Carbon nanostructures for hard tissue engineering

The primary goal in hard tissue engineering is to combine high-performance scaffold materials with living cells to develop biologically active substitutes that can restore tissue functions. This requires relevant knowledge in multidisciplinary fields encompassing chemical engineering, material science, chemistry, biology and nanotechnology. Here we present an overview on the recent progress of how two representative carbon nanostructures, namely, carbon nanotubes and graphene, aid and advance the research in hard tissue engineering. The article focuses on the advantages and challenges of integrating these carbon nanostructures into functional scaffolds for repairing and regenerative purposes. It includes, but is not limited to, the critical physico-chemical properties of carbon nanomaterials for enhanced cell interactions such as adhesion, morphogenesis, proliferation and differentiation; the novel designs of two- and three-dimensional nanostructured scaffolds; multifunctional hybrid materials; and the biocompatible aspects of carbon nanotubes and graphene. Perspectives on the future research directions are also given, in an attempt to shed light on the innovative and rational design of more effective biomedical devices in hard tissue engineering.

The social shaping of packaged software selection

As organisations increasingly engage in the selection, purchase, and adoption of packaged software products, how these activities are carried out in practice becomes increasingly relevant for researchers and practitioners. Our focus in this paper is to propose a framework for understanding the packaged software selection process. The functionalist literature on this area of study suggests a number of generic recommendations, which are based on rational assumptions about the process and view the decision making that takes place as producing the “best technology solution.’” To explore this, we conducted a longitudinal, in-depth study of packaged software selection in a small organisation. For interpretation of the case, we draw upon the Social Construction of Technology, a theoretical framework arguing that technology is socially constituted and regarding the process of development as contradictory and uncertain. We offer a number of contributions. First, we further our understanding of packaged software selection with the critique that we offer of the functionalist literature, drawing insights from the emerging critical/constructivist literature and expanding our domain of interest to encompass the wider environment. Second, we weave this together with our experiences in the field, drawing on social constructivism for theoretical support, to develop a framework of packaged software selection that shows how various actors shape the process.

Activation of toxic chemicals by cytochrome P450 enzymes : regio- and stereoselective oxidation of aflatoxin B1

Cytochrome P450 (P450) enzymes are involved in the oxidations of numerous steroids, eicosanoids, alkaloids, and other endogenous substrates. These enzymes are also the major ones involved in the oxidation of potential toxicants and carcinogens such as those encountered among pollutants, solvents, and pesticides, as well as many natural products. A proper understanding of the basic mechanisms by which the P450 enzymes oxidize such compounds is important in developing rational strategies for the evaluation of the risks of these compounds.

From bench to bedside : immunotherapy for prostate cancer

The mainstay therapeutic strategy for metastatic castrate-resistant prostate cancer (CRPC) continues to be androgen deprivation therapy usually in combination with chemotherapy or androgen receptor targeting therapy in either sequence, or recently approved novel agents such as Radium 223. However, immunotherapy has also emerged as an option for the treatment of this disease following the approval of sipuleucel-T by the FDA in 2010. Immunotherapy is a rational approach for prostate cancer based on a body of evidence suggesting these cancers are inherently immunogenic and, most importantly, that immunological interventions can induce protective antitumour responses. Various forms of immunotherapy are currently being explored clinically, with the most common being cancer vaccines (dendritic-cell, viral, and whole tumour cell-based) and immune checkpoint inhibition. This review will discuss recent clinical developments of immune-based therapies for prostate cancer that have reached the phase III clinical trial stage. A perspective of how immunotherapy could be best employed within current treatment regimes to achieve most clinical benefits is also provided.

