High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue

Engineered biphasic osteochondral tissues may have utility in cartilage defect repair. As bone-marrow-derived mesenchymal stem/stromal cells (MSC) have the capacity to make both bone-like and cartilage-like tissues, they are an ideal cell population for use in the manufacture of osteochondral tissues. Effective differentiation of MSC to bone-like and cartilage-like tissues requires two unique medium formulations and this presents a challenge both in achieving initial MSC differentiation and in maintaining tissue stability when the unified osteochondral tissue is subsequently cultured in a single medium formulation. In this proof-of-principle study, we used an in-house fabricated microwell platform to manufacture thousands of micropellets formed from 166 MSC each. We then characterized the development of bone-like and cartilage-like tissue formation in the micropellets maintained for 8–14 days in sequential combinations of osteogenic or chondrogenic induction medium. When bone-like or cartilage-like micropellets were induced for only 8 days, they displayed significant phenotypic changes when the osteogenic or chondrogenic induction medium, respectively, was swapped. Based on these data, we developed an extended 14-day protocol for the pre-culture of bone-like and cartilage-like micropellets in their respective induction medium. Unified osteochondral tissues were formed by layering 12,000 osteogenic micropellets and 12,000 chondrogenic micropellets into a biphasic structure and then further culture in chondrogenic induction medium. The assembled tissue was cultured for a further 8 days and characterized via histology. The micropellets had amalgamated into a continuous structure with distinctive bone-like and cartilage-like regions. This proof-of-concept study demonstrates the feasibility of micropellet assembly for the formation of osteochondral-like tissues for possible use in osteochondral defect repair.

Submission to Senate Standing Committee on Legal and Constitutional Affairs on the Copyright Amendment (Online Infringement) Bill 2015

We argue that safeguards are necessary to ensure human rights are adequately protected. All systems of blocking access to online content necessarily raise difficult and problematic issues of infringement of freedom of speech and access to information. Given the importance of access to information across the breadth of modern life, great care must be taken to ensure that any measures designed to protect copyright by blocking access to online locations are proportionate. Any measures to block access to online content must be carefully tailored to avoid serious and disproportionate impact on human rights. This means first that the measures must be effective and adapted to achieve a legitimate purpose. The experience of foreign jurisdictions suggests that this legislation is unlikely to be effective. Unless and until there is clear evidence that the proposed scheme is likely to increase effective returns to Australian creators, this legislation should not be introduced. Second, the principle of proportionality requires ensuring that the proposed legislation does not unnecessarily burden legitimate speech or access to information. As currently worded, the draft legislation may result in online locations being blocked even though they would, if operated in Australia, not contravene Australian law. This is unacceptable, and if introduced, the law should be drafted so that it is clearly limited only to foreign locations where there is clear and compelling evidence that the location would authorise copyright infringement if it were in Australia. Third, proportionality requires that measures are reasonable and strike an appropriate balance between competing interests. This draft legislation provides few safeguards for the public interest or the interests of private actors who would access legitimate information. New safeguards should be introduced to ensure that the public interest is well represented at both the stage of the primary application and at any applications to rescind or vary injunctions. We recommend that: The legislation not be introduced unless and until there is compelling evidence that it will have a real and significant positive impact on the effective incomes of Australian creators. The ‘facilitates an infringement’ test in s 115A(1)(b) should be replaced with ‘authorises infringement’. The ‘primary purpose’ test in s 115A(1)(c) should be replaced with: “the online location has no substantial non-infringing uses”. An explicit role for public interest groups as amici curiae should be introduced. Costs of successful applications should be borne by applicants. Injunctions should be valid only for renewable two year terms. Section 115A(5) should be clarified, and cl (b) and (c) be removed. The effectiveness of the scheme should be evaluated in two years.

Race, the senses, and the materials of writing practices

The paper is a critical argument foregrounding race, the senses, and the materials of literacy practices. The author argues that counter-colonial literacies in the contemporary times require openly acknowledgement of the influences of white imperialism and racism in dominant schooling practices. The first concern is narrow conceptions of literacy and schooling that follow a white racial script, and which function as a form of historical reproduction, control, and privilege. The second is the need to acknowledge the need to rediscover the sensory nature of literacy practices that is intrinsic to many cultures, and which is transformed in human interactions with new digital forms of textual production. The final argument is the need to attend to the materiality of literacy practices, including the meanings connected to the material ecology. This principle is particularly relevant to Indigenous culture and experience, but likewise, to all digital environments where the materials of literacy practices are continually shifting.

