An investigation into the folding and assembly of engineered antibodies and novel antibody formats

Monoclonal antibodies and novel antibody formats are currently one of the principal therapeutic in the biopharmaceutical industry worldwide and are widely used in the treatment of autoimmune diseases and cancer. It is for this reason that the productivity and quality of antibody production requires improvement; specifically investigations into the engineering of antibodies and any issues that may arise from the production of these therapeutics. The work presented in this thesis describes an investigation into the folding and assembly of seven antibodies plus the novel antibody format FabFv. IgG is comprised of two identical HCs and two identical LCs. The folding process of immunoglobulin is controlled by the CH1 domain within the HC. The CH1 domain remains in a disordered state and is sequestered by BiP in the endoplasmic reticulum. Upon the addition of a folded CL domain, BiP is displaced, the CH1 domain is able to fold and the complete IgG protein can then be secreted from the cell. The results presented in this thesis however, have outlined an additional mechanism for the folding of the CH1 domain. We have shown that the CH1 domain is able to fold in the absence of LC resulting in the secretion of HC dimers in a VH dependent manner. The proposed mechanism for the secretion of HC dimers suggests that some VH domains can interact with each other in order to bring the CH1 domains in close proximity to enable folding to occur. As HC dimer secretion is a hindrance in antibody production, this result has highlighted an engineering target to improve antibody yield. Examination of the folding of IgG4 with the variable region A33 has revealed the inability to secrete LC dimers, cleavage of the HC during expression and secretion of HC dimers in the Fab, FabFv and full length forms. The attributes described have also been shown to be variable region dependent. This has introduced a new concept that the variable domain is important in determining the expression and secretion of antibodies and their individual chains. Pulse chase and 2D gel electrophoresis analysis of the novel antibody format FabFv has revealed that the folding and expression of the LC and HC causes multimeric species of FabFv to be secreted, as opposed to the monomeric form which is the desired therapeutic. Our hypothesis is that this process occurs via a LC dependent mechanism. The proposed hypothesis suggests that further engineering to the LC could diminish the formation and secretion of FabFv multimers. The results from these investigations can be applied to increase the productivity of therapeutics and increase the biological understanding of the domain interactions of IgG during folding, assembly and secretion.

Formats des groupes et types de discussion dans la recherche sociale qualitative

La dénomination « entretiens de groupe » renvoie à une pluralité de dispositifs de groupes de recherche. Compte tenu de la confusion qui est souvent malheureusement faite entre certains de ces dispositifs, cet article cherche à souligner l’intérêt que représente pour la recherche sociale qualitative le fait de mieux nuancer les différences entre l’entretien simultané, le focus group et le groupe de discussion, concrètement. C’est pourquoi cet article a pour objectif la prise en considération, tout à la fois, de sa configuration socio-historique (en ce qui concerne les entretiens simultanés pionniers ou focused interviews, par exemple), et de la forme distincte de la discussion que chacun met en scène (soit le débat soit la conversation), ainsi que de leurs dynamiques (semi-directive et progressive, pour le focus group, et non directive et processuelle, pour le groupe de discussion). Plaidant pour la possibilité d’une complémentarité des dispositifs plutôt que pour leur chevauchement.

The exploration of consumer power in online brand communities : a comparison case study in Australia and China

