Whole-proteome phylogeny of large dsDNA viruses and parvoviruses through a composition vector method related to dynamical language model

Background The vast sequence divergence among different virus groups has presented a great challenge to alignment-based analysis of virus phylogeny. Due to the problems caused by the uncertainty in alignment, existing tools for phylogenetic analysis based on multiple alignment could not be directly applied to the whole-genome comparison and phylogenomic studies of viruses. There has been a growing interest in alignment-free methods for phylogenetic analysis using complete genome data. Among the alignment-free methods, a dynamical language (DL) method proposed by our group has successfully been applied to the phylogenetic analysis of bacteria and chloroplast genomes. Results In this paper, the DL method is used to analyze the whole-proteome phylogeny of 124 large dsDNA viruses and 30 parvoviruses, two data sets with large difference in genome size. The trees from our analyses are in good agreement to the latest classification of large dsDNA viruses and parvoviruses by the International Committee on Taxonomy of Viruses (ICTV). Conclusions The present method provides a new way for recovering the phylogeny of large dsDNA viruses and parvoviruses, and also some insights on the affiliation of a number of unclassified viruses. In comparison, some alignment-free methods such as the CV Tree method can be used for recovering the phylogeny of large dsDNA viruses, but they are not suitable for resolving the phylogeny of parvoviruses with a much smaller genome size.

Modeling prostate cancer: a perspective on transgenic mouse models

Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.

Examination of process to develop a framework for better implementation of quality practices in building projects

Quality, as well as project success, in construction projects should be capable of being regarded as the fulfillment of expectation of those contributors and stakeholders involved in such projects. Although a significant amount of quality practices have been introduced within the industry, establishment and attainment of reasonable levels of quality internationally in construction projects continues to be an ongoing problem. To date, some investigation into the introduction and improvement of quality practices and stakeholder management in the construction industry has been accomplished independently, but so far no major studies have been completed that examine comprehensively how quality management practices that particularly concentrate on the stakeholders’ perspective of quality can be used to contribute to final project quality outcomes. This paper aims to examine the process for development of a framework for better involvement of stakeholders in quality planning and practices and subsequently to contribute to higher quality outcomes within construction projects. Through extensive literature review it highlights various perceptions of quality, categorizes quality issues with particular focus on benefits and shortcomings and also examines stakeholders’ viewpoint of project quality in order to promote the improvement of outcomes throughout a project’s lifecycle. It proposes a set of arranged information as a basis for development of prospective framework which ultimately aims to improve project quality outcomes. The subsequent framework that will be developed from this research will provide project managers and owners with the required information and strategic direction to achieve their own and their stakeholders’ targets for implementation of quality practices and achievement of high quality outcomes on their future projects.

Bayesian methodology for genetics of complex diseases

Genetic research of complex diseases is a challenging, but exciting, area of research. The early development of the research was limited, however, until the completion of the Human Genome and HapMap projects, along with the reduction in the cost of genotyping, which paves the way for understanding the genetic composition of complex diseases. In this thesis, we focus on the statistical methods for two aspects of genetic research: phenotype definition for diseases with complex etiology and methods for identifying potentially associated Single Nucleotide Polymorphisms (SNPs) and SNP-SNP interactions. With regard to phenotype definition for diseases with complex etiology, we firstly investigated the effects of different statistical phenotyping approaches on the subsequent analysis. In light of the findings, and the difficulties in validating the estimated phenotype, we proposed two different methods for reconciling phenotypes of different models using Bayesian model averaging as a coherent mechanism for accounting for model uncertainty. In the second part of the thesis, the focus is turned to the methods for identifying associated SNPs and SNP interactions. We review the use of Bayesian logistic regression with variable selection for SNP identification and extended the model for detecting the interaction effects for population based case-control studies. In this part of study, we also develop a machine learning algorithm to cope with the large scale data analysis, namely modified Logic Regression with Genetic Program (MLR-GEP), which is then compared with the Bayesian model, Random Forests and other variants of logic regression.

Safety leaders' perceptions of safety culture in a large Australian construction organisation

Safety culture in the construction industry is a growing research area. The unique nature of construction industry works – being project-based, varying in size and focus, and relying on a highly transient subcontractor workforce – means that safety culture initiatives cannot be easily translated from other industries. This paper reports on the first study in a three year collaborative industry and university research project focusing on safety culture practices and development in one of Australia’s largest global construction organisations. The first round of a modified Delphi method is reported, and describes the insights gained from 41 safety leaders’ perceptions and understandings of safety culture within the organisation. In-depth, semi-structured interviews were conducted, and will be followed by a quantitative perception survey with the same sample. Participants included Senior Executives, Corporate Managers, Project Managers, Safety Managers and Site Supervisors. Leaders’ definitions and descriptions of safety culture were primarily action-oriented and some confusion was evident due to the sometimes implicit nature of culture in organisations. Leadership was identified as a key factor for positive safety culture in the organisation, and there was an emphasis on leaders demonstrating commitment to safety, and being visible to the project-based workforce. Barriers to safety culture improvement were also identified, with managers raising diverse issues such as the transient subcontractor workforce and the challenge of maintaining safety as a priority in the absence of safety incidents, under high production pressures. This research is unique in that it derived safety culture descriptions from key stakeholders within the organisation, as opposed to imposing traditional conceptualisations of safety culture that are not customised for the organisation or the construction industry more broadly. This study forms the foundation for integrating safety culture theory and practice in the construction industry, and will be extended upon in future studies within the research program.

