Response : letter to the editor by Al-Azri and Al-Maniri

Firstly, the authors would like to thank the editor for the opportunity to respond to Dr Al-Azri’s and Dr Al-Maniri’s letter. Secondly, while the current authors also accept that deterrence-based approaches should act as only one corner-stone of a suite of interventions and public policy initiatives designed to improve road safety, deterrence-based approaches have nonetheless consistently proven to be a valuable resource to improve road safety. Dr Al-Azri and Dr Al-Maniri reinforce their assertion about the limited utility of deterrence by citing drink driving research, and the issue of drink driving is particularly relevant within the current context given that the problem of driving after drinking has historically been addressed through deterrence-based approaches. While the effectiveness of deterrence-based approaches to reduce drink driving will always be dependent upon a range of situational and contextual factors (including police enforcement practices, cultural norms, etc), the utilisation of this approach has proven particularly effective within Queensland, Australia. For example, a relatively recent comprehensive review of Random Breath Testing in Queensland demonstrated that this initiative not only had a deterrent impact upon self-reported intentions to drink and drive, but was also found to have significantly reduced alcohol-related fatalities in the state. However, the authors agree that deterrence-based approaches can be particularly transient and thus require constant “topping up” not least through sustained public reinforcement, which was clearly articulated in the seminal work by Homel.

Replication of the Frank-Starling response in a Mock Circulation loop

Mock circulation loops (MCLs) are used to evaluate cardiovascular devices prior to in-vivo trials; however they lack the vital autoregulatory responses that occur in humans. This study aimed to develop and implement a left and right ventricular Frank-Starling response in a MCL. A proportional controller based on ventricular end diastolic volume was used to control the driving pressure of the MCL’s pneumatically operated ventricles. Ventricular pressure-volume loops and end systolic pressure-volume relationships were produced for a variety of healthy and pathological conditions and compared with human data to validate the simulated Frank-Starling response. The non-linear Frank-Starling response produced in this study successfully altered left and right ventricular contractility with changing preload and was validated with previously reported data. This improvement to an already detailed MCL has resulted in a test rig capable of further refining cardiovascular devices and reducing the number of in-vivo trials.

Dynamic response of distributed generators in a hybrid microgrid

A microgrid may be supplied from inertial (rotating type) and non-inertial (converter-interfaced) distributed generators (DGs). However the dynamic response of these two types of DGs is different. Inertial DGs have a slower response due to their governor characteristics while non inertial DGs have the ability to respond very quickly. The focus of this paper is to propose better controls using droop characteristics to improve the dynamic interaction between different DG types in an autonomous microgrid. The transient behavior of DGs in the microgrid is investigated during the DG synchronization and load changes. Power sharing strategies based on frequency and voltage droop are considered for DGs. Droop control strategies are proposed for DGs to improve the smooth synchronization and dynamic power sharing minimizing transient oscillations in the microgrid. Simulation studies are carried out on PSCAD for validation.

The legitimacy of graduated response schemes in copyright law

In an attempt to curb online copyright infringement, copyright owners are increasingly seeking to enlist the assistance of Internet Service Providers (‘ISPs’) to enforce copyright and impose sanctions on their users.1 Commonly termed ‘graduated response’ schemes, these measures generally require that the ISP take some action against users suspected of infringing copyright, ranging from issuing warnings, to collating allegations made against subscribers and reporting to copyright owners, to suspension and eventual termination of service.

Demand side response to mitigate electrical peak demand in Eastern and Southern Australia

The aim of this work is to develop a Demand-Side-Response (DSR) model, which assists electricity end-users to be engaged in mitigating peak demands on the electricity network in Eastern and Southern Australia. The proposed innovative model will comprise a technical set-up of a programmable internet relay, a router, solid state switches in addition to the suitable software to control electricity demand at user's premises. The software on appropriate multimedia tool (CD Rom) will be curtailing/shifting electric loads to the most appropriate time of the day following the implemented economic model, which is designed to be maximizing financial benefits to electricity consumers. Additionally the model is targeting a national electrical load be spread-out evenly throughout the year in order to satisfy best economic performance for electricity generation, transmission and distribution. The model is applicable in region managed by the Australian Energy Management Operator (AEMO) covering states of Eastern-, Southern-Australia and Tasmania.

Optimum demand side response of smart grid with renewable energy source and electrical vehicles

The paper presents a demand side response scheme,which assists electricity consumers to proactively control own demands in such a way to deliberately avert congestion periods on the electrical network. The scheme allows shifting loads from peak to low demand periods in an attempt to flattening the national electricity requirement. The scheme can be concurrently used to accommodate the utilization of renewable energy sources,that might be available at user’s premises. In addition the scheme allows a full-capacity utilization of the available electrical infrastructure by organizing a wide-use of electric vehicles. The scheme is applicable in the Eastern and Southern States of Australia managed by the Australian Energy Market Operator. The results indicate the potential of the scheme to achieve energy savings and release capacity to accommodate renewable energy and electrical vehicle technologies.

Glycosaminoglycan and growth factor mediated murine calvarial cell proliferation

Understanding the complex mechanisms underlying bone remodeling is crucial to the development of novel therapeutics. Glycosaminoglycans (GAGs) localised to the extracellular matrix (ECM) of bone are thought to play a key role in mediating aspects of bone development. The influence of isolated GAGs was studied by utilising in vitro murine calvarial monolayer and organ culture model systems. Addition of GAG preparations extracted from the cell surface of human osteoblasts at high concentrations (5 microg/ml) resulted in decreased proliferation of cells and decreased suture width and number of bone lining cells in calvarial sections. When we investigated potential interactions between the growth factors fibroblast growth factor-2 (FGF2), bone morphogenic protein-2 (BMP2) and transforming growth factor-beta1 (TGFbeta1) and the isolated cell surface GAGs, differences between the two model systems emerged. The cell culture system demonstrated a potentiating role for the isolated GAGs in the inhibition of FGF2 and TGFbeta1 actions. In contrast, the organ culture system demonstrated an enhanced stimulation of TFGbeta1 effects. These results emphasise the role of the ECM in mediating the interactions between GAGs and growth factors during bone development and suggest the GAG preparations contain potent inhibitory or stimulatory components able to mediate growth factor activity.

Homodimerization controls the fibroblast growth factor 9 subfamily's receptor binding and heparan sulfate-dependent diffusion in the extracellular matrix

Uncontrolled fibroblast growth factor (FGF) signaling can lead to human diseases, necessitating multiple layers of self-regulatory control mechanisms to keep its activity in check. Herein, we demonstrate that FGF9 and FGF20 ligands undergo a reversible homodimerization, occluding their key receptor binding sites. To test the role of dimerization in ligand autoinhibition, we introduced structure-based mutations into the dimer interfaces of FGF9 and FGF20. The mutations weakened the ability of the ligands to dimerize, effectively increasing the concentrations of monomeric ligands capable of binding and activating their cognate FGF receptor in vitro and in living cells. Interestingly, the monomeric ligands exhibit reduced heparin binding, resulting in their increased radii of heparan sulfate-dependent diffusion and biologic action, as evidenced by the wider dilation area of ex vivo lung cultures in response to implanted mutant FGF9-loaded beads. Hence, our data demonstrate that homodimerization autoregulates FGF9 and FGF20's receptor binding and concentration gradients in the extracellular matrix. Our study is the first to implicate ligand dimerization as an autoregulatory mechanism for growth factor bioactivity and sets the stage for engineering modified FGF9 subfamily ligands, with desired activity for use in both basic and translational research.