Aided by the development of information technology, the balance of power in the market place is rapidly shifting from marketers towards consumers and nowhere is this more obvious than in the online environment (Denegri-Knott, Zwick, & Schroeder, 2006; Moynagh & Worsley, 2002; Newcomer, 2000; Samli, 2001). From the inception and continuous development of the Internet, consumers are becoming more empowered. They can choose what they want to click on the Internet, they can shop and transact payments, watch and download video, chat with others, be it friends or even total strangers. Especially in online communities, like-minded consumers share and exchange information, ideas and opinions. One form of online community is the online brand community, which gathers specific brand lovers. As with any social unit, people form different roles in the community and exert different effects on each other. Their interaction online can greatly influence the brand and marketers. A comprehensive understanding of the operation of this special group form is essential to advancing marketing thought and practice (Kozinets, 1999). While online communities have strongly shifted the balance of power from marketers to consumers, the current marketing literature is sparse on power theory (Merlo, Whitwell, & Lukas, 2004). Some studies have been conducted from an economic point of view (Smith, 1987), however their application to marketing has been limited. Denegri-Knott (2006) explored power based on the struggle between consumers and marketers online and identified consumer power formats such as control over the relationship, information, aggregation and participation. Her study has built a foundation for future power studies in the online environment. This research project bridges the limited marketing literature on power theory with the growing recognition of online communities among marketing academics and practitioners. Specifically, this study extends and redefines consumer power by exploring the concept of power in online brand communities, in order to better understand power structure and distribution in this context. This research investigates the applicability of the factors of consumer power identified by Denegri-Knott (2006) to the online brand community. In addition, by acknowledging the model proposed by McAlexander, Schouten, & Koenig (2002), which emphasized that community study should focus on the role of consumers and identifying multiple relationships among the community, this research further explores how member role changes will affect power relationships as well as consumer likings of the brand. As a further extension to the literature, this study also considers cultural differences and their effect on community member roles and power structure. Based on the study of Hofstede (1980), Australia and China were chosen as two distinct samples to represent differences in two cultural dimensions, namely individualism verses collectivism and high power distance verses low power distance. This contribution to the research also helps answer the research gap identified by Muñiz Jr & O'Guinn (2001), who pointed out the lack of cross cultural studies within the online brand community context. This research adopts a case study methodology to investigate the issues identified above. Case study is an appropriate research strategy to answer “how” and “why” questions of a contemporary phenomenon in real-life context (Yin, 2003). The online brand communities of “Haloforum.net” in Australia and “NGA.cn” in China were selected as two cases. In-depth interviews were used as the primary data collection method. As a result of the geographical dispersion and the preference of a certain number of participants, online synchronic interviews via MSN messenger were utilized along with the face-to-face interviews. As a supplementary approach, online observation was carried over two months, covering a two week period prior to the interviews and a six week period following the interviews. Triangulation techniques were used to strengthen the credibility and validity of the research findings (Yin, 2003). The findings of this research study suggest a new definition of power in an online brand community. This research also redefines the consumer power types and broadens the brand community model developed by McAlexander et al. (2002) in an online context by extending the various relationships between brand and members. This presents a more complete picture of how the perceived power relationships are structured in the online brand community. A new member role is discovered in the Australian online brand community in addition to the four member roles identified by Kozinets (1999), in contrast however, all four roles do not exist in the Chinese online brand community. The research proposes a model which links the defined power types and identified member roles. Furthermore, given the results of the cross-cultural comparison between Australia and China showed certain discrepancies, the research suggests that power studies in the online brand community should be country-specific. This research contributes to the body of knowledge on online consumer power, by applying it to the context of an online brand community, as well as considering factors such as cross cultural difference. Importantly, it provides insights for marketing practitioners on how to best leverage consumer power to serve brand objective in online brand communities. This, in turn, should lead to more cost effective and successful communication strategies. Finally, the study proposes future research directions. The research should be extended to communities of different sizes, to different extents of marketer control over the community, to the connection between online and offline activities within the brand community, and (given the cross-cultural findings) to different countries. In addition, a greater amount of research in this area is recommended to determine the generalizability of this study.

Discourse and assessment

Many contemporary currents in applied linguistics have favored discourse studies within assessment; there have been calls for cross-fertilization with other areas within applied linguistics, critiques of the positivist tradition within language testing research, and the growing impact of Conversation Analysis (CA) and sociocultural theory. This chapter focuses on the resulting increase in discourse-based studies of oral proficiency assessment techniques. These studies initially focused on the traditional oral proficiency interview but have since been extended to new test formats, including paired and group interaction. We discuss the research carried out on a number of factors in the assessment setting, including the role of the interlocutor, candidate, and rater, and the impact of tasks, task performance conditions, and rating criteria. Recent research has also concentrated more specifically on the assessment of pragmatic competence and on the applications of technology within the assessment of spoken language, including the comparability of semidirect and direct methods for such assessment and the use of computer corpora.

Multiple-choice versus short-response items: Differences in omit behavior

The overall rate of omission of items for 28,331 17 year old Australian students on a high stakes test of achievement in the common elements or cognitive skills of the senior school curriculum is reported for a subtest in multiple choice format and a subtest in short response format. For the former, the omit rates were minuscule and there was no significant difference by gender or by type of school attended. For the latter, where an item can be 'worth' up to five times that of a single multiple choice item, the omit rates were between 10 and 20 times that for multiple choice and the difference between male and female omit rate was significant as was the difference between students from government and non-government schools. For both formats, females from single sex schools omitted significantly fewer items than did females from co-educational schools. Some possible explanations of omit behaviour are alluded to.

