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MOTIVATION The spatial conformation of the chromosome has a deep influence on gene regulation and expression. Hi-C technology allows the evaluation of the spatial proximity between any pair of loci along the genome. It results in a data matrix where blocks corresponding to (self-)interacting regions appear. The delimitation of such blocks is critical to(More)
We propose to describe exposure–response relationship of an antiepileptic agent, using mixed hidden Markov modeling methodology, to reveal additional insights in the mode of the drug action which the novel approach offers. Daily seizure frequency data from six clinical studies including patients who received gabapentin were available for the analysis. In(More)
Following the pattern of phase I clinical trials for cytotoxic drugs, dose-finding clinical trials in oncology of molecularly targeted agents (MTA) aim at determining the maximum tolerated dose (MTD). In classical phase I clinical trials, MTD is generally defined by the number of patients with short-term major treatment toxicities (usually called(More)
— The aim of the present paper is to document the need for adapting the definition of hidden Markov models (HMM) to population studies, which rigorous interpretation typically requires the use of mixed-effects models, as well as for corresponding learning methodologies. In this article, mixed hidden Markov models (MHMM) are introduced through a brief state(More)
We consider the problem of variable selection in general nonlinear mixed-eets models, including mixed-eects hidden Markov models. These models are used extensively in the study of repeated measurements and longitudinal analysis. We propose a Bayesian Information Criterion (BIC) that is appropriate for nonstandard situations where both the number of subjects(More)
BACKGROUND INFORMATION During phagocytosis, neutrophils internalise pathogens in a phagosome and produce reactive oxygen species (ROS) by the NADPH oxidase to kill the pathogen. The cytosolic NADPH oxidase subunits p40(phox), p47(phox), p67(phox) and Rac2 translocate to the phagosomal membrane to participate in enzyme activation. The kinetics of this(More)
For about a decade, early clinical development in oncology is facing new challenges. This is due to two main reasons. The first one is linked to the developed molecular targeted agents (MTA) themselves for which the maximum tolerated dose (MTD) is no longer the only dose of interest. The second reason is related to the fact that costs and attrition rates(More)
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