Design, construction, and analysis of cell line arrays and tissue microarrays for gene expression analysis

Cell line array (CMA) and tissue microarray (TMA) technologies are high-throughput methods for analysing both the abundance and distribution of gene expression in a panel of cell lines or multiple tissue specimens in an efficient and cost-effective manner. The process is based on Kononen's method of extracting a cylindrical core of paraffin-embedded donor tissue and inserting it into a recipient paraffin block. Donor tissue from surgically resected paraffin-embedded tissue blocks, frozen needle biopsies or cell line pellets can all be arrayed in the recipient block. The representative area of interest is identified and circled on a haematoxylin and eosin (H&E)-stained section of the donor block. Using a predesigned map showing a precise spacing pattern, a high density array of up to 1,000 cores of cell pellets and/or donor tissue can be embedded into the recipient block using a tissue arrayer from Beecher Instruments. Depending on the depth of the cell line/tissue removed from the donor block 100-300 consecutive sections can be cut from each CMA/TMA block. Sections can be stained for in situ detection of protein, DNA or RNA targets using immunohistochemistry (IHC), fluorescent in situ hybridisation (FISH) or mRNA in situ hybridisation (RNA-ISH), respectively. This chapter provides detailed methods for CMA/TMA design, construction and analysis with in-depth notes on all technical aspects including tips to deal with common pitfalls the user may encounter. © Springer Science+Business Media, LLC 2011.

Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer

OBJECTIVE: This study explored gene expression differences in predicting response to chemoradiotherapy in esophageal cancer. PURPOSE:: A major pathological response to neoadjuvant chemoradiation is observed in about 40% of esophageal cancer patients and is associated with favorable outcomes. However, patients with tumors of similar histology, differentiation, and stage can have vastly different responses to the same neoadjuvant therapy. This dichotomy may be due to differences in the molecular genetic environment of the tumor cells. BACKGROUND DATA: Diagnostic biopsies were obtained from a training cohort of esophageal cancer patients (13), and extracted RNA was hybridized to genome expression microarrays. The resulting gene expression data was verified by qRT-PCR. In a larger, independent validation cohort (27), we examined differential gene expression by qRT-PCR. The ability of differentially-regulated genes to predict response to therapy was assessed in a multivariate leave-one-out cross-validation model. RESULTS: Although 411 genes were differentially expressed between normal and tumor tissue, only 103 genes were altered between responder and non-responder tumor; and 67 genes differentially expressed >2-fold. These included genes previously reported in esophageal cancer and a number of novel genes. In the validation cohort, 8 of 12 selected genes were significantly different between the response groups. In the predictive model, 5 of 8 genes could predict response to therapy with 95% accuracy in a subset (74%) of patients. CONCLUSIONS: This study has identified a gene microarray pattern and a set of genes associated with response to neoadjuvant chemoradiation in esophageal cancer. The potential of these genes as biomarkers of response to treatment warrants further investigation. Copyright © 2009 by Lippincott Williams & Wilkins.

An analysis of regression models for predicting the speed of a wave glider autonomous surface vehicle

An important aspect of robotic path planning for is ensuring that the vehicle is in the best location to collect the data necessary for the problem at hand. Given that features of interest are dynamic and move with oceanic currents, vehicle speed is an important factor in any planning exercises to ensure vehicles are at the right place at the right time. Here, we examine different Gaussian process models to find a suitable predictive kinematic model that enable the speed of an underactuated, autonomous surface vehicle to be accurately predicted given a set of input environmental parameters.

Second-order elastic finite element analysis of steel structures using a single element per member

Finite element frame analysis programs targeted for design office application necessitate algorithms which can deliver reliable numerical convergence in a practical timeframe with comparable degrees of accuracy, and a highly desirable attribute is the use of a single element per member to reduce computational storage, as well as data preparation and the interpretation of the results. To this end, a higher-order finite element method including geometric non-linearity is addressed in the paper for the analysis of elastic frames for which a single element is used to model each member. The geometric non-linearity in the structure is handled using an updated Lagrangian formulation, which takes the effects of the large translations and rotations that occur at the joints into consideration by accumulating their nodal coordinates. Rigid body movements are eliminated from the local member load-displacement relationship for which the total secant stiffness is formulated for evaluating the large member deformations of an element. The influences of the axial force on the member stiffness and the changes in the member chord length are taken into account using a modified bowing function which is formulated in the total secant stiffness relationship, for which the coupling of the axial strain and flexural bowing is included. The accuracy and efficiency of the technique is verified by comparisons with a number of plane and spatial structures, whose structural response has been reported in independent studies.

