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Pathogenesis of colibacillosis caused by avian pathogenic Escherichia coli (APEC) in poultry is unclear and experimental studies reveal substantial inconsistency. In this study, the impact of three infection routes differing in the site of deposition of inoculum in the respiratory tract, were investigated. Two-weeks-old chickens were infected with a lux-tagged APEC strain via aerosol, intranasally or intratracheally, and sequentially sampled along with uninfected birds. At 1 and 3 days post infection (dpi), liver or spleen to body-weight ratios in all infected groups were significantly higher than in negative control, while at 7 dpi, such differences were significant in both organs in the aerosol-infected group. The infection-strain colonized tracheas and lungs in infected birds at 1 dpi and persisted until 7 dpi. Among infected groups, in lungs, bacterial load at 1 dpi was significantly lower in intranasally-inoculated birds. Histology revealed that, independent of infection route, lesions were mostly seen in the lower respiratory organs (lungs and air sacs) characterized by bronchitis/pneumonia and airsacculitis. Birds infected via aerosol showed the highest mean lesion score in lungs while intranasal application caused the mildest pathological changes, and difference between the two groups was significant at 1 dpi. In spleen, heterophilic infiltrations were prominent in affected birds. Interestingly, tracheas were pathologically unaffected. Altogether, the results demonstrated the importance of infection route, with aerosol being the most suitable to induce pathological lesions of colibacillosis without predisposing factors. Furthermore, the lux-tagged APEC strain was discriminated from native isolates enabling exact differentiation and enumeration.RESEARCH HIGHLIGHTSLux-tagged APEC strain was used for infection to differentiate from native E. coli.Pathologically, lungs, air sacs and spleen but not trachea were affected.The route of infection strongly impacts the pathological outcome with APEC.The infection with APEC via aerosol caused the most severe lesions in chickens.

Pathogenesis of colibacillosis caused by avian pathogenic

For obvious reasons, such as, e.g., ethical concerns or sample accessibility, model systems are of highest importance to study the underlying molecular mechanisms of human maladies with the aim to develop innovative and effective therapeutic strategies. Since many years, animal models and highly proliferative transformed cell lines are successfully used for disease modelling, drug discovery, target validation, and preclinical testing. Still, species-specific differences regarding genetics and physiology and the limited suitability of immortalized cell lines to draw conclusions on normal human cells or specific cell types, are undeniable shortcomings. The progress in human pluripotent stem cell research now allows the growth of a virtually limitless supply of normal and DNA-edited human cells, which can be differentiated into various specific cell types. However, cells in the human body never fulfill their functions in mono-lineage isolation and diseases always develop in complex multicellular ecosystems. The recent advances in stem cell-based 3D organoid technologies allow a more accurate in vitro recapitulation of human pathologies. Embryoids are a specific type of such multicellular structures that do not only mimic a single organ or tissue, but the entire human conceptus or at least relevant components of it. Here we briefly describe the currently existing in vitro human embryo models and discuss their putative future relevance for disease modelling and drug discovery.

For decades, clearing and staining with Alcian blue and alizarin red has been the gold standard to image vertebrate skeletal development. Here we present an alternate approach to visualise bone and cartilage based on X-ray microCT imaging, which allows obtaining genuine 3D data of the entire developing skeleton at micron resolution. Our novel protocol is based on ethanolic fixation and staining with ruthenium red, and efficiently contrasts cartilage matrix as demonstrated in whole E16.5 mouse foetuses and limbs of E14 chicken embryos. Bone mineral is well preserved during staining, thus the entire embryonic skeleton can be imaged at high contrast. Differences in X-ray attenuation of ruthenium and calcium enable the spectral separation of cartilage matrix and bone by dual energy microCT (microDECT). Clearing of specimens is not required. The protocol is simple and reproducible. We demonstrate that cartilage contrast in E16.5 mouse foetuses is adequate for fast visual phenotyping. Morphometric skeletal parameters are easily extracted. We consider the presented workflow a powerful and versatile extension to the toolkit currently available for qualitative and quantitative phenotyping of vertebrate skeletal development.

