The probability distribution of a trapped Brownian particle in plane shear flows

We investigate the statistical properties of an over-damped Brownian particle that is trapped by a harmonic potential and simultaneously exposed to a linear shear flow or to a plane Poiseuille flow. Its probability distribution is determined via the corresponding Smoluchowski equation, which is solved analytically for a linear shear flow. In the case of a plane Poiseuille flow, analytical approximations for the distribution are obtained by a perturbation analysis and they are substantiated by numerical results. There is a good agreement between the two approaches for a wide range of parameters.Comment: 5 pages, 4 figur

Direct measurement of shear-induced cross-correlations of Brownian motion

Shear-induced cross-correlations of particle fluctuations perpendicular and along stream-lines are investigated experimentally and theoretically. Direct measurements of the Brownian motion of micron-sized beads, held by optical tweezers in a shear-flow cell, show a strong time-asymmetry in the cross-correlation, which is caused by the non-normal amplification of fluctuations. Complementary measurements on the single particle probability distribution substantiate this behavior and both results are consistent with a Langevin model. In addition, a shear-induced anti-correlation between orthogonal random-displacements of two trapped and hydrodynamically interacting particles is detected, having one or two extrema in time, depending on the positions of the particles.Comment: 4 pages, 4 figure

Dynamics of a trapped Brownian particle in shear flows

The Brownian motion of a particle in a harmonic potential, which is simultaneously exposed either to a linear shear flow or to a plane Poiseuille flow is investigated. In the shear plane of both flows the probability distribution of the particle becomes anisotropic and the dynamics is changed in a characteristic manner compared to a trapped particle in a quiescent fluid. The particle distribution takes either an elliptical or a parachute shape or a superposition of both depending on the mean particle position in the shear plane. Simultaneously, shear-induced cross-correlations between particle fluctuations along orthogonal directions in the shear plane are found. They are asymmetric in time. In Poiseuille flow thermal particle fluctuations perpendicular to the flow direction in the shear plane induce a shift of the particle's mean position away from the potential minimum. Two complementary methods are suggested to measure shear-induced cross-correlations between particle fluctuations along orthogonal directions.Comment: 14 pages, 7 figure

SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints

Background: Genomic disorders are caused by copy number changes that may exhibit recurrent breakpoints processed by nonallelic homologous recombination. However, region-specific disease-associated copy number changes have also been observed which exhibit non-recurrent breakpoints. The mechanisms underlying these non-recurrent copy number changes have not yet been fully elucidated. Results: We analyze large NF1 deletions with non-recurrent breakpoints as a model to investigate the full spectrum of causative mechanisms, and observe that the

A Genetically Hard-Wired Metabolic Transcriptome in Plasmodium falciparum Fails to Mount Protective Responses to Lethal Antifolates

Genome sequences of Plasmodium falciparum allow for global analysis of drug responses to antimalarial agents. It was of interest to learn how DNA microarrays may be used to study drug action in malaria parasites. In one large, tightly controlled study involving 123 microarray hybridizations between cDNA from isogenic drug-sensitive and drug-resistant parasites, a lethal antifolate (WR99210) failed to over-produce RNA for the genetically proven principal target, dihydrofolate reductase-thymidylate synthase (DHFR-TS). This transcriptional rigidity carried over to metabolically related RNA encoding folate and pyrimidine biosynthesis, as well as to the rest of the parasite genome. No genes were reproducibly up-regulated by more than 2-fold until 24 h after initial drug exposure, even though clonal viability decreased by 50% within 6 h. We predicted and showed that while the parasites do not mount protective transcriptional responses to antifolates in real time, P. falciparum cells transfected with human DHFR gene, and adapted to long-term WR99210 exposure, adjusted the hard-wired transcriptome itself to thrive in the presence of the drug. A system-wide incapacity for changing RNA levels in response to specific metabolic perturbations may contribute to selective vulnerabilities of Plasmodium falciparum to lethal antimetabolites. In addition, such regulation affects how DNA microarrays are used to understand the mode of action of antimetabolites