A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone/periodontal ligament complex

This study describes the design of a biphasic scaffold composed of a Fused Deposition Modeling scaffold (bone compartment) and an electrospun membrane (periodontal compartment) for periodontal regeneration. In order to achieve simultaneous alveolar bone and periodontal ligament regeneration a cell-based strategy was carried out by combining osteoblast culture in the bone compartment and placement of multiple periodontal ligament (PDL) cell sheets on the electrospun membrane. In vitro data showed that the osteoblasts formed mineralized matrix in the bone compartment after 21 days in culture and that the PDL cell sheet harvesting did not induce significant cell death. The cell-seeded biphasic scaffolds were placed onto a dentin block and implanted for 8 weeks in an athymic rat subcutaneous model. The scaffolds were analyzed by μCT, immunohistochemistry and histology. In the bone compartment, a more intense ALP staining was obtained following seeding with osteoblasts, confirming the μCT results which showed higher mineralization density for these scaffolds. A thin mineralized cementum-like tissue was deposited on the dentin surface for the scaffolds incorporating the multiple PDL cell sheets, as observed by H&E and Azan staining. These scaffolds also demonstrated better attachment onto the dentin surface compared to no attachment when no cell sheets were used. In addition, immunohistochemistry revealed the presence of CEMP1 protein at the interface with the dentine. These results demonstrated that the combination of multiple PDL cell sheets and a biphasic scaffold allows the simultaneous delivery of the cells necessary for in vivo regeneration of alveolar bone, periodontal ligament and cementum. © 2012 Elsevier Ltd.

Mechanical considerations in fracture fixation

Bone’s capacity to repair following trauma is both unique and astounding. However, fractures sometimes fail to heal. Hence, the goal of fracture treatment is the restoration of bone’s structure, composition and function. Fracture fixation devices should provide a favourable mechanical and biological environment for healing to occur. The use of internal fixation is increasing as these devices may be applied with less invasive techniques. Recent studies suggest however that, internal fixation devices may be overly stiff and suppresses callus formation. The degree of mechanical stability influences the healing outcome. This is determined by the stiffness of the fixation device and the degree of limb loading. This project aims to characterise the fixation stability of an internal plate fixation device and the influence of modifications to its configuration on implant stability. As there are no standardised methods for the determination of fixation stiffness, the first part of this project aims to compares different methodologies and determines the most appropriate method to characterise the stiffness of internal plate fixators. The stiffness of a fixation device also influences the physiological loads experienced by the healing bone. Since bone adapts to this applied load by undergoing changes through a remodelling process, undesirable changes could occur during the period of treatment with an implant. The second part of this project aims to develop a methodology to quantify remodelling changes. This quantification is expected to aid our understanding of the changes in pattern due to implant related remodelling and on the factors driving the remodelling process. Knowledge gained in this project is useful to understand how the configuration of internal fixation devices can promote timely healing and prevent undesirable bone loss.

Influence of plate bending stiffness on mechanical properties of healing fracture, mouse femora

Mechanically well-defined stabilization systems have only recently become available, providing standardized conditions for studying the role of the mechanical environment on mouse bone fracture healing. The aim of this study was to characterize the time course of strength recovery and callus development of mouse femoral osteotomies stabilized with either low or high flexibility (in bending and torsion) internal fixation plates. Animals were euthanized and femora excised at 14, 21, and 28 days post-osteotomy for microCT analysis and torsional strength testing. While a larger mineralized callus was observed in osteotomies under more flexible conditions at all time points, the earlier bridging of the mineralized callus under less flexible conditions by 1 week resulted in an earlier recovery of torsional strength in mice stabilized with low flexibility fixation. Ultimate torque values for these bones were significantly higher at 14 and 21 days post-osteotomy compared to bones with the more flexible stabilization. Our study confirms the high reproducibility of the results that are achieved with this new implant system, therefore making it ideal for studying the influence of the mechanical environment on murine fracture healing under highly standardized conditions.