The ING3 candidate tumour suppressor belongs to a family of histone modifying proteins involved in regulating cell proliferation, senescence, apoptosis, chromatin remodeling, and DNA repair. It is a stoichiometric member of the minimal NuA4 histone acetyl transferase (HAT) complex consisting of EAF6, EPC1, ING3, and TIP60. This complex is responsible for the transcription of an essential cascade of genes involved in embryonic development and in tumour suppression. ING3 has been linked to head and neck and hepatocellular cancers, although its status as a tumour suppressor has not been well established. Recent studies suggest a pro-metastasis role in prostate cancer progression. Here, we describe a transgenic mouse strain with insertional mutation of an UbC-mCherry expression cassette into the endogenous Ing3 locus, resulting in the disruption of ING3 protein expression. Homozygous mutants are embryonically lethal, display growth retardation, and severe developmental disorders. At embryonic day (E) 10.5, the last time point viable homozygous embryos were found, they were approximately half the size of heterozygous mice that develop normally. µCT analysis revealed a developmental defect in neural tube closure, resulting in the failure of formation of closed primary brain vesicles in homozygous mid-gestation embryos. This is consistent with high ING3 expression levels in the embryonic brains of heterozygous and wild type mice and its lack in homozygous mutant embryos that show a lack of ectodermal differentiation. Our data provide direct evidence that ING3 is an essential factor for normal embryonic development and that it plays a fundamental role in prenatal brain formation.

Fluorescence proteins have been useful as genetic reporters for a wide range of applications in biomedical research and are frequently used for the analysis of transgene activity. Here, we show that expression levels of the ubiquitously expressed fluorescent proteins eGFP, mCherry, and tdTomato can be measured in transgenic mouse lines with random or targeted integrations. We identified the tail of the mouse as the tissue best suited for quantifying fluorescence intensity and show that expression levels in the tail correlate with gene dose. This allows for instant non-invasive determination of the genetic condition at the transgenic locus (hemizygous/heterozygous and homozygous), while simultaneously providing an objective comparison for transgene expression levels among different mouse lines. In summary, we demonstrate for the first time that the gene dose of a ubiquitously expressed fluorescence reporter can be reliably quantified and directly linked to the genotype of transgenic mice. Based on this information, animals with the appropriate genotype can be instantly selected without laborious analysis for establishing and breeding of new transgenic lines, reducing the number of "waste" animals. Furthermore, no tissue sampling is necessary, which is a significant refinement of genotyping procedures. Both aspects are important improvements for the genotyping of transgenic mice that follow the principles of the 3 Rs (reduction and refinement).

Intra-bone marrow transplantation (IBMT) may improve the seeding efficiency of transplanted hematopoietic stem cells compared to the routinely used intravenous injection. Current IBMT protocols are optimized for ease of use and to improve experimental results. However, there have been no investigations to assess the impact of IBMT on animal welfare. Here, we report the results of pain assessment after IBMT and the effects of refinements to the current standard procedure. IBMT was performed in either the tibia or the femur of a recipient mouse under general anesthesia. Impact was determined using clinical scoring of different parameters (lameness, grip capacity, body weight loss, footprint analysis), behavioural tests (burrowing, open-field), monitoring of stress hormones and post-mortem histology. The results revealed that IBMT definitely induces severe post-operative distress. Although IBMT in the tibia is technically easier, the degree of impairment and the distress observed were consistently higher than for transplantation in the femur. A refinement for IBMT in the tibia was achieved by using 30- instead of 26-gauge needles and by sparing the patellar tendon. Consequently, for IBMT, we recommend either using the femur, or if the tibia is required due to its better feasibility, using our refined protocol. Furthermore, IBMT should definitely be limited to one leg per animal.

Licensed human papillomavirus (HPV) vaccines, based on virus-like particles (VLPs) self-assembled from major capsid protein L1, afford type-restricted protection against HPV types 16/18/6/11 (or 16/18 for the bivalent vaccine), which cause 70% of cervical cancers (CxCas) and 90% of genital warts. However, they do not protect against less prevalent high-risk (HR) types causing 30% of CxCa, or cutaneous HPV. In contrast, vaccination with the minor capsid protein L2 induces low-level immunity to type-common epitopes. Chimeric RG1-VLP presenting HPV16 L2 amino acids 17–36 (RG1 epitope) within the DE-surface loop of HPV16 L1 induced cross-neutralizing antisera. We hypothesized that RG1-VLP vaccination protects against a large spectrum of mucosal and cutaneous HPV infections in vivo. Immunization with RG1-VLP adjuvanted with human-applicable alum-MPL (aluminum hydroxide plus 3-O-desacyl-4′-monophosphoryl lipid A) induced robust L2 antibodies (ELISA titers 2,500–12,500), which (cross-)neutralized mucosal HR HPV16/18/45/37/33/52/58/35/39/51/59/68/73/26/69/34/70, low-risk HPV6/11/32/40, and cutaneous HPV2/27/3/76 (titers 25–1,000) using native virion- or pseudovirion (PsV)-based assays, and a vigorous cytotoxic T lymphocyte response by enzyme-linked immunospot. In vivo, mice were efficiently protected against experimental vaginal challenge with mucosal HR PsV types HPV16/18/45/31/33/52/58/35/39/51/59/68/56/73/26/53/66/34 and low-risk HPV6/43/44. Enduring protection was demonstrated 1 year after vaccination. RG1-VLP is a promising next-generation vaccine with broad efficacy against all relevant mucosal and also cutaneous HPV types.