A little learning is a dangerous thing? The ethics of teaching accidental tourists in higher education

This paper raises questions about the ethical issues that arise for academics and universities when under-graduate students enrol in classes outside of their discipline - classes that are not designed to be multi-disciplinary or introductory. We term these students ‘accidental tourists'. Differences between disciplines in terms of pedagogy, norms, language and understanding may pose challenges for accidental tourists in achieving desired learning outcomes. This paper begins a discussion about whether lecturers and universities have any ethical obligations towards supporting the learning of these students. Recognising that engaging with only one ethical theory leads to a fragmented moral vision, this paper employs a variety of ethical theories to examine any possible moral obligations that may fall upon lecturers and/or universities. In regards to lecturers, the paper critically engages with the ethical theories of utilitarianism, Kantianism and virtue ethics (Aristotle) to determine the extent of any academic duty to accidental tourists. In relation to universities, this paper employs the emerging ethical theory of organisational ethics as a lens through which to critically examine any possible obligations. Organisational ethics stems from the recognition that moral demands also exist for organisations so organisations must be reconceptualised as ethical actors and their policies and practices subject to ethical scrutiny. The analysis in this paper illustrates the challenges faced by lecturers some of whom, we theorise, may experience a form of moral distress facing a conflict between personal beliefs and organisational requirements. It also critically examines the role and responsibilities of universities towards students and towards their staff and the inherent moral tensions between a market model and demands for ‘good' learning experiences. This paper highlights the tensions for academics, between academics and universities and within university policy and indicates the need for greater reflection about this issue, especially given the many constraints facing lecturers and universities.

The spatialized practices of teaching writing in Australian elementary schools : diverse students shaping discoursal selves

This paper discusses the teaching of writing within the competing and often contradictory spaces of high-stakes testing and the practices and priorities around writing pedagogy in diverse school communities. It uses socio-spatial theory to examine the real-and-imagined spaces (Soja, 1996) that influence and are influenced by teachers’ pedagogical priorities for writing in two linguistically diverse elementary school case studies. Methods of critical discourse analysis are used to examine rich data sets to make visible the discourses and power relations at play in the case schools. Findings show that when teachers’ practices focus on the teaching of structure and skills alongside identity building and voice, students with diverse linguistic backgrounds can produce dramatic, authoritative and resonant texts. The paper argues that “thirdspaces” can be forged that both attend to accountability requirements, yet also give the necessary attention to more complex aspects of writing necessary for students from diverse and multilingual backgrounds to invest in writing as a creative and critical form of communication for participation in society and the knowledge economy.

Analysis of interrelationships between critical waste factors in office building retrofit projects using interpretive structural modelling

The number of office building retrofit projects is increasing. These projects are characterised by processes which have a close relationship with waste generation and therefore demand a high level of waste management. In a preliminary study reported separately, we identified seven critical factors of on-site waste generation in office building retrofit projects. Through semi-structured interviews and Interpretive Structural Modelling, this research further investigated the interrelationships among these critical waste factors, to identify each factor’s level of influence on waste generation and propose effective solutions for waste minimization. “Organizational commitment” was identified as the fundamental issue for waste generation in the ISM system. Factors related to plan, design and construction processes were found to be located in the middle levels of the ISM model but still had significant impacts on the system as a whole. Based on the interview findings and ISM analysis results, some practical solutions were proposed for waste minimization in building retrofit projects: (1) reusable and adaptable fit-out design; (2) a system for as-built drawings and building information; (3) integrated planning for retrofitting work process and waste management; and (4) waste benchmarking development for retrofit projects. This research will provide a better understanding of waste issues associated with building retrofit projects and facilitate enhanced waste minimization.