Practical client puzzles in the standard model

Client puzzles are cryptographic problems that are neither easy nor hard to solve. Most puzzles are based on either number theoretic or hash inversions problems. Hash-based puzzles are very efficient but so far have been shown secure only in the random oracle model; number theoretic puzzles, while secure in the standard model, tend to be inefficient. In this paper, we solve the problem of constucting cryptographic puzzles that are secure int he standard model and are very efficient. We present an efficient number theoretic puzzle that satisfies the puzzle security definition of Chen et al. (ASIACRYPT 2009). To prove the security of our puzzle, we introduce a new variant of the interval discrete logarithm assumption which may be of independent interest, and show this new problem to be hard under reasonable assumptions. Our experimental results show that, for 512-bit modulus, the solution verification time of our proposed puzzle can be up to 50x and 89x faster than the Karame-Capkum puzzle and the Rivest et al.'s time-lock puzzle respectively. In particular, the solution verification tiem of our puzzle is only 1.4x slower than that of Chen et al.'s efficient hash based puzzle.

Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model

Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for establishment of these bone tumours.

Orthopedic bone plates : evolution in structure implementation technique and biomaterial

With many important developments over the last century, nowadays orthopedic bone plate now excels over other types of internal fixators in bone fracture fixation. The developments involve the design, material and implementation techniques of the plates. This paper aims to review the evolution in implementation technique and biomaterial of the orthopedic bone plates. Plates were initially used to fix the underlying bones firmly. Accordingly, Compression plate (CP), Dynamic compression plate (DCP), Limited contact dynamic compression plate (LC-DCP) and Point contact fixator (PC-Fix) were developed. Later, the implementation approach was changed to locking, and the Less Invasive Stabilization System (LISS) plate was introduced as a result. Finally, a combination of both of these approaches has been used by introducing the Locking Compression Plate (LCP). Currently, precontoured LCPs are mainly used for bone fracture fixation. In parallel with structure and implementation techniques, numerous advances have occurred in biomaterials of the plates. Titanium and stainless steel alloys are now the most common biomaterials in production of orthopedic bone plates. However, regarding the biocompatibility, bioactivity and biodegradability characteristics of Mg alloys, Ta alloys, SMAs, carbon fiber composites and bioceramics, these materials are considered as potentially suitable for plates. However, due to poor mechanical properties, they have very limited applications. Therefore, further studies are required in future to solve these problems and make them feasible for heavy-duty bone plates.

Putting the Repository First: Implementing a Repository to RIS Workflow for QUT ePrints

As one of the first institutional repositories in Australia and the first in the world to have an institution-wide deposit mandate, QUT ePrints has great ‘brand recognition’ within the University (Queensland University of Technology) and beyond. The repository is managed by the library but, over the years, the Library’s repository team has worked closely with other departments (especially the Office of Research and IT Services) to ensure that QUT ePrints was embedded into the business processes and systems our academics use regularly. For example, the repository is the source of the publication information which displays on each academic’s Staff Profile page. The repository pulls in citation data from Scopus and Web of Science and displays the data in the publications records. Researchers can monitor their citations at a glance via the repository ‘View’ which displays all their publications. A trend in recent years has been to populate institutional repositories with publication details imported from the University’s research information system (RIS). The main advantage of the RIS to Repository workflow is that it requires little input from the academics as the publication details are often imported into the RIS from publisher databases. Sadly, this is also its main disadvantage. Generally, only the metadata is imported from the RIS and the lack of engagement by the academics results in very low proportions of records with open access full-texts. Consequently, while we could see the value of integrating the two systems, we were determined to make the repository the entry point for publication data. In 2011, the University funded a project to convert a number of paper-based processes into web-based workflows. This included a workflow to replace the paper forms academics used to complete to report new publications (which were later used by the data entry staff to input the details into the RIS). Publication details and full-text files are uploaded to the repository (by the academics or their nominees). Each night, the repository (QUT ePrints) pushes the metadata for new publications into a holding table. The data is checked by Office of Research staff the next day and then ‘imported’ into the RIS. Publication details (including the repository URLs) are pushed from the RIS to the Staff Profiles system. Previously, academics were required to supply the Office of research with photocopies of their publication (for verification/auditing purposes). The repository is now the source of verification information. Library staff verify the accuracy of the publication details and, where applicable, the peer review status of the work. The verification metadata is included in the information passed to the Office of Research. The RIS at QUT comprises two separate systems built on an Oracle database; a proprietary product (ResearchMaster) plus a locally produced system known as RAD (Research Activity Database). The repository platform is EPrints which is built on a MySQL database. This partly explains why the data is passed from one system to the other via a holding table. The new workflow went live in early April 2012. Tests of the technical integration have all been successful. At the end of the first 12 months, the impact of the new workflow on the proportion of full-texts deposited will be evaluated.

