Synthesis of novel inhibitors blocking Wnt signaling downstream of β-Catenin

Large scale screening of libraries consisting of natural and small molecules led to the identification of many small molecule inhibitors repressing Wnt/β-Catenin signaling. However, targeted synthesis of novel Wnt pathway inhibitors has been rarely described. We developed a modular and expedient way to create the aromatic ring system with an aliphatic ring in between. Our synthesis opens up the possibility, in principle, to substitute all positions at the ring system with any desired substituent. Here, we tested five different haloquinone analogs carrying methoxy- and hydroxy-groups at different positions. Bona fide Wnt activity assays in cell culture and in Xenopus embryos revealed that two of these compounds act as potent inhibitors of aberrant activated Wnt/β-Catenin signaling.

Field Companion to the Mammals of Australia

"This invaluable companion to The Mammals of Australia is intended to be taken out into the field and used in conjunction with the more comprehensive volume. Genuinely practical in the outdoors, the book includes accounts of 389 species and newly developed, comprehensive identification keys. The Field Companion is introduced by a Mammal Distribution Matrix, which provides a classified checklist of all mammals in Australia (including those extinguished since European settlement) and the distribution of extant species in each state and territory. Species accounts provide initial differentiation, and include notes on identification, size, abundance, habitat and federal list/status, photograph and distribution map, as well as key references, which provide quick access to all relevant state identification keys in the Field Companion and to the longer entry in The Mammals of Australia. The authors have developed separate keys, illustrated with detailed drawings and maps, for the six states and the Northern Territory, to simplify the identification process and allow the reader to confidently separate all mammal species, no matter how subtle the differences. With the addition of these identification keys, this book becomes more than a field guide - although it is intended primarily to be used outdoors - and allows the user to finish identification based on more obscure characteristics, which is an advantage for some hard-to-identify species groups."--Libraries Australia

Translational approaches to medication development

Alcohol accounts for major disability worldwide and available treatments are insufficient. A massive growth in the area of addiction neuroscience over the last several decades has not resulted in a corresponding expansion of treatment options available to patients. In this chapter, we describe our experience with building translational research programs aimed at developing novel pharmacotherapies for alcoholism. The narrative is based on experience and considerations made in the course of building these programs, and work on four mechanisms targeted by our libraries: cholinergic nicotine receptors, receptors for corticotropin-releasing hormone (CRH), neurokinin 1 (NK1) receptors for substance P (SP) and hypocretin/orexin receptors. Around this experience, we discuss issues we believe to be critical for successful translation of basic addiction neuroscience into treatments, and complementarities between academic and other actors that in our assessment need to be harnessed in order to bring treatments to the clinic.

Protecting web 2.0 services from botnet exploitations

Recently, botnet, a network of compromised computers, has been recognized as the biggest threat to the Internet. The bots in a botnet communicate with the botnet owner via a communication channel called Command and Control (C & C) channel. There are three main C & C channels: Internet Relay Chat (IRC), Peer-to-Peer (P2P) and web-based protocols. By exploiting the flexibility of the Web 2.0 technology, the web-based botnet has reached a new level of sophistication. In August 2009, such botnet was found on Twitter, one of the most popular Web 2.0 services. In this paper, we will describe a new type of botnet that uses Web 2.0 service as a C & C channel and a temporary storage for their stolen information. We will then propose a novel approach to thwart this type of attack. Our method applies a unique identifier of the computer, an encryption algorithm with session keys and a CAPTCHA verification.

Design of a tangible data visualization

In this paper we describe the design of DNA Jewellery, which is a wearable tangible data representation of personal DNA profile data. An iterative design process was followed to develop a 3D form-language that could be mapped to standard DNA profile data, with the aim of retaining readability of data while also producing an aesthetically pleasing and unique result in the area of personalized design. The work explores design issues with the production of data tangibles, contributes to a growing body of research exploring tangible representations of data and highlights the importance of approaches that move between technology, art and design.

