Compilation of somatic mutations of the CDKN2 gene in human cancers : non-random distribution of base substitutions

The CDKN2 gene, encoding the cyclin-dependent kinase inhibitor p16, is a tumour suppressor gene that maps to chromosome band 9p21-p22. The most common mechanism of inactivation of this gene in human cancers is through homozygous deletion; however, in a smaller proportion of tumours and tumour cell lines intragenic mutations occur. In this study we have compiled a database of over 120 published point mutations in the CDKN2 gene from a wide variety of tumour types. A further 50 deletions, insertions, and splice mutations in CDKN2 have also been compiled. Furthermore, we have standardised the numbering of all mutations according to the full-length 156 amino acid form of p16. From this study we are able to define several hot spots, some of which occur at conserved residues within the ankyrin domains of p16. While many of the hotspots are shared by a number of cancers, the relative importance of each position varies, possibly reflecting the role of different carcinogens in the development of certain tumours. As reported previously, the mutational spectrum of CDKN2 in melanomas differs from that of internal malignancies and supports the involvement of UV in melanoma tumorigenesis. Notably, 52% of all substitutions in melanoma-derived samples occurred at just six nucleotide positions. Nonsense mutations comprise a comparatively high proportion of mutations present in the CDKN2 gene, and possible explanations for this are discussed.

Developing a knowledge base for enterprise system success: the role of management and operational staff

Knowledge base is one of the emerging concepts in the Knowledge Management area. As there exists no agreed- upon standard definition of a knowledge base, this paper defines a knowledge base in terms of our research of Enterprise Systems (ES). The knowledge base is defined with reference to Learning Network Theory. Using this theoretical framework, we investigate the roles of management and operational staff in organisations and how their interactions can create a better ES-knowledge base to contribute to ES success. We focus on the post- implementation phase of ES as part of the ES lifecycle. Our findings will facilitate future research directions and contribute to better understandings of how the knowledge base can be integrated and how this integration leads to Enterprise System success.

Internet-enabled international entrepreneurship : a conceptual exploration of the link between a firm’s resource base, dynamic capabilities and international market performance

It has been suggested that the accumulation of valuable resources and capabilities, such as Internet application, is not enough to support a firm’s sustainable competitive advantage, especially for high technology-mediated firms; which often operate in fast changing dynamic environments. While the idea of ‘Internet-enabled resources and capabilities’ has been recognised by RBV theorists, the notion has largely been ignored in conceptual and empirical studies. Given this finding, a conceptual framework is constructed and research issues are then developed in order to focus attention on the relationship between, the Internet and a firm’s resource base, dynamic capabilities and international market performance. We postulate that successful Internet-enabled market performance arises from those international entrepreneurial-oriented firms which encompass: international vision, international business experience, Internet-international marketing capabilities and international networking capabilities. Recommendations for future theory development are presented, along with the implications for international entrepreneurial managers in Australian small and medium sized firms

Tax concessions for charities : competitive neutrality, the tax base and "public goods" choice

It is argued that concerns arise about the integrity and fairness of the taxation regime where charitable organizations, which avail themselves of the tax exemption status while undertaking commercial activities, compete directly with the for-profit sector. The appropriateness of the tax concessions granted to charitable organizations is considered in respect of income derived from commercial activities. It is principally argued that the traditional line of reasoning for imposing limitations on tax concessions focuses on an incorrect underlying inquiry. Traditionally, it is argued that limitations should be imposed because of unfair competition, lack of competitive neutrality, or an arbitrary decision relating to a lack of deserving. However, it is argued that a more appropriate question from which to base any limitations is one which considers the value attached to the integrity of the taxation regime as a whole, and the tax base specifically compared to the public good of charities. When the correct underlying question is asked, sound taxation policy ensues, as a less arbitrary approach may be adopted to limit the scope of tax concessions available to charitable organizations.