PurposeKnowledge maps (KMaps) are a relatively new concept. The purpose of this paper is to identify the factors that encourage or impede the adoption of KMaps by computer software maintenance professionals.Design/methodology/approachIn total, six prototypes were developed for a muti‐national software organisation and demonstrated during 19 semi‐structured interviews conducted to establish adoption factors. Data were analysed qualitatively through NVivoTM software, according to the steps in Carney's Ladder of Analytical Abstraction.FindingsEncouragement factors were found to be those that organisational management has direct control over such as communicating and promoting KMaps and appointing a management champion. Impeding factors were those under the control of software maintenance management and are more difficult to manage. They focused on personal factors (staff's perception of the usefulness and ease of use of KMaps), subjective norms (peer influence and culture), behavioural control (training) and the design of the KMap itself.Research limitations/implicationsWhile the research has provided an exploratory KMap Adoption (KAM) Model, it has done so through the lens of innovation adoption and diffusion theories. There are opportunities to examine the topic in a wider manner to provide a more holistic view of KMap adoption.Practical implicationsFrom adoption factors, the study's explanatory framework, named the KAM, was synthesized and recommendations are made for push and pull strategies to maximise encouragement and minimise impediment factors identified in KAM.Originality/valueKMaps are ideally suited for resolving many of the traceability problems in computer software maintenance. They improve the ability to find the right “expert” to help solve a software problem quickly when it arises.

The aim of this case study is first, to determine the extent to which web 2.0 can be the technology that would enable a strong relationship between government and its citizens to develop in managing road safety and second, to examine the endeavours of the WA Office of Road Safety (ORS) in fostering the relationship. It shows that in ORS’ road safety strategy for 2008-2020, community engagement is strongly advocated for the successful development and execution of its road safety plan but the potential of web 2.0 approaches in achieving it is not recognised. This would involve the use of blogs and RSS as suitable push strategies to get road safety information to the public. Online civic engagement would harness collective intelligence (‘the wisdom of crowds’) and, by enabling the public to annotate information on wikis, layers of value could be added so that the public become co-developers of road safety strategy and policy. The case identifies three major challenges confronting the ORS to become Road Safety 2.0 ready: how to gain the publics’ attention in competition with other government agencies, how to respond internally to online citizen engagement, and how to manage governmental politics.

PurposeThis paper seeks to determine attitudes that impact on knowledge transfer between academics (university teaching and research staff) employed in today's competitive, technology‐based university setting.Design/methodology/approachThe study generated a rich set of data by conducting, first, an exploratory, qualitative study followed by a confirmatory, quantitative study. Through this process, an initial list of 402 attitudes to knowledge transfer was derived which was narrowed to 75 for the quantitative survey which, through factor analysis, was further reduced to 24 variables. The 24 variables were grouped into four factors for which trust and motivation are more relevant to the knowledge provider and absorptive capacity and knowledge regeneration for the receiver.FindingsHigh levels of agreement were found for the propositions that senior academics lacked compensation for mentoring activities, and hence, the motivation to transfer knowledge, and that a heavy teaching load prevented the absorption of transferred knowledge. By contrast, disagreement was found with the propositions that an elderly age impeded the transfer of knowledge or adapting to new ways of transferring knowledge.Practical implicationsFrom the responses obtained it was possible to identify those rated highly and from which conclusions could be drawn that may assist the university concerned to improve knowledge transfer among its academic staff. Compensation to senior academics for their time and effort was seen as the most important pre‐requisite for knowledge transfer. A reduction in teaching loads and the range of expectations to which academics are subjected would also facilitate knowledge transfer as would increasing academics' use of ICT and ability to assess its effectiveness, as well as recognising that knowledge transfer during social interactions may ameliorate the lack of knowledge transfer in the more formal, technology‐based environment.Originality/valueThe paper identifies key attitudes of academics to transferring knowledge to colleagues in the changing work place at universities in which academics are expected to perform at a high level in diverse activities and use technology to maximise their efficiency and effectiveness.

