Genetic evidence for the vital function of osterix in cementogenesis

To date, attempts to regenerate a complete tooth, including the critical periodontal tissues associated with the tooth root, have not been successful. Controversy still exists regarding the origin of the cell source for cellular cementum (epithelial or mesenchymal). This disagreement may be partially due to a lack of understanding of the events leading to the initiation and development of the tooth roots and supportive tissues, such as the cementum. Osterix (OSX) is a transcriptional factor essential for osteogenesis, but its role in cementogenesis has not been addressed. In the present study, we first documented a close relationship between the temporal- and spatial-expression pattern of OSX and the formation of cellular cementum. We then generated 3.6 Col 1-OSX transgenic mice, which displayed accelerated cementum formation vs. WT controls. Importantly, the conditional deletion of OSX in the mesenchymal cells with two different Cre systems (the 2.3 kb Col 1 and an inducible CAG-CreER) led to a sharp reduction in cellular cementum formation (including the cementum mass and mineral deposition rate) and gene expression of dentin matrix protein 1 (DMP1) by cementocytes. However, the deletion of the OSX gene after cellular cementum formed did not alter the properties of the mature cementum as evaluated by backscattered SEM and resin-cast SEM. Transient transfection of Osx in the cementoblasts in vitro significantly inhibited cell proliferation and increased cell differentiation and mineralization. Taken together, these data support 1) the mesenchymal origin of cellular cementum (from PDL progenitor cells); 2) the vital role of OSX in controlling the formation of cellular cementum; and 3) the limited remodeling of cellular cementum in adult mice.

Assessment of function and clinical utility of alcohol and other drug web sites : an observational, qualitative study

Background The increasing popularity and use of the internet makes it an attractive option for providing health information and treatment, including alcohol/other drug use. There is limited research examining how people identify and access information about alcohol or other drug (AOD) use online, or how they assess the usefulness of the information presented. This study examined the strategies that individuals used to identify and navigate a range of AOD websites, along with the attitudes concerning presentation and content. Methods Members of the general community in Brisbane and Roma (Queensland, Australia) were invited to participate in a 30-minute search of the internet for sites related to AOD use, followed by a focus group discussion. Fifty one subjects participated in the study across nine focus groups. Results Participants spent a maximum of 6.5 minutes on any one website, and less if the user was under 25 years of age. Time spent was as little as 2 minutes if the website was not the first accessed. Participants recommended that AOD-related websites should have an engaging home or index page, which quickly and accurately portrayed the site’s objectives, and provided clear site navigation options. Website content should clearly match the title and description of the site that is used by internet search engines. Participants supported the development of a portal for AOD websites, suggesting that it would greatly facilitate access and navigation. Treatment programs delivered online were initially viewed with caution. This appeared to be due to limited understanding of what constituted online treatment, including its potential efficacy. Conclusions A range of recommendations arise from this study regarding the design and development of websites, particularly those related to AOD use. These include prudent use of text and information on any one webpage, the use of graphics and colours, and clear, uncluttered navigation options. Implications for future website development are discussed.

New exact solutions for Hele-Shaw flow in doubly connected regions

Radial Hele-Shaw flows are treated analytically using conformal mapping techniques. The geometry of interest has a doubly-connected annular region of viscous fluid surrounding an inviscid bubble that is either expanding or contracting due to a pressure difference caused by injection or suction of the inviscid fluid. The zero-surface-tension problem is ill-posed for both bubble expansion and contraction, as both scenarios involve viscous fluid displacing inviscid fluid. Exact solutions are derived by tracking the location of singularities and critical points in the analytic continuation of the mapping function. We show that by treating the critical points, it is easy to observe finite-time blow-up, and the evolution equations may be written in exact form using complex residues. We present solutions that start with cusps on one interface and end with cusps on the other, as well as solutions that have the bubble contracting to a point. For the latter solutions, the bubble approaches an ellipse in shape at extinction.

A new tip area function for instrumented nanoindentation at extremely small contact depths

The accuracy of measurement of mechanical properties of a material using instrumented nanoindentation at extremely small penetration depths heavily relies on the determination of the contact area of the indenter. Our experiments have demonstrated that the conventional area function could lead to a significant error when the contact depth was below 40. nm, due to the singularity in the first derivation of the function in this region and thus, the resultant unreasonable sharp peak on the function curve. In this paper, we proposed a new area function that was used to calculate the contact area for the indentations where the contact depths varied from 10 to 40. nm. The experimental results have shown that the new area function has produced better results than the conventional function. © 2011 Elsevier B.V.