The constraints of relevance on prevocational curriculum

This paper reflects on how relevance has been invoked as a curricular principle, both by students and teachers, in curriculum documents and in curriculum theory, to explore its variously conceived parameters and conditions. By posing the questions ‘relevant to whom?’, ‘relevant to what?’, ‘relevant how?’ and ‘relevant when?’ this paper exposes relevance as both a curricular virtue and a curricular constraint. It draws on an empirical project undertaken in the prevocational curriculum offered in Australia’s recently extended compulsory schooling for students in non-academic pathways. Data vignettes offer windows into two settings to exemplify the different ways relevance can be interpreted, stretched or contested. Using Bernstein’s distinction between vertical and horizontal discourses and knowledge structures, the analysis identifies what is gained and what is lost when relevance, variously defined, serves as a principle for curricular selection.

Crowning of dibenzosilole with a naphthalenediimide functional group to prepare an electron acceptor for organic solar cells

A novel, solution-processable non-fullerene electron acceptor 9,9′-(5,5-dioctyl-5H-dibenzo [b,d]silole-3,7-diyl)bis(2,7-dioctyl-4-(octylamino)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone) (B3) based on dibenzosilole and naphthalenediimide building blocks was designed, synthesized, characterized and successfully used in a bulk-heterojunction organic solar cell. B3 displayed excellent solubility, thermal stability and acquired electron energy levels matching with those of archetypal donor polymer poly(3-hexylthiophene). Solution-processable bulk-heterojunction devices afforded 1.16% power conversion efficiency with a high fill factor of 53%. B3 is the first example in the literature using this design principle, where mild donor units at the peripheries of end-capped naphthalenediimide units tune solubility and optical energy levels simultaneously.

Group 14 element-based non-centrosymmetric quantum spin hall insulators with large bulk gap

To date, a number of two-dimensional (2D) topological insulators (TIs) have been realized in Group 14 elemental honeycomb lattices, but all are inversionsymmetric. Here, based on first-principles calculations, we predict a new family of 2D inversion-asymmetric TIs with sizeable bulk gaps from 105 meV to 284 meV, in X2–GeSn (X = H, F, Cl, Br, I) monolayers, making them in principle suitable for room-temperature applications. The nontrivial topological characteristics of inverted band orders are identified in pristine X2–GeSn with X = (F, Cl, Br, I), whereas H2–GeSn undergoes a nontrivial band inversion at 8% lattice expansion. Topologically protected edge states are identified in X2–GeSn with X = (F, Cl, Br, I), as well as in strained H2–GeSn. More importantly, the edges of these systems, which exhibit single-Dirac-cone characteristics located exactly in the middle of their bulk band gaps, are ideal for dissipationless transport. Thus, Group 14 elemental honeycomb lattices provide a fascinating playground for the manipulation of quantum states.

Bank guarantees and the reasonable expectations of beneficiaries

A bank guarantee has traditionally been viewed as a cash equivalent. This view is supported by the operation of the autonomy principle. However, the autonomy principle is subject to certain recognised exceptions both at common law and under statute. One of these exceptions is commonly referred to as the negative stipulation or underlying contract exception. In recent times the operation of this particular exception has given rise to a wealth of case law. This article examines whether this recent case law appropriately recognises the reasonable expectations of the beneficiary of a bank guarantee that a bank guarantee should function not only as a security but as a risk allocation device.

