Co-aggregation with apolipoprotein E modulates the function of amyloid-β in Alzheimer's disease

Which isoforms of apolipoprotein E (apoE) we inherit determine our risk of developing late-onset Alzheimer’s Disease (AD), but the mechanism underlying this link is poorly understood. In particular, the relevance of direct interactions between apoE and amyloid-β (Aβ) remains controversial. Here, single-molecule imaging shows that all isoforms of apoE associate with Aβ in the early stages of aggregation and then fall away as fibrillation happens. ApoE-Aβ co-aggregates account for ~50% of the mass of diffusible Aβ aggregates detected in the frontal cortices of homozygotes with the higher-risk APOE4 gene. We show how dynamic interactions between apoE and Aβ tune disease-related functions of Aβ aggregates throughout the course of aggregation. Our results connect inherited APOE genotype with the risk of developing AD by demonstrating how, in an isoform- and lipidation-specific way, apoE modulates the aggregation, clearance and toxicity of Aβ. Selectively removing non-lipidated apoE4-Aβ co-aggregates enhances clearance of toxic Aβ by glial cells, and reduces secretion of inflammatory markers and membrane damage, demonstrating a clear path to AD therapeutics

A study on factors for retailers implementing CPFR — A fuzzy AHP analysis

[[abstract]]Since collaborative, planning, forecasting, and replenishment (CPFR) was first proposed in 1998, numerous studies have focused on exploring its implementation in retailing contexts. While a considerable body of research has emphasized reduced costs, increased sales and improved forecasting ability, there has been a lack of research on the importance of each of the various factors which affect such implementations. In order to find out the critical success factors affecting CPFR implementation, this paper first collected related influence factors regarding adopting CPFR or business to business (B2B) information systems, and further constructed a factor table with a three-layer hierarchical structure. A pair wise analytic hierarchy process (AHP) questionnaire was designed and distributed to experts who were familiar with implementing CPFR in the retailing industry. After questionnaires were returned, we found out the weights of each impact factor by using a fuzzy analytic hierarchy process (fuzzy AHP) approach. The importance of each critical impact factor was investigated, and the paths of the critical success factors were also analyzed. The results of this study can provide more precise information with regard to allocating optimal resources for retailers implementing CPFR

Factors Affecting the Successful Realisation of Benefits from Systems Development Projects: Findings from Three Case Studies

This article was published in the Journal of Information Technology [© Palgrave Macmillan] and the definitive version is available at: http://dx/doi.org/10.1057/jit.2011.8The return that organisations derive from investments in information systems and technology continues to disappoint. While there is a very significant body of literature on the factors that should facilitate a successful outcome from systems development, there is growing concern that these prescriptions are not having their desired effect. In this paper, we argue that the success of a systems development project should be measured in terms of its ability to deliver meaningful benefits, rather than the timely delivery of a technical artefact, and therefore organisations should adopt an explicit and proactive benefits realisation approach when investing in IT. Consequently, we sought to explore those actionable factors that might facilitate the effective realisation of benefits from systems development initiatives. Three organisations were identified that claimed to adopt a proactive approach to benefits realisation, and detailed studies of their systems development practices were conducted. Our analysis found that whilst one organisation had been successful in its adoption of a benefits realisation perspective, the other two had not, and this allowed us to identify those factors that helped to explain this difference in outcomes. In short, this paper makes an important contribution by identifying how a sub-set of traditional systems success factors might be enhanced, to give them a more explicit benefits realisation orientation. Moreover, it presents a coherent set of principles that can be used for deriving other factors and practices