Genomic resources notes accepted 1 December 2013 - 31 January 2014

This article documents the public availability of (i) transcriptome sequence data, assembled and annotated contigs and unigenes, and BLAST hits from the Queensland fruit fly, Bactrocera tryoni; (ii) 75 single-nucleotide variants (SNVs) from 454 sequencing of reduced representation libraries for Phalangiidae harvestmen, Megabunus armatus, Megabunus vignai, Megabunus lesserti, and Rilaena triangularis; and (iii) expressed sequence tags from 454 sequencing of the lepidopterans Lymantria dispar and Lymantria monacha.

Identification of broad specificity P450CAM variants by primary screening against indole as substrate

High-throughput screening of cytochrome P450CAM libraries, for their ability to oxidise indole to indigo and indirubin, has resulted in the identification of variants with activity towards the structurally unrelated substrate diphenylmethane.

A new plasmid display technology for the in vitro selection of functional phenotype–genotype linked proteins

Background: Display technologies which allow peptides or proteins to be physically associated with the encoding DNA are central to procedures which involve screening of protein libraries in vitro for new or altered function. Here we describe a new system designed specifically for the display of libraries of diverse, functional proteins which utilises the DNA binding protein nuclear factor κB (NF-κB) p50 to establish a phenotype–genotype link between the displayed protein and the encoding gene. Results: A range of model fusion proteins to either the amino- or carboxy-terminus of NF-κB p50 have been constructed and shown to retain the picomolar affinity and DNA specificity of wild-type NF-κB p50. Through use of an optimal combination of binding buffer and DNA target sequence, the half-life of p50–DNA complexes could be increased to over 47 h, enabling the competitive selection of a variety of protein–plasmid complexes with enrichment factors of up to 6000-fold per round. The p50-based plasmid display system was used to enrich a maltose binding protein complex to homogeneity in only three rounds from a binary mixture with a starting ratio of 1:108 and to enrich to near homogeneity a single functional protein from a phenotype–genotype linked Escherichia coli genomic library using in vitro functional selections. Conclusions: A new display technology is described which addresses the challenge of functional protein display. The results demonstrate that plasmid display is sufficiently sensitive to select a functional protein from large libraries and that it therefore represents a useful addition to the repertoire of display technologies.

What now?

On her first day as a liaison librarian not so long ago, Kelly Johnson was filled with excitement but also trepidation. Core duties such as learning and teaching support were safely in her comfort zone. Collection management, however, was still more theory than practice.

A new plasmid display technology for the in vitro selection of functional phenotype-genotype linked proteins

Background Display technologies which allow peptides or proteins to be physically associated with the encoding DNA are central to procedures which involve screening of protein libraries in vitro for new or altered function. Here we describe a new system designed specifically for the display of libraries of diverse, functional proteins which utilises the DNA binding protein nuclear factor κB (NF-κB) p50 to establish a phenotype-genotype link between the displayed protein and the encoding gene. Results A range of model fusion proteins to either the amino- or carboxy-terminus of NF-κB p50 have been constructed and shown to retain the picomolar affinity and DNA specificity of wild-type NF-κB p50. Through use of an optimal combination of binding buffer and DNA target sequence, the half-life of p50-DNA complexes could be increased to over 47 h, enabling the competitive selection of a variety of protein-plasmid complexes with enrichment factors of up to 6000-fold per round. The p50-based plasmid display system was used to enrich a maltose binding protein complex to homogeneity in only three rounds from a binary mixture with a starting ratio of 1:108 and to enrich to near homogeneity a single functional protein from a phenotype-genotype linked Escherichia coli genomic library using in vitro functional selections. Conclusions A new display technology is described which addresses the challenge of functional protein display. The results demonstrate that plasmid display is sufficiently sensitive to select a functional protein from large libraries and that it therefore represents a useful addition to the repertoire of display technologies.

