Structure and assembly of immature HIV

The major structural components of HIV are synthesized as a 55-kDa polyprotein, Gag. Particle formation is driven by the self-assembly of Gag into a curved hexameric lattice, the structure of which is poorly understood. We used cryoelectron tomography and contrast-transfer-function corrected subtomogram averaging to study the structure of the assembled immature Gag lattice to approximate to 17-angstrom resolution. Gag is arranged in the immature virus as a single, continuous, but incomplete hexameric lattice whose curvature is mediated without a requirement for pentameric defects. The resolution of the structure allows positioning of individual protein domains. High-resolution crystal structures were fitted into the reconstruction to locate protein-protein interfaces involved in Gag assembly, and to identify the structural transformations associated with virus maturation. The results of this study suggest a concept for the formation of nonsymmetrical enveloped viruses of variable sizes.

Nanoscale phase domain structure and associated device performance of organic solar cells based on a diketopyrrolopyrrole polymer

We investigate the blend morphology and performance of bulk heterojunction organic photovoltaic devices comprising the donor polymer, pDPP-TNT (poly{3,6-dithiophene-2-yl-2,5-di(2-octyldodecyl)-pyrrolo[3,4-c]pyrrole-1, 4-dione-alt-naphthalene}) and the fullerene acceptor, [70]PCBM ([6,6]-phenyl C71-butyric acid methyl ester). The blend morphology is heavily dependent upon the solvent system used in the fabrication of thin films. Thin films spin-coated from chloroform possess a cobblestone-like morphology, consisting of thick, round-shaped [70]PCBM-rich mounds separated by thin polymer-rich valleys. The size of the [70]PCBM domains is found to depend on the overall film thickness. Thin films spin-coated from a chloroform:dichlorobenzene mixed solvent system are smooth and consist of a network of pDPP-TNT nanofibers embedded in a [70]PCBM-rich matrix. Rinsing the films in hexane selectively removes [70]PCBM and allows for analysis of domain size and purity. It also provides a means for investigating exciton dissociation efficiency through relative photoluminescence yield measurements. Devices fabricated from chloroform solutions show much poorer performance than the devices fabricated from the mixed solvent system; this disparity in performance is seen to be more pronounced with increasing film thickness. The primary cause for the improved performance of devices fabricated from mixed solvents is attributed to the greater donor-acceptor interfacial area and resulting greater capacity for charge carrier generation.

A dual inverter with integrated energy storage for wind power systems

This paper explores the possibility of using grid side inverter as an interface to connect energy storage systems. A dual inverter system, formed by cascading two 2-level inverters through a coupling transformer, is used as the testing model. The inverters are named as “main inverter” and “auxiliary inverter”. The main inverter is powered by the rectified output of the wind generator while the auxiliary inverter is attached to a Battery Energy Storage System (BESS). If there is a surplus of wind power compared to the demand, then that would be stored in BESS while if there is a deficit in wind power then the demand will be satisfied by supplying power from the BESS. This enables constant power dispatch to the grid irrespective of wind changes. Novel modulation and control techniques are proposed to address the problem of non-integer, dynamically-varying dc-link voltage ratio, which is due to random wind changes. Furthermore, a maximum power tracking controller for this unique system is explained in detail. Simulation results verify the efficacy of proposed modulation and control techniques in suppressing random power fluctuations.

The BRICS and R2P : contestation, re-interpretation and norm entrepreneurship

The intra-state humanitarian crises in Libya and Syria have led to renewed debate over the content and implementation of pillar three of the responsibility to protect (R2P). This paper examines the BRICS’ (Brazil, Russia, India, China, South Africa) current perspectives on R2P and their recent efforts to shape the concept’s evolution. While Brazil’s “Responsibility while Protecting” (RwP) proposal has been widely discussed, the central focus here is on the lesser-known, semi-official Chinese idea of “Responsible Protection” (RP). Like RwP, RP proposes decision-making criteria and accountability mechanisms for UN-authorised military intervention under R2P’s third pillar. This paper argues that although RP draws heavily on previous R2P proposals such as the original 2001 ICISS report and Brazil’s RwP, by amalgamating and re-packaging these earlier ideas in a more restrictive form the Chinese initiative represents a new and distinctive interpretation of R2P. However, as it currently stands, some aspects of RP appear to be framed too strictly to provide workable guidelines for determining the permissibility of R2P military intervention, and would, therefore, benefit from clarification and refinement. Of broader significance, China’s RP and Brazil’s RwP initiatives point to the growing willingness of rising, non-Western powers to articulate and promote their own normative preferences on sovereignty, intervention and global governance. This development has potential implications both for R2P’s evolution and for the structure of the international system.

