Probing microscopic origins of confined subdiffusion by first-passage observables

Subdiffusive motion of tracer particles in complex crowded environments, such as biological cells, has been shown to be widepsread. This deviation from brownian motion is usually characterized by a sublinear time dependence of the mean square displacement (MSD). However, subdiffusive behavior can stem from different microscopic scenarios, which can not be identified solely by the MSD data. In this paper we present a theoretical framework which permits to calculate analytically first-passage observables (mean first-passage times, splitting probabilities and occupation times distributions) in disordered media in any dimensions. This analysis is applied to two representative microscopic models of subdiffusion: continuous-time random walks with heavy tailed waiting times, and diffusion on fractals. Our results show that first-passage observables provide tools to unambiguously discriminate between the two possible microscopic scenarios of subdiffusion. Moreover we suggest experiments based on first-passage observables which could help in determining the origin of subdiffusion in complex media such as living cells, and discuss the implications of anomalous transport to reaction kinetics in cells.Comment: 21 pages, 3 figures. Submitted versio

On the joint residence time of N independent two-dimensional Brownian motions

We study the behavior of several joint residence times of N independent Brownian particles in a disc of radius $R$ in two dimensions. We consider: (i) the time T_N(t) spent by all N particles simultaneously in the disc within the time interval [0,t]; (ii) the time T_N^{(m)}(t) which at least m out of N particles spend together in the disc within the time interval [0,t]; and (iii) the time {\tilde T}_N^{(m)}(t) which exactly m out of N particles spend together in the disc within the time interval [0,t]. We obtain very simple exact expressions for the expectations of these three residence times in the limit t\to\infty.Comment: 8 page

Hepatic safety of antibiotics used in primary care

Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug's pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic metabolites. With the exception of trovafloxacin and telithromycin (now severely restricted), hepatotoxicity crude incidence remains globally low but variable. Thus, amoxicillin/clavulanate and co-trimoxazole, as well as flucloxacillin, cause hepatotoxic reactions at rates that make them visible in general practice (cases are often isolated, may have a delayed onset, sometimes appear only after cessation of therapy and can produce an array of hepatic lesions that mirror hepatobiliary disease, making causality often difficult to establish). Conversely, hepatotoxic reactions related to macrolides, tetracyclines and fluoroquinolones (in that order, from high to low) are much rarer, and are identifiable only through large-scale studies or worldwide pharmacovigilance reporting. For antibiotics specifically used for tuberculosis, adverse effects range from asymptomatic increases in liver enzymes to acute hepatitis and fulminant hepatic failure. Yet, it is difficult to single out individual drugs, as treatment always entails associations. Patients at risk are mainly those with previous experience of hepatotoxic reaction to antibiotics, the aged or those with impaired hepatic function in the absence of close monitoring, making it important to carefully balance potential risks with expected benefits in primary care. Pharmacogenetic testing using the new genome-wide association studies approach holds promise for better understanding the mechanism(s) underlying hepatotoxicity

Lévy strategies in intermittent search processes are advantageous

Intermittent search processes switch between local Brownian search events and ballistic relocation phases. We demonstrate analytically and numerically in one dimension that when relocation times are Lévy distributed, resulting in a Lévy walk dynamics, the search process significantly outperforms the previously investigated case of exponentially distributed relocation times: The resulting Lévy walks reduce oversampling and thus further optimize the intermittent search strategy in the critical situation of rare targets. We also show that a searching agent that uses the Lévy strategy is much less sensitive to the target density, which would require considerably less adaptation by the searcher

Renal pathology, glomerular number and volume in a West African urban community

Background. Low glomerular number and large glomerular volume are hypothesized to be risk factors for hypertensive renal disease in adult life. Reports of human glomerular number are based on studies from developed nations and have found single kidney mean values of ∼900 000 per kidney with a roughly 8-fold range matched by a similar range in glomerular volume. Glomerular number and volume have never been investigated in people from a developing country

A comparison of nephron number, glomerular volume and kidney weight in Senegalese Africans and African Americans

Background. Low nephron number is determined in utero and is a proposed risk for essential hypertension. Glomerular volume is inversely correlated with nephron number, and genetic and environmental factors that determine nephron number are thought to determine glomerular volume. This study compared total glomerular (nephron) number (Nglom), mean glomerular volume (Vglom) and kidney weight in two geographically separated black populations with significant common genetic ancestry