Protein complementation assay as a display system for screening protein libraries in the intracellular environment

A wide range of screening strategies have been employed to isolate antibodies and other proteins with specific attributes, including binding affinity, specificity, stability and improved expression. However, there remains no high-throughput system to screen for target-binding proteins in a mammalian, intracellular environment. Such a system would allow binding reagents to be isolated against intracellular clinical targets such as cell signalling proteins associated with tumour formation (p53, ras, cyclin E), proteins associated with neurodegenerative disorders (huntingtin, betaamyloid precursor protein), and various proteins crucial to viral replication (e.g. HIV-1 proteins such as Tat, Rev and Vif-1), which are difficult to screen by phage, ribosome or cell-surface display. This study used the β-lactamase protein complementation assay (PCA) as the display and selection component of a system for screening a protein library in the cytoplasm of HEK 293T cells. The colicin E7 (ColE7) and Immunity protein 7 (Imm7) *Escherichia coli* proteins were used as model interaction partners for developing the system. These proteins drove effective β-lactamase complementation, resulting in a signal-to-noise ratio (9:1 – 13:1) comparable to that of other β-lactamase PCAs described in the literature. The model Imm7-ColE7 interaction was then used to validate protocols for library screening. Single positive cells that harboured the Imm7 and ColE7 binding partners were identified and isolated using flow cytometric cell sorting in combination with the fluorescent β-lactamase substrate, CCF2/AM. A single-cell PCR was then used to amplify the Imm7 coding sequence directly from each sorted cell. With the screening system validated, it was then used to screen a protein library based the Imm7 scaffold against a proof-of-principle target. The wild-type Imm7 sequence, as well as mutants with wild-type residues in the ColE7- binding loop were enriched from the library after a single round of selection, which is consistent with other eukaryotic screening systems such as yeast and mammalian cell-surface display. In summary, this thesis describes a new technology for screening protein libraries in a mammalian, intracellular environment. This system has the potential to complement existing screening technologies by allowing access to intracellular proteins and expanding the range of targets available to the pharmaceutical industry.

Coordinated research support services at Queensland University of Technology, Australia

Queensland University of Technology (QUT) is a large multidisciplinary university located in Brisbane, Queensland, Australia. QUT is increasing its research focus and is developing its research support services. It has adopted a model of collaboration between the Library, High Performance Computing and Research Support (HPC) and more broadly with Information Technology Services (ITS). Research support services provided by the Library include the provision of information resources and discovery services, bibliographic management software, assistance with publishing (publishing strategies, identifying high impact journals, dealing with publishers and the peer review process), citation analysis and calculating authors’ H Index. Research data management services are being developed by the Library and HPC working in collaboration. The HPC group within ITS supports research computing infrastructure, research development and engagement activities, researcher consultation, high speed computation and data storage systems , 2D/ 3D (immersive) visualisation tools, parallelisation and optimization of research codes, statistics/ data modeling training and support (both qualitative and quantitative) and support for the university’s central Access Grid collaboration facility. Development and engagement activities include participation in research grants and papers, student supervision and internships and the sponsorship, incubation and adoption of new computing technologies for research. ITS also provides other services that support research including ICT training, research infrastructure (networking, data storage, federated access and authorization, virtualization) and corporate systems for research administration. Seminars and workshops are offered to increase awareness and uptake of new and existing services. A series of online surveys on eResearch practices and skills and a number of focus groups was conducted to better inform the development of research support services. Progress towards the provision of research support is described within the context organizational frameworks; resourcing; infrastructure; integration; collaboration; change management; engagement; awareness and skills; new services; and leadership. Challenges to be addressed include the need to redeploy existing operational resources toward new research support services, supporting a rapidly growing research profile across the university, the growing need for the use and support of IT in research programs, finding capacity to address the diverse research support needs across the disciplines, operationalising new research support services following their implementation in project mode, embedding new specialist staff roles, cross-skilling Liaison Librarians, and ensuring continued collaboration between stakeholders.

Life in the 'real world': a profile of Queensland University of Technology Library and Information Science graduates.

A graduate destination survey can provide a snap shot in time of a graduate’s career progression and outcome. This paper will present the results of a Queensland University of Technology study exploring the employment outcomes of students who had completed a library and information science course from the Faculty of Information Technology between 2000 and 2008. Seventy-four graduates completed an online questionnaire administered in July 2009. The study found that 90% of the graduates surveyed were working and living in Queensland, with over three quarters living and working in Brisbane. Nearly 70% were working full-time, while only 1.4% indicating that they were unemployed and looking for work. Over 80% of the graduates identified themselves as working in “librarianship”. This study is the first step in understanding the progression and destination of QUT’s library and information science graduates. It is recommended that this survey becomes an ongoing initiative so that the results can be analysed and compared over time.