Development of zonal cartilage constructs : effects of chondrocyte subpopulation, compressive stimulation, and culture models

Articular cartilage is a highly resilient tissue located at the ends of long bones. It has a zonal structure, which has functional significance in load-bearing. Cartilage does not spontaneously heal itself when damaged, and untreated cartilage lesions or age-related wear often lead to osteoarthritis (OA). OA is a degenerative condition that is highly prevalent, age-associated, and significantly affects patient mobility and quality of life. There is no cure for OA, and patients usually resort to replacing the biological joint with an artificial prosthesis. An alternative approach is to dynamically regenerate damaged or diseased cartilage through cartilage tissue engineering, where cells, materials, and stimuli are combined to form new cartilage. However, despite extensive research, major limitations remain that have prevented the wide-spread application of tissue-engineered cartilage. Critically, there is a dearth of information on whether autologous chondrocytes obtained from OA patients can be used to successfully generate cartilage tissues with structural hierarchy typically found in normal articular cartilage. I aim to address these limitations in this thesis by showing that chondrocyte subpopulations isolated from macroscopically normal areas of the cartilage can be used to engineer stratified cartilage tissues and that compressive loading plays an important role in zone-dependent biosynthesis of these chondrocytes. I first demonstrate that chondrocyte subpopulations from the superficial (S) and middle/deep (MD) zones of OA cartilage are responsive to compressive stimulation in vitro, and that the effect of compression on construct quality is zone-dependent. I also show that compressive stimulation can influence pericelluar matrix production, matrix metalloproteinase secretion, and cytokine expression in zonal chondrocytes in an alginate hydrogel model. Subsequently, I focus on recreating the zonal structure by forming layered constructs using the alginate-released chondrocyte (ARC) method either with or without polymeric scaffolds. Resulting zonal ARC constructs had hyaline morphology, and expressed cartilage matrix molecules such as proteoglycans and collagen type II in both scaffold-free and scaffold-based approaches. Overall, my findings demonstrate that chondrocyte subpopulations obtained from OA joints respond sensitively to compressive stimulation, and are able to form cartilaginous constructs with stratified organization similar to native cartilage using the scaffold-free and scaffold-based ARC technique. The ultimate goal in tissue engineering is to help provide improved treatment options for patients suffering from debilitating conditions such as OA. Further investigations in developing functional cartilage replacement tissues using autologous chondrocytes will bring us a step closer to improving the quality of life for millions of OA patients worldwide.

Computationally sound automated proofs of cryptographic schemes

Proving security of cryptographic schemes, which normally are short algorithms, has been known to be time-consuming and easy to get wrong. Using computers to analyse their security can help to solve the problem. This thesis focuses on methods of using computers to verify security of such schemes in cryptographic models. The contributions of this thesis to automated security proofs of cryptographic schemes can be divided into two groups: indirect and direct techniques. Regarding indirect ones, we propose a technique to verify the security of public-key-based key exchange protocols. Security of such protocols has been able to be proved automatically using an existing tool, but in a noncryptographic model. We show that under some conditions, security in that non-cryptographic model implies security in a common cryptographic one, the Bellare-Rogaway model [11]. The implication enables one to use that existing tool, which was designed to work with a different type of model, in order to achieve security proofs of public-key-based key exchange protocols in a cryptographic model. For direct techniques, we have two contributions. The first is a tool to verify Diffie-Hellmanbased key exchange protocols. In that work, we design a simple programming language for specifying Diffie-Hellman-based key exchange algorithms. The language has a semantics based on a cryptographic model, the Bellare-Rogaway model [11]. From the semantics, we build a Hoare-style logic which allows us to reason about the security of a key exchange algorithm, specified as a pair of initiator and responder programs. The other contribution to the direct technique line is on automated proofs for computational indistinguishability. Unlike the two other contributions, this one does not treat a fixed class of protocols. We construct a generic formalism which allows one to model the security problem of a variety of classes of cryptographic schemes as the indistinguishability between two pieces of information. We also design and implement an algorithm for solving indistinguishability problems. Compared to the two other works, this one covers significantly more types of schemes, but consequently, it can verify only weaker forms of security.

