Novel targeting of PEGylated liposomes for codelivery of TGF-β1 siRNA and four antitubercular drugs to human macrophages for the treatment of mycobacterial infection: a quantitative proteomic study

Tuberculosis (TB) is still a major public health issue in developing countries, and its chemotherapy is compromised by poor drug compliance and severe side effects. This study aimed to synthesize and characterize new multimodal PEGylated liposomes encapsulated with clinically commonly used anti-TB drugs with linkage to small interfering RNA (siRNA) against transforming growth factor-β1 (TGF-β1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages that were the host cells of mycobacterium infection. The biological effects of the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis, autophagy, and the gene silencing efficiency of TGF-β1 siRNA in human macrophages. We also explored the proteomic responses to the newly synthesized NP-siRNA liposomes using the stable isotope labeling with amino acids in cell culture approach. The results showed that the multifunctional PEGylated liposomes were successfully synthesized and chemically characterized with a mean size of 265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and TGF-β1 siRNA were endocytosed efficiently by human macrophages as visualized by transmission electron microscopy and scanning electron microscopy. Furthermore, the liposomes showed a low cytotoxicity toward human macrophages. There was no significant effect on cell cycle distribution and apoptosis in THP-1-derived macrophages after drug exposure at concentrations ranging from 2.5 to 62.5 μg/mL. Notably, there was a 6.4-fold increase in the autophagy of human macrophages when treated with the NP-siRNA liposomes at 62.5 μg/mL. In addition, the TGF-β1 and nuclear factor-κB expression levels were downregulated by the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway Analysis data showed that there were over 40 signaling pathways involved in the proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160 proteins mapped. The top five canonical signaling pathways were eukaryotic initiation factor 2 signaling, actin cytoskeleton signaling, remodeling of epithelial adherens junctions, epithelial adherens junction signaling, and Rho GDP-dissociation inhibitor signaling pathways. Collectively, the novel synthetic targeting liposomes represent a promising delivery system for anti-TB drugs to human macrophages with good selectivity and minimal cytotoxicity.

The cost of recovery protocols in web-based database systems

The cost of recovery protocols is important with respect to system performance during normal operation and failure in terms of overhead, and time taken to recover failed transactions. The cost of recovery protocols for web database systems has not been addressed much. In this paper, we present a quantitative study of cost of recovery protocols. For this purpose, we use an experiment setup to evaluate the performance of two recovery algorithms, namely the, two-phase commit algorithm and log-based algorithm. Our work is a step towards building reliable protocols for web database systems.

Modelling relational aspects of critical infrastructure systems

The relational aspects for critical infrastructure systems are not readily quantifiable as there are numerous variability’s and system dynamics that lack uniformity and are difficult to quantify. Notwithstanding this, there is a large body of existing research that is founded in the area of quantitative analysis of critical infrastructure networks, their system relationships and the resilience of these networks. However, the focus of this research is to investigate the aspect of taking a different, more generalised and holistic system perspective approach. This is to suggest that that through applying network theory and taking a ‘soft’ system-like modelling approach that this offers an alternative approach to viewing and modelling critical infrastructure system relational aspects that warrants further enquiry.

Analysis and modelling of critical infrastructure systems

The increasing complexity and interconnectedness of critical infrastructure systems, including the information systems and communication networks that support their existence and functionality, poses questions and challenges. Particularly, in terms of modelling and analysis of the security, survivability and ultimately reliability and continued availability of critical infrastructure systems and the services they deliver to modern society. The focus of this research enquiry is with regard to critiquing and modelling critical infrastructure systems. There are numerous systems analyse and modelling approaches that outline any number of differing methodological approaches, each with their own characteristics, expertise, strengths and weaknesses. The intention of this research is to investigate the merit of applying a ‘softer’ approach to critical infrastructure system security analysis and modelling that broadly views the systems in holistic terms, including their relationships with other systems. The intention is not to discuss or criticise existing research applying quantitative approaches, but to discuss a ‘softer’ system analysis and modelling approach in a security context that is adaptable to analysis modelling of critical infrastructure systems.

Agility in information systems : enabling capabilities for the IT function

This research identifies how the IT function can create agility in existing information systems. Agility is the capability to quickly sense and respond to environmental perturbations. We contrasted perspectives on agility from a widely used industry framework and that of the IS research literature. Beer’s Viable System Model was a useful meta-level theory to house agility elements from IS research and it introduced cybernetic principles to identify the processes required of the IT function. Indeed, our surveys of 70 organizations confirmed that the applied theory better correlates with reported agility than does existing industry best practice.