BioPatML : pattern sharing for the genomic sciences

Computational biology increasingly demands the sharing of sophisticated data and annotations between research groups. Web 2.0 style sharing and publication requires that biological systems be described in well-defined, yet flexible and extensible formats which enhance exchange and re-use. In contrast to many of the standards for exchange in the genomic sciences, descriptions of biological sequences show a great diversity in format and function, impeding the definition and exchange of sequence patterns. In this presentation, we introduce BioPatML, an XML-based pattern description language that supports a wide range of patterns and allows the construction of complex, hierarchically structured patterns and pattern libraries. BioPatML unifies the diversity of current pattern description languages and fills a gap in the set of XML-based description languages for biological systems. We discuss the structure and elements of the language, and demonstrate its advantages on a series of applications, showing lightweight integration between the BioPatML parser and search engine, and the SilverGene genome browser. We conclude by describing our site to enable large scale pattern sharing, and our efforts to seed this repository.

Advancing e-learning policy and practice : influences on academics’ adoption, integration and development of multimodal e-learning courses

Tertiary education is increasingly a contested space where advances in Information Communications Technologies and their application to technology-mediated e-learning environments have forced university administrators and educators to dislocate themselves from traditional correspondence modes of student engagement. Compounding this paradigmatic shift within the traditional sphere of distance education pedagogy are multiple and conflicting pressures on academics to develop flexible, engaging, cost-effective and sustainable interactive learning resources that incorporate both multimedia and hypermedia. This chapter reports on a study that examined factors that influence educators’ decision to adopt and integrate educational technology and convert traditional print-based distance education materials into interactive multimodal e-learning formats. Although the broader study was conducted in a single Australian university and investigated pedagogical, institutional and individual factors, this chapter restricts its focus to solely the pedagogical motivations and concerns of educators. It is argued that findings from the study have significance at the institutional level, particularly in terms of developing an underlying pedagogical rationale that can permeate the e-learning culture throughout the university, while at the same time, providing a roadmap for educators who are yet to fully engage with the e-learning format.

The understanding of avatar design : various types and styles of avatars and the design considerations

People have adopted various formats of media such as graphics, photo and text (nickname) in order to represent themselves when communicate with others online. Avatar is known as a visual form representing a user oneself and one's identity wished. Its form can vary from a two-dimensional model to a three-dimensional model, and can be visualised with various visual forms and styles. In general, two-dimensional images including an animated image are used in online forum communities and live chat software; while three-dimensional models are often used in computer games. Avatar design is often regarded as a graphic designer's visual image creation or a user's output based on one's personal preference, yet it often causes the avatar design having no consideration of its practical visual design and users' interactive communication experience aspects. This paper will review various types and styles of avatar and discuss about avatar design from visual design and online user experience perspectives. It aims to raise a design discourse in avatar design and build up a well-articulated set of design principles for effective avatar design.

Introduction : the global flow of creative ideas

In the era of late modernism, various pressures play a decisive role in shaping the texture and meaning of the world around us. Population, work, transportation, new technologies of information and communication, lifestyle cultures and other forces are increasingly mobile, and this in turn helps make for a new set of public and personal surroundings. Social life everywhere now appears to share more and more in an international (if not a global) order, even if inequality and stratification remain common inside territories and across territories. Still, the perception is that a particular cultural life is increasingly universal. More and more consumers come to share in its practices and products, with those products becoming more and more homogeneous. This standardization argument finds much support in the apparent internationalization of many elements of media, entertainment, leisure and lifestyle cultures, with cultural conglomerates determined to maximize their global market reach. Once upon a time, in order to understand the economic, political and cultural forces affecting citizens and society, it was mostly deemed sufficient to look within the boundaries of the nation-state. Over the past two decades, these same pressures of globalization have impacted on critical research, highlighting the methodological need to adopt an optic that is more cross-border and transcultural as a means of gaining greater understanding of cultural life.

Computer profiling for forensic purposes

Computer forensics is the process of gathering and analysing evidence from computer systems to aid in the investigation of a crime. Typically, such investigations are undertaken by human forensic examiners using purpose-built software to discover evidence from a computer disk. This process is a manual one, and the time it takes for a forensic examiner to conduct such an investigation is proportional to the storage capacity of the computer's disk drives. The heterogeneity and complexity of various data formats stored on modern computer systems compounds the problems posed by the sheer volume of data. The decision to undertake a computer forensic examination of a computer system is a decision to commit significant quantities of a human examiner's time. Where there is no prior knowledge of the information contained on a computer system, this commitment of time and energy occurs with little idea of the potential benefit to the investigation. The key contribution of this research is the design and development of an automated process to describe a computer system and its activity for the purposes of a computer forensic investigation. The term proposed for this process is computer profiling. A model of a computer system and its activity has been developed over the course of this research. Using this model a computer system, which is the subj ect of investigation, can be automatically described in terms useful to a forensic investigator. The computer profiling process IS resilient to attempts to disguise malicious computer activity. This resilience is achieved by detecting inconsistencies in the information used to infer the apparent activity of the computer. The practicality of the computer profiling process has been demonstrated by a proof-of concept software implementation. The model and the prototype implementation utilising the model were tested with data from real computer systems. The resilience of the process to attempts to disguise malicious activity has also been demonstrated with practical experiments conducted with the same prototype software implementation.