Building and sustaining a culture to support peer review of teaching

1. Background/context This presentation will report on emerging results from a two phase project funded by the Australian Learning and Teaching Council (ALTC). The project was designed in partnership with five universities and aimed to embed peer review within the local teaching and learning culture by using a distributive leadership framework. 2. The initiative/practice The presentation will highlight research outcomes that bring together both the fundamentals of peer review of teaching with the broader contextual elements of Integration, Leadership and Development. It will be demonstrated that peer review of teaching can be implemented and have advantages for academic staff, teaching evaluation and an organisation if attention is given to strategies that influence the contexts and cultures of teaching. Peer review as a strategy to develop excellence in teaching is considered from a holistic perspective that by necessity encompasses all elements of an educational environment. Results demonstrate achievements that can be obtained through working to foster conditions needed for sustainable leadership and change. The work has implications for policy, research, teaching development and student outcomes and has potential application world-wide. 3. Method(s) of evaluative data collection and analysis The 2 phase project collected focus group and questionnaire data to inform research results that were analysed using a thematic qualitative approach and statistical exploration. 4. Evidence of effectiveness The presentation will demonstrate the effectiveness of distributive leadership and strategic approaches to working for cultural change through the presentation of project findings.

Developing a culture to support peer review of teaching in higher education

This presentation addresses issues related to leadership, academic development and scholarship of teaching and learning, and highlights research funded by the Australian Office of Learning and Teaching (OLT) designed to embed and sustain peer review of teaching within the culture of 5 Australian universities: Queensland University of Technology, University of Technology, Sydney, University of Adelaide, Curtin University, and Charles Darwin University. Peer review of teaching in higher education will be emphasised as a professional process for providing feedback on teaching and learning practice, which if sustained, can become an effective ongoing strategy for academic development (Barnard et al, 2011; Bell, 2005; Bolt and Atkinson, 2010; McGill & Beaty 2001, 1992; Kemmis & McTaggart, 2000). The research affirms that using developmental peer review models (Barnard et al, 2011; D'Andrea, 2002; Hammersley-Fletcher & Orsmond, 2004) can bring about successful implementation, especially when implemented within a distributive leadership framework (Spillane & Healey, 2010). The project’s aims and objectives were to develop leadership capacity and integrate peer review as a cultural practice in higher education. The research design was a two stage inquiry process over 2 years. The project began in July 2011 and encompassed a development and pilot phase followed by a cascade phase with questionnaire and focus group evaluation processes to support ongoing improvement and measures of outcome. Leadership development activities included locally delivered workshops complemented by the identification and support of champions. To optimise long term sustainability, the project was implemented through existing learning and teaching structures and processes within the respective partner universities. Research outcomes highlight the fundamentals of peer review of teaching and the broader contextual elements of integration, leadership and development, expressed as a conceptual model for embedding peer review of teaching within higher education. The research opens a communicative space about introduction of peer review that goes further than simply espousing its worth and introduction. The conceptual model highlights the importance of development of distributive leadership capacity, integration of policies and processes, and understanding the values, beliefs, assumptions and behaviors embedded in an organizational culture. The presentation overviews empirical findings that demonstrate progress to advance peer review requires an ‘across-the-board’ commitment to embed change, and inherently demands a process that co-creates connection across colleagues, discipline groups, and the university sector. Progress toward peer review of teaching as a cultural phenomenon can be achieved and has advantages for academic staff, scholarship, teaching evaluation and an organisation, if attention is given to strategies that influence the contexts and cultures of teaching practice. Peer review as a strategy to develop excellence in teaching is considered from a holistic perspective that by necessity encompasses all elements of an educational environment and has a focus on scholarship of teaching. The work is ongoing and has implication for policy, research, teaching development and student outcomes, and has potential application world-wide.