The research conducted two quantitative surveys to test the applied theory. The first survey mailed a Likert-type questionnaire to the clients of an Australian IT consultancy. The second survey invited international members of professional interest groups to complete a web-based questionnaire. The responses from the surveys were analyzed using partial-least-squares modeling. The data analysis positively correlated the maturity of IT function processes prescribed by the VSM and the likelihood of agility in existing information systems. We claim our findings generalize to other large organizations in OECD member countries.

The research offers an agility-capability model of the IT function to explain and predict agility in existing information systems. A further contribution is to improve industry ‘best practice’ frameworks by prescribing processes of the IT function to develop in maturity.

Geographical Information Systems (GIS) and their role in sustainable planning : a case study from a Local Government Area (LGA) in Australia

A case study is used to demonstrate the application of Geographical Information Systems (GIS) to inform sustainable development. The suitability of the landscape to support tourism accommodation in a Local Government Area (LGA) is modelled by integrating existing datasets, including conservation areas, residential zones, major roads and known locations of tourism operators into a logistic regression framework. By using a data-driven approach an indication of the relative importance of each explanatory variable can be accounted for, therefore informing planners of the importance of different assets. In a region where tourism is reliant upon natural features, this use of information systems in conjunction with quantitative statistical modelling can value-add to existing datasets. The provision of this kind of knowledge is important as it would otherwise not factor into the decision-making process had the datasets been considered independently of each other – a concept that applies to both the public and private sectors.

Integrating e-simulations in teaching business information systems

Students’ early exposure to the fundamentals of business and Information and Communications Technologies (ICT), creation of a professional skill base, as well as, the gaining of practical experience in applying such knowledge and skills, are the determinants of success in their study and development as Information Systems (IS) professionals. This chapter argues that e-simulations, or computer-based and online simulations, can be effectively used to engage learners in interactive learning activities and provide them with real world practical experience in the safety of an educational setting. A research project is subsequently described. A suite of e-simulations were developed and deployed across two institutions to support teaching and learning of Information Systems. Using staff discussions and online surveys, quantitative and qualitative data were collected from the staff and students. The collected data were then analysed to evaluate and guide a sequence of curriculum and technology changes with a view to arriving at an optimum support model for students and teachers using the e-simulations. The findings of the study emphasise the usefulness of e-simulations to accommodate the learning styles of generation Y students, to stimulate their interest and creative thinking, and in meeting industry expectations of IS graduates’ ability to fulfil professional roles. Based on these insights, in its concluding remarks, the chapter outlines a conceptual framework for the inclusion of e-simulations in Information Systems curriculum development and teaching delivery.

Prediction interval construction using interval type-2 fuzzy logic systems

This study proposes a novel non-parametric method for construction of prediction intervals (PIs) using interval type-2 Takagi-Sugeno-Kang fuzzy logic systems (IT2 TSK FLSs). The key idea in the proposed method is to treat the left and right end points of the type-reduced set as the lower and upper bounds of a PI. This allows us to construct PIs without making any special assumption about the data distribution. A new training algorithm is developed to satisfy conditions imposed by the associated confidence level on PIs. Proper adjustment of premise and consequent parameters of IT2 TSK FLSs is performed through the minimization of a PI-based objective function, rather than traditional error-based cost functions. This new cost function covers both validity and informativeness aspects of PIs. A metaheuristic method is applied for minimization of the non-linear non-differentiable cost function. Quantitative measures are applied for assessing the quality of PIs constructed using IT2 TSK FLSs. The demonstrated results for four benchmark case studies with homogenous and heterogeneous noise clearly show the proposed method is capable of generating high quality PIs useful for decision-making.

Sizing solar home systems for optimal development impact

The paper compares the development impact of three different sized solar home systems (SHS) (10, 40 and 80 Wp) installed in rural East Timor. It describes research aimed to determine whether the higher cost of the larger systems was justified by additional household benefits. To assess the development impact of these different sizes of SHS the research used a combination of participatory and quantitative tools. Participatory exercises were conducted with seventy-seven small groups of SHS users in twenty-four rural communities and supplemented with a household survey of 195 SHS users.