China's "Responsible Protection" concept : re-interpreting the Responsibility to Protect (R2P) and military intervention for humanitarian purposes

This article assesses the extent to which the recently formulated Chinese concept of “Responsible Protection” (RP) offers a valuable contribution to the normative debate over R2P’s third pillar following the controversy over military intervention in Libya. While RP draws heavily on previous proposals such as the original 2001 ICISS report and Brazil’s “Responsibility while Protecting” (RwP), by amalgamating and re-packaging these earlier ideas in a more restrictive form the initiative represents a new and distinctive interpretation of R2P. However, some aspects of RP are framed too narrowly to provide workable guidelines for determining the permissibility of military intervention for civilian protection purposes, and should therefore be clarified and refined. Nevertheless, the Chinese proposal remains significant because it offers important insights into Beijing’s current stance on R2P. More broadly, China’s RP and Brazil’s RwP initiatives illustrate the growing willingness of rising, non-Western powers to assert their own normative preferences on sovereignty, intervention and global governance.

An integrated modeling and risk analysis tool for mine water interactions

Poor mine water management can lead to corporate, environmental and social risks. These risks become more pronounced as mining operations move into areas of water scarcity and/or increase climatic variability while also managing increased demand, lower ore grades and increased strip ratios. Therefore, it is vital that mine sites better understand these risks in order to implement management practices to address them. Systems models provide an effective approach to understand complex networks, particularly across multiple scales. Previous work has represented mine water interactions using systems model on a mine site scale. Here, we expand on that work by present an integrated tool that uses a systems modeling approach to represent mine water interactions on a site and regional scale and then analyses the risks associated with events stemming from those interactions. A case study is presented to represent three indicative corporate, environmental and social risks associated with a mine site that exists in a water scarce region. The tool is generic and flexible, and can be used in many scenarios to provide significant potential utility to the mining industry.

Isolation, structure determination and cytotoxicity studies of tryptophan alkaloids from an Australian marine sponge Hyrtios sp

Mass-guided fractionation of the MeOH extract from a specimen of the Australian marine sponge Hyrtios sp. resulted in the isolation of two new tryptophan alkaloids, 6-oxofascaplysin (2), and secofascaplysic acid (3), in addition to the known metabolites fascaplysin (1) and reticulatate (4). The structures of all molecules were determined following NMR and MS data analysis. Structural ambiguities in 2 were addressed through comparison of experimental and DFT-generated theoretical NMR spectral values. Compounds 1–4 were evaluated for their cytotoxicity against a prostate cancer cell line (LNCaP) and were shown to display IC50 values ranging from 0.54 to 44.9 μM.

Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer

Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2’–deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.

Bayesian hierarchical models for analysing spatial point-based data at a grid level: A comparison of approaches

Spatial data are now prevalent in a wide range of fields including environmental and health science. This has led to the development of a range of approaches for analysing patterns in these data. In this paper, we compare several Bayesian hierarchical models for analysing point-based data based on the discretization of the study region, resulting in grid-based spatial data. The approaches considered include two parametric models and a semiparametric model. We highlight the methodology and computation for each approach. Two simulation studies are undertaken to compare the performance of these models for various structures of simulated point-based data which resemble environmental data. A case study of a real dataset is also conducted to demonstrate a practical application of the modelling approaches. Goodness-of-fit statistics are computed to compare estimates of the intensity functions. The deviance information criterion is also considered as an alternative model evaluation criterion. The results suggest that the adaptive Gaussian Markov random field model performs well for highly sparse point-based data where there are large variations or clustering across the space; whereas the discretized log Gaussian Cox process produces good fit in dense and clustered point-based data. One should generally consider the nature and structure of the point-based data in order to choose the appropriate method in modelling a discretized spatial point-based data.