More is not necessarily better. A biomechanical study on distal screw numbers in volar locking distal radius plates

INTRODUCTION: Currently available volar locking plates for the treatment of distal radius fractures incorporate at least two distal screw rows for fixation of the metaphyseal fragment and have a variable-angle locking mechanism which allows placement of the screws in various directions There is, however no evidence that these plates translate into better outcomes or have superior biomechanical properties to first generation plates, which had a single distal screw row and fixed-angle locking. The aim of our biomechanical study was to compare fixed-angle single-row plates with variable-angle multi-row plates to clarify the optimal number of locking screws. MATERIALS AND METHODS: Five different plate-screw combinations of three different manufacturers were tested, each group consisting of five synthetic fourth generation distal radius bones. An AO type C2 fracture was created and the fractures were plated according to each manufacturer's recommendations. The specimens then underwent cyclic and load-to-failure testing. An optical motion analysis system was used to detect displacement of fragments. RESULTS: No significant differences were detected after cyclic loading as well as after load-to-failure testing, neither in regard to axial deformation, implant rigidity or maximum displacement. The fixed-angle single-row plate showed the highest pre-test rigidity, least increase in post-testing rigidity and highest load-to-failure rigidity and least radial shortening. The radial shortening of plates with two distal screw rows was 3.1 and 4.3 times higher, respectively, than that of the fixed-angle single-row plate. CONCLUSION: The results of our study indicate that two distal screw rows do not add to construct rigidity and resistance against loss of reduction. Well conducted clinical studies based on the findings of biomechanical studies are necessary to determine the optimal number of screws necessary to achieve reproducibly good results in the treatment of distal radius fractures.

What’s in a name : Is there a right to terminate a contract for purchase of a unit if the name changes?

The significance of the proposed name of a building to buyers of units off the plan has received recent attention in Queensland and the ACT with differing results. In Gough v South Sky Investments Pty Ltd the Queensland Court of Appeal concluded that the name of the building was not an essential term of the contract and rejected a claim by a number of buyers to terminate their contracts because of the change of name from Oracle to Peppers. In contrast, Rares J in the Federal Court decision of Madison Constructions Pty Ltd v Empire Building Group (ACT) Pty Ltd considered that the name of the building in a proposed development could potentially form the basis of misleading conduct about the association of the seller with a particular development corporation.

An evidence-informed strategy to prevent osteoporosis in Australia

Osteoporosis imposes a tremendous burden on Australia : 1.2 million Australians have osteoporosis and 6.3 million have Osteopenia. In the 2007-08 financial year, 82000 Australians suffered fragility fractures, of Which >17000 were hip fractures. In the 2000-01 financial year, direct costs were estimated at $1.9 billion per year and an additional $5.6 billion on indirect costs. Osteoporosis was designated a National Health Priority Area in 2002; however, implementation of national plans has not yet matched the rhetoric in terms of urgency. Building healthy bones throughout life, the Osteoporosis Australia strategy to prevent osteoporosis throughout the life cycle, presents an evidence-informed set of recommendations for consumers, health care professionals and policymakers. The strategy was adopted by consensus at the Osteoporosis Australia Summit in Sydney, 20 October 2011. Primary objectives throughout the life cycle are: to maximise peak bone mass during childhood and adolescence to prevent premature bone loss and improve or maintain muscle mass, strength and functional capacity in healthy adults to prevent and treat osteoporosis in order to minimise the risk of suffering fragility fractures, and reduce falls risk, in older people. The recommendations focus on three affordable and important interventions to ensure people have adequate calcium intake, vitamin D levels and appropriate, physical activity throughout their lives. Recommendations relevant to all stages of life include: daily dietary calcium intakes should be consistent with Australian and New Zealand guidelines serum levels of vitamin D in the general population should be above 50 nmol/L in winter or early spring for optimal bone health regular weight-bearing physical activity, Muscle strengthening exercises and challenging balance/ mobility activities should be conducted in a safe environment.