The combined results of these evaluation processes enabled the three sizes of SHS to be compared for two types of benefits—those associated with carrying out important household tasks and attributes of SHS which were advantageous compared to the use of non-electric lighting sources. The research findings showed that the small, 10 Wp SHS provided much of the development impact of the larger systems. It suggests three significant implications for the design of SHS programs in contexts such as East Timor: provide more small systems rather than fewer large ones; provide lighting in the kitchen wherever possible; and carefully match SHS operating costs to the incomes of rural users.

The use of metabolomics in the study of metals in biological systems

Metabolomics may be defined as the comprehensive quantitative and/or qualitative analysis of all metabolites present in a bio-fluid, cell, tissue, or organism. It is essentially the study of biochemical phenotypes (or metabotypes). Metabolic profiles are context dependent, and vary in response to a variety of factors including environment and environmental stimuli, health status, disease and a myriad of other factors; as such, metabolomics has been applied to a wide range of fields and has been increasingly utilised to the study of the roles played by metals in a range of biological systems as well as, encouragingly, in understanding the underlying biochemical mechanisms. The role of metals (and metalloids) in biological organisms is complex and the majority of studies in this area have been performed in plants but the fields of natural product chemistry, human health and even bacterial corrosion of water distribution systems have been investigated using this technique. In this review some of the novel approaches in which the metabolomics toolbox has been used to unravel the roles of metals and metalloids in a range of biological systems are discussed and suggestions made for future research.

Management control systems and organisational learning: the effects of design and use

Purpose – The purpose of this paper is to present a study on relationships between the design of management control systems (MCS), the use of MCS and organisational learning (OL). Design/methodology/approach – This study adopted a survey method. A written questionnaire was prepared and mailed out to collect quantitative data. After analysis of the empirical results, follow-up interviews were conducted to develop a deeper understanding of the empirical results. Findings – Findings of the study show that both the design and use of MCS are significantly associated with levels of OL activities in organisations, and the use of MCS is found to be a more influential factor in OL. Originality/value – This paper contributes to the accounting literature by providing empirical evidence on the relative impacts of the design and use of MCS on OL activities in organisations and the interaction between the design and use of MCS in influencing OL.

Evaluation of a filmed clinical scenario as a teaching resource for an introductory pharmacology unit for undergraduate health students: A pilot study.

BACKGROUND: Simulation is frequently being used as a learning and teaching resource for both undergraduate and postgraduate students, however reporting of the effectiveness of simulation particularly within the pharmacology context is scant. OBJECTIVES: The aim of this pilot study was to evaluate a filmed simulated pharmacological clinical scenario as a teaching resource in an undergraduate pharmacological unit. DESIGN: Pilot cross-sectional quantitative survey. SETTING: An Australian university. PARTICIPANTS: 32 undergraduate students completing a healthcare degree including nursing, midwifery, clinical science, health science, naturopathy, and osteopathy. METHODS: As a part of an undergraduate online pharmacology unit, students were required to watch a filmed simulated pharmacological clinical scenario. To evaluate student learning, a measurement instrument developed from Bloom's cognitive domains (knowledge, comprehension, application, analysis, synthesis and evaluation) was employed to assess pharmacological knowledge conceptualisation and knowledge application within the following fields: medication errors; medication adverse effects; medication interactions; and, general pharmacology. RESULTS: The majority of participants were enrolled in an undergraduate nursing or midwifery programme (72%). Results demonstrated that the majority of nursing and midwifery students (56.52%) found the teaching resource complementary or more useful compared to a lecture although less so compared to a tutorial. Students' self-assessment of learning according to Bloom's cognitive domains indicated that the filmed scenario was a valuable learning tool. Analysis of variance indicated that health science students reported higher levels of learning compared to midwifery and nursing. CONCLUSION: Students' self-report of the learning benefits of a filmed simulated clinical scenario as a teaching resource suggest enhanced critical thinking skills and knowledge conceptualisation regarding pharmacology, in addition to being useful and complementary to other teaching and learning methods.

A community-based complex systems approach to high school completion

High school completion, like many educational phenomena, is the result of processes that, when taken together, constitute a complex system. In this paper, we describe the innovative use of group model building (GMB) as an entry point for complex systems analysis of educational processes that collectively determine high school completion. GMB exercises were conducted in a community in the state of Victoria in Australia. GMB brought together stakeholders from around the community and encouraged them to view high school completion from a complex systems perspective. Not only were participants able to use their experience to create an action plan to increase high school graduation rates but they also provided researchers with valuable information that can be used as input into rigorous, quantitative models of high school completion.