Expression-system-dependent modulation of HIV-1 envelope glycoprotein antigenicity and immunogenicity.

Recombinant expression systems differ in the type of glycosylation they impart on expressed antigens such as the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, potentially affecting their biological properties. We performed head-to-head antigenic, immunogenic and molecular profiling of two distantly related Env surface (gp120) antigens produced in different systems: (a) mammalian (293 FreeStyle cells; 293F) cells in the presence of kifunensine, which impart only high-mannose glycans; (b) insect cells (Spodoptera frugiperda, Sf9), which confer mainly paucimannosidic glycans; (c) Sf9 cells recombinant for mammalian glycosylation enzymes (Sf9 Mimic), which impart high-mannose, hybrid and complex glycans without sialic acid; and (d) 293F cells, which impart high-mannose, hybrid and complex glycans with sialic acid. Molecular models revealed a significant difference in gp120 glycan coverage between the Sf9-derived and wild-type mammalian-cell-derived material that is predicted to affect ligand binding sites proximal to glycans. Modeling of solvent-exposed surface electrostatic potentials showed that sialic acid imparts a significant negative surface charge that may influence gp120 antigenicity and immunogenicity. Gp120 expressed in systems that do not incorporate sialic acid displayed increased ligand binding to the CD4 binding and CD4-induced sites compared to those expressed in the system that do, and imparted other more subtle differences in antigenicity in a gp120 subtype-specific manner. Non-sialic-acid-containing gp120 was significantly more immunogenic than the sialylated version when administered in two different adjuvants, and induced higher titers of antibodies competing for CD4 binding site ligand-gp120 interaction. These findings suggest that non-sialic-acid-imparting systems yield gp120 immunogens with modified antigenic and immunogenic properties, considerations that should be considered when selecting expression systems for glycosylated antigens to be used for structure-function studies and for vaccine use.

Consumer robotic products: studying the factors that influence market adoption

The aim of this article is to identify the key factors that are associated with the adoption of a commercial robot in the home. This article is based on the development of the robot product Cybot by the University of Reading in conjunction with a publisher (Eaglemoss International Ltd.). The robots were distributed through a new part-work magazine series (Ultimate Real Robots) that had long-term customer usage and retention. A part-work is a serial publication that is issued periodically (e.g., every two weeks), usually in magazine format, and builds into a complete collection. This magazine focused on robotics and was accompanied by cover-mounted component parts that could be assembled, with instructions, by the user to build a working robot over the series. In total, the product contributed over half a million operational domestic robots to the world market, selling over 20 million robot part-work magazines across 18 countries, thereby providing a unique breadth of insight. Gaining a better understanding of the overall attitudes that customers of this product had toward robots in the home, their perception of what such devices could deliver and how they would wish to interact with them should provide results applicable to the domestic appliance, assistance/care, entertainment, and educational markets.

The child and the letter: Anne Brontë’s The Tenant of Wildfell Hall

This essay engages with the question of childhood in Anne Brontë’s The Tenant of Wildfell Hall. Despite narrating a conflict concerning child custody, childhood is a subject rarely broached by the critics of the text. Indeed, the only instance of the child being addressed in criticism grants it the power to enclose potentially subversive narrative. This is a function attributed to the framing structure of the novel by other critics. This essay returns the child to Brontë’s text as a disruptive rather than containing force. Through a detailed close analysis of the novel I track such disruptions, and the extent to which these point to wider theoretical or methodological difficulties in critical accounts of childhood and absence in literature. The essay makes interventions into psychoanalysis, childhood studies, and the discourse of ‘framing’ within C19th literature.

‘Scripture its own interpreter’: Mary Martha Sherwood, the Bible and female autobiography

This is a reading of the work of Mary Martha Sherwood, the Victorian Evangelist and Children’s Author (and pupil at the Abbey School, Reading). Based upon research on Sherwood’s private correspondences and diary conducted at UCLA with the aid of a Mitzi Myers (this before my arrival at Reading), the essay offers a radical reinterpretation of her work. Previously understood in terms of a rigid, if self-contradictory and ‘anxious’, Evangelism, the essay reads the diary through Sherwood’s little known Biblical scholarship. Through this I argue that Sherwood grants her own writing the status of Biblical truth precisely because of its contradictions and ‘anxiety’.

The basis of valuations for secured commercial property lending in the UK

In the context of the financial crash and the commercial property market downturn, this paper examines the basis of valuation used in the UK commercial property lending process. Post-crisis there is discussion of countercyclical measures including the monitoring of asset prices; however there is no consideration of a different approach to property valuation. This paper questions this omission, given the role that valuations play in the bank regulatory process. The different bases of valuation available to lenders within International Valuation Standards are identified as Market Value (MV), Mortgage Lending Value (MLV) and Investment Value (IV), with MV being the most used in the UK. Using the different bases in the period before the financial crisis, the UK property market is modelled at a national office, retail and industrial/warehouse sector level to determine the performance of each alternative valuation basis within the context of counter-cyclical pressures on lending. Both MLV and IV would have produced lower valuations and could have provided lenders with tools for more informed and prudent lending. The paper concludes by recognising some of the practical issues involved in adopting the different bases for the bank lending role but recommends a change to IV.