Factors affecting the accuracy of engineers' estimates

Emerging sciences, such as conceptual cost estimating, seem to have to go through two phases. The first phase involves reducing the field of study down to its basic ingredients - from systems development to technological development (techniques) to theoretical development. The second phase operates in the direction in building up techniques from theories, and systems from techniques. Cost estimating is clearly and distinctly still in the first phase. A great deal of effort has been put into the development of both manual and computer based cost estimating systems during this first phase and, to a lesser extent, the development of a range of techniques that can be used (see, for instance, Ashworth & Skitmore, 1986). Theoretical developments have not, as yet, been forthcoming. All theories need the support of some observational data and cost estimating is not likely to be an exception. These data do not need to be complete in order to build theories. As it is possible to construct an image of a prehistoric animal such as the brontosaurus from only a few key bones and relics, so a theory of cost estimating may possibly be found on a few factual details. The eternal argument of empiricists and deductionists is that, as theories need factual support, so do we need theories in order to know what facts to collect. In cost estimating, the basic facts of interest concern accuracy, the cost of achieving this accuracy, and the trade off between the two. When cost estimating theories do begin to emerge, it is highly likely that these relationships will be central features. This paper presents some of the facts we have been able to acquire regarding one part of this relationship - accuracy, and its influencing factors. Although some of these factors, such as the amount of information used in preparing the estimate, will have cost consequences, we have not yet reached the stage of quantifying these costs. Indeed, as will be seen, many of the factors do not involve any substantial cost considerations. The absence of any theory is reflected in the arbitrary manner in which the factors are presented. Rather, the emphasis here is on the consideration of purely empirical data concerning estimating accuracy. The essence of good empirical research is to .minimize the role of the researcher in interpreting the results of the study. Whilst space does not allow a full treatment of the material in this manner, the principle has been adopted as closely as possible to present results in an uncleaned and unbiased way. In most cases the evidence speaks for itself. The first part of the paper reviews most of the empirical evidence that we have located to date. Knowledge of any work done, but omitted here would be most welcome. The second part of the paper presents an analysis of some recently acquired data pertaining to this growing subject.

The naturally imperfect form : investigations of the application of digital sculpting methods - extracted art : incorporating and translating ‘found art’ into the medium of digital sculpture

This dissertation analyses how physical objects are translated into digital artworks using techniques which can lead to ‘imperfections’ in the resulting digital artwork that are typically removed to arrive at a ‘perfect’ final representation. The dissertation discusses the adaptation of existing techniques into an artistic workflow that acknowledges and incorporates the imperfections of translation into the final pieces. It presents an exploration of the relationship between physical and digital artefacts and the processes used to move between the two. The work explores the 'craft' of digital sculpting and the technology used in producing what the artist terms ‘a naturally imperfect form’, incorporating knowledge of traditional sculpture, an understanding of anatomy and an interest in the study of bones (Osteology). The outcomes of the research are presented as a series of digital sculptural works, exhibited as a collection of curiosities in multiple mediums, including interactive game spaces, augmented reality (AR), rapid prototype prints (RP) and video displays.

Cryptographic techniques for managing computational effort

Availability has become a primary goal of information security and is as significant as other goals, in particular, confidentiality and integrity. Maintaining availability of essential services on the public Internet is an increasingly difficult task in the presence of sophisticated attackers. Attackers may abuse limited computational resources of a service provider and thus managing computational costs is a key strategy for achieving the goal of availability. In this thesis we focus on cryptographic approaches for managing computational costs, in particular computational effort. We focus on two cryptographic techniques: computational puzzles in cryptographic protocols and secure outsourcing of cryptographic computations. This thesis contributes to the area of cryptographic protocols in the following ways. First we propose the most efficient puzzle scheme based on modular exponentiations which, unlike previous schemes of the same type, involves only a few modular multiplications for solution verification; our scheme is provably secure. We then introduce a new efficient gradual authentication protocol by integrating a puzzle into a specific signature scheme. Our software implementation results for the new authentication protocol show that our approach is more efficient and effective than the traditional RSA signature-based one and improves the DoSresilience of Secure Socket Layer (SSL) protocol, the most widely used security protocol on the Internet. Our next contributions are related to capturing a specific property that enables secure outsourcing of cryptographic tasks in partial-decryption. We formally define the property of (non-trivial) public verifiability for general encryption schemes, key encapsulation mechanisms (KEMs), and hybrid encryption schemes, encompassing public-key, identity-based, and tag-based encryption avors. We show that some generic transformations and concrete constructions enjoy this property and then present a new public-key encryption (PKE) scheme having this property and proof of security under the standard assumptions. Finally, we combine puzzles with PKE schemes for enabling delayed decryption in applications such as e-auctions and e-voting. For this we first introduce the notion of effort-release PKE (ER-PKE), encompassing the well-known timedrelease encryption and encapsulated key escrow techniques. We then present a security model for ER-PKE and a generic construction of ER-PKE complying with our security notion.