PurposeThe aim of this paper is to provide an understanding of information technology (IT) governance, from both a theory and practice perspective, and to identify current theory‐practice gaps within the organisations studied.Design/methodology/approachThis study developed a complementary and collaborative model of IT governance and used a multiple case approach in which IT governance is examined against the model in four major universities. Case study research is qualitative in nature enabling insights into the “how” and “why” of IT governance to be gained.FindingsBased on underlying theory, the study was able to develop propositions regarding IT governance practices, observe current practices within the participating universities and establish gaps between theory and practice. The study identified theory‐practice gaps in each of three IT governance dimensions: structure, process and people. Gaps ranged in significance from small to large. Two large gaps existed which require attention: they are in respect of integrating IT governance mechanisms and raising the awareness and understanding of the concept among senior management.Research limitations/implicationsThe model of IT governance developed for the research can be further developed and refined. In addition, the university context may have imposed limitations as different findings could arise in different contexts. Furthermore, the participating CIOs and IT directors could have brought their own values and beliefs to the research when interpreting the IT governance objectives of their university.Practical implicationsThe model of IT governance developed for the research enables organisations to assess and map their IT governance against theoretical dimensions. By mapping observed practice against theory, the study was able to provide a mechanism of identifying theory‐practice gaps, where they existed.Originality/valueIT is ubiquitous in nature because modern IT crosses organisational activities and has become strongly aligned with business activities. Thus IT governance can be viewed as an integral part of corporate governance and requires senior management's attention. However, because of the specialised nature of IT, governance in this domain has unique characteristics. Yet, current literature reflects a lack of maturity and points to diverse and inconsistent concepts of IT governance as well as variations in how IT governance is implemented. The paper reduces uncertainty for corporate executives by systematically synthesising current literature, developing a theoretical model and testing it against current practice.

PurposeThe aim of this paper is to benchmark the quality of web sites of major public accounting (PA) firms by seeking the opinions of potential clients and analysing the data to establish best quality practice for PA web sites.Design/methodology/approachThe study was conducted in a controlled laboratory setting in which potential clients of PA firms used a modified version of the WebQual™ questionnaire to evaluate the web sites of six leading PA firms. Design science provided the guiding paradigm but its weaknesses were ameliorated by drawing on constructivism and pragmatism to provide context and practicality for the research.FindingsThe study established web site quality profiles of six leading PA firms. The interpretation of findings is influenced by axiology and rhetoric and are both unbiased (determined by statistical means) and biased (influenced by the researchers' values). Data analysis clearly showed that the usability construct reflected the highest quality at all levels while riskiness was the construct with the lowest quality level.Research limitations/implicationsThe use of multiple paradigms (design science, constructivism, and pragmatism) produced the desired insights to determining web site quality issues for the PA sector for the key reason that they complemented each other rather than being in conflict. However, the usefulness of the approach is dependent on follow‐up research to confirm the findings with the PA firms concerned and to monitor any action taken by them in response to the study's findings.Practical implicationsBy benchmarking a number of PA web sites, practices within the sector will be able to learn from the findings and be able to improve the quality of their web sites thereby retaining the competitive edge to meet their clients' needs.Originality/valueThe paper reflects on the value of the multi paradigm approach to web site quality research design and conduct and discussion of findings. It was concluded that design science provided the necessary research rigour while the other two paradigms enabled the researchers to bring their worldviews on ontology, epistemology, axiology and rhetoric to the research.

Cellular differentiation and programmed cell death are tightly controlled to maintain tissue homeostasis and proper organ function. In a screen for apoptosis specific gene products, we isolated an immediate early apoptosis response gene from myelomonocytic stem cells that appears to play a key regulatory role in a number of cell types and may be of particular importance in cells of the central nervous system. The gene's 28 kDa protein product interacts with the C-terminal ectodomain of the Na + /K + -ATPase (NKA) β 1 subunit and was therefore named NKIP (NKA Interacting Protein). NKIP is coexpressed with NKA, localizes to lysosomes and the endoplasmic reticulum and is predominantly expressed in excitable tissues including polarized epithelia and the central nervous system. NKIP has been characterized as an endogenous suppressor of the NKA as reduction of NKIP in PC12 cells significantly increases NKA activity. In pluripotent NT2 progenitor cells, NKIP induced rapidly K + -level-dependent cell death. NKIP overexpression induced growth factor-independent neurite outgrowth, which was associated with MEK-independent phosphorylation of the transcription factor ERK1/2. Thus, we have identified NKIP as an important novel protein that interacts to the NKA complex, influencing cellular ion balance, induction of apoptosis and neuronal differentiation.