Enhancing MRI of prostate cancer using PSMA-targeting iron oxide magnetic nanoparticles

Introduction Novel imaging techniques for prostate cancer (PCa) are required to improve staging and real-time assessment of therapeutic response. We performed preclinical evaluation of newly-developed, biocompatible magnetic nanoparticles (MNPs) conjugated with J591, an antibody specific for prostate specific membrane antigen (PSMA), to enhance magnetic resonance imaging (MRI) of PCa. PSMA is expressed on ∼90% of PCa, including those that are castrate-resistant, rendering it as a rational target for PCa imaging. Materials and Methods The specificity of J591 for PSMA was confirmed by flow cytometric analysis of several PCa cell lines of known PSMA status. MNPs were prepared, engineered to the appropriate size, labeled with DiR fluorophore, and their toxicity to a panel of PC cells was assessed by in vitro Alamar Blue assay. Immunohistochemistry, fluorescence microscopy and Prussian Blue staining (iron uptake) were used to evaluate PSMA specificity of J591-MNP conjugates. In vivo MRI studies (16.4T MRI system) were performed using live immunodeficient mice bearing orthotopic LNCaP xenografts and injected intravenously with J591-MNPs or MNPs alone. Results MNPs were non-toxic to PCa cells. J591-MNP conjugates showed no compromise in specificity of binding to PSMA+ cells and showed enhanced iron uptake compared with MNPs alone. In vivo, tumour targeting (significant MR image contrast) was evident in mice injected with J591-MNPs, but not MNPs alone. Resected tumours from targeted mice had an accumulation of MNPs, not seen in normal control prostate. Conclusions Application of PSMA-targeting MNPs into conventional MRI has potential to enhance PCa detection and localization in real-time, improving patient management.

Tales of science and defiance : the case for co-learning and collaboration in bridging the science/emotion divide in water recycling debates

Although science is generally assumed to be well integrated into rational decision-making models, it can be used to destabilise consultative processes, particularly when emotions are involved. Water policies are often seen as debates over technical and engineering issues, but can be highly controversial. Recycled water proposals, in particular, can create highly emotive conflicts. Through a case study regarding the rejection of recycled water proposals in the south-east Queensland, Australia, we explore the influence of science and emotions in contemporary water planning. We highlight the dangers inherent in promoting technical water planning issues at the expense of appropriate consideration of citizen concerns. Combining the science–policy interface and stakeholder engagement literatures, we advocate for collaborative decision-making processes that accommodate emotions and value judgements. A more collaborative stakeholder engagement model, founded on the principles of co-learning, has the potential to broaden the decision-making base and to promote better and more inclusive decision-making.

Novel approaches for SER spectroscopic analysis of protein cofactors

Biomimetic systems employed for biotechnological applications i.e. as biosensors or bio fuel cells, require initial formation of conducting support/protein complexes with controlled properties. The specific interaction of the protein with the support determines important qualities of the device such as electrical communication, long-term stability and catalytic efficiency. In this respect the system parameters have to be chosen in a way that high protein loading on the support is achieved while protein denaturation upon adsorption is prevented. The conditions on the surface have to be adjusted in such a way that the desired surface reaction of the protein i.e. electron transfer to either the electrode or a second redox partner, is still guaranteed. Hence the choice of support, its functionlisation as well as the right adjustment of solution parameters play a crucial role in the rational design of these support/protein constructs.

Towards a theory of individual-level discontinuance of information systems use

I develop a model of individuals’ intentions to discontinue information system use. Understanding these intentions is important because they give insights into users’ willingness to carry out system tasks, and provide a basis for maintenance decisions as well as possible replacement decisions. I offer a first conceptualization of factors determining users’ discontinuance intentions on basis of existing literature on technology use, status quo bias and dual factor concepts. The model is grounded in rational choice theory to distinguish determinants of a conscious decision between continuing or discontinuing IS use. I provide details on the empirical test of the model through a field study of IS users in a retail organization. The work will have implications for theory on information systems continuance and dual-factor logic in information system use. The empirical findings will provide suggestions for managers dealing with cessation of information systems and work routine changes in organizations.

