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Lévy flights are known to be optimal search strategies in the particular case of revisitable targets. In the relevant situation of nonrevisitable targets, we propose an alternative model of two-dimensional (2D) search processes, which explicitly relies on the widely observed intermittent behavior of foraging animals. We show analytically that intermittent(More)
Albers-Schönberg disease, or autosomal dominant osteopetrosis, type II (ADO II), is the most common form of osteopetrosis, a group of conditions characterized by an increased skeletal mass due to impaired bone and cartilage resorption. Following the assignment of the gene causing ADO II to chromosome 16p13.3, we now report seven different mutations in the(More)
It has long been appreciated that the transport properties of molecules can control reaction kinetics. This effect can be characterized by the time it takes a diffusing molecule to reach a target-the first-passage time (FPT). Determining the FPT distribution in realistic confined geometries has until now, however, seemed intractable. Here, we calculate this(More)
OBJECTIVE To evaluate ixekizumab, an anti-interleukin-17A (anti-IL-17A) monoclonal antibody, in 2 populations of rheumatoid arthritis (RA) patients: biologics-naive patients and patients with an inadequate response to tumor necrosis factor (TNF) inhibitors. METHODS In this phase II, randomized, double-blind study, placebo or ixekizumab was administered(More)
Falls represent a major public health problem in older people, predominantly due to the resulting injuries which lead to progressive disability, immobilization and resulting comorbidities, dependency, institutionalization, and death. Reduced muscle strength and power have been consistently identified as risk factors for falls and related injuries, and it is(More)
Bone is a dynamic tissue that is subject to the balanced processes of bone formation and bone resorption. Imbalance can give rise to skeletal pathologies with increased bone density. In recent years, several genes underlying such sclerosing bone disorders have been identified. The LDL receptor-related protein 5 (LRP5) gene has been shown to be involved in(More)
Problems of search and recognition appear over different scales in biological systems. In this review we focus on the challenges posed by interactions between proteins, in particular transcription factors, and DNA and possible mechanisms which allow for fast and selective target location. Initially we argue that DNA-binding proteins can be classified,(More)
Gene regulation relies on transcription factors (TFs) exploring the nucleus searching their targets. So far, most studies have focused on how fast TFs diffuse, underestimating the role of nuclear architecture. We implemented a single-molecule tracking assay to determine TFs dynamics. We found that c-Myc is a global explorer of the nucleus. In contrast, the(More)
What is the fastest way of finding a randomly hidden target? Experimental observations reveal that the search behavior of foraging animals is generally intermittent: active search phases randomly alternate with phases of fast ballistic motion. Here, we study the efficiency of this two state search strategy by calculating analytically the mean first passage(More)
CONTEXT Genetic factors are important determinants of bone mineral density (BMD). The fact that mutations in the ClC-7 chloride channel cause autosomal dominant osteopetrosis (ADOII) make the CLCN7 gene an attractive candidate for the regulation of bone density. OBJECTIVE The objective of the study was to investigate the association between polymorphisms(More)