Fit for planning? An evaluation of the application of development viability appraisal models in the UK planning system

The aim of this paper is to critically examine the application of development appraisal to viability assessment in the planning system. This evaluation is of development appraisal models in general and also their use in particular applications associated with estimating planning obligation capacity. The paper is organised into four themes: · The context and conceptual basis for development viability appraisal · A review of development viability appraisal methods · A discussion of selected key inputs into a development viability appraisal · A discussion of the applications of development viability appraisals in the planning system It is assumed that readers are familiar with the basic models and information needs of development viability appraisal rather than at the cutting edge of practice and/or academe

Policy making without legislating: the self-regulation of commercial property leasing

The terms of a commercial property lease covers aspects such as rent, alterations to premises and the ability to leave; consequently they have a significant impact on cash flow and the ability of a business to develop. In contrast to the heavily-legislated residential sector, commercial landlords and tenants in the UK are largely free to negotiate the terms of their contract. Yet, since the property crash of 1989/90, successive governments have taken an interest in commercial leasing; in particular there is a desire to see landlords being more flexible. UK Government policy in this area has been pursued through industry self-regulation rather than legislation; since 1995 there have been three industry codes of practice on leasing. These codes are sanctioned by government and monitored by them. Yet, 15 years after the first code was launched, many in the industry see the whole code concept as ineffective and unlikely to ever achieve changes to certain aspects of landlord behaviour. This paper is the first step in considering the lease codes in the wider context of industry self-regulation. The aim of the paper is twofold: First a framework is created using the literature on industry self-regulation from various countries and industries which suggests key criteria to explain the effectiveness (or ineffectiveness) of self-regulation. This is then applied to the UK lease codes based on research carried out by the authors for the UK Government to monitor the success of all three codes. The outcome is a clearer understanding of the possibilities and limitations of using a voluntary solution to achieve policy aims within the property industry.

The effect of environmental change on human migration

The influence of the environment and environmental change is largely unrepresented in standard theories of migration, whilst recent debates on climate change and migration focus almost entirely on displacement and perceive migration to be a problem. Drawing on an increasing evidence base that has assessed elements of the influence of the environment on migration, this paper presents a new framework for understanding the effect of environmental change on migration. The framework identifies five families of drivers which affect migration decisions: economic, political, social, demographic and environmental drivers. The environment drives migration through mechanisms characterised as the availability and reliability of ecosystem services and exposure to hazard. Individual migration decisions and flows are affected by these drivers operating in combination, and the effect of the environment is therefore highly dependent on economic, political, social and demographic context. Environmental change has the potential to affect directly the hazardousness of place. Environmental change also affects migration indirectly, in particular through economic drivers, by changing livelihoods for example, and political drivers, through affecting conflicts over resources, for example. The proposed framework, applicable to both international and internal migration, emphasises the role of human agency in migration decisions, in particular the linked role of family and household characteristics on the one hand, and barriers and facilitators to movement on the other in translating drivers into actions. The framework can be used to guide new research, assist with the evaluation of policy options, and provide a context for the development of scenarios representing a range of plausible migration futures.

Migration and global environmental change

Introduction to a special issue on migration and global environmental change

Influences on secured lending property valuations in the UK

A significant part of bank lending in the UK is secured on commercial property and valuations play an important part in this process. They are an integral part of risk management within the banking sector. It is therefore important that valuations are independent and objective and are used properly to ensure that secured lending is soundly based from the perspective of both lender and borrower. The purpose of this research is to examine objectivity and transparency in the valuation process for bank lending and to identify any influences which may undermine the process. A detailed analysis of 31 valuation negligence cases has been followed by two focus groups of lenders and valuers and also questionnaire surveys of commercial lenders and valuers. Many stakeholders exist, for example lenders, borrowers and brokers, who are able to influence the process in various ways. The strongest evidence of overt influence in the process comes from the method of valuer selection with borrowers and brokers seen to be heavily involved. There is some also some evidence of influence during the draft valuation process. A significant minority of valuers feel that inappropriate pressure is applied by borrowers and brokers yet there is no apparent part of the process that leads to this. The panel system employed by lenders is found to be a significant part of the system and merits further examination. The pressure felt by valuers needs more investigation along with the question of if and how the process could dispel such feelings. This is seen as particularly important in the context of bank regulation.

Commercial property loan valuations in the UK : the changing landscape of practice and liability

This paper is the first of two which aim to examine the major legal liability implications of changes to the commercial property loan valuation process caused by the recession in the UK property market and to make recommendations to valuers and their professional institutions to improve the quality of the process and the result. This paper identifies the market background to commercial property lending and discusses the implications of the falls in value for lenders and valuers. These include two major strands; first, the outcome of discussions between the representative bodies of these two groups and, second, the increasing litigation caused by lenders suing valuers for professional negligence. The discussions between representative groups have driven a debate on the valuation process leading to a number of reports and guidance notes. This paper discusses the outcomes paying particular attention to the basis of valuation for loan purposes and the provision of additional information in valuation reports. This paper also reviews the legal framework which influences the relationship between the lenders and valuers and discusses the duty of care. The role of instructions in the valuation process, the significance of the identity of the person to be advised and the possibility of a conflict of interest arising are all considered. The paper also addresses the issue of the standards required of a commercial loan valuer, including how this is interpreted by the courts and the legal status of professional guidance notes. The paper concludes by identifying potential areas for dispute within the loan valuation process and raising a number of research questions concerning the operation of this process which are addressed in a following paper.