A new ambiguity acceptance test threshold determination method with controllable failure rate

The ambiguity acceptance test is an important quality control procedure in high precision GNSS data processing. Although the ambiguity acceptance test methods have been extensively investigated, its threshold determine method is still not well understood. Currently, the threshold is determined with the empirical approach or the fixed failure rate (FF-) approach. The empirical approach is simple but lacking in theoretical basis, while the FF-approach is theoretical rigorous but computationally demanding. Hence, the key of the threshold determination problem is how to efficiently determine the threshold in a reasonable way. In this study, a new threshold determination method named threshold function method is proposed to reduce the complexity of the FF-approach. The threshold function method simplifies the FF-approach by a modeling procedure and an approximation procedure. The modeling procedure uses a rational function model to describe the relationship between the FF-difference test threshold and the integer least-squares (ILS) success rate. The approximation procedure replaces the ILS success rate with the easy-to-calculate integer bootstrapping (IB) success rate. Corresponding modeling error and approximation error are analysed with simulation data to avoid nuisance biases and unrealistic stochastic model impact. The results indicate the proposed method can greatly simplify the FF-approach without introducing significant modeling error. The threshold function method makes the fixed failure rate threshold determination method feasible for real-time applications.

The affect heuristic and public support for three types of wood smoke mitigation policies

This study applied the affect heuristic model to investigate key psychological factors (affective associations, perceived benefits, and costs of wood heating) contributing to public support for three distinct types of wood smoke mitigation policies: education, incentives, and regulation. The sample comprised 265 residents of Armidale, an Australian regional community adversely affected by winter wood smoke pollution. Our results indicate that residents with stronger positive affective associations with wood heating expressed less support for wood smoke mitigation policies involving regulation. This relationship was fully mediated by expected benefits and costs associated with wood heating. Affective associations were unrelated to public support for policies involving education and incentives, which were broadly endorsed by all segments of the community, and were more strongly associated with rational considerations. Latent profile analysis revealed no evidence to support the proposition that some community members experience internal “heart versus head” conflicts in which their positive affective associations with wood heating would be at odds with their risk judgments about the dangers of wood smoke pollution. Affective associations and cost/benefit judgments were very consistent with each other.

The potentiality of the embryo and the somatic cell

Recent arguments on the ethics of stem cell research have taken a novel approach to the question of the moral status of the embryo. One influential argument focuses on a property that the embryo is said to posses—namely, the property of being an entity with a rational nature or, less controversially, an entity that has the potential to acquire a rational nature—and claims that this property is also possessed by a somatic cell. Since nobody seriously thinks that we have a duty to preserve the countless such cells we wash off our body every day in the shower, the argument is intended as a reductio ad absurdum of the claim that the embryo should be afforded the same moral status as a fully developed human being. This article argues that this argument is not successful and that it consequently plays into the hands of those who oppose embryonic stem cell research. It is therefore better to abandon this argument and focus instead on the different argument that potentiality, as such, is not a sufficient ground for the creation of moral obligations towards the embryo.

Androgen-targeted therapy-induced epithelial mesenchymal plasticity and neuroendocrine transdifferentiation in prostate cancer : an opportunity for intervention

Androgens regulate biological pathways to promote proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen receptor (AR) targeted therapies exploit this dependence and are used in advanced prostate cancer to control disease progression. Contemporary treatment regimens involve sequential use of inhibitors of androgen synthesis or AR function. Although targeting the androgen axis has clear therapeutic benefit, its effectiveness is temporary, as prostate tumor cells adapt to survive and grow. The removal of androgens (androgen deprivation) has been shown to activate both epithelial-to-mesenchymal transition (EMT) and neuroendocrine transdifferentiation (NEtD) programs. EMT has established roles in promoting biological phenotypes associated with tumor progression (migration/invasion, tumor cell survival, cancer stem cell-like properties, resistance to radiation and chemotherapy) in multiple human cancer types. NEtD in prostate cancer is associated with resistance to therapy, visceral metastasis, and aggressive disease. Thus, activation of these programs via inhibition of the androgen axis provides a mechanism by which tumor cells can adapt to promote disease recurrence and progression. Brachyury, Axl, MEK, and Aurora kinase A are molecular drivers of these programs, and inhibitors are currently in clinical trials to determine therapeutic applications. Understanding tumor cell plasticity will be important in further defining the rational use of androgen-targeted therapies clinically and provides an opportunity for intervention to prolong survival of men with metastatic prostate cancer.

