPV-11 L1 NLS- and not NLS+ VLPs. Evaluation of the same sera concluded that none of them were able to neutralise pseudovirion in vitro. Conclusion We expressed the wild-type HPV-11 L1 NLS- gene in two different plant species and increased yields of HPV-11 L1 protein by between 500 and 1000-fold compared to previous reports. Inoculation of rabbits with extracts from both plant types resulted in a weak immune response, and antisera neither reacted with native HPV-11 L1 VLPs, nor did they neutralise HPV-11 pseudovirion infectivity. This has important and potentially negative implications for the production of HPV-11 vaccines in plants. © 2007 Kohl et al; licensee BioMed Central Ltd.

David M. Thomas : a party disguised as work or work disguised as a party

This article discusses David M. Thomas' 2012 exhibition at Boxcopy. Thomas' exhibition conflates the space of the studio with that of the gallery. In doing so, he draws out complex relationships between production and presentation, subjectivity and sociality. This article focuses on these aspects of Thomas' creative exploration of identity and its mutability through art making.

Jean Baptiste Francois Pompallier, Thomas Arnold and Julian Edmund Tenison Woods and their contribution to the formation and development of Catholic schooling in Australasia

Histories of Catholic education have received little attention by Church historians and are usually written by members of the Catholic clergy, with a strong emphasis placed on the spiritual and building accomplishments of the bishops. This thesis examines the provision of Catholic Education in Australasia, with a focus on the contribution of three men, Jean Baptiste Francois Pompallier, Thomas Arnold and Julian Edmund Tenison Woods. These men received support from the female religious orders in the regions where they worked, frequently with little recognition or praise by Catholic Church authorities. The tenets of their faith gave Pompallier and Woods strength and reinforced their determination to succeed. Arnold, however, possessed a strong desire to change society. All three believed in the desirability of providing Catholic schooling for the poor, with the curriculum facilitating the acquisition of socially desirable values and traits, including obedience, honesty, moral respectability and a strong adherence to Catholic religious values. The beneficiaries included society, future employers, the Church, the children and their parents. With the exception of promoting distinctly Catholic religious values, Roman Catholic schools and National schools in Australasia shared identical objectives. Historians have neglected the contributions of these men.

An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12

Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci. An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1×10−5) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92×10−4), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65×10−4). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women’s Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05). Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63×10−5) is located within the 5′UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.