Cost-effectiveness of bone-anchored prosthesis: the Queensland experience

Individuals with limb amputation fitted with conventional socket-suspended prostheses often experience socket-related discomfort leading to a significant decrease in quality of life. Bone-anchored prostheses are increasingly acknowledged as viable alternative method of attachment of artificial limb. In this case, the prosthesis is attached directly to the residual skeleton through a percutaneous fixation. To date, a few osseointegration fixations are commercially available. Several devices are at different stages of development particularly in Europe and the US. [1-15] Clearly, surgical procedures are currently blooming worldwide. Indeed, Australia and Queensland, in particular, have one of the fastest growing populations. Previous studies involving either screw-type implants or press-fit fixations for bone-anchorage have focused on biomechanics aspects as well as the clinical benefits and safety of the procedure. In principle, bone-anchored prostheses should eliminate lifetime expenses associated with sockets and, consequently, potentially alleviate the financial burden of amputation for governmental organizations. Unfortunately, publications focusing on cost-effectiveness are sparse. In fact, only one study published by Haggstrom et al (2012), reported that “despite significantly fewer visits for prosthetic service the annual mean costs for osseointegrated prostheses were comparable with socket-suspended prostheses”. Consequently, governmental organizations such as Queensland Artificial Limb Services (QALS) are facing a number of challenges while adjusting financial assistance schemes that should be fair and equitable to their clients fitted with bone-anchored prostheses. Clearly, more scientific evidence extracted from governmental databases is needed to further consolidate the analyses of financial burden associated with both methods of attachment (i.e., conventional sockets prostheses, bone-anchored prostheses). The purpose of the presentation will be to share the current outcomes of a cost-analysis study lead by QALS. The specific objectives will be: • To outline methodological avenues to assess the cost-effectiveness of bone-anchored prostheses compared to conventional sockets prostheses, • To highlight the potential obstacles and limitations in cost-effectiveness analyses of bone-anchored prostheses, • To present cohort results of a cost-effectiveness (QALY vs cost) including the determination of fair Incremental cost-effectiveness Ratios (ICER) as well as cost-benefit analysis focusing on the comparing costs and key outcome indicators (e.g., QTFA, TUG, 6MWT, activities of daily living) over QALS funding cycles for both methods of attachment.

Dissociable forms of repetition priming: A computational model

Nondeclarative memory and novelty processing in the brain is an actively studied field of neuroscience, and reducing neural activity with repetition of a stimulus (repetition suppression) is a commonly observed phenomenon. Recent findings of an opposite trend specifically, rising activity for unfamiliar stimuli—question the generality of repetition suppression and stir debate over the underlying neural mechanisms. This letter introduces a theory and computational model that extend existing theories and suggests that both trends are, in principle, the rising and falling parts of an inverted U-shaped dependence of activity with respect to stimulus novelty that may naturally emerge in a neural network with Hebbian learning and lateral inhibition. We further demonstrate that the proposed model is sufficient for the simulation of dissociable forms of repetition priming using real-world stimuli. The results of our simulation also suggest that the novelty of stimuli used in neuroscientific research must be assessed in a particularly cautious way. The potential importance of the inverted-U in stimulus processing and its relationship to the acquisition of knowledge and competencies in humans is also discussed

Do motor vehicle crashes arise from single or multiple unique risk processes? An inquiry into crash causes and modelling

Crashes at any particular transport network location consist of a chain of events arising from a multitude of potential causes and/or contributing factors whose nature is likely to reflect geometric characteristics of the road, spatial effects of the surrounding environment, and human behavioural factors. It is postulated that these potential contributing factors do not arise from the same underlying risk process, and thus should be explicitly modelled and understood. The state of the practice in road safety network management applies a safety performance function that represents a single risk process to explain crash variability across network sites. This study aims to elucidate the importance of differentiating among various underlying risk processes contributing to the observed crash count at any particular network location. To demonstrate the principle of this theoretical and corresponding methodological approach, the study explores engineering (e.g. segment length, speed limit) and unobserved spatial factors (e.g. climatic factors, presence of schools) as two explicit sources of crash contributing factors. A Bayesian Latent Class (BLC) analysis is used to explore these two sources and to incorporate prior information about their contribution to crash occurrence. The methodology is applied to the state controlled roads in Queensland, Australia and the results are compared with the traditional Negative Binomial (NB) model. A comparison of goodness of fit measures indicates that the model with a double risk process outperforms the single risk process NB model, and thus indicating the need for further research to capture all the three crash generation processes into the SPFs.

