Streptococcus pneumoniae infection suppresses allergic airways disease by inducing regulatory T cells

An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whether Streptococcus pneumoniae infection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD). Mice were intratracheally infected or treated with killed S. pneumoniae before, during or after OVA sensitisation and subsequent challenge. The effects of S. pneumoniae on AAD were assessed. Infection or treatment with killed S. pneumoniae suppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment. Respiratory infection or treatment with S. pneumoniae attenuates allergic immune responses and suppresses AAD. These effects may be mediated by S. pneumoniae-induced Tregs. This identifies the potential for the development of therapeutic agents for asthma from S. pneumoniae.

A test vehicle for compliance with resilience requirements in index-based e-health systems

Increasingly, national and international governments have a strong mandate to develop national e-health systems to enable delivery of much-needed healthcare services. Research is, therefore, needed into appropriate security and reliance structures for the development of health information systems which must be compliant with governmental and alike obligations. The protection of e-health information security is critical to the successful implementation of any e-health initiative. To address this, this paper proposes a security architecture for index-based e-health environments, according to the broad outline of Australia’s National E-health Strategy and National E-health Transition Authority (NEHTA)’s Connectivity Architecture. This proposal, however, could be equally applied to any distributed, index-based health information system involving referencing to disparate health information systems. The practicality of the proposed security architecture is supported through an experimental demonstration. This successful prototype completion demonstrates the comprehensibility of the proposed architecture, and the clarity and feasibility of system specifications, in enabling ready development of such a system. This test vehicle has also indicated a number of parameters that need to be considered in any national indexed-based e-health system design with reasonable levels of system security. This paper has identified the need for evaluation of the levels of education, training, and expertise required to create such a system.

Dangers of the after-dark wonderlands : Part A - A review of the impact of physical environment design on nightclub violence

Nightclubs are businesses. Their business is pleasure; however pleasure has its price. People have become increasingly concerned about the problems of violence in society but why do higher levels of violence occur in nightclubs despite the established patterns of behaviour that dictates how we socialise and act? In response, researchers have focused on identifying social and situational factors that may contribute to violence from a government perspective, focusing on a variety of specific issues ranging from financial standpoints with effective target marketing strategies to legal obligations of supplying alcohol and abiding regulatory conditions. There is little research into specific design properties that can determine design standards to ensure/improve the physical design of nightclub environments to reduce patron violence. To address this gap, this current article aims to understand how people experience and respond to the physical environment of nightclubs and how these spaces influence their behaviour. The first section of this paper examines the background on nightclubs and theories concerning the influence of pleasure. The second section of this paper details the findings of existing studies that have examined the nightlife context and the various factors that influence patron violence. The main finding of this paper is that although alcohol likely plays a contributing role in aggressive patron behaviour, there is evidence that the relationship is moderated by a number of significant factors relating to the characteristics of the drinking environment such as: physical comfort; the degree of overall 'permissiveness‘ in the establishment; crowding; and physical environmental elements most influenced by day to-day management practices such as lighting, ventilation, cleanliness and seating arrangements. The findings from this paper have been used to develop a framework to guide exploratory research on how specific elements of the physical environment of nightclubs have an impact on elevated patron aggression and assault (Koleczko & Garcia Hansen, 2011).

Dangers of the after-dark wonderlands : Part B - A review of the impact of the physical environment design on nightclub violence

Violence in nightclubs is a serious problem that has the Australian government launching multimillion dollar drinking campaigns. Research on nightclub violence has focused on identifying contributing social and environmental factors, with many concentrating on a variety of specific issues ranging from financial standpoints with effective target marketing strategies to legal obligations of supplying alcohol and abiding regulatory conditions. Moreover, existing research suggests that there is no single factor that directly affects the rate violence in licensed venues. As detailed in the review paper of Koleczko and Garcia Hansen (2011), there is little research about the physical environment of nightclubs and which specific design properties can be used to determine design standards to ensure/improve the physical design of nightclub environments to reduce patron violence. This current study seeks to address this omission by reporting on a series of interviews with participants from management and design domains. Featured case studies are both located in Fortitude Valley, a Mecca for party-goers and the busiest nightclub district in Queensland. The results and analysis support the conclusions that a number of elements of the physical environment influence elevated patron aggression and assault.

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.

The impact of the Malaysian code on corporate governance: compliance, institutional investors and stock performance

In 2001, the Malaysian Code on Corporate Governance (MCCG) became an integral part of the Bursa Malaysia Listing Rules, which requires all listed firms to disclose the extent of compliance with the MCCG. Our panel analysis of 440 firms from 1999 to 2002 finds that corporate governance reform in Malaysia has been successful, with a significant improvement in governance practices. The relationship between ownership by the Employees Provident Fund (EPF) and corporate governance has strengthened during the period subsequent to the reform, in line with the lead role taken by the EPF in establishing the Minority Shareholders Watchdog Group. The implementation of MCCG has had a substantial effect on shareholders' wealth, increasing stock prices by an average of about 4.8%. Although there is no evidence that politically connected firms perform better, political connections do have a significantly negative effect on corporate governance, which is mitigated by institutional ownership.

Computational approaches for modelling intrinsic noise and delays in genetic regulatory networks

This chapter focuses on the interactions and roles between delays and intrinsic noise effects within cellular pathways and regulatory networks. We address these aspects by focusing on genetic regulatory networks that share a common network motif, namely the negative feedback loop, leading to oscillatory gene expression and protein levels. In this context, we discuss computational simulation algorithms for addressing the interplay of delays and noise within the signaling pathways based on biological data. We address implementational issues associated with efficiency and robustness. In a molecular biology setting we present two case studies of temporal models for the Hes1 gene (Monk, 2003; Hirata et al., 2002), known to act as a molecular clock, and the Her1/Her7 regulatory system controlling the periodic somite segmentation in vertebrate embryos (Giudicelli and Lewis, 2004; Horikawa et al., 2006).

Evolving noisy oscillatory dynamics in genetic regulatory networks

We introduce a genetic programming (GP) approach for evolving genetic networks that demonstrate desired dynamics when simulated as a discrete stochastic process. Our representation of genetic networks is based on a biochemical reaction model including key elements such as transcription, translation and post-translational modifications. The stochastic, reaction-based GP system is similar but not identical with algorithmic chemistries. We evolved genetic networks with noisy oscillatory dynamics. The results show the practicality of evolving particular dynamics in gene regulatory networks when modelled with intrinsic noise.

Evolving genetic regulatory networks performing as stochastic switches

Recent studies have shown that small genetic regulatory networks (GRNs) can be evolved in silico displaying certain dynamics in the underlying mathematical model. It is expected that evolutionary approaches can help to gain a better understanding of biological design principles and assist in the engineering of genetic networks. To take the stochastic nature of GRNs into account, our evolutionary approach models GRNs as biochemical reaction networks based on simple enzyme kinetics and simulates them by using Gillespie’s stochastic simulation algorithm (SSA). We have already demonstrated the relevance of considering intrinsic stochasticity by evolving GRNs that show oscillatory dynamics in the SSA but not in the ODE regime. Here, we present and discuss first results in the evolution of GRNs performing as stochastic switches.