PurposeThe paper seeks to overcome previous research limitations by examining both macro (industry, country) and micro (functions, enterprise) level phenomena within the information communication technologies (ICT) use of small and medium‐sized enterprises (SMEs). Australia and Germany were chosen because both recognise the importance of SMEs.Design/methodology/approachThe study adopted an interpretivist philosophy and a qualitative case study method that enables gathering data which are rich in detail. Semi‐structured, on‐site interviews were carried out in eight firms of various classifications.FindingsThe study found that, for micro enterprises, ICT is only emerging in the form of systems that have the potential to facilitate the interactions with the outside. Small enterprises rely heavily on personal interactions, which they supplement with the use of ICT. In medium enterprises, ICT is more extensively used in interactions, both internally and with the environment. The differences between Australian and German firms do not significantly affect the extent to which ICT is infused into observed SMEs.Research limitations/implicationsThe study used the interpretivist research paradigm which is based on the assumption that reality is socially constructed. Findings indicated the need for increased organisational competencies and greater scope to use ICT to facilitate interaction with the external environment, especially customers and suppliers and forming alliances.Originality/valueThe case studies provided rich stories of ICT infusion in the important SME sector on an international scale and produced context‐aware institutionalised expectations that can help other SMEs understand ICT use. They can use the findings as benchmarks against which to measure their own endeavours.

PurposeThe need to measure organisational effectiveness has become increasingly accepted. Performance measurements can readily be developed but need to be further defined as performance metrics. The paper's aim is to show how the use of the decomposition technique enables the development of electronic commerce (e‐commerce) metrics.Design/methodology/approachIn the approach to value decomposition, value constructs are identified at the highest level, decomposed into the next levels, referred to as value variables, which are further broken down into value metrics. During decomposition, proper splicing has to occur. This implies that values (constructs, variables and metrics) should be carefully specified and that their interconnections should be controlled. Furthermore, functional integrity is required so that a succinct statement can be made for each metric.FindingsThe paper identified value constructs and value variables for six e‐commerce applications. They are aggregated into corporate performance management measures so that the various lower level value metrics can be made to work seamlessly together.Practical implicationsAlthough there is large agreement on the key values obtained from e‐commerce, it is difficult to achieve the degree of integrity required by the decomposition technique. Further research is required.Originality/valuePerformance measures provide a factual representation of important business activities and enable greater preciseness in their execution. The paper provides insight into values and associated measures in important activities of e‐commerce, namely VRM, B2C, B2B, CRM, EP, and ERP.

BACKGROUND Inhibition of clusterin expression has been shown to enhance the sensitivity of prostate cancer cells to chemo and hormone therapy. Clusterin antisense oligonucleotides (ASOs) are currently in phase II human clinical trials for treatment of hormone refractory prostate cancer. However, the role of clusterin in androgen-regulated involution and regeneration of the normal prostate gland has not been established. METHODS Prostate involution and regeneration was examined in clusterin-deficient mice undergoing up to three cycles of androgen withdrawal and restoration. RESULTS Surprisingly, clusterin deficiency did not affect the apoptotic index, and the temporal biochemical and morphological changes associated with involution and regeneration of the normal adult prostate following multiple rounds of androgen withdrawal and replacement. CONCLUSION Clusterin is not critical for normal prostate development or androgen-regulated involution and regrowth of the mouse prostate gland, suggesting that clusterin may have distinct functions in malignant versus normal prostatic epithelial cells. Prostate 66: 1445–1454, 2006. © 2006 Wiley-Liss, Inc.

The Professional Doctorate (ProfDoc) is attracting increasing attention because of its perceived greater than the Doctor of Philosophy’s (Ph.D.’s) focus on meeting the needs of the knowledge economy. The paper examines the nature of the ProfDoc vis-a-vis the Ph.D. and identifies significant characteristics of the ProfDoc, especially in respect of relevance and performativity. It then analyses these characteristics in the context of the professional Doctorate in Business Administration (DBA) in Information Systems (IS) at an Australian university. An ethnographic approach is used to examine the internal (university) and external (student) environments of the DBA(IS). Recommendations are made to increase its effectiveness for the knowledge economy, including moving to a greater student and industry centred approach. Finally, conclusions are drawn to determine its relevance to the knowledge economy.

The key objective of this research was to develop an understanding of what organisations are measuring within the context of knowledge management (KM) evaluation. A comprehensive meta-analysis of international articles dealing with the evaluation of KM, Intellectual Capital and other closely related domains between the years 1992 and 2002 was undertaken. A total of 1539 articles reflected the search topic. A manual review of all abstracts resulted in a narrowed selection of 223 articles, sourced from 126 different journals. Data for 1992–1995 were rejected due to insufficient occurrences of empirical measurement. Content analysis with the use of the NUD*IST® software of the data resulted in 12 evaluation factors being identified. Four factors made up 72% of the study's findings: human capital, financial, process and customer. However, by charting the number of measures within each factor against each year from 1996 to 2002, some identifiable trends were highlighted. Financial, human capital, internal infrastructure and composite measures, such as the Balanced Scorecard, have grown in varying degrees in frequency of use, while customer, process, intellectual property, innovation and quality-related measures have gradually lost ground.

