Generating dynamic higher-order Markov models in web usage mining

Markov models have been widely used for modelling users’ web navigation behaviour. In previous work we have presented a dynamic clustering-based Markov model that accurately represents second-order transition probabilities given by a collection of navigation sessions. Herein, we propose a generalisation of the method that takes into account higher-order conditional probabilities. The method makes use of the state cloning concept together with a clustering technique to separate the navigation paths that reveal differences in the conditional probabilities. We report on experiments conducted with three real world data sets. The results show that some pages require a long history to understand the users choice of link, while others require only a short history. We also show that the number of additional states induced by the method can be controlled through a probability threshold parameter

Body mass index and age at natural menopause: an international pooled analysis of 11 prospective studies

Current evidence on the association between body mass index (BMI) and age at menopause remains unclear. We investigated the relationship between BMI and age at menopause using data from 11 prospective studies. A total of 24,196 women who experienced menopause after recruitment was included. Baseline BMI was categorised according to the WHO criteria. Age at menopause, confirmed by natural cessation of menses for ≥ 12 months, was categorised as < 45 years (early menopause), 45–49, 50–51 (reference category), 52–53, 54–55, and ≥ 56 years (late age at menopause). We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CI) for the associations between BMI and age at menopause. The mean (standard deviation) age at menopause was 51.4 (3.3) years, with 2.5% of the women having early and 8.1% late menopause. Compared with those with normal BMI (18.5–24.9 kg/m2), underweight women were at a higher risk of early menopause (RRR 2.15, 95% CI 1.50–3.06), while overweight (1.52, 1.31–1.77) and obese women (1.54, 1.18–2.01) were at increased risk of late menopause. Overweight and obesity were also significantly associated with around 20% increased risk of menopause at ages 52–53 and 54–55 years. We observed no association between underweight and late menopause. The risk of early menopause was higher among obese women albeit not significant (1.23, 0.89–1.71). Underweight women had over twice the risk of experiencing early menopause, while overweight and obese women had over 50% higher risk of experiencing late menopause

On-Demand Prefetching Heuristic Policies: A Performance Evaluation

International audiencePrefetching is a basic mechanism in the World Wide Web that speculates on the future behaviour of users to avoid the response delays. The relatively new requirement of the instantaneous response in some interactive services like On-Demand applications fuelled the need for ways to represent and reason about the challenging problem of prefetching control and performance evaluation. We study this challenging problem under a network protocol that adopts the simultaneous prefetching with equal-shared bandwidth, and in prefetching situations in which the controller seeks to reach a Zero-Cost system state as quickly as possible. Within this context, our first contribution is providing the backbone of a new paradigm for the performance evaluation of the On-demand prefetching policy. This backbone consists of our previously developed prefetching control model; the PREF-CT model and our previously developed optimal control algorithms; the ONE-PASS and the TREE-DEC algorithms. Our second contribution is developing the prefetching heuristic algorithm: the RBP. Compared to the optimal prefetching policies, the prefetching policies computed by our heuristic algorithm the RBP show significant performance in terms of the user’s latency and the bandwidth utilization

Delivery of CRISPR/Cas9 Plasmid DNA by Hyperbranched Polymeric Nanoparticles Enables Efficient Gene Editing

Gene editing nucleases such as CRISPR/Cas9 have enabled efficient and precise gene editing in vitro and hold promise of eventually achieving in vivo gene editing based therapy. However, a major challenge for their use is the lack of a safe and effective virus-free system to deliver gene editing nuclease elements. Polymers are a promising class of delivery vehicle due to their higher safety compared to currently used viral vectors, but polymers suffer from lower transfection efficiency. Polymeric vectors have been used for small nucleotide delivery but have yet to be used successfully with plasmid DNA (pDNA), which is often several hundred times larger than small nucleotides, presenting an engineering challenge. To address this, we extended our previously reported hyperbranched polymer (HP) delivery system for pDNA delivery by synthesizing several variants of HPs: HP-800, HP-1.8K, HP-10K, HP-25K. We demonstrate that all HPs have low toxicity in various cultured cells, with HP-25K being the most efficient at packaging and delivering pDNA. Importantly, HP-25K mediated delivery of CRISPR/Cas9 pDNA resulted in higher gene-editing rates than all other HPs and Lipofectamine at several clinically significant loci in different cell types. Consistently, HP-25K also led to more robust base editing when delivering the CRISPR base editor “BE4-max” pDNA to cells compared with Lipofectamine. The present work demonstrates that HP nanoparticles represent a promising class of vehicle for the non-viral delivery of pDNA towards the clinical application of gene-editing therapy

Delivery of CRISPR/Cas9 Plasmid DNA by Hyperbranched Polymeric Nanoparticles Enables Efficient Gene Editing

Gene editing nucleases such as CRISPR/Cas9 have enabled efficient and precise gene editing in vitro and hold promise of eventually achieving in vivo gene editing based therapy. However, a major challenge for their use is the lack of a safe and effective virus-free system to deliver gene editing nuclease elements. Polymers are a promising class of delivery vehicle due to their higher safety compared to currently used viral vectors, but polymers suffer from lower transfection efficiency. Polymeric vectors have been used for small nucleotide delivery but have yet to be used successfully with plasmid DNA (pDNA), which is often several hundred times larger than small nucleotides, presenting an engineering challenge. To address this, we extended our previously reported hyperbranched polymer (HP) delivery system for pDNA delivery by synthesizing several variants of HPs: HP-800, HP-1.8K, HP-10K, HP-25K. We demonstrate that all HPs have low toxicity in various cultured cells, with HP-25K being the most efficient at packaging and delivering pDNA. Importantly, HP-25K mediated delivery of CRISPR/Cas9 pDNA resulted in higher gene-editing rates than all other HPs and Lipofectamine at several clinically significant loci in different cell types. Consistently, HP-25K also led to more robust base editing when delivering the CRISPR base editor &ldquo;BE4-max&rdquo; pDNA to cells compared with Lipofectamine. The present work demonstrates that HP nanoparticles represent a promising class of vehicle for the non-viral delivery of pDNA towards the clinical application of gene-editing therapy

Maturity, distance and density (MD 2) metrics for optimizing trust prediction for business intelligence

Trust, Trust prediction, Optimization, Prediction, Business intelligence, Optimized business intelligence,