Community-based protest against construction projects : a case study of movement continuity

Community-based activism against proposed construction projects is growing. Many protests are poorly managed and escalate into long-term and sometimes acrimonious disputes which damage communities, firms and the construction industry as a whole. Using a thematic storytelling approach which draws on ethnographic method, within a single case study framework, new insights into the social forces that shape and sustain community-based protest against construction projects are provided. A conceptual model of protest movement continuity is presented which highlights the factors that sustain protest continuity over time. The model illustrates how social contagion leads to common community perceptions of development risk and opportunity, to a positive internalization of collective values and identity, to a strategic utilization of social capital and an awareness of the need to manage the emotional dynamics of protest through mechanisms such as symbolic artefacts.

Artful inquiry : an arts-based facilitation approach for individual and organisational learning and development

The research undertaken in these two major doctoral studies investigates the field of artsbased learning, a pedagogical approach to individual and organisational learning and development, my professional creative facilitation practice and development as a researcher. While the studies are stand-alone projects they are intended to build on each other in order to tell the evolving story of my research and professional practice. The first study combines The Role of Arts-based Learning in a Creative Economy; The Need for Artistry in Professional Education the art of knowing what to do when you don’t know what to do and Lines of Inquiry: Making Sense of Research and Professional Practice. The Role of Arts-based Learning in a Creative Economy provides an overview of the field of arts-based learning in business. The study focuses on the relevant literature and interviews with people working in the field. The paper argues that arts-based learning is a valuable addition to organisations for building a culture of creativity and innovation. The Need for Artistry in Professional Education continues that investigation. It explores the way artists approach their work and considers what skills and capabilities from artistic practice can be applied to other professions’ practices. From this research the Sphere of Professional Artistry model is developed and depicts the process of moving toward professional artistry. Lines of Inquiry: making sense of research and professional practice through artful inquiry is a self-reflective study. It explores my method of inquiry as a researcher and as a creative facilitation practitioner using arts-based learning processes to facilitate groups of people for learning, development and change. It discusses how my research and professional practice influence and inspire the other and draws on cased studies. The second major research study Artful Inquiry: Arts-based Learning for Inquiry, Reflection and Action in Professional Practice is a one year practice-led inquiry. It continues the research into arts-based and aesthetic learning experiences and my arts-based facilitation practice. The research is conducted with members of a Women’s Network in a large government service agency. It develops the concept of ‘Artful Inquiry’’ a creative, holistic, and embodied approach for facilitation, inquiry, learning, reflection, and action. Storytelling as Inquiry is used as a methodology for understanding participants’ experiences of being involved in arts-based learning experiences. The study reveals the complex and emergent nature of practice and research. It demonstrates what it can mean to do practice-led research with others, within an organisational context, and to what effect.

Exponentiated gradient algorithms for large-margin structured classification

We consider the problem of structured classification, where the task is to predict a label y from an input x, and y has meaningful internal structure. Our framework includes supervised training of Markov random fields and weighted context-free grammars as special cases. We describe an algorithm that solves the large-margin optimization problem defined in [12], using an exponential-family (Gibbs distribution) representation of structured objects. The algorithm is efficient—even in cases where the number of labels y is exponential in size—provided that certain expectations under Gibbs distributions can be calculated efficiently. The method for structured labels relies on a more general result, specifically the application of exponentiated gradient updates [7, 8] to quadratic programs.

Large-Eddy Simulation of physiological pulsatile non-newtonian flow in a channel with double constriction

Physiological pulsatile flow in a 3D model of arterial double stenosis, using the modified Power-law blood viscosity model, is investigated by applying Large Eddy Simulation (LES) technique. The computational domain has been chosen is a simple channel with biological type stenoses. The physiological pulsation is generated at the inlet of the model using the first four harmonics of the Fourier series of the physiological pressure pulse. In LES, a top-hat spatial grid-filter is applied to the Navier-Stokes equations of motion to separate the large scale flows from the subgrid scale (SGS). The large scale flows are then resolved fully while the unresolved SGS motions are modelled using the localized dynamic model. The flow Reynolds numbers which are typical of those found in human large artery are chosen in the present work. Transitions to turbulent of the pulsatile non-Newtonian along with Newtonian flow in the post stenosis are examined through the mean velocity, wall shear stress, mean streamlines as well as turbulent kinetic energy and explained physically along with the relevant medical concerns.

Stochastic models for regulatory networks of the genetic toggle switch

Bistability arises within a wide range of biological systems from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.