A platform - independent product library for BIM

There is considerable interest internationally in developing product libraries to support the use of BIM. Product library initiatives are driven by national bodies, manufacturers and private companies who see their potential. A major issue with the production and distribution of product information for BIM is that separate library objects need to be produced for all of the different software systems that are going to use the library. This increases the cost of populating product libraries and also increases the difficulty in maintaining consistency between the representations for the different software over time. This paper describes a project which uses “software transformation” technology from the field of software engineering to support the definition of a single generic representation of a product which can then be automatically converted to the format required by receiving software. The paper covers the current state of implementation of the product library, the technology underlying the transformations for the currently supported software and the business model for creating a national library in Australia. This is placed within the context of other current product library systems to highlight the differences. The responsibilities of the various actors involved in supporting the product library are also discussed.

An approach for extending Building Information Models (BIM) to specifications

The Construction industry accounts for a tenth of global GDP. Still, challenges such as slow adoption of new work processes, islands of information, and legal disputes, remain frequent, industry-wide occurrences despite various attempts to address them. In response, IT-based approaches have been adopted to explore collaborative ways of executing construction projects. Building Information Modelling (BIM) is an exemplar of integrative technologies whose 3D-visualisation capabilities have fostered collaboration especially between clients and design teams. Yet, the ways in which specification documents are created and used in capturing clients' expectations based on industry standards have remained largely unchanged since the 18th century. As a result, specification-related errors are still common place in an industry where vast amounts of information are consumed as well as produced in the course project implementation in the built environment. By implication, processes such as cost planning which depend on specification-related information remain largely inaccurate even with the use of BIM-based technologies. This paper briefly distinguishes between non-BIM-based and BIM-based specifications and reports on-going efforts geared towards the latter. We review exemplars aimed at extending Building Information Models to specification information embedded within the objects in a product library and explore a viable way of reasoning about a semi-automated process of specification using our product library.

The Nurse Practitioner Standards Project : Toolkit

"The aims of the project have been to conduct research that will inform a description of the core role of the nurse, core competency standards for the nurse and standards for education and program accreditation for nurse preparation leading to regsitration and authorisation. Includes Nurse Practitioner Standards Project: Toolkit, developed from the findings of the Nurse Practitioner standards research project. It presents standards related to Nurse Practitioner practice, education and authorisation/evaluation."--Libraries Australia

The inter-relationships between ovarian-independent growth, tumorigenicity, invasiveness and antioestrogen resistance in the malignant progression of human breast cancer

Among the processes contributing to the progressive acquisition of the highly malignant phenotype in breast cancer are ovarian-independent growth, antioestrogen resistance and increased metastatic potential. We have previously observed that increased invasiveness and development of ovarian-independent growth occur independently. In an attempt to define the inter-relationships between these processes further, we have compared the phenotypes of ovarian-independent, invasive and antioestrogen-resistant sublines of the ovarian-dependent human breast cancer cell line MCF-7. Cells acquiring ovarian-independent growth can retain sensitivity to anti-oestrogens. One clone of MCF-7 cells selected for stable antioestrogen resistance has become non-tumorigenic but its invasive potential remains unaltered. Thus, acquisitions of some characteristics of the progressed phenotype can occur independently. This phenomenon of independent parameters in phenotypic progression could partly explain the considerable intra- and intertumour heterogeneity characteristic of breast tumours.

Using social media to create a participatory library service : an Australian study

Public libraries are increasingly using social media in an attempt to meet users in their own spaces. Social media can be useful when used to create a participatory library service – to engage with users. However, there has been little empirical investigation into the success of social media use by public libraries. This article reports on the findings of a research project that explored the use of social media by Australian public libraries. Two organisations participated in case studies that involved interviews, document analysis, and social media observation. To contextualise the use of social media in the case study organisations, a sub study was undertaking involving observation of an additional 24 public libraries across Australia. This article focuses on the findings from the observation sub study. It presents and applies a methodology for classifying social media content to determine whether the sample libraries’ social media use is indicative of a participatory approach to service delivery. This article explores how a range of social media platforms are used by the sample libraries and considers what ‘best practice’ in participatory library service looks like. The two case study organisations’ use of social media is highlighted as exemplary practice.