Regulation of proteasome structure and function

Proteasomes are cylindrical particles made up of a stack of four heptameric rings. In animal cells the outer rings are made up of 7 different types of alpha subunits and the inner rings are composed of 7 out of 10 possible different beta subunits. Regulatory complexes can bind to the ends of the cylinder.We have investigated aspects of the assembly, activity and subunit composition of core proteasome particles and 26S proteasomes, the localization of proteasome subpopulations, and the possible role of phosphorylation in determining proteasome localization, activities and association with regulatory components.

Decision support for the safe design and operation of unmanned aircraft systems

Unmanned Aircraft Systems (UAS) describe a diverse range of aircraft that are operated without a human pilot on-board. Unmanned aircraft range from small rotorcraft, which can fit in the palm of your hand, through to fixed wing aircraft comparable in size to that of a commercial passenger jet. The absence of a pilot on-board allows these aircraft to be developed with unique performance capabilities facilitating a wide range of applications in surveillance, environmental management, agriculture, defence, and search and rescue. However, regulations relating to the safe design and operation of UAS first need to be developed before the many potential benefits from these applications can be realised. According to the International Civil Aviation Organization (ICAO), a Risk Management Process (RMP) should support all civil aviation policy and rulemaking activities (ICAO 2009). The RMP is described in International standard, ISO 31000:2009 (ISO, 2009a). This standard is intentionally generic and high-level, providing limited guidance on how it can be effectively applied to complex socio-technical decision problems such as the development of regulations for UAS. Through the application of principles and tools drawn from systems philosophy and systems engineering, this thesis explores how the RMP can be effectively applied to support the development of safety regulations for UAS. A sound systems-theoretic foundation for the RMP is presented in this thesis. Using the case-study scenario of a UAS operation over an inhabited area and through the novel application of principles drawn from general systems modelling philosophy, a consolidated framework of the definitions of the concepts of: safe, risk and hazard is made. The framework is novel in that it facilitates the representation of broader subjective factors in an assessment of the safety of a system; describes the issues associated with the specification of a system-boundary; makes explicit the hierarchical nature of the relationship between the concepts and the subsequent constraints that exist between them; and can be evaluated using a range of analytic or deliberative modelling techniques. Following the general sequence of the RMP, the thesis explores the issues associated with the quantified specification of safety criteria for UAS. A novel risk analysis tool is presented. In contrast to existing risk tools, the analysis tool presented in this thesis quantifiably characterises both the societal and individual risk of UAS operations as a function of the flight path of the aircraft. A novel structuring of the risk evaluation and risk treatment decision processes is then proposed. The structuring is achieved through the application of the Decision Support Problem Technique; a modelling approach that has been previously used to effectively model complex engineering design processes and to support decision-making in relation to airspace design. The final contribution made by this thesis is in the development of an airworthiness regulatory framework for civil UAS. A novel "airworthiness certification matrix" is proposed as a basis for the definition of UAS "Part 21" regulations. The outcome airworthiness certification matrix provides a flexible, systematic and justifiable method for promulgating airworthiness regulations for UAS. In addition, an approach for deriving "Part 1309" regulations for UAS is presented. In contrast to existing approaches, the approach presented in this thesis facilitates a traceable and objective tailoring of system-level reliability requirements across the diverse range of UAS operations. The significance of the research contained in this thesis is clearly demonstrated by its practical real world outcomes. Industry regulatory development groups and the Civil Aviation Safety Authority have endorsed the proposed airworthiness certification matrix. The risk models have also been used to support research undertaken by the Australian Department of Defence. Ultimately, it is hoped that the outcomes from this research will play a significant part in the shaping of regulations for civil UAS, here in Australia and around the world.

Sensitivity of the NMR density matrix to pulse sequence parameters : a simplified analytic approach

We present a formalism for the analysis of sensitivity of nuclear magnetic resonance pulse sequences to variations of pulse sequence parameters, such as radiofrequency pulses, gradient pulses or evolution delays. The formalism enables the calculation of compact, analytic expressions for the derivatives of the density matrix and the observed signal with respect to the parameters varied. The analysis is based on two constructs computed in the course of modified density-matrix simulations: the error interrogation operators and error commutators. The approach presented is consequently named the Error Commutator Formalism (ECF). It is used to evaluate the sensitivity of the density matrix to parameter variation based on the simulations carried out for the ideal parameters, obviating the need for finite-difference calculations of signal errors. The ECF analysis therefore carries a computational cost comparable to a single density-matrix or product-operator simulation. Its application is illustrated using a number of examples from basic NMR spectroscopy. We show that the strength of the ECF is its ability to provide analytic insights into the propagation of errors through pulse sequences and the behaviour of signal errors under phase cycling. Furthermore, the approach is algorithmic and easily amenable to implementation in the form of a programming code. It is envisaged that it could be incorporated into standard NMR product-operator simulation packages.