Saviour Siblings and the Regulation of Assisted Reproductive Technology: Harm, Ethics and Law

Advances in the field of Assisted Reproductive Technology (ART) have been revolutionary. This book focuses on the use of ARTs in the context of families who seek to conceive a matching sibling donor as a source of tissue to treat an existing sick child. Such children have been referred to as ‘saviour siblings’. Considering the legal and regulatory frameworks that impact on the accessibility of this technology in Australia and the UK, the work analyses the ethical and moral issues that arise from the use of the technology for this specific purpose. The author claims the only justification for limiting a family’s reproductive liberty in this context is where the exercise of reproductive decision-making results in harm to others. It is argued that the harm principle is the underlying feature of legislative action in Western democratic society, and as such, this principle provides the grounds upon which a strong and persuasive argument is made for a less-restrictive regulatory approach in the context of ‘saviour siblings’.

Perceptions of the prevalence of self-organising amongst Australian road safety stakeholders: A comparative perspective

The Australian road traffic fatality rate is slowing down at a much lower rate than that of comparable high income countries. This slow rate of reduction may be attributable to a wide range of causes such as deficits in coordination and low community engagement. However, it may also be due to the absence of understanding of systems thinking in road safety in Australia. This exploratory study aimed to investigate the perceptions of Australian stakeholders about the prevalence of a principle of the Dynamic Systems Theory, namely: self-organising. The results pointed to a need to decentralize the road traffic injury prevention efforts in Australia through a range of self-organising principles and the adoption of emergent rather than deliberate strategies.

Synthesis of novel poly[(2,5-dimethoxy-p-phenylene)vinylene] precursors having two eliminatable groups: An approach for the control of conjugation length

Poly[(2,5-dimethoxy-p-phenylene)vinylene] (DMPPV) of varying conjugation length was synthesized by selective elimination of organic soluble precursor polymers that contained two eliminatable groups, namely, methoxy and acetate groups. These precursor copolymers were in turn synthesized by competitive nucleophilic substitution of the sulfonium polyelectrolyte precursor (generated by the standard Wessling route) using methanol and sodium acetate in acetic acid. The composition of the precursor copolymer, in terms of the relative amounts of methoxy and acetate groups, was controlled by varying the composition of the reaction mixture during nucleophilic substitution. Thermal elimination of these precursor copolymers at 250 degrees C, yielded partially conjugated polymers, whose color varied from light yellow to deep red. FT-IR studies confirmed that, while essentially all the acetate groups were eliminated, the methoxy groups were intact and caused the interruption in conjugation. Preliminary photoluminescence studies of the partially eliminated DMPPV samples showed a gradual shift in the emission maximum from 498 to 598 nm with increasing conjugation lengths, suggesting that the color of LED devices fabricated from such polymers can, in principle, be fine-tuned.

Fluctuations in protein synthesis from a single RNA template: Stochastic kinetics of ribosomes

Proteins are polymerized by cyclic machines called ribosomes, which use their messenger RNA (mRNA) track also as the corresponding template, and the process is called translation. We explore, in depth and detail, the stochastic nature of the translation. We compute various distributions associated with the translation process; one of them-namely, the dwell time distribution-has been measured in recent single-ribosome experiments. The form of the distribution, which fits best with our simulation data, is consistent with that extracted from the experimental data. For our computations, we use a model that captures both the mechanochemistry of each individual ribosome and their steric interactions. We also demonstrate the effects of the sequence inhomogeneities of real genes on the fluctuations and noise in translation. Finally, inspired by recent advances in the experimental techniques of manipulating single ribosomes, we make theoretical predictions on the force-velocity relation for individual ribosomes. In principle, all our predictions can be tested by carrying out in vitro experiments.

Gaussian Schell-model beams and general shape invariance

We present two six-parameter families of anisotropic Gaussian Schell-model beams that propagate in a shape-invariant manner, with the intensity distribution continuously twisting about the beam axis. The two families differ in the sense or helicity of this beam twist. The propagation characteristics of these shape-invariant beams are studied, and the restrictions on the beam parameters that arise from the optical uncertainty principle are brought out. Shape invariance is traced to a fundamental dynamical symmetry that underlies these beams. This symmetry is the product of spatial rotation and fractional Fourier transformation.