Challenges in the construction of a lunar base

The construction of a Lunar Base is seen as achievable. The paper provides a useful summary of challenges facing pioneers of lunar base construction. It highlights important aspects of the location and use of the facility, the local environment, the human physiological adaptation process, and a principal concern for the construction industry—construction materials and methods required to erect the facility. Specific emphasis is placed on the latter two major issues. The authors believe that a lunar base will be built, operated and maintained by humans. It may be the next generation that carry out these dreams, but it is research of the type reported in this paper that will make these dreams a reality.

Design of a knowledge base to teach programming

Programming is a subject that many beginning students find difficult. This paper describes a knowledge base designed for the purpose of analyzing programs written in the PHP web development language. The aim is to use this knowledge base in an Intelligent Tutoring System that will provide effective feedback to students. The main focus of this research is that a programming exercise can have many correct solutions. This paper presents an overview of how the proposed knowledge base can be utilized to accept different solutions to a given exercise

Designing the knowledge base for a PHP tutor

Programming is a subject that many beginning students students find difficult. This paper descibes a knowledge base designed for the purpose of analyzing programs written in the PHP web development language. The aim is to use this knowledge base in an Intelligent Tutoring System. The main emphasis is on accepting alternative solutions to a given problem.

Proportionality of sanctions under the WADA Code : CAS jurisprudence and the need for a strict approach

This article suggests that the issue of proportionality in anti-doping sanctions has been inconsistently dealt with by the Court of Arbitration for Sport (CAS). Given CAS’s pre-eminent role in interpreting and applying the World Anti-Doping Code under the anti-doping policies of its signatories, an inconsistent approach to the application of the proportionality principle will cause difficulties for domestic anti-doping tribunals seeking guidance as to the appropriateness of their doping sanctions.

Prosecutorial discretion in assisted dying in Canada : a proposal for charging guidelines

An Expert Panel of the Royal Society of Canada and a Select Committee of the Québec National Assembly both recently recommended the issuance of permissive guidelines for the exercise of prosecutorial discretion on voluntary euthanasia and assisted suicide and “medical aid in dying” respectively. It seems timely, therefore, to propose a set of offence-specific guidelines for how prosecutorial discretion should be exercised in cases of voluntary euthanasia and assisted suicide in Canadian provinces and territories. We take as our starting point the only existing guidelines of this sort currently in force in the world (i.e. the British Columbia Guidelines, and the England and Wales Guidelines). In light of certain concerns we have with these guidelines, we outline an approach to constructing guidelines for Canadian jurisdictions that begins with identifying three guiding principles we argue are appropriate for this purpose (respect for autonomy, the need for high-quality prosecutorial decision making, and the importance of public confidence in that decision making), and ends with a concrete and detailed set of proposed guidelines. The paper is consistent with, but also extends, the work of the Royal Society of Canada Expert Panel on End of Life Decision Making. Un panel d’expert de la Société Royale du Canada et une Commission spéciale de l’Assemblée nationale du Québec ont tous les deux récemment recommandé que soit émises des directives permettant exercice d’un pouvoir de poursuite discrétionnaire concernant l’euthanasie et le suicide assisté et « l’assistance médicale pour mourir », respectivement. Il semble donc à propos de proposer une série de directives spécifiques aux offenses sur la façon dont le pouvoir de poursuite discrétionnaire dans les territoires et provinces canadiennes serait appliqué dans les cas d’euthanasie et de suicide assisté. Nous avons pris comme point de départ les seules directives de la sorte existant déjà (c’est-à-dire celle de la Colombie-Britannique et de l’Angleterre et du Pays de Galles). Par contre, compte tenu de certaines de nos réserves concernant ces directives, nous avons ensuite établi les grandes lignes d’une approche permettant de mettre sur pied des directives pour les juridictions canadiennes, qui débute par l’identification de trois principes de base qui sont selon nous appropriées à cette fin (respect de l’autonomie, besoin pour une grande qualité de prise de prise de décision du poursuivant et la confiance du public envers cette prise de décision) pour se terminer par une série de directives concrètes et détaillées. Le présent document est compatible avec le travail de la Société royale du Canada tout en en augmentant la portée.