Digital Modeling, Integrated Project Delivery and Industry Transformation: An Australian Case Study

This research is focused on realizing productivity benefits for the delivery of transport infrastructure in the Australian construction industry through the use of building information modeling (BIM), virtual design and construction (VDC) and integrated project delivery (IPD). Specific objectives include: (I) building an understanding of the institutional environment, business systems and support mechanisms (e.g., training and skilling) which impact on the uptake of BIM/VDC; (II) gathering data to undertake a cross-country analysis of these environments; and (III) providing strategic and practical outcomes to guide the uptake of such processes in Australia. Activities which will inform this research include a review of academic literature and industry documentation, semi-formal interviews in Australia and Sweden, and a cross-country comparative analysis to determine factors affecting uptake and associated productivity improvements. These activities will seek to highlight the gaps between current-practice and best-practice which are impacting on widespread adoption of BIM/VDC and IPD. Early findings will be discussed with intended outcomes of this research being used to: inform a national public procurement strategy; provide guidelines for new contractual frameworks; and contribute to closing skill gaps. Keywords: building information modeling (BIM); virtual design and construction (VDC); integrated project delivery (IPD); transport infrastructure; Australia; procurement

Integrated chronic disease management in primary-secondary care : a systematic literature review of the evidence

Introduction: Diabetes has traditionally been managed as a single chronic disease state, but it exists with co-morbidities such as depression and metabolic syndrome. Treatment is multifaceted, requiring both primary and secondary care, however, the delivery of diabetes care is often fragmented. Integrated chronic disease management is a growing model of interest, and is underpinned by the chronic care model (CCM), devised as a guide for primary care management of patients with chronic conditions. The model identifies six key elements for effective care, and has shown promise in improving the management of diabetes. Aim: To find empirical evidence of integrated care interventions targeted at co-morbidities including diabetes, across primary/secondary care. Method: A systematic review of peer reviewed literature from PubMed, CINAHL, Embase, Cochrane Library and Joanna Briggs was performed. Studies were reviewed according to inclusion criteria- studies published in English, between 2004-2014, empirical studies, studies with evidence of primary/secondary implementation, and those dealing with chronic co-morbid disease states. Results: 51 studies met the inclusion criteria. Included studies were mostly from the US (38), with five from Australia, UK (2), Canada (2), Netherlands (1), Norway (1), Ireland (1), and one multi-country study. It was found that all interventions adopted at least one (average 3-4) of the chronic care model, with the majority implementing delivery system redesign activities within the primary care practice/s. We found evidence of interventions which significantly reduced emergency department and hospital admissions, improved processes of care, patient health outcomes such as HbA1c, improved patient satisfaction, and reduced costs. Conclusion/Implications for practice: Diabetes exists as a co-morbid disease, requiring both primary and secondary care. We found that integrated care interventions adopting elements of the chronic care model positively impacted on patient outcomes, service utilisation, as well as costs. This review has highlighted that it may not be necessary to adopt all CCM elements to improve clinical outcomes, patient satisfaction and costs.

The sideways hourglass : establishing the lemniscate as a narrative structure for writing and reading non-linear stories

This thesis is a study in narratology that examines the pre-theoretical ideas that underlie the study of narrative and time. The thesis explores how the lemniscate can be transported from geometry to narrative in order to structure a non-linear story that breaks the rules of causality and chronology by coupling physical movement through space with the backward pull of memory. The findings offer new possibilities for understanding the nexus between shape and story and for recording non-linear narratives that are marked by simultaneity, counterpoint, and reversal.

Blended delivery and online assessment : scaffolding student reflections in work-integrated learning

This paper documents a teaching innovation addressing the challenges of embedding and assessing reflective practice in work-integrated learning, specifically marketing internships. We identify four issues relating to this problem: lack of knowledge or skill for reflection, limitations of physical journals, facilitation of different forms of reflection, and suitable models for teaching and assessing reflection. The paper outlines a blended approach combining face-to-face workshops and online resources, and using online reflective journals and digital stories as assessment. The approach and assessment tasks can be implemented in a variety of marketing and business units.