PurposeThe objective of the paper is to identify the factors that encourage consumers to adopt internet banking services in Thailand and to use the study's findings to develop strategies for banks on how to maximize the rate of adoption.Design/methodology/approachQuantitative research with a sample size of 600 achieved by sending questionnaires to 15 people in each of 40 large companies in Bangkok. The study is based on the Decomposed Planned Behaviour.FindingsThe attitudinal factors that appear to encourage the adoption of internet banking in Thailand most are “Features of the web site” and “Perceived usefulness”, while the most significant impediment to adoption is a perceived behavioural control, namely “External environment”. The significant moderating factors are gender, educational level, income, internet experience and internet banking experience, but not age.Research limitations/implicationsIn this study, encouragement factors are those that are able to be controlled by banks, while impediment factors are those that are not able to be controlled.Practical implicationsIt is essential for banks to facilitate encouragement and restrict impediment factors. In addition to the direct “push” from internet banks (in respect of the encouragement factors), indirect persuasion should be carried out as a “pull” mechanism (in respect of the impediment factors).Originality/valueThe study identified a number of specific strategies that Thai banks could follow to maximize the adoption of internet banking.

This paper reports the findings from a survey conducted in Australia to explore current practices relating to knowledge management (KM) and intellectual capital (IC). A systematic approach in the form of the intellectual capital web guided the research. Findings revealed that KM was perceived to be more about developing knowledge culture than about managing organisational processes and structure. IC was perceived to be more about human capital than about customer capital and organisational capital. It can therefore be concluded that human capital holds the greatest importance for KM and IC. However, when facilitators for knowledge creation and knowledge sharing were rated, organisation structure was perceived to be more important than organisational culture and information technology. For KM practices, participants indicated that more attention was paid to training and developing employees and less to measurement and reward and incentive issues. The importance of aligning the management of IC and KM was perceived to be more important than the difficulty of doing so.

The paper examined the nature of information technology (IT) outsourcing decision making and developed a theoretical framework consisting of five phases of decision making. The phases augmented those of Simon and consisted of intelligence, analysis and planning, strategy selection, action, and evaluation and monitoring. Australia's largest organisations and government agencies were surveyed by questionnaire to establish the importance of tasks and subtasks to be performed when completing each of the five phases. Participants possessed high experiences with IT in general and IT outsourcing in particular. When the importance of phases vis‐à‐vis each other were established, the action phase and evaluation and monitoring phase were found to be more significant than the other phases. For the action phase, which was statistically the most significant phase, the tasks of selecting an IT‐outsourcing vendor and determining a suitable IT‐outsourcing contract were dominant and strongly correlated. Findings from the study should help organisations identify and therefore better manage critical decision‐making activities during IT outsourcing particularly those related to vendors and contracts.

Investments in information technology (IT) are large and growing and require management attention. This study investigated processes associated with IT benefit management (ITBM) to realise benefits during the development of a new system, to retrofit ITBM processes against an existing system, and to review ITBM processes against an existing system without retrofitting. The case study approach was used to ameliorate the shortage of qualitative research in IT value. The study identified key processes required during IT benefit realisation, changes in processes during retrofitting and strong and weak processes during review. All three approaches were found to be operational effective with the review approach having some strategic effectiveness. Operational effectiveness ensured that social subsystem costs and benefits and complementary assets were identified. To make the review approach more strategically effective requires definitive IT goals to be set. The application of the “3Rs” during case analyses enabled success factors for ITBM to be identified.

The twenty‐first century knowledge driven economy has seen increasing importance being placed on maximising the organisation's intellectual capital (IC). At the same time knowledge management (KM) systems are being developed. The paper establishes similarities between the two and proceeds to develop a systematic approach to linking them through the intellectual capital web (ICW). There are six components with the ICW: strategic objectives, management systems, measurement systems, knowledge workers, catalysts and reward and incentive systems. The integration of IC and KM requires alignment of KM processes with IC assets to meet the organisation's strategic needs. A theoretical conjecture is developed in which the components of elements of ICW are interweaved to achieve strategic objectives. The systematic approach outlined in the paper should offer organisations valuable guidelines to maximising their IC assets and managing their knowledge management processes.