Robust conservation decision-making

Decision-making for conservation is conducted within the margins of limited funding. Furthermore, to allocate these scarce resources we make assumptions about the relationship between management impact and expenditure. The structure of these relationships, however, is rarely known with certainty. We present a summary of work investigating the impact of model uncertainty on robust decision-making in conservation and how this is affected by available conservation funding. We show that achieving robustness in conservation decisions can require a triage approach, and emphasize the need for managers to consider triage not as surrendering but as rational decision making to ensure species persistence in light of the urgency of the conservation problems, uncertainty, and the poor state of conservation funding. We illustrate this theory by a specific application to allocation of funding to reduce poaching impact on the Sumatran tiger Panthera tigris sumatrae in Kerinci Seblat National Park, Indonesia. To conserve our environment, conservation managers must make decisions in the face of substantial uncertainty. Further, they must deal with the fact that limitations in budgets and temporal constraints have led to a lack of knowledge on the systems we are trying to preserve and on the benefits of the actions we have available (Balmford & Cowling 2006). Given this paucity of decision-informing data there is a considerable need to assess the impact of uncertainty on the benefit of management options (Regan et al. 2005). Although models of management impact can improve decision making (e.g.Tenhumberg et al. 2004), they typically rely on assumptions around which there is substantial uncertainty. Ignoring this 'model uncertainty', can lead to inferior decision-making (Regan et al. 2005), and potentially, the loss of the species we are trying to protect. Current methods used in ecology allow model uncertainty to be incorporated into the model selection process (Burnham & Anderson 2002; Link & Barker 2006), but do not enable decision-makers to assess how this uncertainty would change a decision. This is the basis of information-gap decision theory (info-gap); finding strategies most robust to model uncertainty (Ben-Haim 2006). Info-gap has permitted conservation biology to make the leap from recognizing uncertainty to explicitly incorporating severe uncertainty into decision-making. In this paper we present a summary of McDonald-Madden et al (2008a) who use an info-gap framework to address the impact of uncertainty in the functional representations of biological systems on conservation decision-making. Furthermore, we highlight the importance of two key elements limiting conservation decision-making - funding and knowledge - and how they interact to influence the best management strategy for a threatened species. Copyright © ASCE 2011.

Reflexive and automatic violence: A function of aberrant perceptual inhibition

It’s commonly assumed that psychiatric violence is motivated by delusions, but here the concept of a reversed impetus is explored, to understand whether delusions are formed as ad-hoc or post-hoc rationalizations of behaviour or in advance of the actus reus. The reflexive violence model proposes that perceptual stimuli has motivational power and this may trigger unwanted actions and hallucinations. The model is based on the theory of ecological perception, where opportunities enabled by an object are cues to act. As an apple triggers a desire to eat, a gun triggers a desire to shoot. These affordances (as they are called) are part of the perceptual apparatus, they allow the direct recognition of objects – and in emergencies they enable the fastest possible reactions. Even under normal circumstances, the presence of a weapon will trigger inhibited violent impulses. The presence of a victim will also, but under normal circumstances, these affordances don’t become violent because negative action impulses are totally inhibited, whereas in psychotic illness, negative action impulses are treated as emergencies and bypass frontal inhibitory circuits. What would have been object recognition becomes a blind automatic action. A range of mental illnesses can cause inhibition to be bypassed. At its most innocuous, this causes both simple hallucinations (where the motivational power of an object is misattributed). But ecological perception may have the power to trigger serious violence also –a kind that’s devoid of motives or planning and is often shrouded in amnesia or post-rational delusions.