New Insights into the Genetic Etiology of Alzheimer’s Disease and Related Dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Traffic-aware Distribution of e-Commerce Services

e-Commerce services have become a promising and profitable application of the Internet. Nevertheless, the use of the Internet as the communication environment in this case is not without its problems. For an e-commerce site to be successful it has to reduce the negative effects of unreliable connections and high network latencies, among others. Such problems may compromise customer satisfaction and therefore the success of the virtual business. Techniques based on improving the quality of a centralized server do not provide a reliable solution, since the difficulties faced are inherent to the network infrastructure itself, not just the server. A better solution tends to be the distribution of the service over the network, placing servers in multiple locations closer to the final users. The existence of multiple servers tends to increase availability, and assuming the placement iswell planned, it tends to reduce delays and traffic-related costs. In this paper we discuss the distribution of e-commerce services by introducing a traffic-aware cost model and evaluating it through an actual log from an e-tailer. The results show that the model allow system designers to investigate cost compromises and the impact of the application workload on the efectiveness of the distribution in terms of reducing traffic, and thus operational costs and user-perceived latency