Europe and the Media: Building a new kind of Europe; is mass media the key?

The book is a joint effort of eight academics and journalists, Europe specialists from six countries (Australia, Germany, Poland, Slovenia, the United Kingdom and the United States). They give sometimes divergent views on the future of the so-called “European Project”, for building a common European economy and society, but agree that cultural changes, especially changes experienced through mass media, are rapidly taking place. One of the central interests of the book is the operation of the large media centre located at the European Commission in Brussels – the world’s largest gallery of permanently accredited correspondents. Jacket notes: The Lisbon Treaty of December 2009 is the latest success of the European Union’s drive to restructure and expand; yet questions persist about how democratic this new Europe might be. Will Brussels’ promotion of the “European idea” produce a common European culture and society? The authors consider it might, as a culture of everyday shared experience, though old ways are cherished, citizens forever thinking twice about committing to an uncertain future. The book focuses on mass media , as a prime agent of change, sometimes used deliberately to promote a “European project”; sometimes acting more naturally as a medium for new agendas. It looks at proposed media models for Europe, ranging from not very successful pan-European television, to the potentials of media systems based on national markets, and new media based on digital formats. It also studies the Brussels media service, the centre operated by the European Commission, which is the world’s largest concentration of journalists; and ways that dominant national media may come to serve the interests of communities now extending across frontiers. Europe and the Media notes change especially as encountered by new EU member countries of central and eastern Europe.

Fashion manufacturing in New Zealand : can design contribute to a sustainable fashion Industry?

In the late 1990s New Zealand fashion gained some international recognition for its dark edginess and intellectual connection due to its colonial past (Molloy, 2004). In the years since, this momentum seems to have dissipated as local fashion companies have followed a global trend towards inexpensive off shore manufacturing. The transfer of the making of garments to overseas workers appears to have resulted in a local fashion scene where many garments look the same in style, colour, cut and fit. The excitement of the past, where the majority of fashion designers established their own individuality through the cut and shape of the garments that they produced, may have been inadvertently lost. Consequently a sustainable New Zealand fashion and manufacturing industry, with design integrity, seems further out of reach. The first question posed by this research project is, ‘can the design and manufacture of a fashion garment, bearing in mind certain economic and practical restrictions at its inception, result in the development of a distinctive ‘look’ or ‘handwriting’?’ Second, through development of a collection of prototypes, can potential garments be created to be sustainably manufactured in New Zealand?

A summary view of government cost recovery policies in Australia and New Zealand relating to the supply of public sector information

Researching administrative history is problematical. A trail of authoritative documents is often hard to find; and useful summaries can be difficult to organise, especially if source material is in paper formats in geographically dispersed locations. In the absence of documents, the reasons for particular decisions and the rationale underpinning particular policies can be confounded as key personnel advance in their professions and retire. The rationale for past decisions may be lost for practical purposes; and if an organisation’s memory of events is diminished, its learning through experience is also diminished. Publishing this document tries to avoid unnecessary duplication of effort by other researchers that need to venture into how policies of charging for public sector information have been justified. The author compiled this work within a somewhat limited time period and the work does not pretend to be a complete or comprehensive analysis of the issues.----- A significant part of the role of government is to provide a framework of legally-enforceable rights and obligations that can support individuals and non-government organisations in their lawful activities. Accordingly, claims that governments should be more ‘business-like’ need careful scrutiny. A significant supply of goods and services occurs as non-market activity where neither benefits nor costs are quantified within conventional accounting systems or in terms of money. Where a government decides to provide information as a service; and information from land registries is archetypical, the transactions occur as a political decision made under a direct or a clearly delegated authority of a parliament with the requisite constitutional powers. This is not a market transaction and the language of the market confuses attempts to describe a number of aspects of how governments allocate resources.----- Cost recovery can be construed as an aspect of taxation that is a sole prerogative of a parliament. The issues are fundamental to political constitutions; but they become more complicated where states cede some taxing powers to a central government as part of a federal system. Nor should the absence of markets be construed necessarily as ‘market failure’ or even ‘government failure’. The absence is often attributable to particular technical, economic and political constraints that preclude the operation of markets. Arguably, greater care is needed in distinguishing between the polity and markets in raising revenues and allocating resources; and that needs to start by removing unhelpful references to ‘business’ in the context of government decision-making.