Oxidative stress plays a key role in late onset diseases including cancer and neurodegenerative diseases such as Huntington disease. Therefore, uncovering regulators of the antioxidant stress responses is important for understanding the course of these diseases. Indeed, the nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the cellular antioxidative stress response, is deregulated in both cancer and neurodegeneration. Similar to NRF2, the tumor suppressor Homologous to the E6-AP Carboxyl Terminus (HECT) domain and Ankyrin repeat containing E3 ubiquitin-protein ligase 1 (HACE1) plays a protective role against stress-induced tumorigenesis in mice, but its roles in the antioxidative stress response or its involvement in neurodegeneration have not been investigated. To this end we examined Hace1 WT and KO mice and found that Hace1 KO animals exhibited increased oxidative stress in brain and that the antioxidative stress response was impaired. Moreover, HACE1 was found to be essential for optimal NRF2 activation in cells challenged with oxidative stress, as HACE1 depletion resulted in reduced NRF2 activity, stability, and protein synthesis, leading to lower tolerance against oxidative stress triggers. Strikingly, we found a reduction of HACE1 levels in the striatum of Huntington disease patients, implicating HACE1 in the pathology of Huntington disease. Moreover, ectopic expression of HACE1 in striatal neuronal progenitor cells provided protection against mutant Huntingtin-induced redox imbalance and hypersensitivity to oxidative stress, by augmenting NRF2 functions. These findings reveal that the tumor suppressor HACE1 plays a role in the NRF2 antioxidative stress response pathway and in neurodegeneration.

Knowledge management offers significant advantages to organisations, such as public accounting firms, operating in the professional services sector. The paper identifies the driving forces to effectively manage the professional knowledge of these firms as information technology, organisational structure and culture, and technology-based client knowledge services. Frameworks and perspectives for managing knowledge were developed and used to establish the current state of knowledge management in five New Zealand small to medium sized professional accounting practices. The challenges for these firms, and for future research, were found to be - adopting and managing new technology, creating and articulating knowledge, shifting social references, developing client service capabilities, and establishing inter-firm collaboration. It was concluded that knowledge management, particularly the use of the Internet, may enable small and medium sized accounting firms to challenge the domination of the large, multinational practices.

Compares the perceptions of Malaysians (representing eastern, Asian culture) and Australians (representing western, European culture) for four Web site design characteristics – atmospherics, news stories, signs and products and services – as part of the integrated Internet marketing model. Under controlled laboratory conditions, two groupings of 30 subjects evaluated eight Web sites – four in Malaysia and four in Australia – in the retail and services sectors. Hypothesises that the predominant culture is not generalised to another culture. Some tentative support for the research premise is found since where a group’s perceptions for Web design characteristics and their effectiveness was significantly higher, it was for sites originating in that group’s country. Furthermore, perceptions both support and contradict previous research suggesting that Australians prefer an environment of low context and high explicit communications while Asians operate in an environment of high context that stresses implicit communications.

This paper discusses the approach adopted by the author in designing a graduate Information Systems auditing course at the Australian National University. First the paper identifies the environment in which the course operated, the resources available to it and the objectives to be achieved. Particular recognition is given to the pervasive effects of diverse and complex Information Technology on auditing. Next, the teaching components consisting of topics, mode of instruction and grading are outlined. General Systems Theory (GST) provided the hallmarks for identifying the range of topics for the course. As part of its evaluation, the course was compared with advanced IS auditing courses at other universities, both in Australia and Northern America. Students in Australian courses appear to have spent more time on cases and problems and in computer laboratories and less time on the computer audit process than students in the USA/Canada. Recommendations for the Australian National University course are that ...

Cycloadditions. 26. Influence of Substituents in the Allenic ω-Position on the Thermal Behaviour of Aryl Allenecarboxylates The [(aryloxycarbonyl)methyl]triphenylphosphonium salts (1a and i), obtained by reaction of aryl bromoacetates with triphenylphophine, react with the acid chlorides 3 in the presence of two equivalents of triethylamine to give the phenyl-or the (1-naphthyl)-2,3-alkadienoates (4a–d and 4e–h), respectively, in the most cases accompanied by the arylalkynoates 6 and 7 and/or with the naphthyl esters 8 of the used acids. Treatment of the [(aryloxycarbonyl) methyl] triphenylphosphonium salts (1a–i) with triethylamine furnishes the phosphoranes 2a–i, which are transformed by reaction with diphenylketene into the aryl 3,3-diphenyl-2,3-butadienoates (5). Heating of the derivatives 4a–d and 5a, bearing the unsubstituted phenyl nucleus in the ester moiety, leads to destruction, while heating of the naphthyl esters 4e–h and 5i – room temperature is sufficient in some cases-induces the IMDA-reaction to give the benzo-tricycles 9a–e. Heating of the 4,4-diphenyl-2,3-butadienoates (5b–h), bearing the alkylsubstituted phenyl ring within the ester component, induces radical dimerization to give the cylobutanes 10b–h, which represent the head to tail dimers.