Voices of experience : opportunities to influence creatively the designing of school libraries

Using a critical ethnographic approach this study investigates the potential for multiple voices of experience, of educators, designers/architects, education facility planners and students/learners, to influence creatively the designing of school libraries. School libraries are considered as social and cultural entities within the contexts of school life and of wider society. It is proposed that school library designing is a social interaction of concern to those influenced by its practices and outcomes. School library designing is therefore of significance to educators and students as well as to those with professionally accredited involvement in school library designing, such as designers/architects and education facility planners. The study contends that current approaches to educational space designing, including school libraries, amplify the voices of accredited designers and diminish or silence the voices of the user participants. The study is conceptualised as creative processes of discovery, through which attention is paid to the voices of experience of user and designer participants, and is concerned with their understandings and experiences of school libraries and their understandings and experiences of designing. Grounded theory coding (Charmaz) is used for initial categorising of interview data. Critical discourse analysis (CDA, Fairclough) is used as analytical tool for reflection on the literature and for analysis of the small stories gathered through semi-structured interviews, field observations and documents. The critical interpretive stance taken through CDA, enables discussions of aspects of power associated with the understandings and experiences of participants, and for recognition of creative possibilities and creative influence within and beyond current conditions. Through an emphasis on prospects for educators and students as makers of the spaces and places of learning, in particular in school libraries, the study has the potential to inform education facility designing practices and design participant relationships, and to contribute more broadly to knowledge in the fields of education, design, architecture, and education facility planning.

Factors influencing funding decisions by elected politicians at the state/provincial level : a case study of public libraries in Canada

The purpose of this study was to determine factors (internal and external) that influenced Canadian provincial (state) politicians when making funding decisions about public libraries. Using the case study methodology, Canadian provincial/state level funding for public libraries in the 2009-10 fiscal year was examined. After reviewing funding levels across the country, three jurisdictions were chosen for the case: British Columbia's budget revealed dramatically decreased funding, Alberta's budget showed dramatically increased funding, and Ontario's budget was unchanged from the previous year. The primary source of data for the case was a series of semi-structured interviews with elected officials and senior bureaucrats from the three jurisdictions. An examination of primary and secondary documents was also undertaken to help set the political and economic context as well as to provide triangulation for the case interviews. The data were analysed to determine whether Cialdini's theory of influence (2001) and specifically any of the six tactics of influence (i.e, commitment and consistency, authority, liking, social proof, scarcity and reciprocity) were instrumental in these budget processes. Findings show the principles of "authority", "consistency and commitment" and "liking" were relevant, and that "liking" were especially important to these decisions. When these decision makers were considering funding for public libraries, they most often used three distinct lenses: the consistency lens (what are my values? what would my party do?), the authority lens (is someone with hierarchical power telling me to do this? are the requests legitimate?), and most importantly, the liking lens (how much do I like and know about the requester?). These findings are consistent with Cialdini's theory, which suggests the quality of some relationships is one of six factors that can most influence a decision maker. The small number of prior research studies exploring the reasons for increases or decreases in public library funding allocation decisions have given little insight into the factors that motivate those politicians involved in the process and the variables that contribute to these decisions. No prior studies have examined the construct of influence in decision making about funding for Canadian public libraries at any level of government. Additionally, no prior studies have examined the construct of influence in decision making within the context of Canadian provincial politics. While many public libraries are facing difficult decisions in the face of uncertain funding futures, the ability of the sector to obtain favourable responses to requests for increases may require a less simplistic approach than previously thought. The ability to create meaningful connections with individuals in many communities and across all levels of government should be emphasised as a key factor in influencing funding decisions.

School libraries, teacher-librarians and their contribution to student literacy development in Gold Coast schools