An algebraic analysis of trivium ciphers based on the boolean satisfiability problem

Trivium is a stream cipher candidate of the eStream project. It has successfully moved into phase three of the selection process under the hardware category. No attacks faster than the exhaustive search have so far been reported on Trivium. Bivium-A and Bivium-B are simplified versions of Trivium that are built on the same design principles but with two registers. The simplified design is useful in investigating Trivium type ciphers with a reduced complexity and provides insight into effective attacks which could be extended to Trivium. This paper focuses on an algebraic analysis which uses the boolean satisfiability problem in propositional logic. For reduced variants of the cipher, this analysis recovers the internal state with a minimal amount of keystream observations.

Technoeconomic analysis of renewable aviation fuel from microalgae,Pongamia pinnata, and sugarcane

Technoeconomic analysis of renewable aviatin fuels has not been widely considered, despite the increasing global attention that the field has received. We present three process models for production of aviation fuel from microalgae, Pongamia pinnata, and sugarcane molasses. The models and assumptions have been deposited on a wiki (http://qsafi.aibn.uq.edu.au) and are open and accessible to the community. Based on currently available long-term reputable technological data, this analysis indicates that the biorefinieries processing the microalgae, Pongamia seeds, and sugarcane feedstocks would be competitive with crude oil at $1343, $374, and $301/bbl, respectively. Sensitivity analyses of the major economic drivers suggest technological and market developments that would bring the corresponding figures down to $385, $255, and $168/bbl. The dynamic nature of the freely accessible models will allow the community to track progress toward economic competitiveness of aviation fuels from these renewable feedstocks.

Hybrid frequency–time domain models for dynamic response analysis of marine structures

Time-domain models of marine structures based on frequency domain data are usually built upon the Cummins equation. This type of model is a vector integro-differential equation which involves convolution terms. These convolution terms are not convenient for analysis and design of motion control systems. In addition, these models are not efficient with respect to simulation time, and ease of implementation in standard simulation packages. For these reasons, different methods have been proposed in the literature as approximate alternative representations of the convolutions. Because the convolution is a linear operation, different approaches can be followed to obtain an approximately equivalent linear system in the form of either transfer function or state-space models. This process involves the use of system identification, and several options are available depending on how the identification problem is posed. This raises the question whether one method is better than the others. This paper therefore has three objectives. The first objective is to revisit some of the methods for replacing the convolutions, which have been reported in different areas of analysis of marine systems: hydrodynamics, wave energy conversion, and motion control systems. The second objective is to compare the different methods in terms of complexity and performance. For this purpose, a model for the response in the vertical plane of a modern containership is considered. The third objective is to describe the implementation of the resulting model in the standard simulation environment Matlab/Simulink.

Framework of a process laboratory for the operational control of service processes

Service processes such as financial advice, booking a business trip or conducting a consulting project have emerged as units of analysis of high interest for the business process and service management communities in practice and academia. While the transactional nature of production processes is relatively well understood and deployed, the less predictable and highly interactive nature of service processes still lacks in many areas appropriate methodological grounding. This paper proposes a framework of a process laboratory as a new IT artefact in order to facilitate the holistic analysis and simulation of such service processes. Using financial services as an example, it will be shown how such a process laboratory can be used to reduce the complexity of service process analysis and facilitate operational service process control.

An analysis of dispute review boards and settlement mediation as used in the Australian construction industry

If there is a silver lining to the adversarial, dispute-prone nature of the building and construction industry, it can be found in the concomitant rise of innovative dispute resolution mechanisms. Time, cost and relationship concerns have meant that the formal adversarial system holds little appeal for disputing parties. As these alternative forms of dispute avoidance/resolution have matured in Australia over the last 20 years, attention has turned to the key characteristics of each process and their suitability to the building and construction industry. This article considers the role of dispute review boards (DRBs) and mediation as two alternative methods for avoiding/resolving disputes in the construction industry. Criteria are established for evaluating the efficacy of these procedures and their sensitivity to the needs of construction industry disputants. The ultimate conclusion reached is that DRBs represent a powerful, yet underutilised dispute resolution tool in Australia, and possess many industry-specific advantages that more traditional forms of alternative dispute resolution (particularly mediation) do not provide.