In cancers with a highly altered genome, distinct genetic alterations drive subsets rather than the majority of individual tumours. Here we use a sequential search across human tumour samples for transcript outlier data points with associated gene copy number variations that correlate with patient's survival to identify genes with pro-invasive functionality. Employing loss and gain of function approaches in vitro and in vivo, we show that one such gene, MTSS1, promotes the ability of melanocytic cells to metastasize and engages actin dynamics via Rho-GTPases and cofilin in this process. Indeed, high MTSS1 expression defines a subgroup of primary melanomas with unfavourable prognosis. These data underscore the biological, clinical and potential therapeutic implications of molecular subsets within genetically complex cancers.

The aim of this case study is first, to determine the extent to which web 2.0 can be the technology that would enable a strong relationship between government and its citizens to develop in managing road safety, and second, to examine the endeavours of the WA Office of Road Safety (ORS) in fostering the relationship. It shows that in ORS’ road safety strategy for 2008-2020, community engagement is strongly advocated for the successful development and execution of its road safety plan, but the potential of web 2.0 approaches in achieving it is not recognised. This would involve the use of blogs and RSSes as suitable push strategies to get road safety information to the public. Online civic engagement would harness collective intelligence (the wisdom of crowds) and, by enabling the public to annotate information on wikis, layers of value could be added so that the public become co-developers of road safety strategy and policy. The case identifies three major challenges confronting the ORS to become Road Safety 2.0 ready: how to gain the publics’ attention in competition with other government agencies, how to respond internally to online citizen engagement, and how to manage governmental politics.

Cycloadditions. 24 Synthesis and Reactions of sec. N-Aryl-2,3-butadienamides The reaction of aryl isocyanates (1) with allenyl magnesium bromide (2) furnishes the sec. N-aryl-3-butynamides (4), which tend to tautomerize to the 2,3-butadienamides (5). Further heating of 5a–f (bearing benzoid nuclei) leads to decomposition, only 5g (bearing the naphthyl group) undergoes the expected intramolecular Diels-Alder (IMDA) reaction, leading to the benzo-tricycle (7g). By reaction of a second molecule isocyanate 1 the carbomoylation of the NH moiety of 5a, c and of 3g and 4g, resp. takes place. The thereby formed N-aryl-N-butadienoyl ureas (9) either cyclize to furnish the the N-carbamoyl-2-quinolones (10) or undergo the IMDA-reaction leading to the tricyclic compounds (11). The N-butadienoyl-N-(1-naphthyl)ureas (12) only furnish the IMDA-benzo-tricycles (13).

The business benefits that can be achieved have dominated the considerations as to whether or not to outsource information systems (IS). Very little attention appears to have been given to the compromises in IS security and control that follows such a move. Evaluates the loss in IS security and control when IS outsourcing occurs and proposes a new security framework for such a situation. Under IS outsourcing the emphasis changes from the physical protection of assets to the recovery of these resources, and application controls become less important relative to general controls. To be successful, the security and control framework for IS outsourcing needs to be integrated into the broader relationship that exists with the outsourcing vendor.

While the S-alkyl- or S-phenyl-2,3-butadienethioates 4 a-c are synthesized via the usual “Wittig ylide way”, the corresponding 2-methyl-2,3-butadienethioates 9 a-d and the 2-methyl-4.4-diphenyl-2,3-butadienethioates 9 e,f are obtained by condensation of the allenic acids 7 a,b with the thiols and thiophenols 8 in the presence of dicyclohexylcarbodiimide (DCC) and a catalytic am ount of 4-dimethylaminopyridine (DMAP). In contrast to N- or O-phenyl 2,3- butadienamides or -esters, resp., the phenyl derivatives of 4 and 9 do not undergo the intram olecular Diels-Alder reaction, but by heating, all representatives of 4 only decompose, while 9 a-d and 9 e,f rearrange to 3-alkyl(aryl)thio-2-cyclobuten-1-ones 12a-d and to 3-arylthio- 1-naphthols 14a, b, resp. Heating of the cyclobutenone 12d in the presence of N-methylaniline furnishes the 2-butenanilide 16. On reacting 1-phenylthio-1-propyne 17 with diphenylketene 18, the diphenylacetate 19 is isolated, where the naphthol derivative 14a represents the ester moiety.