This is the first research focusing on Gold Coast school libraries and teacher- librarians. It presents a detailed picture of library provision and staffing at a representative group of 27 government and non-government schools at the Gold Coast. It shows links between employment of a teacher-librarian and higher NAPLAN reading and writing scores. And it presents the principals’ generally positive views about teacher-librarians’ contribution to reading and literacy at their schools. The findings respond in part to the recent government inquiry’s call (House of Representatives, 2011) for research about the current staffing of school libraries in Australia, and the influence of school libraries and teacher-librarians on students’ literacy and learning outcomes. While the study has focused on a relatively small group of school libraries, it has produced a range of significant outcomes: • An extensive review of international and Australian research showing impacts of school libraries and teacher-librarians on students’ literacy and learning outcomes • Findings consistent with international research showing: - An inverse relationship between lower student to EFT library staff ratio and higher school NAPLAN scores for reading and writing - Schools that employ a teacher-librarian tend to achieve school NAPLAN scores for respective year levels that are higher than the national mean It is anticipated that the study’s findings will be of interest to education authorities, school leadership teams, teacher-librarians, teachers and researchers. The findings provide evidence to: • inform policy development and strategic planning for school libraries that respond to the literacy development needs of 21st century learners • inform school-based management of school libraries • inform curriculum development and teacher-librarian practice • support further collaborative research on a State or national level • enhance conceptual understandings about relationship(s) between school libraries, teacher-librarians and literacy/information literacy development • support advocacy about school libraries, teacher-librarians and their contribution to literacy development and student learning in Australian schools SLAQ President Toni Leigh comments: “It is heartening to see findings which validate the critical role teacher-librarians play in student literacy development and the positive correlation of higher NAPLAN scores and schools with a qualified teacher-librarian. Also encouraging is the high percentage of school principals who recognise the necessity of a well resourced school library and the positive influence of these libraries on student literacy”. This research arises from a research partnership between School Library Association of Queensland (SLAQ) and Children and Youth Research Centre, QUT. Lead researcher: Dr Hilary Hughes, Children and Youth Research Centre, QUT Research assistants: Dr Hossein Bozorgian, Dr Cherie Allan, Dr Michelle Dicinoski, QUT SLAQ Research Reference Group: Toni Leigh, Marj Osborne, Sally Fraser, Chris Kahl and Helen Reynolds Reference: House of Representatives. (2011). School libraries and teacher librarians in 21st century Australia. Canberra: Commonwealth of Australia. http://www.aph.gov.au/Parliamentary_Business/Committees/House_of_Representatives_Committees?url=ee/schoollibraries/report.htm

Information skills coursework for postgraduate students : investigation and response at the Queensland University of Technology

In response to current developments In the tertiary education sector, the Queensland University of Technology Library has mounted an Intensive course - Advanced Information Retrieval Skills - for higher degree students. In determining need for such a course, a survey of postgraduate students and their supervisors was conducted. Results of this survey are discussed and details of the four credit point subjects are outlined.

Influence and increased funding in Canadian public libraries : the case of Alberta in fiscal year 2009–10

This exploratory case study examined the role of social influence in the decision-making process to increase public library funding in the Canadian province of Alberta in the 2009–10 fiscal year. Using Robert Cialdini’s theory of factors of influence (i.e., commitment and consistency, authority, liking, social proof, scarcity, and reciprocity) as a framework for analysis, findings show that consistency and commitment and authority were relevant and that liking was also important. These findings are consistent with Cialdini’s theory, which suggests that the quality of relationships is one factor that can most strongly influence a decision maker. This study gives insight into the factors motivating those involved in public library funding allocation decisions. No prior studies have examined the construct of influence in decision making about funding for public libraries at any level of government.

Educating cultural heritage information professionals for Australia's galleries, libraries, archives and museums: A grounded Delphi study

This research explored the knowledge, skills, qualities, and professional education needs, of information professionals in galleries, libraries, archives and museums (GLAM) in Australia. The findings revealed that although full convergence of these sectors is unlikely, many of the skills, knowledge and qualities would be required across all four sectors. The research used the Grounded Delphi Method, a relatively new methodological extension of the Delphi method that incorporates aspects of Grounded Theory. The findings provide the first empirically based guidelines around what needs to be included in an educational framework for information professionals who will work in the emerging GLAM environment. As the first study of GLAM education requirements in Australia and the wider Asia-Pacific region to take a holistic approach by engaging information professionals across all four sectors, this thesis makes a contribution to the GLAM research field and to information education generally.

Exploring the relationships between design & public libraries through the lens of service design

Design is ubiquitous to the life of contemporary societies and key to their progress, but for some, it is an elitist concept. This thesis investigates the role of public libraries contribution to the general public's understanding of 'Design'. This study compared participants views in the context of State Libraries in two cities: Brisbane and Curitiba. Findings revealed that exploring four new aspects in the Development and Deliver Stages of a service design framework for public libraries can be an effective tool to enhance people's access and experiences of Design, and ultimately, it can contribute to the democratization of design.

Exploring the relationships between design and public libraries through the lens of service design

Design is ubiquitous to the life of contemporary societies and key to their progress, but for some, it is an elitist concept. This thesis investigates the role of public libraries contribution to the general public's understanding of "Design". This study compared participants views in the context of State Libraries in two cities: Brisbane and Curitiba. Findings revealed that exploring four new aspects in the Development and Deliver Stages of a service design framework for public libraries can be an effective tool to enhance people"s access and experiences of Design, and ultimately, it can contribute to the democratisation of design.