Procuring OSM : base-line models of off-site manufacture business processes in Australia

A pressing cost issue facing construction is the procurement of off-site pre-manufactured assemblies. In order to encourage Australian adoption of off-site manufacture (OSM), a new approach to underlying processes is required. The advent of object oriented digital models for construction design assumes intelligent use of data. However, the construction production system relies on traditional methods and data sources and is expected to benefit from the application of well-established business process management techniques. The integration of the old and new data sources allows for the development of business process models which, by capturing typical construction processes involving OSM, provides insights into such processes. This integrative approach is the foundation of research into the use of OSM to increase construction productivity in Australia. The purpose of this study is to develop business process models capturing the procurement, resources and information flow of construction projects. For each stage of the construction value chain, a number of sub-processes are identified. Business Process Modelling Notation (BPMN), a mainstream business process modelling standard, is used to create base-line generic construction process models. These models identify OSM decision-making points that could provide cost reductions in procurement workflow and management systems. This paper reports on phase one of an on-going research aiming to develop a proto-type workflow application that can provide semi-automated support to construction processes involving OSM and assist in decision-making in the adoption of OSM thus contributing to a sustainable built environment.

Assessment of recycled concrete aggregate for road base and sub-base

Population increase and economic developments can lead to construction as well as demolition of infrastructures such as buildings, bridges, roads, etc and used concrete is the main waste product of them. Recycling of waste concrete to obtain the recycled concrete aggregates (RCA) for base and/or sub-base materials in road construction is a foremost application to be promoted to gain economical and sustainable benefits. As the mortar, bricks, glass and asphalt present in different constituents in RCA, it exhibits inconsistent properties and performance. In this study, six different types of RCA samples were subjected classification tests such as particle size distribution, plasticity, compaction test and California Bearing Ratio (CBR). Results were compared with those of the standard road materials used in Queensland, Australia and found that ‘RM1-100/RM3-0’ and ‘RM1-80/RM3-20’ samples are sitting in the margin of the minimum required specifications of base materials while others are lower than that.

Large amplitude Fourier transformed AC voltammetric investigation of the active state electrochemistry of a copper/aqueous base interface and implications for electrocatalysis

The higher harmonic components available from large-amplitude Fourier-transformed alternating current (FT-ac) voltammetry enable the surface active state of a copper electrode in basic media to be probed in much more detail than possible with previously used dc methods. In particular, the absence of capacitance background current allows low-level Faradaic current contributions of fast electron-transfer processes to be detected; these are usually completely undetectable under conditions of dc cyclic voltammetry. Under high harmonic FT-ac voltammetric conditions, copper electrodes exhibit well-defined and reversible premonolayer oxidation responses at potentials within the double layer region in basic 1.0 M NaOH media. This process is attributed to oxidation of copper adatoms (Cu*) of low bulk metal lattice coordination numbers to surface-bonded, reactive hydrated oxide species. Of further interest is the observation that cathodic polarization in 1.0 M NaOH significantly enhances the current detected in each of the fundamental to sixth FT-ac harmonic components in the Cu*/Cu hydrous oxide electron-transfer process which enables the underlying electron transfer processes in the higher harmonics to be studied under conditions where the dc capacitance response is suppressed; the results support the incipient hydrous oxide adatom mediator (IHOAM) model of electrocatalysis. The underlying quasi-reversible interfacial Cu*/Cu hydrous oxide process present under these conditions is shown to mediate the reduction of nitrate at a copper electrode, while the mediator for the hydrazine oxidation reaction appears to involve a different mediator or active state redox couple. Use of FT-ac voltammetry offers prospects for new insights into the nature of active sites and electrocatalysis at the electrode/solution interface of Group 11 metals in aqueous media.