The Politics of Pulp Investment and the Brazilian Landless Movement (MST)

The Politics of Pulp Investment and the Brazilian Landless Movement (MST) The paper industry has been moving more heavily to the global South at the beginning of the 21st century. In a number of cases the rural populations of the global South have engaged in increasingly important resistance in their scuffle with the large-scale tree plantation-relying pulp investment model. The resistance had generally not yet managed to slow down Southern industrial tree plantation expansion until 2004. After all, even the MST, perhaps the strongest of the Southern movements, has limited power in comparison to the corporations pushing for plantation expansion. This thesis shows how, even against these odds, depending on the mechanisms of contention and case-specific conflict dynamics, in some cases the movements have managed to slow and even reverse plantation expansion. The thesis is based on extensive field research in the Brazilian countryside. It outlines a new theory of contentious agency promotion, emphasizing its importance in the shaping of corporate resource exploitation. The thesis includes a Qualitative Comparative Analysis of resistance influence on the economic outcomes of all (14) Brazilian large-scale pulp projects between 2004-2008. The central hypothesis of the thesis is that corporate resource exploitation can be slowed down more effectively and likely when the resistance is based on contentious agency. Contentious agency is created by the concatenation of five mutually supporting mechanisms of contention: organizing and politicizing a social movement; heterodox framing of pulp projects; protesting; networking; and embedding whilst maintaining autonomy. The findings suggest that contentious agency can slow or even reverse the expansion of industrial plantations, whereas when contentious agency promotion was inactive, fast or even unchecked plantation expansion was always the outcome. The rule applied to all the assessed 14 pulp conflict cases. The hypothesis gained strong support even in situations where corporate agency promotion was simultaneously active. In previous studies on social movements, there has been a lack of contributions that help us understand the causal mechanisms of contention influencing economic outcomes. The thesis answers to the call by merging a Polanyian analysis of the political economy with the Dynamics of Contention research program and making a case for the impact of contentious agency on capital accumulation. The research concludes that an efficient social movement can utilize mechanisms of contention to promote the potential of activism among its members and influence investment outcomes. Protesting, for example via pioneering land occupations, seemed to be particularly important. Until now, there has been no comprehensive theory on when and how contentious agency can slow down or reverse the expansion of corporate resource exploitation. The original contribution of this research is to provide such a theory, and utilize it to offer an extensive explanation on the conflicts over pulp investment in Brazil, the globalization of the paper industry, and slowing of industrial plantation expansion in the global South.

Assessment of In-House Natural Product and Synthetic Compound Libraries Based on In vitro Inhibition of Cholinesterases

The first line medication for mild to moderate Alzheimer s disease (AD) is based on cholinesterase inhibitors which prolong the effect of the neurotransmitter acetylcholine in cholinergic nerve synapses which relieves the symptoms of the disease. Implications of cholinesterases involvement in disease modifying processes has increased interest in this research area. The drug discovery and development process is a long and expensive process that takes on average 13.5 years and costs approximately 0.9 billion US dollars. Drug attritions in the clinical phases are common due to several reasons, e.g., poor bioavailability of compounds leading to low efficacy or toxic effects. Thus, improvements in the early drug discovery process are needed to create highly potent non-toxic compounds with predicted drug-like properties. Nature has been a good source for the discovery of new medicines accounting for around half of the new drugs approved to market during the last three decades. These compounds are direct isolates from the nature, their synthetic derivatives or natural mimics. Synthetic chemistry is an alternative way to produce compounds for drug discovery purposes. Both sources have pros and cons. The screening of new bioactive compounds in vitro is based on assaying compound libraries against targets. Assay set-up has to be adapted and validated for each screen to produce high quality data. Depending on the size of the library, miniaturization and automation are often requirements to reduce solvent and compound amounts and fasten the process. In this contribution, natural extract, natural pure compound and synthetic compound libraries were assessed as sources for new bioactive compounds. The libraries were screened primarily for acetylcholinesterase inhibitory effect and secondarily for butyrylcholinesterase inhibitory effect. To be able to screen the libraries, two assays were evaluated as screening tools and adapted to be compatible with special features of each library. The assays were validated to create high quality data. Cholinesterase inhibitors with various potencies and selectivity were found in natural product and synthetic compound libraries which indicates that the two sources complement each other. It is acknowledged that natural compounds differ structurally from compounds in synthetic compound libraries which further support the view of complementation especially if a high diversity of structures is the criterion for selection of compounds in a library.